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SCHOLAR Study Guide
CfE Higher Human Biology
Unit 4: Immunology and Public
Health
Authored by:
Eoin McIntyre (Previously Auchmuty High School)
Reviewed by:
Sheena Haddow (Perth College)
Previously authored by:
Mike Cheung
Eileen Humphrey
Eoin McIntyre
Jim McIntyre
Heriot-Watt University
Edinburgh EH14 4AS, United Kingdom.
First published 2014 by Heriot-Watt University.
This edition published in 2016 by Heriot-Watt University SCHOLAR.
Copyright © 2016 SCHOLAR Forum.
Members of the SCHOLAR Forum may reproduce this publication in whole or in part for
educational purposes within their establishment providing that no profit accrues at any stage,
Any other use of the materials is governed by the general copyright statement that follows.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system
or transmitted in any form or by any means, without written permission from the publisher.
Heriot-Watt University accepts no responsibility or liability whatsoever with regard to the
information contained in this study guide.
Distributed by the SCHOLAR Forum.
SCHOLAR Study Guide Unit 4: CfE Higher Human Biology
1. CfE Higher Human Biology Course Code: C740 76
ISBN 978-1-909633-19-3
Print Production and Fulfilment in UK by Print Trail www.printtrail.com
Acknowledgements
Thanks are due to the members of Heriot-Watt University’s SCHOLAR team who planned and
created these materials, and to the many colleagues who reviewed the content.
We would like to acknowledge the assistance of the education authorities, colleges, teachers
and students who contributed to the SCHOLAR programme and who evaluated these materials.
Grateful acknowledgement is made for permission to use the following material in the
SCHOLAR programme:
The Scottish Qualifications Authority for permission to use Past Papers assessments.
The Scottish Government for financial support.
The content of this Study Guide is aligned to the Scottish Qualifications Authority (SQA)
curriculum.
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i
Contents
1 Non-specific defences
1.1 Introduction . . . . . . . . . . . . . . . . . . .
1.2 The immune system . . . . . . . . . . . . . .
1.3 Non-specific defences - physical and chemical
1.4 The inflammatory response . . . . . . . . . .
1.5 Non-specific cellular responses . . . . . . . .
1.6 Learning points . . . . . . . . . . . . . . . . .
1.7 Extended response question . . . . . . . . . .
1.8 End of topic test . . . . . . . . . . . . . . . . .
2 Specific cellular defences
2.1 Immune surveillance . . . .
2.2 Clonal selection theory . . .
2.3 T- and B-lymphocytes . . . .
2.4 The action of T-lymphocytes
2.5 The action of B-lymphocytes
2.6 Immunological memory . . .
2.7 Learning points . . . . . . .
2.8 Extended response question
2.9 End of topic test . . . . . . .
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3 The transmission and control of infectious diseases
3.1 Infectious diseases caused by pathogens . . . . .
3.2 Methods of transmission of pathogens . . . . . .
3.3 Control of spread of pathogens . . . . . . . . . .
3.4 Epidemiological studies of infectious diseases . .
3.5 Learning points . . . . . . . . . . . . . . . . . . .
3.6 Extended response question . . . . . . . . . . . .
3.7 End of topic test . . . . . . . . . . . . . . . . . . .
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4 Active immunisation
4.1 Active immunisation and vaccination . . . . . . . . . . .
4.2 Herd Immunity . . . . . . . . . . . . . . . . . . . . . . . .
4.3 Immunisation programmes . . . . . . . . . . . . . . . . .
4.4 The evasion of specific immune responses by pathogens
4.5 Learning points . . . . . . . . . . . . . . . . . . . . . . .
4.6 Extended response question . . . . . . . . . . . . . . . .
4.7 End of topic test . . . . . . . . . . . . . . . . . . . . . . .
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5 End of unit test
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81
ii
CONTENTS
Glossary
85
Answers to questions and activities
1
Non-specific defences . . . . . . . . . . . . . . . . .
2
Specific cellular defences . . . . . . . . . . . . . . .
3
The transmission and control of infectious diseases .
4
Active immunisation . . . . . . . . . . . . . . . . . .
5
End of unit test . . . . . . . . . . . . . . . . . . . . .
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87
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91
95
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102
© H ERIOT-WATT U NIVERSITY
1
Topic 1
Non-specific defences
Contents
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
Introduction . . . . . . . . . . . . . . . . . . .
The immune system . . . . . . . . . . . . . .
Non-specific defences - physical and chemical
The inflammatory response . . . . . . . . . .
1.4.1 Inflammation . . . . . . . . . . . . . . .
1.4.2 The cellular basis of inflammation . . .
Non-specific cellular responses . . . . . . . .
1.5.1 Phagocytes . . . . . . . . . . . . . . . .
1.5.2 Natural killer (NK) cells . . . . . . . . .
Learning points . . . . . . . . . . . . . . . . .
Extended response question . . . . . . . . . .
End of topic test . . . . . . . . . . . . . . . . .
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2
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Prerequisite knowledge
You should already know about:
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defences against disease (phagocytosis, antibodies, vaccination);
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diseases (viruses, bacteria, fungi, parasites);
•
hygiene (personal, sexual, food, water).
Learning objectives
By the end of this topic, you should be able to:
•
state that the body’s capacity to protect itself against pathogens, some toxins and
cancer cells is achieved by means of the immune system;
•
describe the nature of the body’s chemical and physical defences against
pathogens;
•
describe the inflammatory response;
•
describe the non-specific cellular responses.
2
TOPIC 1. NON-SPECIFIC DEFENCES
1.1
Introduction
If it were possible that an intelligent life-form from another planet in our galaxy could
visit Earth, and that we could communicate with it, we might ask what it thought of
the place. If we enquired about what it considered to be the dominant life-form, we
might be surprised at the answer because it has been estimated that 90% of the energy
processed by organisms on the planet is done so by bacteria. Likewise, the total
biomass of bacteria on the planet is thought to exceed that of all other living things
put together. With an average size of 1µm, they have found niches virtually everywhere,
from the bedrock, to the clouds, the deep sea floor, and hot springs. And, of course,
nine tenths of the cells within our bodies are bacteria.
It may be a bit disconcerting to conceive of ourselves as habitats, but we are just that
(and a very attractive one!) to bacteria and other microbes. Our tissues are warm
and constantly bathed in nutrient- and oxygen-rich fluid, conditions which are perfect for
microbes to thrive in. Much of this is true of all multicellular organisms, and so, to exist
at all, they have had to evolve methods of countering colonisation by microbes.
A common misconception is that all microbes are potential pathogens, but that is far
from true. We could not live a healthy life without our varied and complex gut flora of
bacteria, and trees could not absorb nutrients from the soil without the aid of the fungal
threads attached to their roots.
It should also be remembered that although we tend to think of bacteria in relation to
infection, the heterotrophic organisms that test our defences come from all categories,
so we have to be able to defend ourselves against viruses (e.g. flu), bacteria (e.g.
pneumonia), fungi (e.g. athlete’s foot), protozoans (e.g. malaria), and even quite large
animals (e.g. tapeworms). We will leave the discussion about whether viruses are alive
to another time.
This unit addresses the natural defences that our bodies have against microbial attack
in the form of our immune system, and the precautions that human societies put in place
to counter the spread of disease in the shape of public health measures.
1.2
The immune system
Learning objective
By the end of this section, you should be able to:
•
state that the function of the immune system is to protect the body against
pathogens, some toxins and cancer cells.
The body’s capacity to protect itself against pathogens, some toxins and cancer cells
is achieved by means of the immune system. We have three lines of defence against
attack by pathogens.
1. The first line of defence is non-specific - an external barrier of skin and mucous
membranes and the secretions that they produce. The skin provides a physical
barrier of dry, dead cells and mildly acidic conditions. Areas of the body which
© H ERIOT-WATT U NIVERSITY
TOPIC 1. NON-SPECIFIC DEFENCES
3
are not protected by this barrier, such as the eyes and mouth, have secretions in
the form of tears and saliva, which contain a variety of antimicrobial enzymes, e.g.
lysozyme which degrades bacterial cell walls.
2. The second line of defence is also non-specific, and comes into play when the
first line of defence is breached and an intruder, such as a bacterium, gets into
the body tissues. The intruder produces chemical signals that are detected by a
variety of white blood cells which will attack it in a number of ways, e.g. neutrophils
and macrophages which engulf the invading cells, and natural killer cells (NK cells)
which release chemicals that cause their death. An area of inflammation indicates
that the second line of defence has been deployed.
3. The third line of defence, the specific immune response (to be covered in Topic 2)
comes into play at the same time as the second line of defence. Here, the immune
system directly targets the invader, which can be any organism or substance that
carries foreign molecules.
Immunity is the ability of the body to resist or overcome an infection by a pathogen and
can be either innate or acquired. Innate immunity is inborn, non-specific, and does not
change over time. Examples include:
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phagocytosis by phagocytes;
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skin epithelial cells;
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mucus membranes of the lungs and gut;
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ciliated cells of the respiratory tract;
•
lysozyme in tears.
Acquired immunity develops throughout a person’s life time and can be induced either
naturally or artificially. It involves another group of white blood cells, lymphocytes,
which respond to marker chemicals on the surface of the foreign cells called antigens,
producing antibodies against them. A second response is the production of memory
cells, which enable the immune system to react more quickly and vigorously to reinfection by pathogens.
The immune system: Questions
Q1: What is the function of the immune system?
..........................................
Q2: List two examples of non-specific first line of defence against diseases.
..........................................
Q3: What is the function of the lysozyme in tears?
..........................................
Q4: Explain the term ’innate immunity’ and list two examples.
..........................................
Q5: What is a phagocyte?
..........................................
© H ERIOT-WATT U NIVERSITY
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4
TOPIC 1. NON-SPECIFIC DEFENCES
1.3
Non-specific defences - physical and chemical
Learning objective
By the end of this section, you should be able to:
•
give examples of the body’s chemical and physical defences against pathogens;
•
explain that epithelial cells form a physical barrier and produce secretions
against infection.
You should remember from Unit 1 that epithelial cells provide the inner and outer linings
of body cavities, for example the stomach and the urinary tract. They act as the barrier
between the external environment and the body tissues.
The skin is considered to be the first line of defence for the human body. Its structure
ensures that very few microorganisms can penetrate unless it is damaged. In addition,
the secretion of antimicrobial chemicals by the skin and tear glands offers additional
protection.
The outermost part of the skin, or epidermis, is a multilayered tissue. At its base are
stem cells which divide to continually replace the layers above it. As they move from the
base towards the surface, the cells gradually change their structure to give the epidermis
its tough elastic properties. The outer layer consists of dead cells, which are regularly
sloughed off as a result of friction with the environment. These are dry and provide an
environment which is inhospitable to microbes.
Associated with the hair follicles on the skin are the sebaceous glands, which secrete the
waxy sebum that keeps the skin supple and contains fatty acids which have antimicrobial
properties. Similarly, earwax contains chemicals which inhibit the growth of pathogenic
bacteria and fungi.
Certain types of epithelial cells secrete fluids that are necessary for processes such as
digestion, protection, excretion of waste products and the regulation of the metabolic
processes of the body, e.g. the goblet cells which secrete mucus.
Epithelial tissues containing goblet cells
© H ERIOT-WATT U NIVERSITY
TOPIC 1. NON-SPECIFIC DEFENCES
5
Some epithelial tissues are specialised to secrete specific substances, such as
enzymes, hormones and lubricating fluids, to defend against infections. The goblet
cells in the trachea secrete mucus which, being a sticky substance, is able to adhere to
foreign particles, thus holding them on the surface. This adhesion allows the cilia which
line the bronchi to sweep the mucus, with its entrapped particles, up into the pharynx
where it is swallowed. Antimicrobial chemicals are also found in the mucus, secreted by
the epithelial linings of the respiratory and upper gastrointestinal tracts.
The body can also provide other physical and chemical defences:
•
tiny hairs at the entrance to the nose;
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cough and sneeze reflexes;
•
acid secretions which kill microbes, e.g. stomach;
•
the so-called ’friendly’ bacteria which are the many harmless microbes normally
found on the skin and epithelial linings that are exposed to the external
environment - by means of a variety of mechanisms, these microbes can suppress
the growth of other potentially more dangerous and harmful ones.
Non-specific defences - physical and chemical: Questions
Q6: State two ways in which the skin is a physical barrier to microbes.
..........................................
Q7: State two ways in which the epithelium presents a chemical barrier to microbes.
..........................................
© H ERIOT-WATT U NIVERSITY
Go online
6
TOPIC 1. NON-SPECIFIC DEFENCES
1.4
The inflammatory response
Learning objective
By the end of this section, you should be able to:
•
state that mast cells release histamine;
•
explain that histamine causes vasodilation and increases capillary permeability;
•
state that mast cells also secrete cytokines which act as signalling molecules;
•
explain that the increased blood flow and the secretion of cytokines lead to:
1.4.1
◦
accumulation of phagocytes such as macrophages and neutrophils;
◦
delivery of antimicrobial proteins and clotting elements to the site of
infection/damage.
Inflammation
We are all familiar with the reddening which follows the infection of a scratch, bite or
sting. However, in medical terms, inflammation is a more complex issue. It is a response
of the immune system to an infection or irritation. Some 2000 years ago, inflammation
was characterised into:
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rubor - redness;
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calor - heat;
•
tumour - swelling;
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dolo - pain;
•
functio laesa, the fifth sign of inflammation, which results in the dysfunction of the
organs involved.
© H ERIOT-WATT U NIVERSITY
TOPIC 1. NON-SPECIFIC DEFENCES
7
Main events in the inflammatory response
Go online
10 min
..........................................
1.4.2
The cellular basis of inflammation
The main purpose of the complex inflammatory process is to bring fluids, proteins and
cells from the blood to the damaged tissues. It should be remembered that the fluid that
bathes the cells of the body’s tissues and organs lacks most of the proteins and cells
that are found in the blood because they are not able to pass through the capillary walls.
Thus, to combat damage and infections, there must be mechanisms which allow these
proteins and cells to move out of the blood circulation and into the surrounding tissue
fluid. This process can be broken down into six stages.
Stage 1: The action of mast cells
Mast cells are found in connective tissue, where they cluster around blood vessels and
nerves. They are most common where our tissues meet the outside world, e.g. skin, gut,
mouth, eyes and nose. Although they resemble certain white blood cells and, like them,
are produced by stem cells in the bone marrow, they are derived from a different cell
line. Perhaps best known for mediating allergies, they also play a key role in protection
against infection. They are activated by chemicals that are released during an infection
or from damaged cells, as a result of which they release histamine in large quantities.
© H ERIOT-WATT U NIVERSITY
8
TOPIC 1. NON-SPECIFIC DEFENCES
A mast cell
Stage 2: Vasodilation and increased capillary permeability
Histamine is a small, organic, nitrogenous molecule which has many roles in the body.
In the inflammatory response, it stimulates the arterioles of the affected area to dilate,
increasing blood flow into the capillary beds, and the walls of the capillaries to become
more permeable, allowing plasma, proteins and white blood cells (neutrophils) to pass
through. Within minutes of an injury, this is noticeable as a swelling and reddening of
the area, and a feeling of heat.
Stage 3: Secretion of cytokines
The mast cells and the neutrophils also release a type of signalling compound called
cytokines. Like histamine, these have a wide range of roles in the body, but in this case
they act to attract another type of white blood cell, monocytes, to the area.
Stage 4: Phagocytosis
Once in the tissue, the neutrophils begin the removal of invading bacteria by
phagocytosis.
They are soon joined by the monocytes, which mature into
macrophages and then clean up the damaged area by engulfing cell debris and
bacteria by phagocytosis. After digestion is complete, the identifying surface molecules
(antigens) of invading cells are transported to the surface of the macrophages where
they assist the other cells of the immune system to develop protection against the
invader.
The term ’phagocyte’ is used to refer to a general grouping which includes macrophages,
neutrophils and mast cells, all of which are capable of phagocytosis, but which differ in
other respects.
Stage 5: The complement system
The complement system is so-called because it helps, and indeed amplifies, the action
of the phagocytes in combating infection. It comprises over 25 small proteins found in
the blood, which are synthesised by the liver. These remain in an inactive form until
stimulated by one of several triggers; in particular the cascade is triggered if cells which
lack the surface proteins typical of the body are encountered.
© H ERIOT-WATT U NIVERSITY
TOPIC 1. NON-SPECIFIC DEFENCES
9
Activation of the first complement protein leads to activation of the second, which
activates the third, and so on, resulting in a cascade effect. These substances have
several basic functions, including enhancing phagocytosis, attracting macrophages and
neutrophils, and rupturing the membranes of microbes.
Stage 6: Clotting elements and the coagulation system
The increased permeability of the capillary walls leads to an increased flow of proteins
(’clotting elements’) as well as white blood cells into the tissues, and a second cascade
system (the ’coagulation system’) becomes active. In the infected tissue, a chemical
’tissue factor’ is released that initiates the cascade which results in the conversion of the
soluble protein fibrinogen to insoluble fibrin. The fibrin strands form a web which helps
to contain the infection and inflammation.
The cellular basis of inflammation: Questions
Q8: Where are mast cells found?
..........................................
Q9: State two effects of the histamine released by mast cells.
..........................................
Q10: Name the chemical signalling molecule which is released by mast cells and
neutrophils.
..........................................
Q11: Which type of white blood cells are attracted by this chemical?
..........................................
Q12: By what process do these cells remove bacteria from the site of infection?
..........................................
Q13: Name the cascade system which delivers antimicrobial proteins to the infected
site.
..........................................
Q14: Name the soluble and insoluble proteins at the end of the coagulation system.
..........................................
© H ERIOT-WATT U NIVERSITY
Go online
10
TOPIC 1. NON-SPECIFIC DEFENCES
1.5
Non-specific cellular responses
Learning objective
By the end of this section, you should be able to:
•
state that the white blood cells involved in the non-specific response are
phagocytes and natural killer (NK) cells;
•
state that phagocytes and NK cells release cytokines;
•
explain that cytokines stimulate the specific immune response;
•
state that phagocytes recognise surface antigen molecules on pathogens;
•
state that phagocytes destroy pathogens by phagocytosis;
•
explain that phagocytosis is engulfing and digesting solid particles;
•
state that NK cells induce pathogens to produce self-destructive enzymes;
•
state that this process of induced self-destruction by enzymes is called
apoptosis.
The business of defending the body against foreign cells and molecules which have
penetrated the first line of defence falls to certain types of white blood cell. In this
section, we will consider the non-specific role of two groups: the phagocytes (monocytes
and neutrophils) and natural killer (NK) cells.
1.5.1
Phagocytes
The name ’phagocyte’ is an umbrella term encompassing several types of white blood
cell and mast cells; their common features include their origin in the bone marrow, their
ability to move about (motility) and their ability to carry out phagocytosis.
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Phagocytosis: Steps
Go online
10 min
..........................................
The two most important phagocytes are the white blood cells: neutrophils and
monocytes. A question to be asked is how do the phagocytes (and the complement
system mentioned earlier) identify bacteria; what makes them stand out from the cells of
the body itself? The answer lies in proteins located on the surface of the cell membrane.
If a phagocyte encounters a cell which is lacking the protein markers typical of cells
belonging to the body, then a response is triggered.
Neutrophils
Neutrophils make up two thirds of the white blood cells in the blood and are the main
cells found in pus. They are attracted to the site of infection by the cytokines released
by the damaged cells, arriving in large numbers within minutes. The neutrophils also
release cytokines themselves, but their immediate effect is the engulfing of bacteria.
Their lifespan is short, being only 5-7 days in the circulation, and 1-2 days at an infection
site. This reflects the fact that they cannot replenish the digestive enzymes with which
they break down ingested bacteria.
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Once they have engulfed bacteria, the neutrophils express signal molecules on their cell
membranes which identify them to the larger macrophages, which then consume them
in turn. In addition, they secrete antimicrobial chemicals which kill bacteria by disrupting
their cell walls.
Monocytes
Monocytes are the largest of the white blood cells; at up to 20µm they are nearly
twice the size of neutrophils. They are much less common than neutrophils, making
up only some 5% of the total white blood count. About half of the body’s complement
of monocytes is held in reserve in the spleen, the other half circulating in the blood and
migrating into the tissues where they mature into macrophages capable of phagocytosis.
Attracted by cytokines that are released by neutrophils and damaged cells, additional
monocytes migrate from the blood to an infection site and turn into macrophages. They
then begin to engulf damaged cells, bacteria and ’old’ neutrophils. Unlike neutrophils,
macrophages can live for several months. Also, they express the antigens of ingested
bacteria on their outer membranes to help the other white blood cells of the immune
system (lymphocytes) identify the invaders and produce specific antibodies to combat
them.
Phagocytes: Questions
Q15: Name the chemical produced by phagocytes and NK cells.
Go online
..........................................
Q16: What is the function of this chemical?
..........................................
Q17: By what do phagocytes recognise pathogens?
..........................................
Q18: What is phagocytosis?
..........................................
1.5.2
Natural killer (NK) cells
NK cells are attracted to the site of an infection (or a tumour) after about three days by
the cytokines released by the damaged cells. They identify infected cells and tumour
cells by the presence of certain key surface chemicals and then release two types of
enzymes: perforin and a type of protease known as granzyme.
The perforin causes pores to develop in the cell membrane of the target cell so that the
granzyme can enter the cell and induce programmed cell death (apoptosis). The cell
contains apoptosis pathways which allow it to self-destruct by enzyme action and thus
be recycled in a controlled way; these pathways are activated by the granzymes and,
critically, they also cause the destruction of the viruses in the cell. Like neutrophils, NK
cells also secrete antimicrobial chemicals.
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Action of a natural killer cell
Apoptosis: Steps
Go online
5 min
..........................................
Apart from their role in non-specific response, phagocytes and NK cells are also involved
in the specific immune response (described later). After their action against invading
pathogens, they then secrete interleukin, a cytokine that stimulates the specific immune
response by activating T lymphocytes.
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Natural killer (NK) cells: Questions
Q19: What do the NK cells induce target cells to produce?
Go online
..........................................
Q20: What is the process of programmed self-destruction in cells called?
..........................................
1.6
Learning points
Summary
Physical and chemical defences
•
The function of the immune system is to protect the body against pathogens,
some toxins and cancer cells.
•
Give examples of the body’s chemical and physical defences against
pathogens, e.g. sebum secreted onto the skin contains fatty acids with
antimicrobial properties; the dry outer layers of the epidermis create an
environment hostile to pathogens.
The inflammatory response
•
Mast cells release histamine.
•
Histamine causes vasodilation and increases capillary permeability.
•
Mast cells also secrete cytokines which act as signalling molecules.
•
The increased blood flow and the secretion of cytokines lead to:
◦
◦
accumulation of phagocytes such as macrophages and neutrophils;
delivery of antimicrobial proteins and clotting elements to the site of
infection/damage.
Non-specific cellular responses
•
The white blood cells involved in the non-specific response are phagocytes
and natural killer (NK) cells.
•
Phagocytes and NK cells release cytokines.
•
Cytokines stimulate the specific immune response.
•
Phagocytes recognise surface antigen molecules on pathogens.
•
Phagocytes destroy pathogens by phagocytosis.
•
Phagocytosis is engulfing and digesting solid particles.
•
NK cells induce pathogens to produce self-destructive enzymes.
•
The process of induced self-destruction by enzymes is called apoptosis.
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1.7
15
Extended response question
The activity which follows presents an extended response question similar to the style
that you will encounter in the examination.
You should have a good understanding of the inflammatory response before attempting
the question.
You should give your completed answer to your teacher or tutor for marking, or try to
mark it yourself using the suggested marking scheme.
Extended response question: The inflammatory response
Give an account of the inflammatory response. (8 marks)
..........................................
1.8
End of topic test
End of Topic 1 test
Q21: Complete the sentences by matching the parts on the left and the right. (8 marks)
Go online
The immune system protects the body against
cytokines.
Sebum on the skin contains fatty acids with
a hostile environment.
Pathogens find the dry outer layers of the skin to be
histamine.
Mast cells release
clotting elements.
Histamine causes
antimicrobial properties.
Cytokines act as
pathogens.
Increased blood flow leads to delivery of
signalling molecules.
Phagocytes are attracted by
vasodilation.
..........................................
Q22: Complete the paragraphs by selecting words from the list. (10 marks)
response are
The white blood cells involved in the
) cells. Both phagocytes and NK cells release
killer (
stimulate the specific immune response.
and natural
which
molecules on their
Phagocytes target pathogens which they recognise by the
and digesting them in a process
cell surface. They then destroy them by
.
called
The NK cells release
enzymes of
the
which induce infected cells and pathogens to produce
pathways.
Word list: antigen, apoptosis, cytokines, engulfing, enzymes, NK, non-specific,
phagocytes, phagocytosis, self-destructive.
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..........................................
Q23: What is the function of the immune system? (1 mark)
..........................................
Q24: State two ways in which the skin prevents infection. (2 marks)
..........................................
Q25: Name the cells which release histamine. (1 mark)
..........................................
Q26: State the functions of histamine. (2 marks)
..........................................
Q27: Name the signalling molecules released by these cells. (1 mark)
..........................................
Q28: State the function of the signalling molecules. (1 mark)
..........................................
Q29: What is delivered by the increased blood flow to the site of infection? (2 marks)
..........................................
Q30: Name the two types of white blood cells involved in the non-specific response. (1
mark)
..........................................
Q31: How do phagocytes recognise pathogens? (1 mark)
..........................................
Q32: Describe the process of phagocytosis. (1 mark)
..........................................
Q33: What do NK cells induce infected cells and pathogens to produce? (1 mark)
..........................................
Q34: Name the process of programmed cell death. (1 mark)
..........................................
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Topic 2
Specific cellular defences
Contents
2.1
Immune surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18
2.2
2.3
Clonal selection theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
T- and B-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
20
23
2.4
2.5
The action of T-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The action of B-lymphocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . .
26
27
2.6
2.7
Immunological memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
30
32
2.8
2.9
Extended response question . . . . . . . . . . . . . . . . . . . . . . . . . . . .
End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33
34
Learning objectives
By the end of this topic, you should be able to:
•
describe the immune surveillance system in terms of the cells involved and their
functions;
•
explain clonal selection theory and its role in the specific immune response;
•
describe the functions of T- and B-lymphocytes;
•
explain the role of immunological memory in the development of immunity.
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In the previous topic, the body’s general response to invasion by pathogens or other
damage was described. This topic deals with the very sophisticated system which allows
the body, once it has met a particular pathogen, to respond very promptly and efficiently
to a second (or later) invasion by that organism.
2.1
Immune surveillance
Learning objective
By the end of this section, you should be able to:
•
describe the role of white blood cells as constantly monitoring the tissues;
•
explain that pathogens, and other foreign cells or materials, are recognised by
their antigens, which are molecules on their surfaces that activate the immune
system;
•
state that cytokines are released when tissues are damaged or invaded;
•
explain that cytokines attract specific white blood cells (monocytes) to the
infected/damaged tissue;
•
explain that some of these cells absorb pathogens and display fragments of their
cell membranes on their surface.
The immune system operates by means of the activities of several different types of cell.
It responds to the presence of pathogens, and other foreign cells or materials which
are recognised by their antigens; that is molecules on their surfaces which activate the
immune system.
The cells of the non-specific immune response are the mast cells, phagocytes and
natural killer (NK) cells, whereas the specific immune response operates by means of
the B- and T-lymphocytes. These cells, along with red blood cells (erythrocytes) and
platelets (thrombocytes), are all produced by division of the multipotent stem cells in the
red bone marrow (the haematopoietic stem cells). A simplified diagram of this family
tree is shown below.
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Haematopoiesis
The haematopoietic stem cells give rise to two families of cells, namely those formed
from the common myeloid progenitor, and those from the common lymphoid progenitor.
The myeloid group includes red blood cells (erythrocytes), thrombocytes (platelets),
mast cells and the various white blood cells involved in the non-specific response.
Cells of the surveillance system
The cells involved in the specific immune response, namely the T- and B-lymphocytes,
belong to the lymphoid family. An exception is the natural killer (NK) cell which, though
belonging to the lymphoid group, acts as part of the non-specific response.
The cells associated with the non-specific response provide a surveillance system in the
following ways:
1. mast cells are found within the tissues and respond within seconds to damage or
infection by releasing histamine;
2. neutrophils, which circulate in the blood, enter the tissues when the histamine
released by the mast cells causes increased blood flow to the affected tissue,
increasing permeability of the capillary walls - they are attracted to the damaged
area by chemical signals released by damaged cells;
3. the mast cells and neutrophils, as well as mopping up damaged cells and invading
pathogens by phagocytosis, also release cytokines which attract monocytes to the
tissue - these mature into macrophages which engulf damaged cells, pathogens,
and any neutrophils which are signalling that they have themselves engulfed
pathogens;
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4. some of the macrophages present fragments of the cell membrane of engulfed
pathogens on their own cell surface - these cells migrate to the lymph nodes where
the pathogen fragments, carrying their unique antigens, activate the B- and Tlymphocytes which are stored there.
Immune surveillance: Questions
Go online
Q1: Name the cells of the nonspecific immune system which first respond to infection
and are located within the tissues.
..........................................
Q2: Name the cells of the nonspecific immune system which first respond to infection
and are located in the blood.
..........................................
Q3:
Name the chemicals which attract monocytes to the damaged tissue.
..........................................
Q4:
Where are the B- and T-lymphocytes stored?
..........................................
Q5: How do some of the cells that monocytes develop into identify pathogens to the
specific immune system?
..........................................
..........................................
2.2
Clonal selection theory
Learning objective
By the end of this section, you should be able to:
•
state that clonal selection theory explains the way in which lymphocytes are
developed to respond to specific antigens which invade the body;
•
state that lymphocytes have a single type of receptor on the cell membrane
which is specific to one antigen;
•
explain how antigen binding leads to repeated lymphocyte division, which
results in a clonal population of lymphocytes.
The Theory
Clonal Selection Theory was proposed in 1957 by an Australian medical researcher,
Frank Macfarlane Burnet, as an answer to the question: how do we account for the
immune system’s ability to produce antibodies in response to new antigens?
A radical feature of the theory was that the body actually has lymphocytes carrying
antibodies for antigens which it has never encountered. Given the vast range of potential
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21
antigens that exists, this seems highly improbable. However, subsequent research,
most recently into the genes controlling the production of antibodies, has confirmed
the validity of Burnet’s concept and, indeed, it underpins our whole understanding of the
operation of the adaptive immune system. Several Nobel Prizes have been awarded for
research in this field.
The steps in the development of lymphocytes which carry receptors specific to one
antigen is summarised below. As the process is similar in the B- and T-lymphocytes
(covered in the next section), they have not been dealt with separately here.
Clonal selection theory: Steps
Go online
1. In the red bone marrow, haematopoietic stem cells divide to produce daughter
cells.
2. As a result of genetic rearrangement, during differentiation these immature
lymphocytes each develop a different antigen receptor on their cell membranes.
3. Those immature lymphocytes which carry a receptor that will bind with an antigen
from the body’s own tissues are destroyed in the bone marrow.
4. The lymphocytes carrying other antigen receptors are released from the bone
marrow and move through the circulatory system to the lymph glands or thymus
gland where they mature into inactive lymphocytes.
5. Most of these inactive lymphocytes will never encounter an antigen to match their
receptor.
6. Inactive lymphocytes which do meet an antigen matching their receptor become
activated and divide to produce many clones of themselves.
..........................................
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Genetic background to antibody variability
To understand better how the variability of the receptors (and the antibodies to which
they are related) arises, it is necessary to delve a little into the genetic control of antibody
production. Antibodies (also known as immunoglobulins) exist in two forms, one which
is bound to the outer surface of the cell membrane of lymphocytes, and another which
is secreted by these cells and exists as soluble protein in the blood plasma, tissue fluid
and lymph.
These antibody molecules are made up of four basic polypeptide chains that are coded
for by three genes which are located on three different chromosomes. Each of these
genes is composed of many segments. In the course of differentiation, these segments
are subject to such a degree of alternative splicing during DNA transcription that there
are approximately 3 × 10 11 unique potential antibody molecules that could be expressed
on the cell membrane. Only one of these would be found on any particular lymphocyte.
The development of immunity
The receptors on the inactive lymphocytes act like antibodies in that they specifically
bind to a single antigen molecule. If this happens, then a series of changes are triggered
in the lymphocyte. The combination of gene segments becomes fixed, and only that
combination will be used to produce antibodies by that cell and its clones.
The activated lymphocyte begins to divide to produce two types of cloned daughter cell:
1. plasma cells, which have extensive folded membrane layers in the cytoplasm that
are covered with ribosomes to produce large quantities of the polypeptides which
will be formed into antibodies in the Golgi apparatus;
2. memory cells, which remain in the lymph glands ready to be activated by
subsequent encounters with the same antigen - during the first exposure to the
antigen, e.g. during an infection, these cells undergo a considerable degree of
minor mutations and the mutants with the best match of receptor to antigen are
maintained, the being remainder destroyed - during a second infection, these cells
produce a much more rapid and effective response.
Clonal selection theory: Questions
Q6:
Go online
Put the steps from clonal selection theory into the correct order.
•
Those immature lymphocytes, which carry a receptor that will bind with an antigen
from the body’s own tissues, are destroyed in the bone marrow.
•
As a result of genetic rearrangement, during differentiation these immature
lymphocytes each develop a different antigen receptor on their cell membranes.
•
Inactive lymphocytes, which do meet an antigen matching their receptor, become
activated and divide to produce many clones of themselves.
•
Most of these inactive lymphocytes will never encounter an antigen to match their
receptor.
•
In the red bone marrow, haematopoietic stem cells divide to produce daughter cells.
•
The lymphocytes that carry other antigen receptors are released from the bone
marrow and move through the circulatory system to the lymph glands or thymus
gland where they mature into inactive lymphocytes.
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..........................................
Q7: What does clonal selection theory explain?
..........................................
Q8: To how many different types of antigen do the receptors on each lymphocyte
respond?
..........................................
..........................................
2.3
T- and B-lymphocytes
Learning objective
By the end of this section, you should be able to:
•
state that lymphocytes respond specifically to antigens on foreign cells, cells
infected by pathogens and toxins released by pathogens;
•
state that T-lymphocytes have specific surface proteins that allow them to
distinguish between the surface molecules of the body’s own cells and cells
with foreign molecules on their surface;
•
explain that autoimmune diseases arise as a result of a failure of immune system
regulation, leading to a response by T-lymphocytes to self antigens;
•
state that activated B-lymphocytes secrete antibodies into the blood and lymph;
•
explain that allergies are a hypersensitive B-lymphocyte response to an antigen
that is normally harmless.
Distinguishing ’self-’ from ’non-self’ antigens
As was described in Section 2.1, T- and B-lymphocytes are produced by the
haematopoietic stem cells in the red bone marrow and they belong to the lymphoid
group of cells. Both have the ability to respond to specific antigens, which may be: part
of foreign cells; attached to the surface of cells which are infected by pathogens; or
toxins (biologically produced poisons). This response to specific antigens is achieved
by the cells having receptor proteins on their cell membranes which are only capable
of binding with that antigen. Given that lymphocytes which carry receptors for the
body’s own (’self’) antigens are eliminated before they can leave the bone marrow,
this enables the lymphocytes collectively to distinguish between the foreign (’non-self’)
antigens and those of the body’s own cells. The mechanism of antigen binding and the
subsequent response of the cell are the main differences between actions of the T- and
B-lymphocytes.
Once released from the bone marrow, T- and B-lymphocytes differ in the locations where
they mature. For T-lymphocytes it is the thymus gland which is found in front of the heart
underneath the sternum (breast bone); for B-lymphocytes it is small patches of cells in
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the extensive network of lymph glands associated with the intestine. Once mature, the
lymphocytes may be found throughout the body, but in particular they locate in the lymph
glands and the spleen, where they can readily detect foreign antigens in the lymph and
blood which are filtered through these organs.
Autoimmune disease
An autoimmune disease is a disorder in which the immune system is triggered by one or
more of the body’s own self antigens. What causes the immune system to no longer
distinguish between self and non-self antigens is unknown. One suggestion is that
some microorganisms (such as bacteria or viruses) or drugs may induce some of these
changes, especially in people who are genetically predisposed to develop autoimmune
disorders.
More than eighty such diseases have been identified and T-lymphocytes are principally
involved, although some disorders are caused by B-lymphocytes. Examples include
Celiac disease, Multiple sclerosis, Rheumatoid arthritis, and Type-1 diabetes.
Treatment is dependent on the nature of the disease: Type-1 diabetes is addressed by
the injection of the missing hormone (insulin); others may be controlled by reducing the
immune system’s response with immunosuppressive drugs.
Allergy
Allergies are very common. According to Allergy UK, one in four people in the UK
suffers from an allergy at some point in their lives. The numbers are increasing every
year and up to half of those affected are children. Common allergies include hay fever
and eczema although, strictly, these are symptoms of an allergy to grass pollen and a
substance such as latex. The most severe allergies cause anaphylactic shock, which
can be rapidly fatal; although most often associated with foods, such as peanuts, or
insect stings, anaphylaxis can be caused in those who are susceptible by almost any
foreign substance.
An allergy is an immune response to substances in the environment that are usually
not harmful. The causes of allergies are both genetic and environmental. Not only
has the immune system to separate self from non-self antigens, but it must not initiate
a response to antigens from harmless sources such as food or pollen. For most
substances this works perfectly, but, occasionally, instead of ignoring a harmless
antigen, the B-lymphocytes respond to an otherwise harmless antigen and set the
immune response in motion.
When a person first encounters an antigen to which they are genetically susceptible,
the cells that react in this sensitising exposure are B-lymphocytes. These secrete the
antibody IgE (immunoglobulin E) which attaches to mast cells and activates them.
A second exposure to this antigen causes the mast cells to release large quantities of
histamine and cytokines which, in turn, cause symptoms such the swelling of the tissues,
irritation of the eyes and nose, and, in the most severe cases, the loss of blood pressure
which is known as shock.
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Mast cells: Steps
Go online
1. The first time an allergy-prone person encounters an allergen such as ragweed. . .
2. . . .he or she makes large amounts of ragweed IgE antibody.
3. These IgE molecules attach themselves to mast cells.
4. The second time that person has a brush with ragweed the IgE-primed mast
cells release granules and powerful chemical mediators, such as histamine and
cytokines.
5. These chemical mediators cause the characteristic symptoms of allergy.
..........................................
T- and B-lymphocytes: Questions
Q9: What substances trigger the immune response?
..........................................
Q10: How do T-lymphocytes distinguish between self and non-self antigens?
..........................................
Q11: What causes an autoimmune disease?
..........................................
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TOPIC 2. SPECIFIC CELLULAR DEFENCES
Q12: State the reaction of B-lymphocytes to being activated.
..........................................
Q13: What causes an allergy?
..........................................
2.4
The action of T-lymphocytes
Learning objective
By the end of this section, you should be able to:
•
state that one group of T-lymphocytes destroys infected cells by inducing
apoptosis;
•
state that another group of T-lymphocytes secrete cytokines that activate Blymphocytes and phagocytes;
•
explain that, when pathogens infect tissue, some phagocytes capture the
pathogen and display fragments of its antigens on their surface;
•
explain that these antigen-presenting cells activate the production of a clone of
T-lymphocytes that move to the site of infection under the direction of cytokines.
T-lymphocytes, of which there are several types, are so-called because they mature
in the thymus gland (and the tonsils). T-lymphocytes (along with phagocytes) are
responsible for the cell-mediated response of the adaptive immune system. Two of
these types are described here.
Cytotoxic T cells
Also known as Killer T cells, Cytotoxic T cells carry protein receptors on their cell
membrane like all T cells. This allows them to recognise specific antigens when they
come into contact with them on the surface of pathogens or cancer cells. Once attached
to the target cell, they use an enzyme to perforate the wall of the cell and then inject
other enzymes which induce the cell to undergo apoptosis (programmed cell death).
Helper T cells
As their name implies, these cells assist other white blood cells, e.g. by inducing the
maturation of B-lymphocytes into plasma cells and memory B cells, and the activation
of cytotoxic T cells and macrophages. Their receptors only detect antigens when they
are expressed on the surface of antigen-presenting cells (APCs) such as macrophages,
certain B-lymphocytes, and dendritic cells (another white blood cell type formed in
haematopoietic stem cells of the red bone marrow). These APCs either engulf and
digest pathogens, or they absorb the antigens which are attached to their receptors,
and then display the antigens on their cell surface.
Once activated, the Helper T cells divide rapidly, and then secrete the cytokines which
activate B-lymphocytes and direct them along with macrophages to the site of the
infection.
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The action of T-lymphocytes: Questions
Q14: What do Cytotoxic T Cells induce to destroy pathogens?
..........................................
Go online
Q15: How do antigen-presenting cells acquire the antigens which they present?
..........................................
Q16: What do Helper T Cells secrete to activate B-lymphocytes?
..........................................
Q17: What activates Helper T cells?
..........................................
2.5
The action of B-lymphocytes
Learning objective
By the end of this section, you should be able to:
•
explain that B-lymphocytes are activated by antigen-presenting cells or Tlymphocytes;
•
explain that these activated cells divide repeatedly to produce a clone of Blymphocytes that secrete antibodies into the lymph and blood, through which
they make their way to the infected area;
•
state that each B-lymphocyte clone produces a specific antibody molecule that
will recognise a specific antigen surface molecule on a pathogen or a toxin;
•
explain that antigen-antibody complexes may inactivate a pathogen or toxin, or
render it more susceptible to phagocytosis;
•
state that in other cases the antigen-antibody complex stimulates a response
which results in cell lysis.
The activation of B-lymphocytes
B-lymphocytes may be activated in two ways. Antigen-presenting cells, such as
macrophages which have engulfed pathogens, migrate from the site of infection to the
lymph nodes, where they display the antigens of the pathogen on their cell membrane.
These are transferred directly to the B-lymphocytes there which carry the receptor for
that antigen, so activating them.
Alternatively (and more frequently), T-lymphocytes which have come into contact with
the pathogens carry the foreign antigens, in combination with carrier molecules on their
cell surface, to the B-lymphocytes in the lymph nodes. These antigens are likewise
transferred to the receptors of the B-cells and activate them.
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The production of antibodies
B-lymphocytes are responsible for the humoral response of the adaptive immune
system. Their principal function is to produce antibodies specific to particular antigens,
although some also act as antigen-presenting cells and develop into memory B cells.
Antigens may either be proteins on the surface of pathogens or toxins.
When activated by an antigen binding to their specific receptors, B-lymphocytes divide
repeatedly by mitosis to form a clone of plasma cells. These clones are identical to the
parent cells, and so all produce and release large quantities of the antibody which is
specific to the antigen responsible for the initial activation.
The action of antibodies
Antibodies (also known as immunoglobulins) are large Y-shaped protein molecules
which are released into the blood, tissue fluid or lymph. If they encounter their target
antigen, they bind to it, forming an antigen-antibody complex.
What follows depends on the actual antigens and pathogens involved:
1. the antibodies cluster around viruses, blocking the sites at which they bind to
their host cells - in a similar fashion, antibodies may bind with bacterial toxins
so rendering them harmless and identifying them to macrophages;
2. antibodies binding to the surface of bacteria may also cause them to cluster
together (agglutinate);
3. some antigens are soluble and circulate in the plasma and lymph - antibodies
cause these to precipitate;
4. macrophages patrolling the tissues will be attracted to pathogens and antigens
which are identified by the antibodies attached to their surfaces, and remove them
by phagocytosis;
5. as mentioned in an earlier section, the complement system involves over twenty
plasma proteins which act in a cascade to bring about several actions as part of
the innate immune system. However, the complement systems is also activated
by the binding of antibodies to the antigens of pathogens and other foreign cells
(e.g. red blood cells of a different blood group to the host). In this case, their effect
is to create pores lined with complement proteins in the pathogen’s cell membrane
(known as the ’membrane attack complex’), through which fluid floods into the cell
causing its lysis.
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Inflammatory response
The action of B-lymphocytes: Questions
Q18: Which cells activate B-lymphocytes?
..........................................
Q19: Explain what a clone is.
..........................................
Q20: When activated, what do B-lymphocytes release?
..........................................
Q21: Explain what is meant by the term ’specific’ in relation to antibodies.
..........................................
Q22: When an antibody attaches to an antigen, what is formed?
..........................................
Q23: How do antibodies de-activate viruses?
..........................................
Q24: How do antibodies prepare bacteria for phagocytosis?
..........................................
Q25: Explain how antibodies cause the lysis of pathogen cells.
..........................................
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TOPIC 2. SPECIFIC CELLULAR DEFENCES
2.6
Immunological memory
Learning objective
By the end of this section, you should be able to:
•
state the some of the cells produced when lymphocytes are activated survive
long-term as memory cells;
•
explain that a second exposure to the same antigen stimulates these memory
cells rapidly to divide and produce a new clone of lymphocytes;
•
state that these new cloned lymphocytes produce a secondary response which
is much more rapid and greater in terms of antibody production.
So far, this topic has described the very efficient way in which the body reacts to invasion
by pathogens and foreign antigens. However, the cleverest part of the story remains to
be told: once it has met a particular pathogen or antigen, the immune system is able to
remember the foreign antigen signature so that, in any future exposure to that antigen,
it can respond so quickly and effectively that the infection is stopped before it can begin.
The formation of memory cells
When an inactive lymphocyte meets the antigen which matches its receptors, it is
activated into rapid cell division. Most of these cloned cells will move to another part
of the lymph glands (as plasma cells in the case of B-lymphocytes) or to the site of the
infection (in the case of T-lymphocytes).
A proportion remain behind in the original areas of the lymph nodes where they undergo
a selection process which weeds out the cells with the least effective antibodies in terms
of fitting the antigen. As a result, by the time the initial infection is brought under control,
the antibodies being produced are much more effective than those first released. These
memory cells are long-lived, and their numbers increase at each re-exposure to the
antigen until an optimum level is reached.
Both B- and T-lymphocyte memory cells are found not only in the lymph nodes, but in
the spleen as well where blood is filtered and so can be monitored. In addition, there are
T-lymphocyte memory cells which circulate in the blood and so are in constant contact
with the tissues.
The secondary response
When a particular antigen invades the body a second time, the memory cells are
activated very quickly, dividing to form plasma cells and more memory cells, which
are again subject to selection for most effective antibody production. In consequence,
the secondary response is much quicker than the primary response and involves much
higher concentrations of (more effective) antibodies.
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Primary and secondary immune responses
A concurrent infection involving a different antigen will not be met with this rapid and
massive production of antibodies. This is because of the specific nature of the antibody
response; it only responds to the antigen which activated it. Other antigens have to start
at the beginning of the process.
Immunological memory: Questions
Q26: What is the source of lymphocyte memory cells?
..........................................
Q27: State the effect that a second exposure to an antigen has on lymphocyte memory
cells.
..........................................
Q28: How does the secondary immune response differ from the primary response?
..........................................
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TOPIC 2. SPECIFIC CELLULAR DEFENCES
2.7
Learning points
Summary
Immune surveillance
•
The role of white blood cells as constantly monitoring the tissues.
•
Pathogens, and other foreign cells or materials, are recognised by their
antigens - molecules on their surfaces that activate the immune system.
•
Cytokines are released when tissues are damaged or invaded.
•
Cytokines attract specific
infected/damaged tissue.
•
Some of these cells absorb pathogens and display fragments of their cell
membranes on their surface.
white
blood
cells
(monocytes)
to
the
Clonal selection theory
•
Clonal selection theory explains the way in which lymphocytes are
developed to respond to specific antigens which invade the body.
•
Lymphocytes have a single type of receptor on the cell membrane which is
specific to one antigen.
•
Antigen binding leads to repeated lymphocyte division, which results in a
clonal population of lymphocytes.
T- and B-lymphocytes
•
Lymphocytes respond specifically to antigens on foreign cells, cells infected
by pathogens and toxins released by pathogens.
•
T-lymphocytes have specific surface proteins that allow them to distinguish
between the surface molecules of the body’s own cells and cells with foreign
molecules on their surface.
•
Autoimmune diseases arise as a result of a failure of immune system
regulation, leading to a response by T-lymphocytes to self antigens.
•
Activated B-lymphocytes secrete antibodies into the blood and lymph.
•
Allergies are a hypersensitive B-lymphocyte response to an antigen that is
normally harmless.
T-lymphocytes
•
One group of T-lymphocytes destroys infected cells by inducing apoptosis.
•
Another group of T-lymphocytes secrete cytokines that activate Blymphocytes and phagocytes.
•
When pathogens infect tissue, some phagocytes capture the pathogen and
display fragments of its antigens on their surface.
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Summary continued
•
These antigen-presenting cells activate the production of a clone of Tlymphocytes that move to the site of infection under the direction of
cytokines.
B-lymphocytes
•
B-lymphocytes are activated by antigen-presenting cells or T-lymphocytes.
•
These activated cells divide repeatedly to produce a clone of B-lymphocytes
that secrete antibodies into the lymph and blood, through which they make
their way to the infected area.
•
Each B-lymphocyte clone produces a specific antibody molecule that will
recognise a specific antigen surface molecule on a pathogen or a toxin.
•
Antigen-antibody complexes may inactivate a pathogen or toxin, or render it
more susceptible to phagocytosis.
•
In other cases the antigen-antibody complex stimulates a response which
results in cell lysis.
Immunological memory
2.8
•
Some of the cells produced when lymphocytes are activated survive longterm as memory cells.
•
A second exposure to the same antigen stimulates these memory cells
rapidly to divide and produce a new clone of lymphocytes.
•
These new cloned lymphocytes produce a secondary response which is
much more rapid and greater in terms of antibody production.
Extended response question
The activity which follows presents an extended response question similar to the style
that you will encounter in the examination.
You should have a good understanding of clonal selection theory before attempting the
question.
You should give your completed answer to your teacher or tutor for marking, or try to
mark it yourself using the suggested marking scheme.
Extended response question: Clonal selection theory
Give an account of clonal selection theory. (6 marks)
..........................................
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TOPIC 2. SPECIFIC CELLULAR DEFENCES
2.9
End of topic test
End of Topic 2 test
Q29: Match the phrases on the left with the words and phrases on the right. (8 marks)
Go online
Constantly monitoring the tissues:
autoimmune.
Identify pathogens to the immune system:
monocytes.
Released by damaged cells:
receptors.
Attracted to infected tissues:
specific.
Located on the cell membrane of lymphocytes:
allergic.
Receptor only binds to one antigen:
white blood cells.
A response by T-lymphocytes to the body’s own antigens:
cytokines.
antigens.
A hypersensitive response by B-lymphocytes:
..........................................
Q30: Complete the sentences by matching the parts on the left and the right. (7 marks)
T-lymphocytes destroy infected cells by inducing
T-lymphocytes.
T-lymphocytes secrete cytokines that activate
a clone of T-lymphocytes.
Antigen-presenting cells activate the production of
an antigen-antibody
complex.
B-lymphocytes are activated by antigen-presenting
phagocytosis.
Each B-lymphocyte clone produces
B-lymphocytes.
Antigen-antibody complexes render pathogens
susceptible to
apoptosis.
a specific antibody
molecule.
..........................................
Cell lysis is a response stimulated by
Q31: Explain how T-lymphocytes identify pathogens. (2 marks)
..........................................
Q32: Describe what happens after B-lymphocytes are activated. (2 marks)
..........................................
Q33: Explain why the secondary response to a pathogen is more effective than the
primary response. (2 marks)
..........................................
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Topic 3
The transmission and control of
infectious diseases
Contents
3.1
Infectious diseases caused by pathogens . . . . . . . . . . . . . . . . . . . . .
36
3.2
3.3
Methods of transmission of pathogens . . . . . . . . . . . . . . . . . . . . . .
Control of spread of pathogens . . . . . . . . . . . . . . . . . . . . . . . . . .
42
44
3.4
Epidemiological studies of infectious diseases . . . . . . . . . . . . . . . . . .
3.4.1 Epidemiology and the spread of disease . . . . . . . . . . . . . . . . . .
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49
3.5
3.4.2 Control measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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3.6
3.7
Extended response question . . . . . . . . . . . . . . . . . . . . . . . . . . . .
End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Learning objectives
By the end of this topic, you should be able to:
•
describe the nature of pathogens and disease;
•
describe the ways in which pathogens may be transmitted;
•
describe the methods by which the spread of pathogens may be controlled;
•
list the different degrees of spread of infectious diseases;
•
explain the measures which can be taken to control the spread of a disease within
a population.
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
In the previous topics of this unit, the body’s immune defences, both specific and nonspecific, were described. In this topic, the focus is on the ways in which diseases spread
through populations and the means by which they may be controlled.
3.1
Infectious diseases caused by pathogens
Learning objective
By the end of this section, you should be able to:
•
list the types of infectious agent that cause disease;
•
name an example of a disease caused by each type of pathogen.
Pathogen is a very broad term which encompasses anything that can produce disease
in its host. It is generally used to refer to some sort of micro-organism, and includes
viruses, bacteria, fungi, protozoans, and even the misfolded proteins that are prions.
Excluded are carcinogens, for example blue asbsestos (crocodilite), and neurotoxins,
such as that produced by the bacterium Clostridium botulinum.
Pathogens are, of course, just trying to make a living like any other organism; the
problem lies in that they use us as their habitat and source of nutrition, causing our
bodies damage in the process. It should be remembered that on our body surfaces, in
our intestinal tract, and within our tissues we harbour huge numbers of micro-organisms
which do us no harm or, indeed, are extremely beneficial to us.
The term disease also needs definition as a condition in which the body malfunctions
in some way; in this topic, we are concerned only with diseases which are caused by
pathogens, rather than inherited, psychological or deficiency diseases. New diseases
are discovered every year, with more than 30 being described in the last 20 years.
Estimates of the total number of human diseases vary considerably, although something
in excess of 30,000 is a common suggestion.
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Viruses
Bird flu virus
http://blog.patentology.com.au/2011/11/shades-of-gray-as-dispute-over.html (https://pl
us.google.com/116299882295651429004/about) / http://creativecommons.org/licenses
/by-nc-sa/3.0/au/
Most viruses have a diameter of between 20 and 300nm (nanometres, 10 -9 m). All
consist of a protein coat containing a molecule of nucleic acid (RNA or, more rarely,
DNA), but they lack any other cellular organelles and are consequently dependent on
other cells for their reproduction. They are found in all other life-forms.
Diseases caused by viruses range in severity from mild infections such as the common
cold and herpes (cold-sores) to those with very high mortality rates such as smallpox
and ebola.
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
Bacteria
Escherichia coli
A bacterium is typically between 0.5 and 5.0µm (micrometres, 10 -6 m) in length. They
have a cell membrane inside a cell wall, but lack any membrane-enclosed organelles
such as a nucleus.
However, their cytoplasm is organised by a cytoskeleton of structural proteins and
contains ribosomes. Their genes are carried on a single circular chromosome of DNA,
and on smaller DNA plasmids.
Diseases caused by bacteria include tetanus, typhoid fever, diphtheria, syphilis, cholera,
salmonella, pneumonia, meningitis and tuberculosis.
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
Fungi
Athlete’s foot fungus in lab culture
(http://commons.wikimedia.org/wiki/Category:Athlete%27s_foot#mediaviewer/File:Athl
ete%27s_Foot_Fungus_microscope.jpg by Ecorahul, licensed under http://creativecom
mons.org/licenses/by-sa/3.0 via http://commons.wikimedia.org/)
Comprised of a cell wall made of chitin (the same protein as makes up insect
exoskeletons), cytoplasm with organelles, and a nucleus with chromosomes, most fungi
exist as long filaments of cells called hyphae which are typically 5µm wide; some are
found as single cells (e.g. yeast).
Relatively few fungi cause diseases in humans, but they can lead to serious
complications in certain situations. Those that people are most likely to be familiar
with are the mild, if annoying, infections such as athlete’s foot and thrush. However, the
latter shows just how these microbes can cause serious problems if they gain entry to
the deeper body tissues. If the Candida yeast (which causes thrush) invades the tissues
after a transplant operation for which the patient’s immune system has been suppressed,
the result can be systemic candidiasis, which has a mortality rate of up to 50%.
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
Protozoans
Plasmodium, (about 12µm long) the protozoan causing malaria, among host’s red
blood cells
In many ways, the members of this very diverse group of organisms resemble free-living
animal cells, in that they have a cell membrane, nucleus and organelles. Diseases
caused by protozoans include: several involving insect vectors as alternate hosts, e.g.
malaria, Chagas disease, sleeping sickness; toxoplasmosis, with cats as an alternate
host; and amoebic dysentery, which is spread through faecal contamination of food or
water.
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Prions
Cow brain tissue, showing the microscopic holes typical of bovine spongiform
encephalopathy (BSE)
Prions are not organisms but a type of misfolded protein which appear to be passed
from host to host by consumption of infected tissue. They are thought to cause protein
to alter and accumulate in the host’s brain and other neural tissue, a change which
is untreatable and ultimately fatal. Examples are kuru and Creuztfeldt-Jakob Disease
(CJD). Their size is a matter of speculation, but one estimate is about 10nm.
Infectious diseases caused by pathogens: Question
Q1: Complete the following table to show the types of organism that are pathogens
and examples of the infectious diseases which they cause.
Type of pathogen
Example of disease
Pathogens and diseases: bacteria, candidiasis, CJD, fungi, herpes, malaria,
pneumonia, prion, protozoa, virus.
..........................................
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
3.2
Methods of transmission of pathogens
Learning objective
By the end of this section, you should be able to:
•
explain that pathogens may be transmitted by direct physical contact, water,
food, body fluids, inhaled air or vector organisms.
Pathogens which cause infectious diseases are very sensitive to their environments.
They only have the ability to survive and multiply if there is the availability of correct
nutrients and the right environmental conditions. Some microbes such as bacteria,
for example, require an optimum temperature range (20 to 40 ◦ C), sufficient moisture,
correct pH and oxygen levels. However, some bacterial spores can survive extreme
environmental conditions.
The transmission of an infectious disease is the passing on of a pathogen from an
infected host individual to another individual by one or more of the following methods:
•
physical contact (contagious diseases)
◦
direct physical contact takes place by touch, like a handshake or sexual
contact - even though the skin is host to many microbes, the majority
of these are benign unless they gain access to the internal organs; the
most common bacteria found on the skin that can cause infection are
Staphalococcus and Streptococcus, and the most notorious is methycillinresistant Staphalococcus aureus (MRSA);
◦
indirect physical contact usually takes place by touching contaminated
surfaces, like a door handle or floor - free living microbes, such as bacteria
and fungi, can survive on non-living objects longer than viruses; Rhinoviruses
(cold) and gastroenteritis can be spread in this manner, as can some
pathogenic fungi such as the Trychophyton species which cause athlete’s
foot
•
water-borne diseases are most often spread via drinking water that has been
contaminated with human or animal faeces; this is the faecal-oral infection route
- in Economically Less Developed Countries, four-fifths of all the illnesses are
caused by water-borne pathogens, with diarrhoea caused by cholera or dysentery
being the leading cause of child mortality;
•
food-borne diseases, of which there are over 250, are caused by a variety of
bacteria, viruses, and parasites - they usually result from poor personal hygiene,
poor hygiene in food preparation, or in the food material supply chain; diseases
caused by food-borne organisms include: cholera, rotavirus, shigellosis (bacillary
dysentery), typhoid fever, hepatitis A and hepatitis E;
•
body fluids - a healthy person who gets infected mucus into their eyes, nose,
or mouth can become infected with certain diseases that are spread in the
blood or which grow in the flesh around a wound where the body may produce
pus (a viscous, yellowish-white fluid that is formed in infected tissues mainly
from white blood cells), e.g. hepatitis (in its several forms); some diseases are
caused by microbes which are carried in the fluids exchanged during sexual
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relations, e.g. HIV (human immunodeficiency virus) which causes AIDS (acquired
immunodeficiency syndrome);
•
air-borne transmission occurs when microbes are attached to droplets of moisture
in the air (e.g. from a sneeze) or to dust particles that are inhaled - such microbes
can travel long distances before they are inhaled by other people, e.g. the measles
virus, bacteria such as Mycobacterium tuberculosis (TB), and Bacillus anthracis
(anthrax);
•
vector organisms provide a pathway for a pathogen to be transmitted between
animals and humans or other animals, with some vector organisms providing this
transport by blood-sucking - the vectors are largely unaffected by the pathogen,
thus allowing for the successful transport of the disease. According to WHO,
the most deadly vector-borne disease is Malaria, killing over 1.2 million people
annually, mostly African children under the age of five. Another vector-borne
disease is dengue fever (DF), a viral disease also spread by mosquitoes. Together
with associated dengue haemorrhagic fever (DHF), DF is the world’s fastest
growing vector-borne disease. In Britain, Lyme disease is of increasing concern;
it is caused by bacteria of the Borelia genus and is spread by ticks when they take
a blood meal on a human, dog, or other mammals such as deer.
Methods of transmission of pathogens: Question
Q2: Complete the following table to show the types of organism that are pathogens
and examples of the infectious diseases which they cause.
Method of transmission
Example of disease
Methods of transmission and diseases: body fluids, dengue fever, direct physical
contact, dysentery, food, gastroenteritis, HIV, indirect physical contact, inhaled air,
measles, MRSA, typhoid, vectors, water.
..........................................
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
3.3
Control of spread of pathogens
Learning objective
By the end of this section, you should be able to:
•
state that the spread of pathogens can be controlled by quarantine and
antisepsis;
•
explain the role of individual responsibility by means of good hygiene, care in
sexual health, and appropriate storage/handling of food;
•
describe the role of community responsibility by means of quality of water
supply, safe food webs, and appropriate waste disposal systems;
•
explain the role of vector control in reducing the spread of pathogens.
Quarantine
Quarantine controls the spread of an infectious disease by keeping potentially infected
individuals, i.e. those who may have been exposed to the disease, apart from the
remainder of the population. Persons who are known to be ill with a contagious disease
are isolated from all others.
The Apollo 11 astronauts are quarantined following their return to Earth
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During the global outbreak of SARS (severe acute respiratory syndrome) in 2003,
public health officials introduced measures aimed at controlling its spread in affected
areas. Initially, this was done by alerting health-care providers and providing them with
diagnostic protocols. Many of the SARS cases were quickly identified. However, it was
soon recognised that the disease had spread at a much greater rate than was initially
thought. As a result, several countries/regions introduced the use of mass quarantine
for all individuals suspected of having had contact with a confirmed SARS case. These
coordinated global efforts were remarkably effective in controlling the spread of SARS
and, to date, the disease has not made a significant re-emergence.
Modern quarantine lasts only as long as necessary to protect the public by providing
health care, such as immunisation or drug treatment. Nowadays, quarantine is more
likely to involve limited numbers of exposed persons in small areas rather large numbers
in whole neighbourhoods or cities.
Antisepsis
Antiseptics are chemicals which are applied to skin or living tissue to reduce the
possibility of transmission of pathogens, and to counter the infection of healthy tissue, or
the decomposition of dead or damaged tissue. They act against microbes by disrupting
cell structures including: cell wall/membrane, internal membranes, protein structures,
DNA and RNA. In so doing, antiseptics also either kill the pathogens or inhibit their
growth and reproduction.
Hand washing is at once the simplest and yet one of the most effective techniques.
Decontamination of the hands can be achieved either with plain soap and water, or by
use of an antiseptic hand gel. The use of soap is important as it helps lipids dissolve and
so dislodges bacteria held in natural skin oils. Although it does not counter the spread
of droplet-borne infections, hand washing is very effective against pathogens spread by
the faecal-oral route. Therefore, hand washing is very important after using the toilet,
touching raw food, changing a baby’s nappies, cleaning up after a pet, or removing
rubbish bins.
Disinfectants are also antimicrobial agents which work by destroying the cell wall of
pathogens or by interfering with their metabolism. They are used on non-living surfaces
such as food preparation areas in the domestic kitchen or commercial premises such as
butcher’s shops, restaurants, and of course in hospitals.
Individual responsibility
An individual’s personal behaviour can have a considerable impact on the control and
prevention of the spread of disease. This applies not just to the health of their own
immediate household, but collectively it contributes greatly to community health.
Emphasis should be placed on an individual’s responsibility to:
•
provide good hygiene both personally and within the home;
•
be sensitive to oneself and to others in matters of sexual health;
•
take care over the appropriate handling and storage of food.
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
Community responsibility
Once humans ceased to be hunter-gatherers and started to live in groups larger than
a family, there had to be a division of labour, and we began to depend on the others in
the community to carry out certain key tasks for us. Today, few of us kill and butcher our
own meat, or have our own private water supply. In Britain we expect our rubbish to be
collected and only country-dwellers rely on a septic tank to process their sewage.
The most fundamental of community responsibilities is the provision of clean, safe
(potable) drinking water. This can only be assured if contamination by sewage is
prevented by ensuring that waste water and drinking water cannot mix. To achieve this,
we have sewerage systems to remove waste water and our drinking water is taken from
(relatively) uncontaminated sources, filtered, purified to remove dangerous chemicals,
and disinfected to eliminate most bacteria. It is interesting that in Britain we wash our
cars, water the garden and flush our toilets with water of drinking quality when potable
water is a scarce and valuable resource to much of the world’s population.
Waste water treatment works
The other side of the coin to the provision of potable water is the provision of effective
sanitation. This requires not just the clear separation of sewage from drinking water,
but the disposal of sewage in such way that it cannot contaminate cooking, washing or
bathing water, or indeed the water children swim in. We should remember that only fifty
years ago, Scottish coastal towns were still pouring raw sewage straight into the sea,
often close to bathing beaches.
Over one-third of the world’s population, nearly 2.5 billion people, have inadequate
access to sanitation, and over one billion people do not have access to enough safe
water. These conditions, combined with poor hygiene, are largely responsible for the
fact that there are globally between 1.7 and 5 billion cases of diarrhoea annually (e.g.
typhoid, cholera, dysentery). Of those affected, about three million die each year.
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Community responsibility can reduce the number of cases of diseases, and actions may
include:
•
access to safe drinking water;
•
improved sanitation;
•
supervision of food chains, by insisting on minimum standards of hygiene, e.g. in
abattoirs, restaurants, fast-food outlets, supermarkets, market stalls;
•
health education of all age-groups, especially children, parents and the elderly.
Control of vectors
Most vector organisms are blood-sucking arthropods, particularly insects and
arachnids (ticks). The relationship between the pathogen and its hosts is one that has
evolved over a long time because the pathogens can often only complete their life cycle
if they have access to a different host species at each stage.
On a global scale, the Anopheles mosquitoes which spread malaria are the most
important insect vectors. They carry the Plasmodium protozoan, which passes part of its
life-cycle in the mosquito as its primary host, but must then be transferred to a mammal
such as a human as a secondary host to complete its life cycle. For the disease to
spread, the pathogen must be again taken into a mosquito in a blood meal.
Female Anopheles mosquito feeding
The most effective way to combat the disease is to limit the available habitat for the larval
stages of the mosquito, which means removing the stagnant water in which the eggs
are laid, for example that collected in old tyres. Other techniques include: the sterile
male technique, in which large quantities of laboratory-bred sterile male mosquitoes are
released, and the introduction of fish which eat the mosquito larvae. In Britain, five
species of Anopheles are found (three in Scotland), but since most of the marshland
in the country has long since been drained, malaria died out several centuries ago.
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TOPIC 3. THE TRANSMISSION AND CONTROL OF INFECTIOUS DISEASES
Insecticides have also been used, but as with antibiotics, over-use and misuse have led
to the development of resistant varieties.
In Scotland, Ixodes ricinus (sheep tick) spreads Borrelia bacteria which cause Lyme
disease. The bacteria are passed between the tick and two types of mammal host.
Unlike the mosquitoes, where only mature females take a blood meal, all ticks of all
sizes feed on blood.
Sheep ticks mating (the larger size of the female gives an idea of the size that a male
would grow to after feeding)
In the earliest stages of the life cycle, ticks prefer mice as their hosts (although they will
attach to any available food source), and can only pick up Borrelia from them. In the final
stage, ticks prefer large mammals, such as deer, foxes or sheep (or humans), to whom
they can transfer the bacteria, but from whom none of the stages can get the bacteria.
In the context of the increasing occurrence of large wild mammals in and around
urban areas, and the growing use of forests for recreation, ticks pose a serious health
risk which is not widely appreciated. The obvious vector control measure of severely
reducing deer and fox populations is likely to be controversial.
Control of spread of pathogens: Questions
Q3:
Go online
Describe how the spread of pathogens is controlled by quarantine.
..........................................
Q4:
Describe how the spread of pathogens is controlled by antisepsis.
..........................................
Q5: List the ways in which individuals should take responsibility for the control of the
spread of pathogens.
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49
..........................................
Q6: State the areas of control of pathogens that are the responsibility of communities
in More Economically Developed Countries.
..........................................
Q7: Explain the role of vector control in reducing the spread of pathogens.
..........................................
3.4
Epidemiological studies of infectious diseases
Learning objective
By the end of this section, you should be able to:
•
state that epidemiology is the study of the causes and patterns of spread of
disease;
•
describe the patterns of disease spread as:
•
3.4.1
◦
sporadic (occasional occurrence);
◦
endemic (regular cases occurring in an area);
◦
epidemic (unusually high number of cases in an area);
◦
pandemic (a global epidemic).
describe control measures to include preventing transmission, drug therapy,
immunisation or a combination of these.
Epidemiology and the spread of disease
Epidemiology is the study of the causes and patterns of spread of disease. As such, it
underpins public health decisions, provides the foundation for the development of policy
and the direction of research.
At different times and places, diseases show different patterns of spread.
Sporadic
In an age of global travel, it is inevitable that an infected person will arrive in a country
and develop a disease which is not normally present in that area. If the local population
are mostly vaccinated against that disease, or no vector species exists, then the
pathogen will be unable to find an alternative host before the patient’s immune system
eradicates it, and so it dies out in that area.
An example would be malaria in Britain. Every year people arrive in the country
carrying the Plasmodium protozoan in their blood, but as the Anopheles mosquitoes are
restricted to very specific uncommon habitats, the disease is usually unable to spread
before the patient is treated and the pathogen eliminated.
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Endemic
An infection is said to be endemic when that infection is maintained in the population
without the need for external inputs. For example, rubella and the common cold
rhinovirus are endemic in Britain, but malaria is not. To maintain this steady state, the
pathogen must be able to find new hosts sufficiently frequently to avoid extinction, but
not so often that the number of cases begins to increase significantly. This equilibrium
depends on the relationship between the number of new cases that one infected person
can generate before their infectious period is over (as their immune system controls the
infection), and the number of susceptible people in the population.
Epidemic
An epidemic occurs when the number of cases of a disease increases significantly
above that normally recorded. For this to happen, the equilibrium of the endemic
state must be disturbed in some way. It might, of course, also be the result of some
new pathogen arriving, against which the immune systems of the population give no
immediate protection.
Every winter in Scotland, susceptible individuals (over 65, pregnant women, those
with particular health conditions, pre-school and primary school children) are offered
an injection of the flu vaccine which counters the strains of Influenzavirus which are
expected in the coming flu season. This is always something of a gamble, as the
flu virus mutates frequently and the health authorities have to judge which strains will
predominate in any winter.
Pandemic
When a disease reaches epidemic proportions in many different countries, it is classed
as a pandemic. Modern air transport links make the potential for the global spread of
a disease much greater, but this is countered by a much deeper understanding of the
behaviour of diseases and more sophisticated methods of tracing potentially infected
individuals. Thus, while the swine flu pandemic of 2009 killed roughly 18,000 people,
the Spanish flu pandemic of 1918 is estimated to have killed between 20 and 100 million.
Both of these outbreaks involved the H1N1 variant of the type A Influenzavirus.
Epidemiology and the spread of disease: Question
Q8:
Match the phrases on the left with the words on the right.
Go online
The disease occurs occasionally in a population:
endemic.
Cases of the disease occur regularly in an area:
pandemic.
There are unusually high numbers of cases in an area:
sporadic.
Unusually high numbers of cases in many countries:
..........................................
epidemic.
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3.4.2
Control measures
When an outbreak of disease is anticipated or has already begun, there are a number
of strategies that health authorities can adopt to control the outbreak and reduce the
possibility of it reaching epidemic or pandemic proportions. These may be applied singly
or in combination.
Preventing transmission
If a disease outbreak has already begun, infected individuals can be isolated and
known contacts quarantined. The media can be used to inform the public of symptoms,
and information can be gathered by communication with travel companies, immigration
officials, business contacts and others who might have knowledge of an infected
person’s movements. Airport officials can be alerted so that passengers on flights from
particular countries can be screened and alerted to the symptoms.
An extreme case involves the Ebola virus, which sporadically erupts in West Africa.
This is an example of a pathogen that transfers to humans from other animals, in this
case mainly fruit bats. As is typical of a pathogen that is not adapted to a new host,
Ebola rapidly kills most of the patients it infects. It is also highly contagious, spreading
quickly from human to human in a population. The standard approach to containing such
an outbreak is to isolate the community, give such medical relief as is possible (there
is no cure), and wait until the survivors are no longer infectious (about two months).
Interestingly, the rate of mortality amongst patients is much higher early in an outbreak
than towards the end, indicating that the selection pressure on the virus in the course of
the outbreak favours less virulent strains.
Drug therapy
Once an outbreak is under way, people who are infected may be treated in a number of
ways to combat the disease or ameliorate the symptoms.
The most frequent treatment is some form of antibiotic. These are chemicals that are
naturally produced by fungi or bacteria to impede the growth of competing microbes,
penicillin being the famous first example to be discovered. Today, most antibiotics are
manufactured synthetically, although some still involve an element of biosynthesis, e.g.
streptomycin. Broad spectrum antibiotics target a wide range of bacteria, whereas
narrow spectrum antibiotics act against specific types of bacteria. Antibiotics affect
bacteria in a wide range of different ways. Some attack the bacterial cell wall or cell
membrane, others interfere with essential enzymes or with protein synthesis.
Antibiotics only work against bacteria; other types of drugs that are used as bactericides
are sulphonamides and quinolones. Viruses are addressed with antiviral drugs that
target particular viral proteins which are as different as possible from any found in the
human body. These attack the virus at different stages in its life cycle:
•
before it enters the cell, e.g. pleconaril, which is used against the common cold
Rhinovirus, and the virus causing meningitis;
•
during viral synthesis, e.g. zidovudine (AZT) countering HIV, and so-called
’antisense’ antivirals against dengue fever;
•
at the release phase from the cell, e.g. Relenza and Tamiflu used against flu.
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Another approach to counter viruses is to stimulate the immune system, e.g. interferon
used against hepatitis B and C.
All of these drugs are subject to the development of drug resistance, as exposure of the
microbes to the drug exerts strong selection pressure in favour of those bacteria and
viruses less seriously affected by the drug.
Individuals who have been exposed to infection may be injected with antibodies to
provide passive immunity to a disease. This may be used to counter tetanus, rabies,
rubella, hepatitis A and B.
Immunisation
The theory of immunisation is covered in the next topic. By exposing a person to the
surface proteins (antigens) of a pathogen (usually by injection), their immune system
will be stimulated to develop the lymphocyte memory cells necessary to initiate a
rapid, strong secondary response if the pathogen itself is encountered. This is the
principle behind the provision of annual winter flu injections and the MMR, TB and
tetanus vaccination programmes. Clearly, immunisation is not a treatment for those
already infected, and it does depend on an informed guess as to exactly which strains
of pathogen are likely to be encountered.
Control measures: Questions
Go online
Q9: What is the most suitable treatment for a person who has flu caused by the H1N1
virus?
a) Antibiotics
b) Immunisation
c) Isolation
..........................................
Q10: Long-term resistance to tetanus is achieved by:
a) Antibiotics
b) Antivirals
c) Immunisation
..........................................
Q11: A person who has contracted the bacterial infection tetanus should be treated
with:
a) Antibiotics
b) Antibodies
c) Antivirals
..........................................
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3.5
Learning points
Summary
Methods of transmission of pathogens
•
Pathogens may be transmitted by direct physical contact, water, food, body
fluids, inhaled air or vector organisms.
Control of spread of pathogens
•
The spread of pathogens can be controlled by quarantine and antisepsis.
•
The role of individual responsibility by means of good hygiene, care in
sexual health and appropriate storage/handling of food.
•
The role of community responsibility by means of quality of water supply,
safe food webs, and appropriate waste disposal systems.
•
The role of vector control in reducing the spread of pathogens.
Epidemiological studies of infectious diseases
•
Epidemiology is the study of the causes and patterns of spread of disease.
•
The patterns of spread of disease are:
•
3.6
◦
sporadic (occasional occurrence);
◦
endemic (regular cases occurring in an area);
◦
epidemic (unusually high number of cases in an area);
◦
pandemic (a global epidemic).
Control measures include preventing
immunisation or a combination of these.
transmission,
drug
therapy,
Extended response question
The activity which follows presents an extended response question similar to the style
that you will encounter in the examination.
You should have a good understanding of the control of spread of pathogens before
attempting the question.
You should give your completed answer to your teacher or tutor for marking, or try to
mark it yourself using the suggested marking scheme.
Extended response question: Control of spread of pathogens
Describe the role of community responsibility in the control of the spread of pathogens.
(6 marks)
..........................................
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3.7
End of topic test
End of Topic 3 test
Go online
Q12: Complete the paragraph by selecting words from the list. Some words may be
used more than once. (12 marks)
contact, water,
, body fluids,
Pathogens may be transmitted by direct
or
organisms. The spread of pathogens can be controlled by
inhaled
.
quarantine and
, care
Individuals have a responsibility to control disease by means of good
health and appropriate storage/
of food. The role of community is
in
supply, safe food
, and appropriate
to ensure the quality of
disposal systems. Communities may also reduce the spread of disease by means of
control.
programmes of
Word list: air, antisepsis, food, handling, hygiene, physical, sexual, vector, waste, water,
webs.
..........................................
Q13: Explain how quarantine helps control the spread of disease. (2 marks)
..........................................
Q14: State two ways in which health authorities ensure drinking water is safe. (2 marks)
..........................................
Q15: Name a vector-borne disease and state one way in which its spread may be
controlled. (2 marks)
..........................................
Q16: What is an endemic disease? (1 mark)
..........................................
Q17: Explain how an endemic disease, e.g. flu, can become an epidemic. (1 mark)
..........................................
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Topic 4
Active immunisation
Contents
4.1
Active immunisation and vaccination . . . . . . . . . . . . . . . . . . . . . . .
56
4.1.1 Active immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.2 Vaccine clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
57
59
4.2
4.3
Herd Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Immunisation programmes . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
63
67
4.4
The evasion of specific immune responses by pathogens . . . . . . . . . . . .
4.4.1 Antigenic variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
70
70
4.4.2 Antigenic variation in different pathogens . . . . . . . . . . . . . . . . .
4.4.3 Direct attack on the immune system . . . . . . . . . . . . . . . . . . . .
72
75
4.4.4 Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.5 Learning points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
77
78
4.6
4.7
79
80
Extended response question . . . . . . . . . . . . . . . . . . . . . . . . . . . .
End of topic test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Learning objectives
By the end of this topic, you should be able to:
•
describe the development of active immunisation;
•
explain the purpose of vaccinations, the development of vaccines and associated
public health programmes;
•
describe the way in which some pathogens evade the specific immune response.
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TOPIC 4. ACTIVE IMMUNISATION
4.1
Active immunisation and vaccination
An individual will develop an immunological memory (Topic 2.6) against a foreign antigen
as a result of exposure to that antigen. This may be caused by natural exposure to the
antigen, e.g. by contracting the disease, which was the way children in Britain became
immune to measles, mumps and rubella before 1988. Alternatively, an injection of
vaccine containing the antigen can be given to stimulate the development of artificial
immunity. Since 1988, all British children have been offered such artificial immunisation
before their first birthday as part of their routine vaccination schedule.
The first well-documented use of artificial immunisation was in China in the 16 th century,
and the practice was recorded from India, Africa and Turkey in the 18 th century at about
the same time that it began to be practised in Britain and other countries of western
Europe. The disease involved was smallpox, which can kill up to 60% of those infected
(and up to 80% of children under five years of age). The technique was inoculation, in
which scabs taken from an infected person were introduced (either whole or powdered)
into an incision on the arm of an uninfected person. Surprisingly, perhaps, rather than
promptly killing a high proportion of the patients, this technique caused a relatively mild
infection which had the desired effect of protecting them in subsequent exposures to the
disease. It did, however, depend on the presence of the disease in the community for
the necessary supply of scabs.
The process of using a source of antigens other than the pathogen itself was first
introduced by Edward Jenner (and others) in the late 18 th century. He used pus from
scabs caused by cowpox to inoculate patients who later proved to be immune to the
much more serious and related disease smallpox. Nearly a century later, the procedure
was significantly refined by Louis Pasteur. Because of the early use of cowpox in the
process, the treatment was called vaccination (vacca is Latin for cow).
Although the terms vaccination and inoculation are now often used interchangeably,
strictly speaking vaccination refers to the use of some weakened form of a pathogen,
whereas inoculation uses the real thing (and is consequently a much more dangerous
business). Inoculation is also the term used for the addition of a culture of microbes
to a growth medium in the lab. There is no doubt that vaccination is the single most
important discovery in the control of disease. Without it, serious diseases such as polio
and smallpox would still be claiming millions of lives around the planet every year.
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4.1.1
57
Active immunity
Learning objective
By the end of this section, you should be able to:
•
state that active immunity can be developed by vaccination with antigens from
infectious pathogens;
•
explain that vaccination creates an immunological memory;
•
state that vaccines include antigens from infectious pathogens, including
inactivated pathogen toxins, dead pathogens, parts of pathogens and weakened
pathogens;
•
state that the antigens in vaccines are usually mixed with an adjuvant to
enhance the immune response.
Immunity against a pathogen can be developed in a number of ways.
fundamentally, immunity may either be active or passive:
Most
•
active immunity involves the development of immunological memory, either as
a result of exposure to the pathogen’s antigens (naturally acquired) or through
exposure to the same antigens in a vaccination (artificially acquired);
•
passive immunity involves the acquisition of antibodies, either naturally across
the placenta or from breast milk, or artificially through an injection (e.g. in the
treatment of rabies).
Of these, only the development of artificial active immunity by means of vaccination
programmes is of practical importance, although the valuable role of breast feeding in
protecting infants should also be stressed in the course of antenatal classes.
Vaccination
Vaccination is the deliberate introduction of pathogen antigens into the body, usually by
injection but, in some cases, orally or nasally. Exposure to the antigen induces a primary
response from the adaptive immune system, in particular leading to the development of
an immunological memory in the form of memory B- and T-lymphocytes. In a second or
subsequent exposure to the same antigen, a secondary response is triggered. As soon
as the antigen is detected, memory cells begin rapid division to generate large numbers
of B-lymphocyte plasma cells. These cells release their antibodies into the circulation,
leading to such a quick build up of antibodies that the invading pathogen is neutralised
before it can cause any harm. However, while vaccination greatly reduces the chance
of infection, it cannot entirely eliminate it.
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Primary and secondard responses after vaccination
Adjuvants
In addition to the antigenic ingredient, vaccines contain chemicals which act to modify
the immune response engendered by the vaccine, either by increasing the production of
antibodies or by making the protection provided last longer, or sometimes only activating
T-lymphocytes. The most commonly used adjuvant is alum (potassium aluminium
sulphate), although several other substances may be used including paraffin oil and
bacterial products.
Antigens
There are a variety of sources used to provide the essential antigens in a vaccine.
•
Live attenuated microbes - these contain the same antigens as the pathogen,
but the microbes have been sub-cultured many times in the laboratory so that they
become an ’attenuated’ strain, i.e. they can no longer cause the full-blown disease,
although they may cause a very mild form of it. The first vaccine, the smallpox
vaccine, consisted of a live attenuated virus. The MMR (measles, mumps and
rubella) vaccine falls into this category.
•
Toxoid - these are inactivated toxins; vaccines include Diphtheria and tetanus (part
of DTaP combined immunisation).
•
Dead pathogens - the microbes are destroyed by heat and chemicals although the
dead pathogen still carries the antigens which stimulate the immune response;
vaccines for Hepatitis A, polio and cholera fall into this category.
•
A fragment of a pathogen - the viral coat component can be used as a vaccine;
the HPV vaccine has the viral protein coat protein of the Human Papilloma Virus,
as does the vaccine for Hepatitis B.
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59
Administration of vaccines
Vaccines are most commonly administered by injection, although some are given as a
nasal spray or by mouth. Inhaled (nasal) vaccine can be used against influenza and
ingested (oral) vaccines for protection against polio.
New techniques of vaccine administration include a patch application, in which a patch
containing a matrix of extremely tiny needles delivers a vaccine without the use of a
syringe. This method of delivery could be particularly useful in remote areas because
its application would not require delivery by a trained medical person.
Active immunity: Questions
Q1: Complete the following table concerning vaccines using the words and phrases
from the list.
Component
Go online
Function
Word and phrase list: adjuvant, antigen, creates immunological memory, enhances
immune response.
..........................................
Q2: State the four different sources of antigen found in vaccines.
..........................................
4.1.2
Vaccine clinical trials
Learning objective
By the end of this section, you should be able to:
•
•
describe key aspects of the protocol for any vaccine clinical trial as being that
the trial should be:
◦
randomised;
◦
double-blind;
◦
placebo-controlled;
explain the importance of group size in reducing experimental error and
increasing statistical significance.
Vaccine Clinical Trials
Before a licence can be issued for a vaccine or a drug to be administered to the public,
it must be subjected to an intensive series of trials to establish its safety and efficacy.
In advance of any human trials, the vaccine must undergo extensive laboratory research,
including tests on cell cultures and laboratory animals. These pre-clinical trials allow
vaccine researchers to gain a better understanding of how the treatment works and of
any side effects. A new cancer drug can take up to six years of testing in the laboratory
before it reaches the clinical trials stage. Even then, very few drugs get to the clinical
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trials; only one in every one thousand new drugs reaches the clinical trials.
The next step is to seek approval from the regulatory authority of the member state
in which the trial is to be conducted. In the UK, this is the Medicines and Healthcare
products Regulatory Agency (MHRA).
Protocols must be drawn up at this stage for the trials, these may include:
•
target groups for the trials;
•
number of subjects involved in these trials;
•
other treatments with which to be compared;
•
procedures for collection and interpretation of data.
The protocol will now undergo independent scientific review and, at the same time, it
must be approved by the ethics committee. These steps are intended to ensure that the
trial is foolproof and will respect rights, dignity, safety and well-being of the subjects.
In the UK, all clinical trials have to meet the standard set by the European Union Clinical
Trials Directive. The process ensures all trials are carried out to the same standard
wherever they take place in Europe. The process for clinical trials is summarised below.
Summary of clinical trial protocols
A protocol is a predefined procedure for conducting a scientific investigation which will
allow the method to be standardised so that the study can be repeated exactly. The key
features of a vaccine clinical trial protocol are that the procedure should be:
•
randomised - all subjects in the trial should have an equal chance of being given
vaccine or the placebo, usually done by allocating individuals to treatments using
some kind of random-number generator;
•
double-blind - neither the subjects nor the persons carrying out the trial know
which subjects are getting the vaccine and which the placebo;
•
placebo-controlled - the trial subjects are divided into two groups, one receiving
the vaccine and the other receiving the placebo, a treatment which is similar in all
respects to the vaccine apart from the active ingredient being tested.
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The importance of group size
By this stage in their science studies, all students should be aware that increasing the
number of individuals in a study, or repeating the investigation, will make the results more
reliable. However, few are usually able to explain why this is so. Before addressing this,
a few key concepts need to be defined.
Sample
Rarely is it possible to study all the individuals in the population being investigated. Even
in a general election, not all of the people eligible to vote actually do so; in fact, those who
vote are a self-selected group who may not at all represent the views of those who do not
vote. A scientist might approach the challenge of ensuring fair representation differently.
Firstly, not all individuals need be consulted. Rather a much smaller representative
group would be selected for study; that is the sample.
This sample would be selected randomly, i.e. everyone in the population would have an
equal chance of being included. The population would be divided up into different socioeconomic and geographical groupings, and the number of people chosen from each
grouping would be in proportion to the size of this grouping in the whole population.
This would ensure that all groups are represented in the sample, and no one group has
a disproportionate influence.
Of course, general elections will never be run this way, as ’one person, one vote’ is a
fundamental principal of democracy, but it is exactly the way in which national opinion
polls are run.
True values versus sample estimates
Imagine being asked to estimate the mean height of boys in the second year of the
local high school, but only being allowed enough time to measure thirty of them. If the
boys are selected randomly, with all having an equal chance of being in the sample, the
mean calculated from this group would be representative of the year group. However,
that sample mean is very unlikely to be same value as the one that would have been
achieved if every boy had indeed been measured to find the true value.
A key task in sampling is to ensure that the estimate value derived from a sample is
acceptably close to the true value, and this is increasingly likely as the sample size is
increased.
Experimental error
This is not to do with mistakes, although these do of course get made e.g. misreading
scales, omitting numbers. Such blunders usually stand out and should be excluded from
any analysis.
Experimental error is any deviation of the measured value from the true value. It is
inherent in any technique, although efforts are always made to minimise it. Suppose
a simple task of weighing out chemicals is required. First of all the balance must be
properly zeroed and operated at the correct voltage and temperature; these sources of
error can be minimised.
However, if the balance only measures to 1g, then if the reading is 10g, the balance
is really saying that the sample weighs somewhere between 9.50g and 10.49g (to two
decimal places). This source of error is a function of the apparatus used, and the larger
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the sample size, the less effect it will have.
Statistical significance
Many biology students seem to have a horror of maths, in which they include statistics.
However, there are two principal reasons why this attitude is misplaced:
1. firstly, without statistical analysis, no scientist has any idea of the significance of
their experimental results. In that regard, statistics is as important a tool in biology
as the microscope;
2. secondly, biologists are not required to understand the mathematics that underpin
any of the statistical techniques which they use, although it is essential to be aware
of the type of technique that is appropriate to the data to be analysed. Other than
that, it is just a case of plugging numbers into a formula.
Statistical analysis allows scientists to determine the likelihood of a particular outcome.
Results are usually expressed in terms of percentage significance, either 5%
(’significant’) or 1% (’highly significant’). These numbers mean that there is only 1
chance in 20 (5% level) or 1 chance in 100 (1% level) that such a result would have
occurred by chance. It is only possible to analyse experimental results statistically if
samples are randomly selected.
Thus, at the end of vaccine clinical trial, if the number of people in the vaccine group
who had contracted the disease was lower than the number catching the disease in
the placebo group, the results would be analysed to discover the possibility of such a
difference arising by purely random processes. The statistical test would assess how
likely it would be to get such a large difference if the individual subject’s results had just
been randomly placed into two groups irrespective of their treatment.
The significance of any difference is very strongly dependent on the size of the sample
groups. Quite a large difference may not be found to be statistically significant if the
sample size is small, whereas quite small differences may prove significant if the sample
size is large.
Vaccine clinical trials: Questions
Go online
Q3: Explain what is meant by the statement that vaccine clinical trials should be
randomised, double-blind and placebo controlled.
..........................................
Q4: State two ways in which increasing sample size will affect the results of an
experiment.
..........................................
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TOPIC 4. ACTIVE IMMUNISATION
4.2
63
Herd Immunity
Learning objective
By the end of this section, you should be able to:
•
state that herd immunity is important in the control of infectious diseases;
•
state that herd immunity occurs when a large percentage of a population are
immunised;
•
explain that, as a result of herd immunity, non-immune individuals are protected
as there is a lower probability they will come into contact with infected
individuals;
•
explain that the herd immunity threshold depends on the disease, the efficacy
of the vaccine and the contact parameters for the population.
The creation of herd immunity
When a person is immunised against a disease, it provides protection in two ways.
Firstly, should that person meet the pathogen a second time, they are very unlikely
to develop the disease. Secondly, because the pathogen cannot use them as a host
from which to spread to other people, the chance of an infection spreading through the
population is reduced. This is the basis of the herd immunity which is crucial in the
control of infectious diseases.
For an infection to spread through a community, the pathogen must be able to find a
new host before its current host’s immune system eliminates it. The fewer contacts the
infected person has with unprotected individuals, the less likely this is. When a certain
critical level of immunisation in the community is reached, the disease will always fail
to spread in that community, although sporadic cases may occur. In this situation, not
only are those who have been vaccinated protected, but also others who have not, e.g.
people whose immune systems have been suppressed for transplant surgery. This is
because they are less likely to come into contact with infected individuals as there are
few of them and the disease will only be present in the population for a short time.
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The three stages of creating herd immunity
Go online
..........................................
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Most vaccination programmes and policies are aimed at the creation of herd immunity.
The childhood vaccination programme in this country ensures that when any of the
diseases involved enter the population, they will not spread to create an epidemic and
infect children or adults who have not been previously vaccinated or exposed to the
disease. The creation of herd immunity is especially important in areas where people
are in close and frequent contact, with the potential for the rapid spread of infection, e.g.
schools, densely populated housing.
The creation of herd immunity does not always guarantee success in containing the
spread of infectious diseases. Mutations can occur in the pathogen which changes the
antigen, an entirely new strain may be brought into the country, or batches of vaccine
may prove faulty. Additionally, if a sufficiently large percentage of the population fails
to get vaccinated, the pathogen will be able to find new hosts sufficiently frequently for
the infection to spread and the non-immunised members of the population become very
vulnerable to this disease.
Herd immunity thresholds
The threshold level of vaccination necessary to create herd immunity in a population
varies from as low as 40% (for Pandemic Flu - H1N1) to up to 94% (pertussis and
measles). This is dependent on several factors concerned with the pathogen:
•
the virulence of the pathogen involved, i.e. how easily it infects people: higher
virulence requires a higher threshold;
•
the length of time that a person with the disease remains infectious (the period of
infectivity): the longer the infective period, the higher the threshold;
•
the ease of transmission of the pathogen, i.e. how easily the pathogen in passed
from individual to individual: the more easily the pathogen is transmitted, the
higher the threshold;
•
the means of transmission of the pathogen: the more effective the means of
transmission, the higher the threshold.
In addition, some vaccines have a higher efficacy than others, meaning that they
establish immunity more efficiently and so require a lower level of immunity in the
population to contain any disease outbreak. In order to sustain herd immunity, the
population may need to receive regular boosters as some vaccinations lose their efficacy
over a period of time.
The other factors of importance in determining the threshold level are the contact
parameters of the population. This is the extent to which people come into contact
with each other or share the same space; the threshold for an isolated rural community
will be lower than that for an over-crowded inner city.
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The herd immunity thresholds for some diseases are shown in the following table.
Likely transmission
methods
Disease
Herd immunity threshold
Diphtheria
Saliva
84 %
Measles
Airborne
86 - 94 %
Mumps
Airborne droplet
78 - 86 %
Pertussis
Airborne droplet
92 - 94 %
Polio
Faecal-oral route
82 - 86 %
Rubella
Airborne droplet
82 - 85 %
Smallpox
Social contact
80 - 85 %
Pandemic flu
Social contact
about 40 %
Herd immunity thresholds for vaccine-preventable diseases
In addition to being used in disease prevention, the establishment of herd immunity is
also used to fight ongoing outbreaks of a disease.
Herd Immunity: Questions
Go online
Q5: Explain why herd immunity will protect individuals who are not immune to a
disease when an infected person arrives in their community.
..........................................
Q6: Explain how each of the following aspects of a pathogen affects the herd immunity
threshold:
•
low virulence;
•
short infectious period;
•
easily transmitted.
..........................................
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Immunisation programmes
Learning objective
By the end of this section, you should be able to:
•
explain the reasons for public health immunisation programmes;
•
state that public health immunisation programmes seek to establish herd
immunity to a number of diseases;
•
explain the difficulties caused when widespread vaccination is not possible
because of malnutrition, poverty or a vaccine being rejected by a percentage
of the population.
The purposes of public health immunisation programmes are to protect vulnerable
individuals, either directly by vaccination or indirectly by establishing herd immunity. The
winter flu vaccination programmes are an example of protecting vulnerable individuals
rather than attempting to reach a threshold of immunity. On the other hand, the
childhood vaccination programmes are very strongly geared to that aim.
Childhood vaccinations in Scotland
Many people will be aware that the routine immunisation of children and infants has
dramatically reduced the incidence of infectious diseases, for example measles and
whooping cough (pertussis), and has led to the global eradication of smallpox. However,
for those not recently involved in the rearing of young children, it might come as a
surprise just how many vaccinations are routinely given to our children.
While some are tempted to say that the diseases involved are rare and it seems unfair to
put young children through the trauma of repeated injections, it only takes a moment’s
reflection to appreciate that the risks of any vaccination are minimal compared to the
potential impact of the disease itself, and that the only reason the diseases are rare is
the fact that the vast majority of children are immunised against them.
(Note: the following list is not in the syllabus!)
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Childhood vaccinations
Challenges to widespread vaccination
As there are always groups within a community who cannot be vaccinated for various
reasons, e.g. pregnant women, transplant patients, people whose immune systems are
deficient, it is vital that all those for whom the vaccination poses no significant threat
are immunised so that the herd immunity threshold is reached. There are three key
challenges to achieving these threshold values:
•
malnutrition weakens the immune system so that even if children have been
vaccinated, they will be less able to fight off infection;
•
children living in poverty show much lower vaccination rates than more affluent
children as a result of lower engagement with the public health system;
•
vaccination as a process may be rejected by groups on religious or other grounds.
Whereas the first two points can only be addressed by means of improving living
standards, and are closely inter-related, the latter must be addressed by means of
sensitive education and publicity.
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Immunisation programmes: Questions
Q7: Apart from protecting vulnerable individuals, what do public health immunisation
programmes attempt to establish?
..........................................
Q8: Explain how each of the following reduces the effectiveness of vaccination
programmes:
•
malnutrition;
•
poverty;
•
rejection of vaccination.
..........................................
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4.4
The evasion of specific immune responses by
pathogens
Learning objective
By the end of this section, you should be able to:
•
state that many pathogens have evolved mechanisms that evade the specific
immune system which has consequences for vaccination strategies;
•
state that antigenic variation is a process by which a pathogen is able to change
its surface proteins;
•
state that antigenic variation may be brought about by:
◦
small genetic mutations that gradually change the surface antigens;
◦
sudden large genetic change when two different strains undergo genetic
recombination;
•
explain that antigen variation allows some pathogens to avoid the effect of
immunological memory;
•
describe role and impact of antigenic variation in diseases like malaria,
trypanosomiasis and influenza;
•
state that some pathogens directly attack the immune system;
•
explain that HIV attacks lymphocytes, which is the major cause of AIDS;
•
explain that tuberculosis (TB) survives within phagocytes and so avoids immune
detection.
The specific immune system is one of the primary limitations on the replication of
pathogens within the body; these immune responses target specific antigens expressed
by the pathogen. However, as a result of a long association with us, many pathogens
have evolved mechanisms that allow them to evade the specific immune system and
cause infection. Clearly, such developments must be taken into account when public
vaccination strategies are formulated.
4.4.1
Antigenic variation
Antigenic variation is a process by which a pathogen is able to change its surface
proteins so that it can evade the host immune responses. The antigenic profile
(sometimes called antigenic diversity), will change as the pathogen passes through
the host population or in the original infected host. Antigenic variation is particularly
important for pathogens as it allows them to:
•
target hosts which are long-lived or susceptible to the pathogen;
•
infect a single host on more than one occasion;
•
transmit the disease easily.
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Antigenic variation can occur in two distinct ways:
1. the slow accumulation of small genetic mutations (antigenic drift) that gradually
change the surface antigens;
2. a sudden large genetic change (antigenic shift) brought about when two different
strains undergo genetic recombination.
Antigenic variation
These processes will be explored in more detail when changes in influenza viruses are
studied.
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Pathogens which undergo antigenic variation have a selective advantage over more
genetically stable ones. Antigenic variation happens through three genetic processes:
1. gene mutation;
2. recombination;
3. gene switching, which occurs when certain members of a family of genes are
switched on while others in the family shut down - it is a process that is common
during embryonic development.
The resulting pathogens are immunologically different from the parental strains. Thus,
pathogens which can vary their antigenic signature are able to avoid triggering the
immunological memory which had been developed in response to their parental strain.
Antigenic variation: Question
Q9:
List the genetic processes which cause antigenic variation.
Go online
..........................................
4.4.2
Antigenic variation in different pathogens
Viruses
The influenza virus genome is fragmented and can go through a high rate of genetic
re-assortment during replication. This can result in the emergence of a new virus
that codes for a new haemagglutinin (HA) and/or neuraminidase (NA); the two large
glycoproteins on the outside of the viral particles. Most flu epidemics are due to the
emergence of these new virus strains (usually type A) and can be brought about via
antigenic shift and antigenic drift.
Drift and shift in flu viruses
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Antigenic shift in flu viruses can occur when:
•
an aquatic bird passes a bird strain of influenza A to an intermediate host such
as a chicken or pig and a person passes a human strain of influenza A to the
same chicken or pig - when the viruses infect the same cell, the genes from the
bird strain mix with genes from the human strain to yield a new strain, which can
spread from the intermediate host to humans;
•
an avian strain of influenza A (without undergoing genetic change) jumps directly
from a duck or other aquatic bird to humans;
•
an avian strain of influenza A (without undergoing genetic change) jumps directly
from a duck or other aquatic bird to an intermediate animal host and then to
humans.
This genetic change enables influenza strains to jump from one animal species to
another, including humans. What happens, in fact, is that when two strains of the
pathogen recombine, any one of the eight influenza proteins can be replaced by a
different protein acquired as a result of genetic re-assortment. In this case, the RNA
that codes for the HA is replaced for one from another source (i.e. from avian or porcine
sources). This is illustrated below; the change of the glycoproteins (HA) on the surface
of the viral particles is illustrated by a colour change on the surface of the virus.
Diagrams of a highly pathogenic avian strain virus and a human strain
The influenza pandemic of 1918-19 was caused by a virus which had a HA protein
normally found in swine influenza strains. Antigenic shift results in a more immediate
and extensive change in the genetic information of this ’newly formed’ pathogen.
These changes in the haemagglutinin and neuraminidase types are used to characterise
the various strains of the flu viruses. Some of the variants that caused notable epidemics
are shown below.
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Flu pandemics since 1890: the ’Spanish’, ’Asian’ and ’Hong Kong’ strains of flu involve
avian variants; the ’swine’ strain has porcine variants
In terms of the global impact, the 1918 Spanish Flu pandemic was by far the worst, with
an estimated 50 to 100 million deaths worldwide.
Antigenic drift is a result of genetic point mutations accumulated by the viral genome
over an extended period of time. This drift results in small antigenic changes in the
pathogen population and will reduce the efficacy of B and T cell memory during the host
immune response. Antigenic drift is prominent in the influenza virus, and is becoming
more and more evident in the rapid evolution of rhinoviruses and enteroviruses.
Antigenic drift contributes to our susceptibility to influenza infections year after year.
The human immunodeficiency virus (HIV) exhibits antigenic drift within the particular
host due to its high rate of replication.
Protozoa
Antigenic variation occurs in diseases such as malaria and trypanosomiasis and is one
of the reasons why they are still so common in many parts of the world.
Protozoa represent the most biologically complex pathogens presented to the human
immune system. Trypanosomes (causing sleeping sickness) and Plasmodium (causing
malaria) use antigenic variation to evade immune responses and prolong the duration of
infections. Trypanosomes exhibit unique processes of gene conversion, whereby any
one of hundreds of genes coding for variable surface glycoproteins can be expressed.
As the Trypanosomes multiply inside the host, the host makes antibodies against them.
After five to seven days, these antibodies destroy most of the Trypanosomes and the
symptom decreases. About this time, a new wave of Trypanosomes appears because
these are unaffected by antibodies generated against the previous wave. The immune
system has to start over again. This process continues, essentially indefinitely, until
the death of the host. During this time, the body continues to make primary responses
against new antigens. One consequence of this is that the immune system becomes
quite exhausted and the blood levels of the antibody (immunoglobulin IgM) increase
dramatically, but to no useful effect.
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In the protozoa Plasmodium falciparum, an aetiological agent (aetiology is the study
of causes or origins) for malaria undergoes gene switching, resulting in the variable
expression of surface proteins produced on infected red blood cells during the
erythrocytic, asexual phase. These protozoan processes of antigenic variation lead
to a gradual exhaustion of the host immunity in the terminal stages of disease.
Antigenic variation in different pathogens: Questions
Q10: Explain what is meant by gene conversion in Trypanosomes.
..........................................
Go online
Q11: How does gene conversion provide Trypanosomes with the ability to evade the
host immune system.
..........................................
4.4.3
Direct attack on the immune system
Learning objective
By the end of this section, you should be able to:
•
explain why the absence or failure of some components of the immune system
results in increased susceptibility to infection;
•
explain how HIV attacks lymphocytes and is the major cause of acquired
immunodeficiency in adults;
•
explain how the pathogen which causes Tuberculosis (TB) can survive within
phagocytes and avoids immune detection.
Some pathogens directly attack the immune system by destroying lymphocytes. The
Human Immunodeficiency Virus (HIV) is the best known example.
HIV and AIDS
Acquired Immune Deficiency Syndrome (AIDS) is the fatal condition that results from
infection with HIV. AIDS itself is not a disease but describes the opportunistic diseases
that infect and are often fatal to an HIV-positive individual. It is widely accepted that HIV
develops into AIDS, although there have been a few cases where people have remained
completely symptomless.
HIV is carried in the blood, semen, vaginal fluids and breast milk, but it is unable to
survive outside of the human body for long so can only be transmitted by the exchange
of body fluids. The main ways in which HIV can be transmitted between people are:
•
intimate sexual contact;
•
intravenous drug use and blood transfusions;
•
from mother to child across the placenta and through breast milk.
The vast majority of infections occur as a result of sexual intercourse, both heterosexual
and homosexual. The virus that causes this disease is a lentivirus (slow virus) that
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infects both the immune and central nervous systems over a period of years. Many
people experience flu-like symptoms when they are first infected and become HIVpositive, but serious symptoms do not generally appear until years later. As the HIV
multiplies, it weakens the immune system by destroying the T-helper cells that mediate
the immune response, as shown below. Eventually the immune system is destroyed,
making sufferers more susceptible to diseases. As sufferers are immunocompromised,
these diseases are more harmful and are frequently fatal. As the T-helper cells
are destroyed and the immune system is less able to defend the body opportunistic
infections occur, such as:
•
oral thrush, caused by the fungus Candida albicans;
•
Kaposi’s sarcoma, a rare form of skin cancer;
•
tuberculosis;
•
a rare form of pneumonia caused by Pneumocystis carinii.
Graphs of HIV concentration and T-cell concentration
Initially, it was thought that HIV and AIDS only affected homosexuals and drug users
because most of the first cases were seen in these two groups. It is now known that
anyone can be infected with HIV, but there is still a lot of stigma associated with the
disease.
Direct attack on the immune system: Question
Q12: Why does HIV cause AIDS?
Go online
..........................................
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4.4.4
77
Tuberculosis
Tuberculosis (TB) is a contagious disease caused by the bacteria Mycobacterium
tuberculosis (human) and M. bovis (cattle). It is transmitted in the same way as the
common cold - by droplets from the respiratory tract of individuals that have the active
disease. When they cough, sneeze, talk or spit, tiny droplets containing the bacterium
are expelled from their lungs, which may then be inhaled by other people. Only a
few bacilli are required for a person to become infected, making this disease easily
transmissible. It is also possible to become infected with M. bovis via contact with
susceptible animals and their products (e.g. unpasteurised milk); this form of TB is
more common in economically less developed countries.
Not all people infected with TB are actually infectious. Only those who actually develop
TB symptoms are infectious, but, if untreated, they can potentially infect 10-15 others
every year. It is estimated that at any one time a third of the world’s population is infected
with TB, but only a small number will develop the disease. However, tuberculosis
continues to kill more than two million people every year, a figure that is rising as the
AIDS epidemic increases and drug-resistant TB spreads.
TB can be categorised into three types:
1. in the majority of cases, the immune system of the infected person kills the bacteria
and the person experiences no further symptoms;
2. latent TB, in which the sufferer does not experience any symptoms, but the
bacteria remain in the body, surviving within phagocytes and thus avoiding
detection - latent TB can sometimes develop into an active TB infection, especially
if the infected person’s immune system is weakened;
3. active TB, in which the immune system fails to kill or contain the infection and it
slowly spreads to the person’s lungs.
The bacteria that cause tuberculosis can remain inactive in a human for many years,
but can become active if its host’s immune system has been weakened. This causes
serious complications for people who are already immunocompromised, such as those
infected with HIV. It accounts for the majority of AIDS deaths.
Tuberculosis spreads rapidly in overcrowded areas and outbreaks are often seen among
the poor and homeless. The incidence of TB in economically more developed countries
was considerably reduced when the standards of housing and nutrition improved. The
introduction of a vaccine further decreased the impact of TB and it was thought that it
had almost been eradicated from the developed world. However, it is now making a
comeback as inner city poverty, homelessness, drug resistance, AIDS and migration to
big cities are all rising. Drug resistance in Mycobacterium is also developing by natural
selection, particularly as a result of people failing to complete courses of antibiotics.
Tuberculosis: Question
Q13: How does TB evade detection by the immune system?
..........................................
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4.5
Learning points
Summary
Active Immunity
•
Active immunity can be developed by vaccination with antigens from
infectious pathogens.
•
Vaccination creates an immunological memory.
•
Vaccines include antigens from infectious pathogens, including inactivated
pathogen toxins, dead pathogens, parts of pathogens and weakened
pathogens.
•
The antigens in vaccines are usually mixed with an adjuvant to enhance the
immune response.
Vaccine Clinical Trials
•
•
Key aspects of the protocol for any vaccine clinical trial are that the trial
should be:
◦
randomised;
◦
double-blind;
◦
placebo-controlled.
The importance of group size in reducing experimental error and increasing
statistical significance.
Herd Immunity
•
Herd immunity is important in the control of infectious diseases.
•
Herd immunity occurs when a large percentage of a population are
immunised.
•
As a result of herd immunity, non-immune individuals are protected as there
is a lower probability they will come into contact with infected individuals.
•
The herd immunity threshold depends on the disease, the efficacy of the
vaccine and the contact parameters for the population.
Immunisation programmes
•
The reasons for public health immunisation programmes.
•
Public health immunisation programmes seek to establish herd immunity to
a number of diseases.
•
Difficulties arise when widespread vaccination is not possible because of
malnutrition, poverty or a vaccine being rejected by a percentage of the
population.
The evasion of specific immune responses by pathogens
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TOPIC 4. ACTIVE IMMUNISATION
Summary continued
4.6
•
Many pathogens have evolved mechanisms that evade the specific immune
system which has consequences for vaccination strategies.
•
Antigenic variation is a process by which a pathogen is able to change its
surface proteins.
•
Antigenic variation may be brought about by:
◦
small genetic mutations that gradually change the surface antigens;
◦
sudden large genetic change when two different strains undergo
genetic recombination.
•
Antigen variation allows some pathogens to avoid the effect of
immunological memory.
•
The role and impact of antigenic variation in diseases such as malaria,
trypanosomiasis and influenza is to continuously alter the surface antigens
of the pathogens, leading to sporadic epidemics and the failure of
vaccination programmes.
•
Some pathogens directly attack the immune system.
•
HIV attacks lymphocytes, which is the major cause of AIDS.
•
Tuberculosis (TB) survives within phagocytes and so avoids immune
detection.
Extended response question
The activity which follows presents an extended response question similar to the style
that you will encounter in the examination.
You should have a good understanding of public health immunisation programmes
before attempting the question.
You should give your completed answer to your teacher or tutor for marking, or try to
mark it yourself using the suggested marking scheme.
Extended response question: Public health immunisation programmes
State the aim of public health immunisation programmes and explain why they may fail
to protect non-immunised individuals. (6 marks)
..........................................
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4.7
End of topic test
End of Topic 4 test
Q14: Complete the paragraphs by selecting words from the list. (12 marks)
Go online
can be developed by
with antigens from
An immunological
. This is known as
immunity. Vaccines include
infectious
from infectious pathogens, including inactivated pathogen
,
dead pathogens, parts of pathogens and weakened pathogens. The antigens in
to enhance the
response.
vaccines are usually mixed with an
for any vaccine clinical trial are that the trial should be
Key aspects of the
, double-blind and placebo-controlled. Group size is important in reducing
and increasing
significance.
experimental
Word list: active, adjuvant, antigens, error, immune, memory, pathogens, protocol,
randomised, statistical, toxins, vaccination.
..........................................
Q15: Explain the term ’antigenic variation’. (1 mark)
..........................................
Q16: Describe one way in which pathogens develop antigenic variation. (2 marks)
..........................................
Q17: State the role of antigenic variation in diseases like malaria, trypanosomiasis and
influenza. (1 mark)
..........................................
Q18: State the impact of antigenic variation in such diseases. (1 mark)
..........................................
Q19: Explain how HIV leads to the development of AIDS. (2 marks)
..........................................
Q20: State how TB evades immune detection. (1 mark)
..........................................
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Topic 5
End of unit test
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TOPIC 5. END OF UNIT TEST
End of Unit 4 test
Q1:
Go online
An example of the body’s physical barriers to infection is: (1 mark)
a) epidermis
b) histamines
c) sebum
..........................................
Q2:
Histamines are released by: (1 mark)
a) mast cells
b) NK cells
c) phagocytes
..........................................
Q3:
Cytokines stimulate the: (1 mark)
a) apoptosis
b) non-specific immune response
c) specific immune response
..........................................
Q4:
Autoimmune diseases are caused by an incorrect response by: (1 mark)
a) B-lymphocytes
b) macrophages
c) T-lymphocytes
..........................................
Q5:
Community responsibility for control of pathogen spread involves: (1 mark)
a) good hygiene
b) sexual health
c) waste disposal
..........................................
Q6:
A disease which is always present in a population is: (1 mark)
a) endemic
b) epidemic
c) pandemic
..........................................
Q7:
Vaccines contain pathogen: (1 mark)
a) antibodies
b) antigens
c) antiseptics
..........................................
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TOPIC 5. END OF UNIT TEST
Q8: Herd immunity thresholds are less likely to be reached because of: (1 mark)
a) malnutrition
b) poor personal hygiene
c) unsafe food webs
..........................................
Q9: Name an example of the body’s non-specific chemical defences against
pathogens and state its function. (2 marks)
..........................................
The graph shows the immune response of two people, one of whom has been
vaccinated against a disease and the other not.
Q10: Which of the two lines on the graph represents the response of a person who has
been vaccinated against the disease? (1 mark)
a) A
b) B
..........................................
Q11: Explain the response of a person who has been vaccinated against the disease.
(1 mark)
..........................................
Q12: In the later stages of the infection, a person infected with HIV would show a
different pattern to either of these curves. Describe this difference. (1 mark)
..........................................
Q13: Explain this difference. (1 mark)
..........................................
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The following diagram shows clonal selection in lymphocytes.
Q14: Describe what is shown in the upper half of the diagram. (1 mark)
..........................................
Q15: Explain the lower half of the diagram. (2 marks)
..........................................
Q16: State how some T-lymphocytes activate B-lymphocytes. (1 mark)
..........................................
Q17: State two ways in which pathogens may be transmitted. (1 mark)
..........................................
Q18: How does quarantine control the spread of a pathogen? (1 mark)
..........................................
Q19: State the three key aspects of the protocol for any vaccine clinical trial. (1 mark)
..........................................
Q20: Describe the importance of group size in vaccine clinical trials. (2 marks)
..........................................
Q21: Explain how antigenic variation enables a pathogen to evade the specific immune
response. (2 marks)
..........................................
..........................................
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GLOSSARY
Glossary
Acquired immunity
immunity developed throughout a person’s life time; can be induced either naturally
or artificially
Arthropods
invertebarate animals with a segemented body, jointed limbs and an external
exoskeleton, e.g. insects, crustaceans and arachnids
Enterovirus
a virus which causes diseases such as polio and meningitis
Erythrocytic asexual phase
the pathogenic portion of the vertebrate phase of the life cycle of malarial
organisms that takes place in the red blood cells
Gene conversion
occurs during DNA genetic recombination and at high frequencies during meiosis;
it is one of the ways a gene may undergo mutation
HA
(haemagglutinin) a protein that mediates the binding of the virus to target cells
Influenza A
a virus which causes influenza in birds and mammals; Influenza B and C are
mainly confined to humans
Innate immunity
inborn immunity
Lysis
cell breakdown
Lysozyme
an enzyme found in tears, saliva, and mucus which can destroy bacteria
NA
(neuraminidase) involved in the release of progeny virus from infected cells
Phagocytes
white blood cells that protect the body by ingesting/phagocytosing harmful foreign
particles, bacteria, and dead or dying cells
Phagocytosis
the engulfing of pathogens or solid material into a vesicle with which lysosomes
then fuse, releasing their digestive enzymes into it
Rhinovirus
one of the viruses which cause the common cold
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GLOSSARY
Trypanosomiasis
diseases caused by the protozoa Trypanosomes such as sleeping sickness and
Chagas disease
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ANSWERS: TOPIC 1
Answers to questions and activities
1 Non-specific defences
The immune system: Questions (page 3)
Q1: To protect the body against pathogens, some toxins and cancer cells.
Q2: Skin epithelial cells and lysozyme in tears and saliva.
Q3: It degrades bacterial walls.
Q4: This is immunity that is inborn, non-specific, and does not change over time.
Any two examples from:
•
phagocytosis by phagocytes;
•
skin epithelial cells;
•
mucus membranes of the lungs and gut;
•
ciliated cells of the respiratory tract;
•
lysozyme in tears.
Q5: A type of white blood cell which engulfs bacteria.
Non-specific defences - physical and chemical: Questions (page 5)
Q6: Any two from:
•
dry dead cells;
•
tiny hairs;
•
mucus in the trachea.
Q7: Sebum contains antimicrobial fatty acids and the stomach produces acid
secretions.
The cellular basis of inflammation: Questions (page 9)
Q8: In connective tissue, especially around nerves and blood vessels.
Q9: It stimulates vasodilation and increases permeability of capillary walls.
Q10: Cytokines
Q11: Phagocytes / macrophages / neutrophils
Q12: Phagocytosis
Q13: Complement system
Q14: Fibrinogen and fibrin
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Phagocytes: Questions (page 12)
Q15: Cytokines
Q16: To stimulate the specific immune response.
Q17: Antigen molecules on the cell surface.
Q18: Engulfing and digesting solid particles.
Natural killer (NK) cells: Questions (page 14)
Q19: Self-destructive enzymes
Q20: Apoptosis
Extended response question: The inflammatory response (page 15)
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checking the answer, the number of the point being allocated a mark should be written
on the answer paper. A maximum of eight marks can be gained.
1. Mast cells. . .
2. . . .release histamine.
3. Histamine causes vasodilation. . .
4. . . .and increases capillary permeability.
5. Mast cells also secrete cytokines.
6. Cytokines act as signalling molecules.
7. The increased blood flow and the secretion of cytokines lead to. . .
8. . . .the delivery of antimicrobial proteins. . .
9. . . .and clotting elements to the site of infection/damage.
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End of Topic 1 test (page 15)
Q21:
The immune system protects the body
against
pathogens.
Sebum on the skin contains fatty acids
with
antimicrobial properties.
Pathogens find the dry outer layers of
the skin to be
a hostile environment.
Mast cells release
histamine.
Histamine causes
vasodilation.
Cytokines act as
signalling molecules.
Increased blood flow leads to delivery of
clotting elements.
Phagocytes are attracted by
cytokines.
Q22:
The white blood cells involved in the non-specific response are phagocytes and
natural killer (NK) cells. Both phagocytes and NK cells release cytokines which
stimulate the specific immune response.
Phagocytes target pathogens which they recognise by the antigen molecules on their
cell surface. They then destroy them by engulfing and digesting them in a process
called phagocytosis.
The NK cells release enzymes which induce infected cells and pathogens to produce
the self-destructive enzymes of apoptosis pathways.
Q23: To protect the body against pathogens.
Q24:
•
It has antimicrobial chemicals/sebum on its surface.
•
Its dry outer layers are a hostile environment for pathogens.
Q25: Mast cells
Q26: Causes vasodilation AND increases capillary permeability.
Q27: Cytokines
Q28: They attract phagocytes (to the site of infection).
Q29:
•
Antimicrobial proteins.
•
Clotting elements.
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ANSWERS: TOPIC 1
Q30:
•
Phagocytes.
•
Natural killer/NK cells.
Q31: Antigens on the cell surface.
Q32: Engulfing (and digesting) of solid particles.
Q33: Self-destructive enzymes
Q34: Apoptosis
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ANSWERS: TOPIC 2
2 Specific cellular defences
Immune surveillance: Questions (page 20)
Q1: Mast cells
Q2: Neutrophils
Q3: Cytokines
Q4: Lymph nodes
Q5: They present fragments of the cell membrane of engulfed pathogens, which carry
the antigens which uniquely identify the pathogen, on their cell surface.
Clonal selection theory: Questions (page 22)
Q6:
1. In the red bone marrow, haematopoietic stem cells divide to produce daughter cells.
2. As a result of genetic rearrangement, during differentiation these immature
lymphocytes each develop a different antigen receptor on their cell membranes.
3. Those immature lymphocytes, which carry a receptor that will bind with an antigen
from the body’s own tissues, are destroyed in the bone marrow.
4. The lymphocytes that carry other antigen receptors are released from the bone
marrow and move through the circulatory system to the lymph glands or thymus
gland where they mature into inactive lymphocytes.
5. Most of these inactive lymphocytes will never encounter an antigen to match their
receptor.
6. Inactive lymphocytes, which do meet an antigen matching their receptor, become
activated and divide to produce many clones of themselves.
Q7: The way in which lymphocytes are developed to respond to specific antigens.
Q8: 1
T- and B-lymphocytes: Questions (page 25)
Q9: Antigens on foreign cells, cells infected by pathogens and toxins released by
pathogens.
Q10: They have specific surface proteins.
Q11: A failure of immune system regulation, leading to a response by T-lymphocytes to
self antigens.
Q12: They secrete antibodies into the blood and lymph.
Q13: A hypersensitive B-lymphocyte response to an antigen that is normally harmless.
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The action of T-lymphocytes: Questions (page 27)
Q14: Apoptosis
Q15: By engulfing pathogens.
Q16: Cytokines
Q17: Antigens expressed on the surface of antigen-presenting cells.
The action of B-lymphocytes: Questions (page 29)
Q18: Antigen-presenting cells/macrophages, T-lymphocytes
Q19: A group of cells which are produced by mitosis from a single parent cell.
Q20: Antibodies
Q21: The antibody will only attach to one particular antigen.
Q22: An antigen-antibody complex
Q23: They block their binding sites.
Q24: They cause them to cluster together/agglutinate.
Q25: Antibodies attach to the surface of the pathogens.
The antigen-antibody complex stimulates the complement system.
Complement proteins form pores in the pathogen membrane, causing lysis.
Immunological memory: Questions (page 31)
Q26: Activated lymphocytes in the lymph nodes
Q27: They are rapidly stimulated to divide and produce a new clone of lymphocytes.
Q28: It is faster and involves greater production of antibodies.
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Extended response question: Clonal selection theory (page 33)
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checking the answer, the number of the point being allocated a mark should be written
on the answer paper. A maximum of six marks can be gained.
1. Clonal selection theory explains the way in which lymphocytes are developed to
respond to specific antigens which invade the body.
2. Antigens are molecules on the surface of pathogens and other foreign cells or
materials which activate the immune system.
3. Lymphocytes have a single type of receptor on the cell membrane.
4. This receptor is specific to one antigen.
5. Antigen binding leads to repeated lymphocyte division. . .
6. . . .which results in a clonal population of lymphocytes.
End of Topic 2 test (page 34)
Q29:
Constantly monitoring the tissues:
white blood cells.
Identify pathogens to the immune system:
antigens.
Released by damaged cells:
cytokines.
Attracted to infected tissues:
monocytes.
Located on the cell membrane of lymphocytes:
receptors.
Receptor only binds to one antigen:
specific.
A response by T-lymphocytes to the body’s own antigens:
autoimmune.
A hypersensitive response by B-lymphocytes:
allergic.
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ANSWERS: TOPIC 2
Q30:
T-lymphocytes destroy infected cells by inducing
apoptosis.
T-lymphocytes secrete cytokines that activate
B-lymphocytes.
Antigen-presenting cells activate the production of
a clone of T-lymphocytes.
B-lymphocytes are activated by antigen-presenting
T-lymphocytes.
Each B-lymphocyte clone produces
a specific antibody
molecule.
Antigen-antibody complexes render pathogens
susceptible to
phagocytosis.
Cell lysis is a response stimulated by
an antigen-antibody
complex.
Q31: They have specific surface proteins that allow them to distinguish between the
surface molecules of the body’s own cells and cells with foreign molecules on their
surface.
Q32: They divide repeatedly to produce clones of B-lymphocytes that secrete
antibodies into the lymph and blood.
Q33: A second exposure to the same antigen stimulates memory cells to divide rapidly
and produce new clones of lymphocytes which produce a secondary response that is
much more effective in terms of antibody production.
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3 The transmission and control of infectious diseases
Infectious diseases caused by pathogens: Question (page 41)
Q1:
Type of pathogen
Example of disease
Bacteria
Pneumonia
Fungi
Candidiasis
Prion
CJD
Protozoa
Malaria
Virus
Herpes
Methods of transmission of pathogens: Question (page 43)
Q2:
Example of disease
Method of transmission
Body fluids
HIV
Direct physical contact
MRSA
Food
Typhoid
Indirect physical contact
Gastroenteritis
Inhaled air
Measles
Vectors
Dengue fever
Water
Dysentery
Control of spread of pathogens: Questions (page 48)
Q3: Keeps individuals who have potentially been infected separate from healthy
individuals.
Q4: The use of chemicals which either kill or inhibit the growth and reproduction of
pathogens.
Q5:
•
Care in the storage and handling of food.
•
Care in sexual health.
•
Good personal and domestic hygiene.
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ANSWERS: TOPIC 3
Q6:
•
Appropriate waste disposal system.
•
Safe supply chains of foods.
•
Supply of water of a quality that is safe to drink.
Q7: The spread of diseases which are contracted from vectors can be reduced by
removal of vector habitat, the sterile male technique, or the use of pesticides.
Epidemiology and the spread of disease: Question (page 50)
Q8:
The disease occurs occasionally in a population:
sporadic.
Cases of the disease occur regularly in an area:
endemic.
There are unusually high numbers of cases in an area:
epidemic.
Unusually high numbers of cases in many countries:
pandemic.
Control measures: Questions (page 52)
Q9:
c) Isolation
Q10: c) Immunisation
Q11: b) Antibodies
Extended response question: Control of spread of pathogens (page 53)
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by a solidus (/); if both such answers are given, only a single mark is allocated. In
checking the answer, the number of the point being allocated a mark should be written
on the answer paper. A maximum of six marks can be gained.
1. Quality of water supply - drinking water must be safe to drink.
2. Not contaminated with sewage.
3. Free from harmful chemicals and bacteria.
4. Supervision of food chains - enforcing minimum hygiene standards.
5. In abattoirs, restaurants, fast-food outlets, supermarkets, market stalls. (any two)
6. Health education.
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ANSWERS: TOPIC 3
7. Waste disposal - refuse collection.
8. Sewage treatment.
End of Topic 3 test (page 54)
Q12:
Pathogens may be transmitted by direct physical contact, water, food, body fluids,
inhaled air or vector organisms. The spread of pathogens can be controlled by
quarantine and antisepsis.
Individuals have a responsibility to control disease by means of good hygiene, care
in sexual health and appropriate storage/handling of food. The role of community is
to ensure the quality of water supply, safe food webs, and appropriate waste disposal
systems. Communities may also reduce the spread of disease by means of programmes
of vector control.
Q13: Quarantine keeps people who have been potentially exposed to an infection. . .
. . .separate from the rest of the population.
Q14:
•
Purify water before supplying it to households.
•
Ensure sewage and drinking water are kept separate.
Q15: Disease: malaria / dengue. (or other suitable)
Spread control: removal of areas of stagnant water / other breeding areas, e.g. old
tyres.
Q16: A disease that is found at a constant low level in a population.
Q17: By the introduction of a new strain of the disease against which there is no
immunity.
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ANSWERS: TOPIC 4
4 Active immunisation
Active immunity: Questions (page 59)
Q1:
Component
Function
Antigen
Creates immunological memory
Adjuvant
Enhances immune response
Q2:
•
Dead pathogens.
•
Inactivated pathogen toxins.
•
Parts of pathogens.
•
Weakened pathogens.
(two sources for one mark, all four for two marks)
Vaccine clinical trials: Questions (page 62)
Q3: Randomised - all subjects in the trial should have an equal chance of being given
vaccine or the placebo.
Double-blind - neither the subjects nor the persons carrying out the trial know which
subjects are getting the vaccine and which the placebo.
Placebo-controlled - the trial subjects are divided into two groups, one receiving the
vaccine and the other a treatment which is similar in all respects to the vaccine apart
from the active ingredient being tested (the placebo).
Q4: Increasing sample size reduces the effect of experimental error. . .
. . .and increases the statistical significance of the results
Herd Immunity: Questions (page 66)
Q5: Herd immunity reduces the chances of non-immune individuals coming in contact
with an infected person.
Q6:
•
Low virulence - decreases the threshold.
•
Short infectious period - decreases the threshold.
•
Easily transmitted - increases the threshold.
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Immunisation programmes: Questions (page 69)
Q7: Herd immunity
Q8:
•
Malnutrition: weakens the immune system so that even if children have been
vaccinated, they will be less able to fight off infection.
•
Poverty: children living in poverty show much lower vaccination rates than more
affluent children, as a result of lower engagement with the public health system.
•
Rejection of vaccination: vaccination as a process may be rejected by certain
groups on religious or other grounds, reducing the percentage of the population
which is immunised.
Antigenic variation: Question (page 72)
Q9:
1. gene mutation;
2. recombination;
3. gene switching.
Antigenic variation in different pathogens: Questions (page 75)
Q10: It occurs when one of hundreds of genes coding for variable surface glycoproteins
are expressed.
Q11: A new wave of Trypanosomes appears which are unaffected by the current
antibodies.
Direct attack on the immune system: Question (page 76)
Q12: The HIV virus destroys (T-helper) lymphocytes, which weakens the immunes
system and allows other infections to produce the symptoms of AIDS.
Tuberculosis: Question (page 77)
Q13: It survives within phagocytes.
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ANSWERS: TOPIC 4
Extended response question: Public health immunisation programmes (page 79)
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by a solidus (/); if both such answers are given, only a single mark is allocated. In
checking the answer, the number of the point being allocated a mark should be written
on the answer paper. A maximum of six marks can be gained.
1. Public health immunisation programmes seek to establish herd immunity to a
number of diseases.
2. Herd immunity occurs when a large percentage of a population are immunised.
3. This percentage is called the herd immunity threshold.
4. Non-immune individuals are protected because there is a lower probability they
will come into contact with infected individuals.
5. Difficulties arise when widespread vaccination is not effective because of
malnutrition, which weakens the immune system. . .
6. . . .or poverty, which reduces vaccination rates. . .
7. . . .or a vaccine being rejected by a percentage of the population.
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ANSWERS: TOPIC 4
End of Topic 4 test (page 80)
Q14:
An immunological memory can be developed by vaccination with antigens from
infectious pathogens. This is known as active immunity. Vaccines include antigens
from infectious pathogens, including inactivated pathogen toxins, dead pathogens,
parts of pathogens and weakened pathogens. The antigens in vaccines are usually
mixed with an adjuvant to enhance the immune response.
Key aspects of the protocol for any vaccine clinical trial are that the trial should be
randomised, double-blind and placebo-controlled. Group size is important in reducing
experimental error and increasing statistical significance.
Q15: A process by which a pathogen is able to change its surface proteins so that it can
avoid the effect of immunological memory.
Q16: Either one of:
•
The slow accumulation of small genetic mutations (antigenic drift). . .
. . .that gradually change the surface antigens.
•
A sudden large genetic change (antigenic shift). . .
. . .brought about when two different strains undergo genetic recombination.
Q17: To continuously alter the surface antigens of the pathogens.
Q18: Causes sporadic epidemics and the failure of vaccination programmes.
Q19: HIV attacks lymphocytes which reduces the effectiveness of the immune
system. . .
. . .allowing other pathogens to invade and kill the host.
Q20: It survives within phagocytes.
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ANSWERS: TOPIC 5
5 End of unit test
End of Unit 4 test (page 82)
Q1:
a) epidermis
Q2:
a) mast cells
Q3:
c) specific immune response
Q4:
c) T-lymphocytes
Q5:
c) waste disposal
Q6:
a) endemic
Q7:
b) antigens
Q8:
a) malnutrition
Q9: Name: sebum (or other suitable)
Function: contains antimicrobial chemicals.
Q10: a) A
Q11: It is quicker and greater because memory cells have been activated.
Q12: The curve would be slower to rise and would peak much lower.
Q13: HIV destroys the B-lymphocytes which release the antibodies.
Q14: Lymphocytes have a single type of receptor on the cell membrane which is specific
to one antigen.
Q15: Antigen binding to receptors on lymphocyte ’Y’ leads to repeated lymphocyte
division. . .
. . .which results in a clonal population of type ’Y’ lymphocytes only.
Q16: They secrete cytokines.
Q17: Any two from:
•
body fluids;
•
food;
•
inhaled air;
•
physical contact;
•
vector organisms;
•
water.
Q18: Individuals who are infected or have been in contact with an infected person are
isolated.
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ANSWERS: TOPIC 5
Q19: They must be:
1. double-blind;
2. placebo-controlled;
3. randomised.
Q20: Increasing group size reduces experimental error. . .
. . .and increases statistical significance.
Q21: It enables a pathogen to change its surface proteins.
Memory cells are no longer activated by the new antigens.
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