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8
Immunity: defence
against disease
KEY KNOWLEDGE
This chapter is designed to enable students to:
• understand that the immune system provides
a defence against invasion by micro-organisms
and other foreign material
• demonstrate a knowledge of the non-specific
defence mechanisms present in the body and
distinguish these from specific immunity
system and their ability to detect ‘self’ from
‘non-self’ molecules
• appreciate that the body can acquire specific
immunities, some of which last for life
• understand that some reactions of the
immune system may have adverse results
• enhance their knowledge and understanding
of membrane receptors on cells of the immune
• demonstrate an understanding of the defence
mechanisms that plants have against disease.
Figure 8.1 The Triumph of Death, a copy by Jan Breughel
estimated that up to three-quarters of the population of Asia
and Europe died when a plague pandemic spread through those
areas from 1347 to 1351. In this chapter we explore defences
against disease, including cells and functions of the immune
system, disorders of the immune system and the mechanisms of
immunity.
(1568–1625) of the painting by his father, Pieter (c. 1517–1569).
This painting depicts a street scene during a plague epidemic.
A common plague was bubonic plague, which was also called
‘black death’ because bleeding under the skin developed into
black blotches on the skin of an infected person close to death.
Bubonic plague still exists in many countries. It has been
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NATURE OF BIOLOGY BOOK 1
A vaccine for cervical cancer
The cervix is the lower part, or
neck, of the uterus and opens into
the vagina.
Cervical cancer is the eighth most common cancer in Australian women and
is responsible for more than 300 deaths each year. One significant risk factor
associated with cervical cancer is infection with the common human papilloma
virus (HPV). HPV (figure 8.2) usually causes warts on hands and feet but also
is a common sexually transmitted disease that causes genital warts. Cigarette
smoking is another risk factor associated with cervical cancer. Cervical cells
develop abnormalities, many of which are due to common infections that are
‘cured’ by the body. Others persist and may develop further into cervical cancer.
The Pap test, introduced in Australia in 1991 in the National Cervical Screening
Program, can detect cervical cell abnormalities that lead to cancer. It is recommended that women have a Pap test every two years until age 70, commencing a
year or two after they become sexually active. If an abnormality is detected, appropriate treatment is available and further development into cancer may be avoided.
Figure 8.2 Computer artwork (left)
and coloured transmission electron
micrograph (TEM, right) of human
papilloma virus (HPV). The protein
coats, or capsids (red), enclose the
genetic material. The capsids are
studded with surface proteins (blue).
For further information on cervical
cancer go to www.betterhealth.vic.
gov.au.
Although the Pap smear is currently the best means of preventing the development of cervical cancer, a new treatment is on the horizon. Professor Ian
Frazer, who leads the University of Queensland’s Centre for Immunology and
Cancer Research, has been recognised as Australian of the Year for 2006 (figure
8.3). Professor Frazer’s award acknowledges his work toward the development
of a vaccine against HPV. Use of his vaccine in worldwide trials
has shown that it prevents papilloma virus infection, and
reduces Pap smear abnormalities by ninety per cent.
The vaccine is expected to be on the market about
a year after publication of this book and will
assist the prevention of cervical cancer in
more than half a million women world wide
each year.
In this chapter, we explore defences
against disease, including the use of
vaccines, cells of the immune system,
and their characteristics and functions.
We also examine some disorders of the
immune system.
Figure 8.3 Professor Ian Frazer, recognised as
Australian of the Year 2006 for his work in developing a
vaccine against the papilloma virus
IMMUNITY: DEFENCE AGAINST DISEASE
245
Immunity
Infection is entry into the body
of a micro-organism that may
cause disease. Infection does not
necessarily lead to disease.
The immune system is able to distinguish foreign material from material that is made
by the body. Material made by the body’s cells is called ‘self’. Foreign material is
called ‘non-self’ and includes material such as snake venom, dust, pollen, viruses
and micro-organisms, such as bacteria. Normally, the immune system has the
ability to distinguish ‘non-self’ material from ‘self’ material. If a person becomes
infected with foreign material, the immune system is activated and attempts to
remove the foreign material before it causes harm to tissues in the body.
The immune system has two kinds of response to the entry of foreign material.
One response involves natural or innate immunity, which is non-specific. It acts
in the same way for every infection. Non-specific immunity involves many
physical and chemical barriers to infection and is not affected by prior contact
with a particular micro-organism. It has no ‘memory’ of a prior infection.
The other response involves acquired or adaptive immunity, which is highly
specific. Specific immunity involves the production of specialised cells and
chemical substances known as antibodies which act against a particular infection. Specific immunity has a ‘memory’ so that when another infection from the
same organism occurs, an increased response is obtained. This is why a childhood
infection of diphtheria results in lifelong immunity against a further infection.
The two kinds of response of the immune system (see table 8.1) interact
together to provide immunity for an individual.
Table 8.1 The immune system has
Non-specific responses
two kinds of response, non-specific
and specific.
react in the same way to all infections
react in a specific way to each infection
have no ‘memory’ about prior
infections
have a ‘memory about prior infections
level of response same for each
infection of the same organism
much greater response on a second
infection by the same organism
Specific responses
Non-specific immunity
Assume that you come into contact with Clostridium tetani, a bacterial species
that affects the nervous system and causes a muscle rigidity called tetanus. A
number of features of your body prevent entry of bacteria.
The first line of defence
The best action against micro-organisms is to prevent their entry into the body
altogether. This first line of defence against infection takes place at the body
surfaces (see figure 8.4).
Skin
Alimentary canal
Respiratory system
Mucus
Salt
Cilia
Acid
Figure 8.4 The first line of defence
against infection is the body surface
which acts as a barrier. Chemicals
on the body surface also inhibit
infective organisms.
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NATURE OF BIOLOGY BOOK 2
Acid
Normal
bacterial flora
Gut
Lungs
Fatty
acids
Mucus
Urinary and
reproductive systems
ODD FACT
Sometimes hair
follicles and glands become
infected by the bacterial species
Staphylococcus aureus, the
‘golden staph’, which leads to a
highly contagious skin infection
called impetigo.
Skin
An intact skin acts as a barrier against entry by micro-organisms. A cut or abrasion
will allow entry of bacteria or viruses. Glands in the skin secrete fatty acids and
sweat contains salt, both of which inhibit bacteria.
Mucous membranes
Mucus secreted by the cells lining your respiratory tract traps bacteria which are
then swept upward to the back of the throat by the action of cilia which line much
of the respiratory tract. Some of the mucus and bacteria are swallowed. Some are
removed when you blow your nose. Some bacteria are also removed from the
respiratory tract when you cough or sneeze.
Mucus that lines the digestive tract forms a protective barrier and makes it
difficult for micro-organisms to penetrate the cells beneath.
Natural secretions
Bactericidal = capable of killing
bacteria
Many secretions of the body contain bactericidal agents. Tears and saliva contain
lysozyme, an enzyme that causes bacteria to lyse or burst. Acid in the stomach kills
many bacteria. Milk contains lactoperoxidase and semen contains spermine.
Natural flora
Many different bacteria are normally found on the skin, in the gut and (in females)
in the vagina. These bacteria are the natural flora of the body and are generally
non-pathogenic in those areas. The presence of these bacteria inhibits the growth
of pathogenic bacteria in those places because they compete more successfully
for the space and nutrients that are available.
In special circumstances, such as when a person takes antibiotics, the natural
flora may be disturbed. Pathogenic organisms are then able to move in. This type
of infection is called an opportunistic infection.
The second line of defence
Assume that your first line of defence has failed. Your skin has been cut and
Clostridium tetani bacteria enter your body. A second line of defence has a
number of parts as outlined below.
Phagocytes and killer cells
Figure 8.5 Human blood showing
different kinds of blood cells. Red
blood cells are pink. Various white
blood cells have densely staining
nuclei. (Also look at figure 8.10a.)
Cells called phagocytes move to the point of entry of the bacteria. Phagocytes
are white blood cells (see figure 8.5) that engulf and destroy micro-organisms
and other foreign materials that enter the body in much the same way as an
amoeba engulfs its food. Phagocytes are produced by cells in the bone marrow
and include neutrophils (see figure 8.6a), the most common of the white blood
cells, and monocytes, the largest of the white blood cells.
When monocytes leave the bloodstream, they become macrophages (figure
8.6b) which gather in various tissues. They occur throughout connective tissue,
in the lungs, liver, spleen, kidneys, the brain and bone. Macrophages are particularly active against micro-organisms that can live inside the cells of the person
they infect.
Immediately a bacterium or other micro-organism is engulfed by a phagocyte,
enzymes and other factors are released into the vacuole containing the bacterium
and the bacterium is killed. Some material may be used by the cell, and unwanted
material from the dead bacterium is released by the phagocyte.
Some white blood cells that kill virus-infected body cells are called natural
killer (NK) cells. Other white blood cells attach to, and help destroy, larger blood
parasites such as worms that are too large to be engulfed (phagocytosed).
IMMUNITY: DEFENCE AGAINST DISEASE
247
(a)
(b)
Figure 8.6 (a) Neutrophil cells
that have ingested bacteria. The
bacteria appear as the smaller purple
rod shapes inside the cells.
(b) Radioactively labelled
macrophages and a few lymphocytes
Complement
Bacteria
Phagocyte
Bacteria
lysis
attracts
coats
Figure 8.7 Complement proteins
lyse many bacterial species. This
attracts phagocytes to the site
of infection. Bacteria which have
been coated by other complement
proteins are readily ingested by the
phagocytes.
Complement proteins
How do your phagocytes recognise and attach to the Clostridium tetani cells so
that they can engulf them? Blood proteins called complement proteins assist
in this task (see figure 8.7). There are about 20 different complement proteins.
Most complement proteins are made in the liver and circulate in the blood in
an inactive state. When infection occurs, antibody–antigen complexes form and
these activate complement proteins. The activation of one kind of complement
protein results in a cascade effect where each activated complement protein then
activates another, and so on down the chain.
Complement proteins assist in the second line of defence in a number of ways.
Some complement proteins stick to invading micro-organisms that then become
more readily identifiable as foreign to phagocytes. Some stimulate phagocytes
to become more active. Some attract phagocytes to the site of infection. Other
complement proteins destroy the membranes of invading micro-organisms.
Complement proteins also play a role in acquired immunity (see page 263).
Interferon
Another group of proteins important in immunity are interferons. Interferons
are secreted by some cells when they are infected by virus particles. These interferons act on uninfected cells making them more resistant to the virus. Interferons
are produced very early during a viral infection and are particularly important in
our ability to resist some viral infections. They cause dozens of antivirol proteins
to be made.
Different viruses infect different tissues. The further a virus must travel
to reach its target cell then the more likely it is to be destroyed before it gets
there. Interferons are particularly important if a virus hasn’t far to travel. This
is the case with cold and influenza viruses that infect cells in the nose or throat.
Because infection occurs quickly, the body sometimes doesn’t have the time to
develop antibodies against these viruses and relies on interferon for its defence.
If a person develops a cold or flu, interferon has failed to prevent infection.
Cytokines
Cytokines are protein molecules that act as messengers between cells. They are
produced by virtually all cells of the immune system, but particularly by certain
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NATURE OF BIOLOGY BOOK 2
T cells. Hence, cytokines act as the messengers between cells of the immune
system in much the same way that
hormones act as the messengers within the
endocrine system. Cytokines also communicate with cells in other body systems,
including the nervous system. As in other
cellular communicating systems, a cell
can respond to a message from a cytokine
only if it has an appropriate receptor. A
cell must also regulate the duration of its
response to cytokines in order to maintain
its proper functioning. SOCS3 (figure
8.8) is a member of a family of proteins
that suppress the signalling of a variety
of cytokines, including growth hormone.
Abnormalities in SOCS3 are associated
with a variety of inflammatory diseases.
Figure 8.8 Two views of a
Inflammation
ribbon diagram (three-dimensional
structure) of SOCS3. The two views
are related by 180°.
You may have noticed a reddening or inflammation around the cut in your skin
where the Clostridium tetani have entered. Inflammation is a reaction to the
infection and occurs when arterioles in the area around the cut dilate, resulting
in an increased blood supply to the area. Inflammation is controlled by a number
of plasma enzyme systems and other compounds, including serotonin, produced
by mast cells, platelets and basophils. Serotonin increases dilation of arterioles
and permeability of vascular tissue. The blood carries phagocytes to the area.
Phagocytes also move from nearby tissues towards the cut (see figure 8.9).
Chemicals
released by
damaged cells
Bacteria enter on
sliver of glass
Epidermis
(a)
Abscess
starting to
form
(c)
(b)
Platelet
Monocyte
Capillary wall
Bacterium
Erythrocyte
Neutrophil
Basophil
Macrophage
Blood
vessel
Dermis
Nerve
(d)
Blood
clot
Subcutaneous
Bacterium
Figure 8.9 Inflammation occurs
if bacteria enter a cut. (a) Injury
to an otherwise healthy skin
(b) Vasodilation and increased
permeability (c) Phagocyte migration
from capillaries to cut area
(d) Phagocytosis of bacteria and
other cellular debris by neutrophils
and macrophages
Neutrophil
Capillary walls in the area become more permeable to phagocytes which move
out of the capillaries into the surrounding area. Phagocytes that arrive early at
the scene of the injury release chemicals such as histamine that attract more and
more phagocytes to the infection.
As the invading Clostridium tetani bacteria are killed and engulfed by the
phagocytes, material that has leaked from the capillaries will form a clot around
the infection and prevent its spread. You will probably also have pus in the
inflamed area. Pus contains white blood cells that are dead as a result of the many
bacteria they have engulfed. It also contains living white blood cells as well as
other cell debris.
IMMUNITY: DEFENCE AGAINST DISEASE
249
Eventually the pus and other dead or damaged cells are reabsorbed by other
cells of the body or released from the skin and tissue repair occurs. Your skin
heals and all outward signs of the infection disappear.
All of the features discussed in this section are non-specific in their action.
Exactly the same responses would have operated whatever micro-organism or
foreign material you encountered and whether or not you had been previously
infected by the organism.
KEY IDEAS
• The defence system of the body is called the immune system.
• The immune system is able to identify ‘non-self’ material from ‘self’.
• The immune system can produce two kinds of response to invading
foreign material, namely non-specific and specific.
• Micro-organisms are prevented from entering the body by a number of
non-specialised features. This is the first line of defence.
• There is a second line of defence against foreign material that enters
the body.
QUICK-CHECK
1 What is meant by the terms ‘self’ and ‘non-self’?
2 Indicate one way in which a non-specific immune response differs from
a specific response.
3 Give an example of the first line of defence of the body against infection.
4 List two kinds of cells that form part of the second line of defence of the
body.
5 What is complement protein? How does it act as part of the second line
of defence?
6 What is interferon? How does it act as part of the second line of defence?
7 What roles do cytokines play in the immune system?
Specific immunity
Once a micro-organism enters your body, the presence of this foreign material
initiates a response known as the third line of defence. This line of defence
involves a specific response by the immune system to that particular infection
and results in adaptive or acquired immunity. The specific immunity acquired is
generally long lasting, often for life.
The third line of defence involves special white blood cells known as lymphocytes. They recognise invading cells or particles, react to that invasion and
‘remember’ the particular type of invader. If the same infection occurs again, the
response to it occurs more rapidly.
Cells of the third line of defence
Two main groups of lymphocytes are involved in specific immunity. All lymphocytes are produced in the bone marrow (figure 8.10a). Some mature in the
bone marrow into B lymphocytes or B cells. Other lymphocytes leave the bone
marrow before they are fully developed and travel to the thymus gland where they
differentiate into mature T lymphocytes or T cells. (T cell stands for ‘thymusdependent’ cell.) There are different kinds of B and T cells (figure 8.10b).
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NATURE OF BIOLOGY BOOK 2
Figure 8.10 (a) Blood cells all
(a)
Bone marrow cell
develop from special cells, called
stem cells, in the bone marrow.
Stem cells continually reproduce by
mitosis and then differentiate. Of
the differentiated cells, all are white
blood cells except the red blood cells
and platelets. (b) Different kinds of
B and T lymphocytes. Th = helper T
cells, Tc = cytotoxic T cells.
Stem cell
Stem cell
Stem cell
Monocyte
Red blood cell
Platelets
Basophils
and mast
cells
B lymphocyte
and plasma T lymphocyte
cell
Neutrophil
Eosinophils
Stem cell
in bone marrow
(b)
B cell progenitor
Humoral
response
Maturation occurs in bone marrow
T cell progenitor
Cell
mediated
response
Maturation occurs in thymus
Trachea
Many
different
kinds of
B cells
formed
Antibody
different on
each kind
of B cell
Each kind
of B cell
can give
rise to
Thymus
Heart
Antigenbinding
receptor of
antibody
T cell
Th cells
Tc cells
B memory
cells
Plasma cells
that produce
antibodies
Activated
Th cell
Th memory
cell
Activated
Tc cell
Tc memory
cell
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COLONY STIMULATING FACTORS — CSFs
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NATURE OF BIOLOGY BOOK 2
10
White cell count x 10–9/L
Neutrophils and monocyte-macrophages are of special
importance in protecting the body against acute infection.
These cells are produced by cells in bone marrow which
reproduce continually because the cells in the blood
have a relatively short life. Scientists were able to show
that the continued growth of bone marrow cells did not
occur spontaneously but was regulated by some factor
that was given the name of colony stimulating factor
(CSF). Professor Donald Metcalf (see figure 8.11b), an
Australian scientist at the Walter and Eliza Hall Institute
of Medical Research (WEHI) in Melbourne, discovered
CSF. CSF is detectible in the serum and urine and in
extracts of a variety of tissues.
From the late 1960s until 1984, work was carried out
to try and isolate CSF. Special methods of cell culture
and purification of cell products were developed. By
1984, four different CSFs had been isolated. Only very
small amounts of CSF had been obtained and it was
calculated that 200 million mice would be required to
produce one gram of purified CSF. Scientists used new
DNA technology to clone CSF genes that were then
inserted into bacteria, yeast or mammalian cells. These
cells were cultured and relatively large amounts of CSF
became available.
It was shown that injections of CSF into mice and
primates stimulated production of neutrophils and
macrophage formation without significant toxic effects.
Clinical trials commenced in 1987, and today two of
the CSFs are available to treat people who have very
low levels of white cells in their blood.
What application has this discovery had?
In some diseases, and as a result of certain forms of
treatment, such as chemotherapy for cancer, the number
of neutrophils and macrophages produced by the body
declines significantly. This reduction in immune cells
means reduced resistance against infection. The CSFs
are now used to prevent the fall in neutrophils and
prevent the infection that can otherwise occur following
treatment with chemotherapy.
Leukaemia is a cancer, or malignancy, of the blood.
Acute myeloid leukaemia is a cancer in which a
person produces faulty white blood cells. Something
has gone wrong with the blood-forming tissue. There
is no point in giving CSF to patients with faulty bone
marrow. They would respond by making even more of
the faulty cells. Other treatment must be given before
injection with CSF.
Treatment of patients with acute myeloid leukaemia
is really a three-step process. The first step is to irradiate the patient to kill the faulty bone marrow cells.
In the second step, the patient is given a transplant of
compatible bone marrow cells, often from a relative.
8
6
4
••
2
•
•
0
(a)
•
• •• • •
• ••
••
• •• • •
••
• • • • •• • •
5
10
15
20
25
Days after marrow transfusion
30
(b)
Figure 8.11 (a) Patients (15) who received a bone marrow
transplant after irradiation of their own marrow were injected
with CSF. The upper curve shows the average production of
white blood cells in these patients. The lower curve shows
the average white cell production in a sample of patients (18)
before CSF was available. Most of the increase was due to an
increase in neutrophil production.
(b) Professor Donald Metcalf, scientist, Walter and Eliza Hall
Institute of Medical Research, Melbourne, Australia. Professor
Metcalf discovered the CSFs which have been used in the
treatment of patients with various diseases. He is a leading
scientist whose contribution has made a difference not only
in basic knowledge, but also in the treatment of disease in his
lifetime.
Bone marrow transplants can be very successful.
The transplanted marrow behaves as the patient’s own
and produces healthy white blood cells. Provided
sufficient white blood cells grow, the patient has full
resistance against infection. Sometimes the bone
marrow cells do not grow at a sufficiently high rate
to prevent infection. A third step in the treatment
can help to solve this problem. Injection of CSF significantly increases the number of neutrophils and
macrophages produced in the bone marrow recipient
(see figure 8.11a). This, in turn, significantly increases
the chance that a patient will be restored to full health.
This was the case with José Carreras, a world-famous
opera singer who was one of the first people to be
treated with CSF.
Australians can be proud that the work of their
medical scientists has led to these exciting advances.
The box on pages 260–3 outlines other work being
carried out at WEHI.
In another world-first, scientists and physicians in
Melbourne discovered that the CSFs cause cells that
are normally resident in the bone marrow to move into
the blood. This was completely unexpected. They then
also discovered that these blood cells could be used
instead of bone marrow cells in bone marrow transplantation (but now really ‘blood cell’ transplantation).
This is much safer as blood can be collected instead
of bone marrow, which removes the requirement of an
anaesthetic. In addition, these blood cells work much
better than the bone marrow cells and recovery is much
faster after transplantation. For these reasons, blood
cell transplantation has overtaken bone marrow transplantation around the world. Australians can be proud
of this important medical research.
How do B cells and T cells identify
foreign material?
Proteins on cell membranes are determined by genes. These genes are called the
major histocompatibility complex (MHC) and the proteins produced by these
genes are called markers. All cells have MHC markers on their surfaces.
Distinguishing ‘self’ from ‘non-self’
In humans, two major groups of MHC markers exist. Class 1 markers are found
on all cells of the body except red blood cells. Class 2 markers are found only on
T cells, B cells and some macrophages. MHC markers produced in a person are
called ‘self’. Markers that are not produced within a person are called ‘non-self’.
B cells and T cells recognise and ignore cells that have the same MHC markers
as themselves. When material such as pollen, or infecting agents, such as bacteria
and viruses, enter a person, the B cells and T cells
recognise the MHC markers on those as foreign or
‘non-self’ and react. Foreign material may also be
a toxic chemical such as snake venom.
The material (or marker) that triggers a response
from a B cell or a T cell is called an antigen (see
figure 8.12). Antigens are usually proteins, but can
also include carbohydrate.
Figure 8.12 Antigens (black dots marked by
curved arrow) on the surface of the motile protozoan
Leishmania, which causes leishmaniasis, a disease with
symptoms that can resemble malaria. This is a transverse
section in the region of the flagella. Antigens have been
stained with gold particles. Bar equals 1 µm.
IMMUNITY: DEFENCE AGAINST DISEASE
253
Like all cells, immune cells such as T cells and B cells have their own antigens
that are called self antigens. In addition, they have receptor sites (figure 8.12).
Some of these receptors are self receptors; that is, they determine if a molecule or
cell the immune cell comes into contact with has the appropriate structures that
show it is part of the same organism. Other receptors are for non-self receptors;
that is, they identify molecules or cells that are ‘foreign’ to those of the immune
cell. If they are identified as foreign, an immune response occurs.
Self antigens
Immune
cell
Figure 8.13 Immune cells have
self antigens on their surfaces.
In addition, they have receptors.
Some are self receptors that identify
self antigens. Some are non-self
receptors.
Receptors
for self
Receptors
for non-self
Because B cells and T cells can recognise ‘non-self’, they must have some
mechanism for detecting the millions of different kinds of ‘non-self’ MHC
markers that exist. This occurs in a very specific way.
Many kinds of B cells
Antigen
binding
sites
B cell
membrane
Nucleus
Antigen
Surface
immunoglobulin
antibody
Figure 8.14 Immunoglobulins
on the surface of B cells identify
antigens (not to scale). Each B cell
identifies one kind of antigen only.
ODD FACT
A clone of cells is a
group of cells, each identical
with the cell from which they
have been derived.
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NATURE OF BIOLOGY BOOK 2
B cells have immunoglobulins on their surfaces. Immunoglobulins are proteins
that identify antigens. Immunoglobulins are also called antibodies. The immunoglobulins of each B cell have a specific structure and recognise only one kind of
antigen (see figure 8.14).
There are millions of antigens to which the body must be able to respond.
When B cells are maturing in the bone marrow, a particular part of the genetic
material undergoes change and only a few of each kind of B cell are made. In
this way millions of different B cells are made with different immunoglobulins
on their surfaces. These are able to identify the millions of different antigens with
which a person may come into contact.
Although B cells combine with antigens, the few B cells specific for any one
antigen would not be sufficient to counter a massive infection of bacteria. A
person must have some way of producing large numbers of a specific antibody
against antigens encountered. When a B cell identifies an antigen, it replicates
rapidly to produce large numbers of special cells called plasma cells which
produce antibodies and release them into body fluids. Generally, many more
cells are produced than are needed. Excess cells die by apoptosis.
The clonal-selection theory of
antibody production
When an antigen enters the body it probably passes many B cells before it meets
one with immunoglobulin with which it can combine. In effect, the antigen
‘selects’ the B cell that will lead to its death. The B cell selected by the antigen
reproduces rapidly to give rise to a number of identical cells. Each of these
cells also reproduces rapidly to produce a large clone of cells. This is called
clonal expansion. Cells cloned in this way will all have exactly the same genetic
material and the same immunoglobulins. Most of these cells then differentiate
into plasma cells and produce the same kind of antibody (see figure 8.15).
Antigen
Clonal selection
Each B cell
combines with
only one kind
of antigen.
All recognition sites on a
B cell are identical. This B
cell has four antibodies
on its surface, so it has
eight binding sites.
Clonal expansion
or proliferation
Differentiation
Clone of plasma cells
Memory cells
Figure 8.15 Clonal selection.
Each B cell produces a clone of
plasma cells which make only one
kind of antibody. Note the antigen
fits only one of the surface receptors
(immunoglobulins) shown here.
Memory cells also form.
Production of antibody
An Australian, Sir Macfarlane Burnet, first proposed the clonal selection
theory in 1955.
There is a delay in this type of immune response because clonal expansion
is necessary before sufficiently large amounts of antibodies can be made. This
means that, if the infecting bacteria are able to reproduce to form relatively large
numbers, a person may become quite ill before antibodies are produced that can
react with the bacteria.
Some of the B cells produced differentiate into other cells called B-memory
cells. B-memory cells also have the same antibody–antigen specificity as the parent
B cell. Plasma cells survive for only a few days but memory cells can survive for
several years and, in some cases, for life. If a second infection of the bacterium
occurs, the B-memory cells react faster and more vigorously than the initial B-cell
reaction to the first infection. There is not usually a noticeable effect from a second
infection by the same antigen because the body reacts very quickly to eliminate the
‘non-self material’. The person is said to be immune to the particular disease.
When recovery from infection is complete, fewer plasma cells and antibodies
are produced. Because most of the cells produced by clonal expansion are no
longer required after recovery from the infection, they die by apoptosis.
How much antibody is produced?
Look at figure 8.16. It shows the level of antibody production after infection by
an organism for the first time. This is called the primary antibody response. Note
the decline in antibody level after the infection has cleared.
On a second infection by the same organism, there is a secondary antibody
response. In this, the immune system responds much more quickly because there
IMMUNITY: DEFENCE AGAINST DISEASE
255
Figure 8.16 An initial infection
or vaccination causes a primary
response which occurs about 10
days after infection and results in
a low level of antibody production.
A second exposure to the same
organism results in the secondary
antibody response which is faster to
appear and more effective than the
primary response.
Natural infection
Primary
antibody
response
Antibody production
and response
(arbitrary units)
Initial
infection or
vaccination
Secondary
antibody
response
Time
is no need for clonal expansion. The concentration of antibodies rises much more
rapidly than during the primary response and many more antibodies are released.
In addition, note that the antibody level after a second infection has cleared
remains much higher for much longer than after the primary response.
Even if the time between a primary and a secondary infection is several years,
the presence of even low numbers of B-memory cells produces a rapid and
increased secondary response.
Structure of an antibody
The two ‘arms’ of an antibody have
the same shape.
An antibody molecule has four polypeptide chains, two long heavy chains and
two shorter light chains joined together (see figure 8.17a). The free ends where
the light and heavy chains are adjacent to each other are the regions that combine
with antigen. These areas are called the ‘antigen-binding sites’ and differ in different antibodies. The hinge area allows the antibody to bend if necessary to
maintain a better link with the antigen to which it binds. The way in which the
combining sites of an antibody and its antigen match is shown in figure 8.17b.
(a)
(b)
Antibody binds to antigen
at these positions.
Light chain
Hinge
region
Heavy chain
Different antibodies have different
shaped antigen-binding sites.
Figure 8.17 (a) The basic antibody has two identical light polypeptide chains and two identical heavy polypeptide chains linked
together. There are five different kinds of heavy chains. Why do antibodies have a hinge region? (b) Computer-generated image of
an antigen (left-hand side) and its antibody (right-hand side). The surfaces come close together when the antigen–antibody complex
forms. The polypeptide chains of the antibody are colour coded, heavy chains red and light chains blue.
256
NATURE OF BIOLOGY BOOK 2
There are five different kinds of heavy chains and this results in five different
classes of antibody molecules (see table 8.2) — also known as immunoglobulins (Ig). Different classes of antibodies are made of different numbers of basic
antibody units. IgG, IgD and IgE each comprise a single molecule; IgA has two
and IgM has five molecules. Immunity involving antibodies in body fluids is
called humoral immunity.
Table 8.2 Some of the characteristics of the different types of antibodies found
in body fluids
Type of antibody
IgG
IgA
IgM
IgD
IgE
approx. concentration in serum
(mg/mL)
12
2
1
0.04
0.000.02
ability to cross placenta
yes
no
no
no
no
present in saliva and tears
no
yes
no
no
no
present in milk
yes
yes
no
no
no
active against viruses
yes
yes
some
no
no
active against some bacteria
yes
yes
yes
no
no
involved in allergy reactions
no
no
no
no
yes
KEY IDEAS
• If non-specialised defences fail to prevent infection, specialised
responses occur.
• All cells have protein markers on their surfaces.
• Non-self markers on cells entering a person are called antigens.
• A number of different kinds of cell are involved in specific immunity.
• The phenotype is the physical, biochemical or physiological expression
of the genotype.
• Some cells produce antibodies that circulate in body fluids and react
with specific antigens.
QUICK-CHECK
8 What are the two main groups of cells involved in specific immunity
and where do they mature?
9 What role do protein markers on foreign cells play in the immune
response?
10 What is an immunoglobulin? Where would you find one?
11 What cells are produced by the cloning of B cells? What is their
function?
12 Why is cloning of B cells important in the immune response?
13 What are the main features of the primary antibody response?
14 In what ways does the secondary antibody response differ from the
primary antibody response?
15 Are all maternal antibodies equally important for a fetus? Explain.
IMMUNITY: DEFENCE AGAINST DISEASE
257
Different kinds of antibodies
IgM and IgG antibodies activate macrophages and the complement system and
are particularly active against bacteria and their toxins. IgA antibodies play an
important role in surfaces that are vulnerable to infection and are present in
saliva, tears, the lungs and along the lining of the gut. IgE antibodies activate
mast cells which release histamines. These are important in allergies (see page
269). The function of IgD antibodies is unknown.
Because the basic antibody unit has two antigen-binding sites, it can bind to
two antigens. A lattice is built up of the antibody and its specific antigen bound
together, and the antigen is ‘disarmed’. The antigen is no longer able to damage
host cells (see figure 8.18). This is what happens when an antivenom is injected
into a person after a snakebite. The antivenom combines with the venom and the
venom can no longer act against cells.
■
■
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■
■
■
■
■
■
■
■
■
■
■
Antibody
■ ■
■
■
■
■
■
■
Antigen
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■ ■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
■
Antigen
■
Cross-linking
of antigens on
different cells
■ ■
■
■
■
■
■
■
■
■ ■
■
■
■
■
■
■
■
■
■
Figure 8.18 Antibodies react
with specific antigens. An antigen
involved in such a response is no
longer able to damage host cells.
If an invading micro-organism has
different antigens on the surface
membrane then, for each different
antigen, a different kind of B cell will
be activated and a different kind of
antibody made.
■
■
■
■
■
■
■
■
Ig = immunoglobulin
Antigen–antibody complex
may be agglutination of cells
If the antigen is a bacterium, additional help is required to remove the
antibody–antigen complex. Macrophages have receptors that identify the part
of the antibody where the ends of the two heavy chains come together. Macrophages bind to that part of the antibody–antigen complex (see figure 8.19) and
engulf and digest the antibody and its associated antigen.
Microbe
Receptor site
Figure 8.19 Antibody
reacts with a microbe to
give antibody–antigen
complex. This is identified by
a macrophage which engulfs
and digests the antibody–
antigen complex.
Macrophage
Antibody and
antigen complex
T cells
When T cells mature in the thymus, many different kinds of T cells are produced
which recognise many different antigens. As with B cells, only a few of each
kind are produced. After encountering their specific antigens, T cells reproduce
rapidly in the same way as B cells, and T-memory cells also form. T cells do not
make antibodies. There are different types of T cells and each type reacts with
other cells in the immune response.
Immunity involving T cells and phagocytes is called cellular immunity.
Helper T cells
Phagocytes that have ingested foreign material carry some of the foreign antigen
on their surfaces as well as their usual class 2 marker proteins. One type of
258
NATURE OF BIOLOGY BOOK 2
Th = helper T cells
T cells, called helper T cells (Th), recognises these antigens and stimulates B
cells (see figure 8.20). B cells will not reproduce and form plasma cells without
this assistance from Th cells. Th cells also secrete a protein that stimulates other
T cells and B cells.
(a)
Figure 8.20 (a) When phagocytes
ingest antigens, some of the antigen
attaches to the phagocyte surface.
(b) Helper T cells help B cells to
recognise foreign antigen on the
surface of phagocytes.
(c) The B cells reproduce to
form plasma cells which produce
antibodies against the antigen.
(b)
(c)
Help
Antigen
Th
Proliferation of plasma cells
B
Antibody
secretion
Phagocyte
Cytotoxic T cells
Tc = cytotoxic T cells
Some scientists suggest that there
is a third kind of T cell, known as
suppressor T cells, which act as an
infection recedes.
ODD FACT
Plasma leaking
from blood capillaries into
the surrounding tissues forms
tissue fluid. When tissue fluid
moves into the lymphatic
vessels it is called lymph.
Lymph nodes,
tonsils and
adenoids
Lymph
nodes in
axilla
(armpit)
Lymphoid
tissue in
lungs,
bronchi,
gut and
urogenital
tract
Another type of T cell, cytotoxic T cells (Tc), kills body cells that have been
infected with a virus. In this case the infected body cell has foreign antigen on
its surface as well as class 1 protein markers. A Tc cell identifies its antigen, in
this case a viral protein coat that is left outside the infected cell, and the class 1
marker and kills the infected cell before the virus has time to replicate. Tc cells
kill the infected cell by secreting proteins that punch holes in the membrane of
the cell and the contents ooze out.
Tc cells cannot kill isolated virus particles. They can kill the virus only when
it is inside a cell.
Some Tc cells also destroy cancer cells.
T cells and B cells travel around the body
B cells and T cells develop from primary lymphoid tissues: bone marrow and thymus
respectively. They enter the bloodstream, then leave it and move around the body.
The immune system also contains a
number of other lymphoid tissues and
organs, including the spleen, tonsils and
lymph nodes (see figure 8.21), which
are connected by a network of lymphatic
Thymus
vessels. White blood cells of many types are
packed together in these lymphatic tissues.
Lymphatic vessels contain lymph, which
drains from nearby tissues. Memory T and
B cells, in particular, circulate in the lymph,
Bone marrow
ready to react with their antigens. Antigens
that enter the body are carried in lymph to
a lymphatic organ where there is a high
concentration of white cells. If the antigen
Spleen
hasn’t been destroyed along the way, the
immune response begins when it comes into
contact with cells in the lymph nodes. Your
lymph nodes can sometimes be swollen and
Gut-associated
sore, indicating that you have an infection
lymph nodes
of some kind.
Lymph nodes
in groin
Figure 8.21 Distribution of lymphoid organs
and tissues which make up the immune system
IMMUNITY: DEFENCE AGAINST DISEASE
259
KEY IDEAS
• The immune response produces different kinds of T cells.
• Different kinds of T cells have different functions.
• The immune system contains many lymphoid organs and tissues.
QUICK-CHECK
16
17
18
19
Explain why immunity involving T cells is called cellular immunity.
What is the function of cytotoxic cells?
What does lymph contain?
Name three lymphoid tissues or organs.
THE WALTER AND ELIZA HALL
INSTITUTE OF MEDICAL RESEARCH
Melbourne’s Walter and Eliza Hall Institute (WEHI),
founded in 1915, was Australia’s first medical research
institute. From the beginning, the Institute has been
closely associated with the Royal Melbourne Hospital
and today it is located in a striking building (figure
8.22) adjacent to the hospital in Parkville. It is also
closely linked to The University of Melbourne.
The Institute first came on to the world stage in
virology and immunology under the leadership of
Sir Macfarlane Burnet (Director 1944–64), who was
awarded the Nobel Prize in 1960 (figure 8.23; see page
212). Renowned immunologist Sir Gustav Nossal,
Director from 1965 to 1996, greatly expanded and
diversified the Institute’s research programs and today,
led by molecular biologist Professor Suzanne Cory, the
Institute has major programs in cancer, haematology
and inflammation, immunology and autoimmunity, and
infectious diseases.
Figure 8.22
The Walter and Eliza Hall
Institute at dusk
Figure 8.23 WEHI has had three
directors — Sir Macfarlane Burnet (left)
(Director 1944–64), Sir Gustav Nossal
(Director 1965–96) and Professor Suzanne
Cory (Director 1996 to present [2006]).
260
NATURE OF BIOLOGY BOOK 2
The Institute has a staff of over 600 scientists and
support staff with diverse skills. The team leaders include
biochemists, molecular biologists, cell biologists,
structural biologists, bioinformaticians, geneticists and
medicinal chemists. Some commenced their careers
in science, others in medicine. Postdoctoral fellows,
postgraduate students and technicians all play important roles in their research laboratories, supported by
core technologists such as computer scientists, librarians, animal technicians, veterinarians, photographers,
administrators, accountants and engineers. Research
opportunities are provided for undergraduate students
to enable them to taste life in the research world.
WEHI pioneered the innovative GTAC program
(named for the four letters of the genetic code), which
introduces molecular and cell biology to primary and
secondary school students from all over Victoria.
GTAC’s exciting facility (figures 8.24 and 8.25) is
located at University High School, right next door to
WEHI, and many WEHI PhD students serve as demonstrators and mentors in GTAC programs. You and
your school can find out more about GTAC programs
by going to www.gtac.edu.au.
Figure 8.25 The DNA helix on the floor of the Australian
Genome Research Facility
Figure 8.24 The GTAC building with WEHI in the background
WEHI’s talented science animator Drew Berry
(figure 1.34 on page 27) was a major contributor to
the amazing film DNA interactive, which was made to
celebrate the 50th anniversary of the discovery of DNA
by James Watson and Francis Crick. This film won an
Emmy and also an award from the British Academy
of Film and Television Arts. Excerpts of Drew’s work
have been exhibited at the Museum of Modern Art in
New York and at the Pompidou Centre in Paris.
‘This is an incredibly exciting time to be a scientist,’
says Professor Suzanne Cory, Director of the Institute.
‘The DNA revolution and the Human Genome Project
[figure 8.25] have opened up amazing opportunities for
identifying the critical molecular mistakes underlying
many diseases. This is enabling scientists to target these
lesions and develop more effective therapies.’
‘The human body is a very complex machine,’ she
continues, ‘with multiple interactive component parts.
If one component malfunctions, this can have devastating consequences for the entire system. At WEHI,
our major focus is the body’s self-defence system. This
complex system is derived from a single rare stem cell
in the bone marrow. We are studying how this amazing
cell can generate its diverse repertoire of white and red
blood cells and how these cells function in health and
disease.
‘The immune system can protect us from innumerable pathogens. It swiftly recognises ‘foreign’
macromolecules (antigens) and mounts an offensive
to destroy them. Three main cell types are involved:
B and T lymphocytes, and dendritic cells. Dendritic cells
process foreign proteins into bite-size bits (antigens)
and ‘present’ them on a halo of tentacles (figure 8.26)
to T cells, galvanising them into action. One type of
T cell then ‘helps’ B cells make antibodies to neutralise
foreign proteins, while another type of T cell attacks
infected cells.
(continued)
IMMUNITY: DEFENCE AGAINST DISEASE
261
‘Leukaemias and lymphomas are cancers of
lymphocytes. Occasionally, the normal process of
DNA rearrangement that goes on in a lymphocyte to
produce an antigen receptor goes awry and activates an
oncogene: that is, a gene with the potential to cause
cancer. Most oncogenes cause cells to overproliferate,
but others stop cells from dying when they should. Cell
death occurs by a process known as apoptosis (figure
8.27). Our scientists are world experts in apoptosis and
are using this knowledge to develop new and
more effective cancer therapies.
(a)
Figure 8.27 A normal lymphocyte and
one undergoing programmed cell death,
apoptosis. Note the ‘blebs’ on the
dying cell.
‘Occasionally, immune cells are
provoked to attack normal cells or
tissues, producing devastating autoimmune disorders. Scientists at WEHI are studying several
of these diseases, particularly diabetes, multiple
sclerosis, coeliac disease and autoimmune
arthritis. Their goal is to develop more effective treatments and preventative vaccines.
‘The malaria parasite infects red blood cells
and changes them to evade the immune system
(figure 8.28). Malaria is a devastating disease
that kills up to 3 million people every year, most of
whom are children under 5 years of age. Our malaria
(b)
Figure 8.26 (a) Antigen-presenting dendritic cell, which
stimulates the body’s immune response (b) Dendritic cell
stained for antigen-presenting molecules (green), nucleus
(DNA, blue) and endosomes (red)
‘The cells communicate via a complex maze of
surface molecules called cytokines and chemokines;
rather like television, radio, telephone and e-mail operating all at once. Furthermore, within each cell, there
are equally complicated signalling links between the
cell surface, the nucleus and the genes. It is, therefore,
very hard to predict what might happen if the balance is
altered by, say, injecting a drug or vaccine. One of our
groups is developing computer models for predicting
the outcome to better manipulate this vital defence
system.
262
NATURE OF BIOLOGY BOOK 2
Figure 8.28 A Drew Berry (see page 27) illustration of
malaria parasites, Plasmodium falciparum, (green) invading red
blood cells
researchers are hot on the trail of the evasion
strategy used by malaria to develop an effective
vaccine and better antimalarial drugs. They have
links in many endemic areas — Papua New Guinea,
Malawi, Indonesia and Vietnam — and run international workshops to help train researchers from
these countries (see figure 8.29).
‘One of the most exciting recent discoveries from
WEHI is the identification of the cell that makes the
breast. Our breast cancer researchers used an instrument called a laser-driven, fluorescence-activated
cell sorter (FACS) to fractionate cells labelled with
different fluorescent antibodies. They found a very
rare cell capable of regenerating complete breast
tissue when transplanted into another mouse (refer
to chapter 16, page 641). Indeed, when the female
becomes pregnant, the regenerated breast tissue
even makes milk! This is the first time the breast
stem cell has been isolated. The scientists are now
trying to isolate breast stem cells from human tissue
and are looking at breast cancers to see if they are
derived from altered stem cells.’
If you would like to learn more about the research
being done at WEHI, go to www.wehi.edu.au and
click on the WEHI link for this chapter.
Macfarlane Burnet once said, ‘Science to me is
the finest sport in the world.’ Perhaps you would
like to play one day!
Figure 8.29 Hamish Scott (left), Pauline Crewther,
Chelsee Hewitt, Ping Cannon, Catherine Carmichael and
Joelle Michaud (from the Scott Laboratory based at WEHI)
discuss results.
Acquiring specific immunity
A person makes antibodies against a disease-causing organism only after coming
into contact with the organism. Because of the presence of specific antibodies,
a person is able to resist infection and is said to be immune to further infection
by that organism. This kind of immunity is called specific immunity. Antibodies
are acquired and so the term acquired immunity is also used. Specific immunity
is also acquired when antibodies are received from an outside source. This is
called passive immunity. The term active immunity is used when antibodies
are produced within a person. Active and passive immunity can be achieved in
different ways.
Active immunity
Active immunisation involves the production of antibodies within a person in
response to exposure to a particular antigen. In addition, B-memory cells and
T cells are produced that react quickly if another encounter occurs with the same
organism.
Active immunity can be acquired in two ways: naturally or induced.
Natural active immunity
When a person comes into contact with a particular disease-causing organism for
the first time, no antibodies against the organism (the antigen) will be present. It
IMMUNITY: DEFENCE AGAINST DISEASE
263
ODD FACT
In 1885, Alfred
Russell Wallace (1823–1913),
who held many of the same
ideas about evolution as Darwin,
published a pamphlet claiming
vaccination to be both useless
and dangerous.
takes a few days for the appropriate plasma cells and antibodies to form (note the
primary response shown in figure 8.16) and during that time the person begins to
show symptoms of the disease.
The antibodies formed have identical sites for binding to the foreign material.
As the amount of antibody increases, the infecting micro-organisms begin to be
destroyed and the person starts to recover. If sufficient antibodies are made to
destroy all the infecting micro-organisms, the person recovers completely.
This type of immunity is called naturally acquired active immunity. It is
called active because the immune system in the infected individual has made the
antibodies and continues to do so. The immunity was acquired naturally after
infection.
In some cases, the level of infection is sufficient to activate the immune system
and yet there may be no outward visible sign that the person has a disease. Such
an infection is called a sub-clinical infection and results in antibody formation in
the same way as an obvious infection. Both situations result in immunity against
further infection with that disease and the individual would show a secondary
response similar to that outlined in figure 8.16.
In some cases, if the infecting organism or toxin acts quickly before the
immune system can make sufficient antibodies, a person can die.
Induced active immunity
Today we can make use of the body’s immune response to induce actively
acquired immunity. Vaccines, which contain dead or treated living microorganisms, are used to activate the immune system to produce antibodies against
specific disease-causing organisms without actually causing the disease. This
is possible because bacteria and viruses can be killed or treated in some way
so that they are no longer able to cause disease (see figure 8.30). Because the
same antigens are present on these treated micro-organisms they will produce
an immune response if they are used in vaccines. Organisms that are not killed
by the special treatment given during the preparation of a vaccine are said to be
attenuated. They can still reproduce, but the special treatment has removed their
disease-causing capability.
▲
■
■
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■
■
▲
▲
■
▲
▲
Remove capsule
■
▲
■
▲
A bacterium
with a capsule
causes disease.
■
▲
▲
▲
■
■
■
▲
▲
■
▲
bacterium may remove its diseasecausing characteristic without
affecting its antigens. The immune
system responds to the antigens
in the same way it would to a fully
virulent organism. Some vaccines
contain live attenuated microorganisms. The advantage of this
is that the bacterium continues to
reproduce initially and stimulates
a much higher level of antibody
production.
■
Figure 8.30 Treatment of a
▲
Immunisation = vaccination =
injection of dead or attenuated
micro-organisms
Without its capsule, the
bacterium no longer
causes disease, but
still acts as an antigen.
When a vaccine is injected into a person, the immune system shows a primary
antibody response similar to that shown in figure 8.16. A second injection of
vaccine produces a secondary antibody response. The antibody is specific for the
treated micro-organism used in the vaccine, so if the person comes into contact
with the live organisms at some future date, memory cells and antibodies will be
ready to act and the person is immune to infection.
Some micro-organisms cause disease by secreting toxins or poisonous substances. These toxins can be treated to form toxoids. Toxoids are made of the
same material as the toxin, and so act as antigens, but are unable to cause disease.
Some vaccines contain toxoids.
A summary of the various types of acquired immunity is shown in figure 8.35.
Read about work to develop a vaccine against malaria on page 117.
264
NATURE OF BIOLOGY BOOK 2
ODD FACT
Since 1977
no naturally transmitted cases
of smallpox have been recorded
anywhere in the world.
Figure 8.31 Prior to
the 1980s, Australians
travelling abroad had to
carry vaccination booklets
to prove they had been
immunised against smallpox.
Eradicating a disease by
vaccination
Before the 1960s, smallpox, a disease caused by the variola virus, was widespread in many countries. Australians travelling overseas were required to carry
a vaccination certificate (see figure 8.31) to show that they had been vaccinated
against the disease.
The World Health Organization (WHO) began
an extensive vaccination program against smallpox
in 1959 and, by December 1979, they announced
that the disease had been eradicated. Because of
the widespread vaccination against smallpox, the
infecting virus could no longer find appropriate
hosts who were not immune.
Although support had been given to a WHO
proposal that all live stocks of smallpox virus be
destroyed by 30 June 1999, Russia and the United
States confirmed in May 1999 that they did not
intend to proceed with the destruction. Claims
have been made that scientific opportunities will
be lost if all stocks are destroyed.
Australians no longer have to be vaccinated
against smallpox. If they travel to some parts of
South America or Africa they would still be vaccinated against yellow fever, a viral infection that
is transmitted from person to person by the Aedes
aegypti mosquito.
In Australia, the viral disease poliomyelitis has
been eliminated. Vaccination against polio began
in 1956 and still continues, usually in the form of
‘OPV’ — oral poliomyelitis vaccine (Sabin type).
A standard injection-type vaccine against polio
is also available, but the oral vaccine has two
advantages:
1. It contains attenuated poliovirus which becomes established in the intestine
and in the blood so antibodies are formed in both locations giving additional
protection to the individual.
2. It is much easier to administer than an injection which requires sterile needles
and swabbing of the skin.
The incidence of a number of other diseases — the bacterial diseases diphtheria (caused by Corynebacterium diphtheriae), tetanus (Clostridium tetani),
and pertussis (also known as whooping cough and caused by Bordetella pertussis) and the viral diseases measles, mumps and rubella (also called German
measles) — has also been significantly decreased by the use of vaccines. A range
of immunisations are recommended for Australian children by the National
Health and Medical Research Council (NHMRC). Those provided free by the
Victorian Government under that program are given in table 8.3. The national
program also includes special vaccines not relevant in Victoria. In Victoria, each
child starting primary school must have a school entry immunisation certificate
unless they have special dispensation.
If a pregnant woman is infected with the rubella virus, the development of
the fetus may be affected. Defects in sight, hearing or other characteristics may
occur. This is why the NHMRC recommends vaccination against rubella for
teenage girls. The immunity they acquire will remain with them in adulthood.
IMMUNITY: DEFENCE AGAINST DISEASE
265
Why do we continue to get colds and flu?
Cold and flu viruses are continually changing to give new strains of the viruses.
These act as new antigens. Look at the influenza virus in figure 8.32. Haemagglutinin and neuraminidase are the antigens. These proteins can change to give
rise to new forms and hence new antigens. Although we may have antibodies
specific for a previous cold or flu infection, they will not act against the new type
of antigen. The immune system has to learn how to make specific antibodies
for the new antigen, but the infection develops before sufficient antibodies are
made.
Figure 8.32 An electron micrograph
of influenza virus particles. a and b =
entire particles showing outer layer of
neuraminidase (N) and haemagglutinin
(H) spikes, c = disintegrating
particle and d = partly disrupted
influenza virus particle showing
coiled nucleoprotein folded in parallel
repeating bands surrounded by an
outer membrane or envelope to which
N and H spikes are attached.
The coiled nucleoprotein does not
change from year to year, whereas
N and H spikes do.
Antibody concentration
(arbitrary units)
The majority of the 20 million people who died during the influenza pandemic
of 1918–1919 were young adults. This was unusual because it is usually the very
young and the very old that suffer most in an influenza epidemic. It has been
suggested that old people may have survived because they had been exposed to
a similar influenza virus when they were young. If so, they would have made
antibodies to that particular strain and were immune. The anti-flu drug, Relenza,
that was discussed in chapter 4 reduces the severity and length of an influenza
infection. Because of the availability of the drug, future outbreaks of the disease
should result in fewer deaths than epidemics of the past.
Passive immunity
Approximately
2–3 weeks
Time
Antibodies
injected
Figure 8.33 Introduced antibodies
(passive immunity) give immediate
protection against infection but their
action lasts for a relatively short
time.
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NATURE OF BIOLOGY BOOK 2
Antibodies produced in one person and introduced into another can react with
antigens to provide immunity. When this occurs, the individual receiving the
antibodies has passive immunity — it is called passive because the antibodies
have not been made by the user. You will recall that in active immunity, an individual continues to make a particular antibody, often for life.
The advantage of passive immunity is that it gives immediate protection to
the person receiving the antibodies. However, you will see from figure 8.33 that
introduced antibodies decline relatively quickly and do not provide long lasting
immunity to the receiver.
Passive immunity can be acquired in two ways: naturally or induced.
Natural passive immunity
Birth
1200
Immunoglobulin (mg/100 mL)
1100
Maternal IgG
1000
Total
antibody
900
800
Infant IgG
700
600
500
Newborn IgG
400
300
IgM
200
IgA
100
0
2
4
6
8 0 2 4 6 8 10 12
Months
Figure 8.34 The immune system
does not complete development until
sometime after birth. A fetus obtains
IgG antibodies from the mother
before birth. These maternal IgG
antibodies will gradually disappear
from the baby’s body after birth. At
birth, a baby makes a low level of its
own IgM. By 12 months of age, an
infant produces about 60 per cent of
its adult level of IgG, 75 per cent of
its adult IgM level and 20 per cent of
its adult IgA level.
A developing fetus receives maternal antibodies across the placenta. Look at
table 8.2 on page 257. What kind of antibodies are these? These antibodies
provide important protection for the fetus and baby because the baby’s immune
system does not mature fully until after birth (see figure 8.34).
A baby also acquires antibodies through the mother’s milk. Colostrum is the
thick yellowish milk the mother produces for the first two or three days after the
birth and this is particularly rich in antibodies. One of the reasons breast feeding
is recommended is because of the protection against infection that the mother’s
antibodies give the baby.
Induced passive immunity
Assume a member of your family develops infectious hepatitis (hepatitis A). You
will be at risk of also being infected. If you immediately receive an injection
of antibodies specific for hepatitis A then infection may be avoided. The antibodies used in such injections are obtained from blood collected from voluntary
donors by the Australian Red Cross Society. The antibodies, or immunoglobins,
are extracted from the blood plasma collected from persons known to have had
hepatitis A. The plasma will contain many different antibodies including those
against hepatitis A.
We can now summarise the ways in which immunity can be acquired (see
figure 8.35).
Acquired immunity
Active
Natural
Antibodies
made after
exposure to
infection
Figure 8.35 A summary of
different types of acquired immunity
Passive
Induced
Antibodies made after
immunisation with
toxoid or with killed
or treated organisms
Memory B cells and T cells
Natural
Antibodies
acquired by
baby across
placenta or in
mother’s milk
Induced
Antibodies acquired
through injection of
immunoglobulins
No memory cells
Rabbits as antibody-making machines
Horses are also used to make
antivenoms.
When a person receives antivenom against the venom injected into them during
a snakebite, they are receiving antibodies that act specifically against the snake
venom and so they are given immediate protection. The antivenom combines
with the venom, which is no longer free to damage body cells.
The antivenom is produced in rabbits which receive injections of venom. Why
aren’t the rabbits killed? Initially, only a very small dose of venom is injected
into each rabbit. The dose is so small that the rabbits survive and are able to
produce antivenom. A slightly higher dose of venom is then injected into the
rabbits, which respond by producing a higher level of antivenom. At an appropriate time, blood is taken from the rabbits, the antivenom is extracted and used
in vaccines for people and other animals that are bitten by snakes.
Taking blood from the rabbits is like taking blood from people. It will be
replenished by the rabbit, the rabbit continues to make antivenom and more
blood can be taken from the rabbit at another time. The rabbits are antivenom- or
antibody-making machines that help to save human lives.
IMMUNITY: DEFENCE AGAINST DISEASE
267
Table 8.3 The immunisation schedule recommended for Australians by the NHMRC
Age
Disease
Vaccine
birth
• hepatitis B
• hepB
2 months
•
•
•
•
•
hepatitis B
diphtheria, tetanus and pertussis
Haemophilus influenzae type b
poliomyelitis
pneumococcal infections
•
•
•
•
•
hepB
DTPa
Hib
IPV
7vPCV
4 months
•
•
•
•
•
hepatitis B
diphtheria, tetanus and pertussis
Haemophilus influenzae type b
poliomyelitis
pneumococcal infections
•
•
•
•
•
hepB
DTPa
Hib
IPV
7vPCV
6 months
•
•
•
•
•
hepatitis B1
diphtheria, tetanus and pertussis
Haemophilus influenzae type b1
poliomyelitis
pneumococcal infections
•
•
•
•
•
hepB
DTPa
Hib
IPV
7vPCV
12 months
•
•
•
•
hepatitis B
Haemophilus influenzae type b
measles, mumps and rubella
meningococcal infections
•
•
•
•
hepB
Hib
MMR
MenCCV
18 months
• chickenpox
• VZV
4 years
• diphtheria, tetanus and pertussis
• measles, mumps and rubella
• poliomyelitis
• DTPa
• MMR
• IPV
year 7
• hepatitis B
• chickenpox
• hepB
• VZV
year 10
• diphtheria, tetanus and pertussis
• DTPa
non-immune women shortly after delivery
• measles, mumps and rubella
• MMR
50 years
• diphtheria and tetanus
• ADT
50 years and over
(Aboriginal and Torres Strait Islander people)
• influenza (annual)
• pneumococcal infections
• influenza
• 23PPV
65 years and over
• influenza (annual)
• pneumococcal infections
• influenza
• 23PPV
1All
immunisations on the table except these are provided free by the Victorian Government.
DTPa
= diphtheria–tetanus–pertussis infant/child formulation
ADT
= diphtheria–tetanus adult formulation
IPV
= inactivated poliomyelitis vaccine
MMR
= measles–mumps–rubella vaccine
VZV
= varicella zoster vaccine
7vPCV = 7-valent pneumococcal conjugate vaccine
23vPP
= 23-valent pneumococcal polysaccharide vaccine
MenCCV = meningococcal C conjugate vaccine
Schedules vary between regions. Contact your state or territory health department for details.
Source: Immunise Australia Program, Department of Health and Ageing (2005)
and Immunisation Program, Department of Human Services Victoria
268
NATURE OF BIOLOGY BOOK 2
KEY IDEAS
• Specific immunity can be acquired in different ways.
• In actively acquired immunity, the immune system of a person produces
antibodies in response to antigens.
• In passively acquired immunity, a person receives antibodies from an
outside source.
• Both active and passive immunity can be acquired naturally or
artificially.
QUICK-CHECK
20 A child develops the disease tuberculosis and later recovers. Explain
whether the child is likely to have immunity to the disease five years
later.
21 Not all adults have been vaccinated against tetanus. One such person
stands on a rusty nail and is at risk of developing the disease. The
person receives an injection of antitoxin shortly after the accident.
Explain whether the person is likely to have an immunity to tetanus
five years later.
22 Explain the main differences between non-specific immunity and
specific immunity.
23 Outline one way in which vaccines or antivenoms are made.
ODD FACT
One of the
Australian fur seals,
Arctocephalus pusillus, at the
Melbourne Zoo is allergic
to pollen and has been trained
to receive injections for
the condition.
ODD FACT
People who are
allergic to red strawberries
develop itching and swelling
in the mouth and throat. These
people are often able to eat
white strawberries so the allergy
is probably related in some way
to the red pigment.
Adverse events associated
with immunity
Allergies
Mast cells are immune cells involved in allergic responses. Mast cells are fixed
cells found around blood vessels, in connective tissue, near the lining of the gut and
in the lungs. Circulating basophil cells are also involved in allergic responses, but
to a much lesser extent. Both kinds of cells contain large granules of histamine.
You will recall that there are five different types of antibody. One type is
IgE, which binds to mast cells and, to some extent, to basophils. IgE antibodies
are made against antigens such as dust, pollen and plant spores. If a person
contains IgE antibodies for a particular antigen, they are said to be sensitised to
that antigen. If the person is further exposed to the same antigen, cross links are
formed between the antibody on the mast cells and the antigen. These antibody–
antigen cross links trigger mast cells to release active agents such as histamine.
Histamine causes contraction of smooth muscle, including the muscle around
tubules leading to the lungs. The diameter of the tubules decreases and this leads
to difficulty in breathing, as in asthma. Histamine also causes blood vessels to
dilate allowing cells and serum to move into the surrounding tissue causing
swelling and inflammation.
An allergic response can occur very quickly and can be fatal, particularly if it
is widespread in the body. Treatment includes use of antihistamine drugs. Read
Trent’s story on page 270. Trent has an allergy to peanuts and dairy products.
Allergic responses can be avoided in some cases if the person is desensitised.
This occurs by treating the person with small doses of the antigen to which they
IMMUNITY: DEFENCE AGAINST DISEASE
269
TRENT — ALLERGIC TO PEANUTS
AND DAIRY PRODUCTS
Trent and his mother each tell a story.
Mother’s story
We have redefined ‘normal’ in our house. We have
endeavoured to treat Trent as normal but just with different restrictions.
There are two important factors when it comes to a
person with allergies.
1. The diet must be restricted, especially so when you
need to exclude things like dairy and peanuts. Dairy
is the big one. Dairy includes cheese, butter, ice
cream and milk.
2. The risk in eating something wrong is always present.
An anaphylactic reaction happens in minutes and is
life threatening.
A restricted diet means that often Trent can’t eat
what other children do. We always ensure Trent has the
equivalent food wherever possible and never misses
out. He gets safe alternatives. We don’t think we should
raise him to feel any more deprived or precious than
other children; it just comes down to the fact that he
(and we) need to make different choices. It is normal,
just different from most other people.
Going out is difficult. At other people’s houses, we
always take food, as most times people don’t know
what to offer Trent. At restaurants, we sometimes
take his food from home or something he can eat; for
example, a McDonalds ‘happy meal’ can be bought on
the way and is fortunately seen as a real treat by Trent.
This, of course, is easier to do for a young child but
may become more difficult for Trent as he gets older
and really wants to be the same as others. He can eat
at a restaurant only if they can guarantee there are no
dairy products or peanuts in the food. Most restaurants
try to be helpful as they don’t want to be the cause of
any ‘accidents’. Trent usually takes his own food to a
birthday party; I check with the hosting mother and
send along something similar to what the other children
are eating. Occasionally, if I am sure about the brand
of foods being served, he will share in some of what is
offered to the other children. Trent is always very wary
of this, though, and looks for my reassurance that it will
be OK for him to eat.
Having an anaphylactic reaction is the other worry. If
Trent somehow eats the wrong thing, is there someone
present to administer the Epipen? An Epipen is a selfinjecting shot of adrenaline that would probably save
his life. It is not difficult to administer but requires a
certain technique. The reaction develops very quickly
and the Epipen injection would need to be given even
before an ambulance arrived. I really need to trust the
270
NATURE OF BIOLOGY BOOK 2
people at his school, where Trent stays or where he
goes to play.
Emotionally, this is all rather enormous for a 7-yearold to worry about. The restrictions and risks greatly
impose on his life but Trent handles it so well. We are
extremely proud of him. Food is something you can
never really get away from. Many celebrations and
occasions are planned around food, yet Trent finds fun
in where he goes and what he does in life.
Trent can do many things well; he loves school and
sport. He has a positive attitude about his allergies and
has always handled it with a sense of maturity and
wisdom. Even as a small child, he never had a tantrum
when he couldn’t have what the other children were
having. He always appreciated his own ‘treat’ and was
excited to have that. He is wary of food and never eats
something without checking with his Mum and Dad
first.
Trent realises that he is indeed fortunate. Many
children are born with worse illnesses and disabilities.
He thinks having allergies is no big deal, as you will
read below.
Trent’s story
Hi, my name is Trent.
I am 7 and I am allergic to dairy and
peanuts.
It is a little bit hard with allergies
because:
• I get lots of hayfever. [Mum’s note:
Hayfever is also an allergic/immune
response that goes hand in hand
with food allergies.]
• I can’t eat certain foods.
• Everyone in my class eats
chocolate and I don’t.
Good stuff about
allergies:
• My Mummy gives me
treats instead of the
stuff I can’t have.
• I also trust Mum and Dad to give
me the right food.
I have had allergies for a long
time. It is like a normal life. At
school, I love sport, art, maths and
writing stories. Having allergies
doesn’t mean you can’t do stuff like
other people because I can still play
football really, really well.
Figure 8.36 Trent
are sensitive. This antigen links with the IgE and so makes less IgE available for
any future reaction. The severity of any future reaction will be reduced.
Why do we have an antibody that can lead to such problems? It has been suggested that IgE assists in the destruction of infections by larger organisms such
as some worms that cannot be engulfed by phagocytes.
Some allergies can also be caused by T cells. These reactions occur much more
slowly than those involving antibodies and generally no treatment is required.
Rhesus incompatibility
Human blood can be classified as Rhesus positive or Rhesus negative depending
on the presence or absence of the Rhesus protein on red blood cells. The blood
group to which an individual belongs is genetically determined (see chapter 9 for
more details). Depending on the father’s blood group, it is possible for a Rhesus
negative mother to have a Rhesus positive child. In some cases, the activation
of an immune response can lead to severe problems in the baby. How does this
immune response arise and how can it be prevented?
During a first pregnancy in which a Rhesus negative mother has a Rhesus
positive child there is generally no problem. Few, if any, blood cells from the
fetus move across the placenta into the mother. At the birth of the child, when the
placenta separates away from the uterus wall, significant numbers of the baby’s
red blood cells may cross into the mother’s bloodstream. The Rhesus protein
on the red blood cells is foreign to the mother and this stimulates her immune
response. The mother then makes Rhesus antibodies (see figure 8.37).
Rh = Rhesus
During first
pregnancy
Placenta
Rh-ve
mother
At first birth
Rh-ve
mother
Shortly after birth
Subsequent pregnancy
mother is sensitised
Rh-ve
mother
Rh-ve
mother
B
NO
TREATMENT
anti-Rh
Rh+ve red
cells
anti-Rh
Rh+ve fetus
Rh+ve fetus
Lysis
Rh+ve fetus
Anti-Rh from mother moves
across placenta into fetus —
fatal damage may occur
Generally no problems
Red blood cells of Rh+ve
fetus move into mother
Mother’s plasma cells
produce Rhesus antibodies
and continue to do so
During first
pregnancy
At first birth
Within 72 hours after birth
Subsequent pregnancy
no sensitisation
Rh-ve
mother
Rh-ve
mother
Rh-ve
mother
Rh-ve
mother
Placenta
Placenta
TREATMENT
Rh+ve red
cells
Rh+ve fetus
Generally no problems
Rh+ve fetus
Red blood cells of Rh+ve
fetus move into mother
Mother receives injection of
anti-Rh which react with
fetal Rh+ve red blood cells
Rh+ve fetus
Generally no problems.
Mother receives injection
of anti-Rh at any
subsequent birth
Figure 8.37 Haemolytic disease of the newborn can occur when an Rh negative mother has an Rh positive child.
Treatment is now available that has led to a significant reduction in incidence of this disease in recent years.
IMMUNITY: DEFENCE AGAINST DISEASE
271
If another pregnancy follows in which the mother again has a Rhesus positive
child, a problem can arise. Some of the Rhesus antibodies made by the mother
pass across the placenta into the fetus where they react with the Rhesus protein on
the red blood cells of the Rhesus positive child. If this happens, serious damage
occurs to tissues and organs, including the liver. Blood cells are destroyed and
their contents, including haemoglobin breakdown products, circulate in the bloodstream giving the baby a yellow jaundiced appearance. The problem increases
with each pregnancy and can result in the death of the baby. The disease is called
haemolytic disease of the newborn.
Treatment is now available for Rhesus negative women who have Rhesus
positive babies. Within 72 hours after the birth of the first Rhesus positive baby
(or after a miscarriage), the mother is given an injection of immunoglobulin high
in Rhesus antibody. She is passively immunised with Rhesus antibodies. These
react with and remove fetal red blood cells from the mother’s circulation. This
prevents the development of Rhesus antibodies by the mother and the development of memory cells that would give a greater response during the next
pregnancy. The injection is repeated in any subsequent pregnancy.
These events are summarised in figure 8.37.
How does a fetus survive the mother’s
immune system?
We have seen, in the case of Rhesus incompatibility, that antibodies made by the
mother in specific response to a fetal protein can cross the placenta and react with
cells within the fetus. Antibodies that pass through the placenta are generally
maternal IgG antibodies.
Half the genetic material of a fetus is inherited from the father and so many
of the compounds made by a fetus are foreign to the mother and are capable of
acting as antigens. Some of these antigens cross the placenta from the fetus into
the mother and result in the production of antibodies by the mother. This occurs
with increasing frequency as pregnancy proceeds. Why don’t these antibodies
cross the placenta back into the fetus and cause a massive rejection of the fetus
by the mother’s body?
This doesn’t happen because the placenta acts as a selective barrier to antibodies. The placenta allows only some antibodies to cross from the mother into
the fetus. Generally, anti-fetus antibodies made in the mother are absorbed by
cells in the placenta and so are prevented from crossing into the fetus. In addition,
an antibody ‘blocking factor’ is found in maternal serum that inhibits the function
of maternal lymphocytes that have been sensitised by fetal antigens.
Some women have repeated spontaneous miscarriages without apparent
cause. Some of these miscarriages may be due to a rejection of the fetus because
anti-fetal antibodies have crossed the placenta and reacted with fetal cells. Some
of the women who have repeated miscarriages have reduced levels of ‘blocking
factor’. In some cases, when a woman with a history of recurrent miscarriages
is immunised against the white blood cells of the father of the children, the fetus
seems to be protected against rejection. Maternal antibodies specific for fetal
antigens react with cells in the placenta and prevent the passage of fetal antigens
which would otherwise initiate an immune response in the mother.
Auto-immune diseases
Sometimes the ability of the immune system to recognise self from non-self
breaks down. When this occurs, the system reacts as if some of the body’s own
cells are non-self. In this case B and T cells attack and destroy self cells in the
same way that they attack and destroy invading micro-organisms.
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NATURE OF BIOLOGY BOOK 2
Conditions that develop because of this self attack are called auto-immune
diseases. The attack can occur generally throughout the body or against a specific
organ. Some auto-immune diseases and their features are listed in table 8.4. Read
Rachel’s story on pages 276–7. She has the autoimmune disease systemic lupus
erythematosus.
Table 8.4 Some auto-immune
diseases and their features. In some
auto-immune diseases, particular
organs are affected more than others.
General reactions occur throughout
the body in other auto-immune
diseases. See pages 276–7 for
Rachel’s story about lupus.
Disease
Features
Main site
of action
Graves’ disease
increased production of thyroid hormone
thyroid
pernicious anaemia
vitamin B12 deficiency, abnormal red blood
cells
stomach
insulin-dependent
diabetes mellitus
diabetes responsive to insulin treatment
pancreas
rheumatoid arthritis destruction of joint cartilage
joints
multiple sclerosis
progressive paralysis, myelin layers around
axons degenerate
CNS
systemic lupus
erythematosus
fever, pain in joints, damage to CNS,
heart and kidneys
kidneys
Multiple sclerosis: an auto-immune disease
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS).
It is thought to be an example of an auto-immune disease, a group of disorders in
which the body’s immune cells attack its own tissues. It is also a relatively common
disease affecting up to one per 1000 people of northern European origin.
In MS there is a breakdown of the fatty myelin sheath that surrounds the processes of nerve cells (see figure 8.38). This myelin
sheath is produced by specialised cells called oligodendrocytes
and it normally speeds transmission of nerve impulses by electrically insulating nerves from the surrounding environment.
Damage to the myelin sheath can short-circuit communication
between different parts of the CNS (either within the brain or
along the spinal cord). It also impairs the transmission of information between the CNS and the peripheral nerves, that part of
the nervous system which sends messages to the muscles and
which relays information from the sensory organs. The damage
to the myelin sheath is thought to be caused in a stepwise way
by immune cells that invade the CNS in discrete waves.
The sites of damage are patchy and scattered throughout
the CNS. Therefore, different people with MS often have different symptoms, ranging from loss of coordination and muscle
weakness, to sensory impairment such as loss of feeling in the
arms or legs, or visual defects, and sometimes even problems
with various aspects of thinking and memory. For most people
the disease starts as a single attack that usually improves. In
some patients this is the only attack that they ever experience but
for others this is followed by a series of further attacks that also
usually get better. Some of these attacks start after infections
Figure 8.38 Brain scan. Multiple sclerosis results in extensive
damage to the myelin sheaths of nerve processes in the CNS. Compare
this brain with the one on page 187.
IMMUNITY: DEFENCE AGAINST DISEASE
273
affecting the lungs or urine, presumably caused by activation of immune cells.
This includes reactivation of ‘memory’ cells that have previously damaged CNS
myelin in earlier attacks.
Approximately half of the people who have had discrete attacks enter a progressive phase of the disease. Whereas early in the disease the damage can be
repaired, with repeated attacks the tissue injury may become permanent. This
leads to multiple plaque-like areas of scarring or sclerosis (hence ‘multiple
sclerosis’) within the CNS. During this phase of the disease there is permanent
impairment of nerve transmission and worsening disability. Recently, it has been
suggested that this progressive phase is a result of damage to the processes of the
nerve cells that cross the plaques.
In the past, the diagnosis of MS was based on the combined assessment of the
patient’s symptoms and of the doctor’s examination findings. However, diagnostic
accuracy improved dramatically in the 1990s because of a new way to image the
brain that relies on the use of magnetic fields and radio-frequency pulses. This
test, known as magnetic resonance imaging, provides a very accurate assessment of water content in the brain. Because the amount of water is increased
in the plaques of MS, these lesions can now be detected with a high degree of
accuracy.
The cause of MS is unknown. It has been suggested that exposure to infectious agents such as viruses could be involved, possibly setting off auto-immune
disease directed against myelin. This could occur via a process known as
molecular mimicry. This occurs when there is a similarity between proteins
expressed by infectious agents, against which an immune attack is appropriately
directed, and myelin proteins, against which the immune attack is mistakenly
continued. Much research has attempted to find unique features in the immune
systems of patients with MS that makes them more likely to have ongoing
disease. To date, no clear cut difference has been found, apart from some possible
differences in the way that the various proteins might be presented to the immune
cells via molecules known as human leucocyte antigens (HLA). Furthermore,
despite intensive investigation, no single infectious cause has been identified
and it is possible that exposure to a variety of environmental factors can trigger
the disease. In both northern and southern hemispheres, a latitudinal gradient
exists in the prevalence of MS, with more cases identified in colder regions. In
Australia, the prevalence of MS in Tasmania is several times greater than that of
northern Queensland, providing some of the strongest evidence for an environmental influence on the development of MS.
Nevertheless, MS also has an obvious hereditary component, as indicated by
the observation that if one identical twin has MS there is a 25–30 per cent chance
that the other twin will also get the disease, whereas the risk is only 3–5 per cent
amongst non-identical twins. Consequently, there is active research attempting to
identify genes that alter the risk of the disease.
The auto-immune hypothesis has led to attempts to treat MS with medications
that change the immune response. Cortisone (a steroid) speeds the rate of recovery
from acute attacks of demyelination. A new drug called beta-interferon (which
is a substance normally produced by the body as part of the defence mechanism
against virus infection) reduces the frequency of attacks in patients with mild
disease and reduces the rate of progressive MS, on average, by about 20 per cent.
These recent advances are useful, but more effective treatments are required. In
order to design such therapies we will almost certainly need to understand more
about the cause of the disease.
Rejection of transplanted organs
Perfect matching of tissues occurs only if identical twins are involved in organ
donation. In most cases, transplanted donor tissue will not match that of the
274
NATURE OF BIOLOGY BOOK 2
recipient perfectly and the immune system of the recipient will react against the
non-self material. T cells are particularly important in tissue transplants. Helper
T cells identify unmatched tissue and attack the grafted organ.
Before an organ is transplanted from one person into another, the donor and
potential recipient have their tissues ‘typed’ to find out the major antigens that
are present in each. The amount of foreign or non-self material introduced into a
recipient is minimised by matching the tissues as closely as possible. The better
the match of MHC markers between donor and recipient, then the higher the
chance that the transplant will be successful.
Drugs are available that inhibit the immune response. Recipients of foreign
tissue transplants must take the chemical cyclosporin for the rest of their lives
to prevent rejection of the transplanted tissue. The beauty of cyclosporin is that
it acts specifically against T cells and so the remainder of the immune system is
available to act against disease-causing organisms. A range of other drugs are
also used in association with cyclosporin.
Immune deficency diseases
ODD FACT
The longest a child
has lived without an immune
system is 12 years. David lived
in the USA in a sterile plastic
enclosure and was known as ‘the
boy in the bubble’.
In 1997, 947 Australians received
a bone marrow transplant.
The immune system at birth is relatively immature (see figure 8.34). If maturation fails to occur then a baby has no protection against infection. Once the
antibodies obtained from the mother via the placenta and milk are no longer
active, a baby with an inactive immune system develops a range of infections
as the baby encounters various micro-organisms. A baby with such a deficiency
generally dies at a young age.
Immune deficiency is a malfunction or a deficiency in one or more components of the immune system. Immune deficiency disorders can be inherited or
may develop as a result of some other disease.
Remember that bone marrow plays an important role in producing cells for the
immune system. Bone marrow is a tissue that can be transplanted from person to
person. Unlike heart and liver transplants that require the death of a donor, bone
marrow is taken from a living donor without long-term ill effects.
An Australian Bone Marrow Donor Registry was established in 1989. The
registry exists in a number of States and is coordinated from Sydney. The Australian registry is also linked with registries in other countries.
Just as tissues have to be typed for organ transplants, bone marrow also has to
be typed so that donor and recipient tissues can be matched as closely as possible
and the chance of rejection of the transplant by the recipient is reduced. Even
if the potential donor and recipient have matched class 1 and class 2 markers,
additional tests may reveal other incompatibilities. Mismatched transplants are
rarely done in Australia.
Acquired immune deficiency syndrome (AIDS)
It is generally accepted that acquired immune deficiency syndrome (AIDS) is
caused by the human immunodeficiency virus (HIV) (see figure 8.41). This
virus infects only cells carrying a particular protein marker. The marker is found
mainly on mature helper T cells and to a lesser extent on macrophages.
Because HIV destroys a key component of the immune system, T helper cells,
AIDS patients have greatly reduced defence against other invading organisms
and develop a number of opportunistic diseases. They are also susceptible to
Kaposi cancer, a rare cancer of blood vessel tissue.
The development of disease after infection with HIV is variable. In some
people the virus remains in infected cells for years with few or no apparent
problems. In other people, the virus becomes active in a relatively short time
and all the serious symptoms of AIDS appear. Once these occur, death usually
follows within about two years. Some drugs delay the onset of the symptoms of
‘full blown’ AIDS.
IMMUNITY: DEFENCE AGAINST DISEASE
275
PERSONAL STORY
Rachel’s story — a case of systemic lupus erythematosus (sle)
‘Hey, Rachel. How come your face is so fat but the rest
of your body is normal?’
Another comment about my weight — my somewhat
‘bloated’ appearance. I could cope with people’s
interest and concern but not my physical changes. Why
did everyone have to comment? Why couldn’t they
be happy that I was getting well? Why hadn’t anyone
heard of lupus?
A small chilblain on my left middle finger initiated
a series of strange, painful and ultimately debilitating
symptoms that would eventually transform the normality of my adolescent world into a time of absolute
confusion and despair. Systemic lupus erythematosus
(SLE), or simply lupus, is a chronic autoimmune
disease caused by inflammation in different parts of the
body. Lupus commonly affects the skin and joints, and
possibly organs such as the kidneys, heart, brain and
other internal organs. Symptoms I suffered included joint
and muscle pain, skin rashes, extreme fatigue, weakness,
fever, headaches, hair and weight loss, and sensitivity to
sunlight. Those who develop lupus are usually women in
their childbearing years. I was only 14.
From age 14 to 16, doctors couldn’t diagnose my
peculiar symptoms. Blood tests indicated no signs of
disease activity. I visited every specialist imaginable
but to no avail. At times I was too sick to attend school
in years 8 and 9, but, in year 10, I didn’t make it to
school at all. Bedridden, in constant joint pain and overwhelmingly fatigued, I felt my dreams and aspirations
crashing down around me. My dreams of completing
VCE, attending university and becoming a teacher
were in doubt. I just wanted to be my old, normal self
again. While all of my friends were at school, working
part-time jobs, socialising at parties and having boyfriends, I spent each day lying in my bed and trying to
find the strength to walk with the aid of a walking stick
throughout my house. I would watch from my window,
waiting each day for friends to visit me. No one came.
Teachers didn’t call. Life went on for those around me,
while my body succumbed to the pain. I had never felt
so alone.
At the beginning of year 11, aged 16, I was finally
diagnosed with lupus. Great joy — my symptoms had
a name. I could now inform people about my illness
and explain what was wrong with me. I could actually
take drugs, corticosteroids, that would help relieve my
pain. I would soon discover that they were to be both
my best friend and worst enemy. With time, effort and
determination, I was well enough to attend the last few
weeks of year 10 prior to my diagnosis. My mother,
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NATURE OF BIOLOGY BOOK 2
who didn’t drive, would push me to school in a wheelchair for half-day visits when I was well enough. So,
you could imagine how happy I was at the prospect of
taking medication that would give me enough energy
to walk to and from school, to survive a full school day
and to concentrate and attend to my numerous work
requirements as a VCE student, just like everyone
else.
Although my hope for a promising future had been
renewed, it wasn’t easy. Steroids had a range of side
effects. I gained weight, particularly in my face which
created a bloated appearance, and suffered severe
acne, hair loss (not very attractive features to have in
year 11!!) and regular infections ranging from colds
to urinary tract and candida infections. However, I
managed to cope positively with these side effects with
support from my teachers, who extended time for my
work requirements when necessary. Socially, my return
to school wasn’t easy. One student lamented, ‘We
heard you were dying,’ to which I replied, ‘Gee, thanks
for coming to say good-bye.’ Re-establishing friendship groups was very hard. I felt like a new student
but I guess in many ways, I was. With time, I had a
support group of friends who helped me enjoy each day
at school.
Figure 8.39
Rachel fulfils her
dream of graduating
and becoming a
teacher.
Returning to school was a challenging time but I
never doubted my will and ability to succeed. I sacrificed
the social life of a VCE student in exchange for the life
of a lupus student striving to achieve her dreams. I was
successful in many ways. At the completion of year 12,
I received the student award for Best All-Rounder. I was
accepted in my chosen university course and studied
a double degree of Teaching and Applied Science for
four years. I was honoured as ‘Most Outstanding Home
Economics Student Teacher of the Year’ and became a
member of an honours society for students who were
in the top 15% of their course. I am extremely proud of
these achievements, which symbolise a time in my life
when I felt destined to fulfil my dream of teaching.
At the time I first wrote this piece [for Nature of
Biology Book 2, Second Edition], I was a graduate
secondary teacher of VCE and junior classes in Food
Technology and Human Development. I was battling
daily joint pain, fatigue and sensitivity to sunlight.
Today, I am concluding my eighth year of secondary
teaching and continue to suffer these symptoms in
varying degrees. There has been no significant breakthrough in medical treatment for lupus patients, and I
am still taking the course of medication I began almost
14 years ago. I have taken greater amounts of corticosteroids and immunosuppressant medication, which
have made serious changes to my pain management.
Their side effects have been extremely strong and
I have had to cope with much discomfort. I seem to
relapse into flares of the disease when under stress and
cannot reach a state of complete remission.
Whilst achieving great academic success in my
younger years, beginning my career as a secondary
teacher was where the real learning began. As a student,
I could seek support from teaching staff who would
extend time for me to complete important tasks. As a
full-time secondary teacher in the workplace, I cannot
always be awarded such leniency. Thus, adjusting to
life in the workplace as a chronically ill person with a
disease that is not well known is an ongoing challenge
for me. Disclosure of my illness to teaching colleagues
has at times proved frustrating yet, ultimately, integral
to my survival in the workplace; without the understanding, compassion and patience I have received, I
would find it extremely difficult to achieve the standard
of professionalism as a teacher to which I aspire.
I will be honest; teaching is not exactly the type
of profession my doctors would wish me to pursue!
Teaching requires much energy, commitment and resilience in responding to its many changing demands. I
have experienced the challenge of aspiring to reach my
goal of becoming a teacher, and the ongoing challenge
of learning how to sustain my teaching life. Learning
how to grow and extend my skills and knowledge as a
teacher without exacerbating my lupus is extremely difficult and there are some aspects of my job that I know I
will not completely fulfil. However, it is also important
that I remember not to rule anything out completely,
to focus on what I can do, not what I can’t do. This is
paramount to my true success as a person suffering a
chronic illness.
Yes, I still have lupus, for which there is still no
known cure. Yes, I still battle daily with a myriad of
symptoms. Years of treatment are starting to show
effects on my body as I am in the early stages of osteoporosis and I find that my symptoms have slightly
changed over the years. I don’t seem to pull up from
severe bouts of lupus as well as I used to when I was
younger! Yes, I am still a secondary teacher, one who
has progressed with more experience, and I so enjoy
the many rewards of making a difference in the lives of
my students. I believe I am living a happy, fulfilled life,
but I do not always find it easy to get that balance of
working and looking after myself — such is the life of
a chronically ill person. What I do have is the strength
to keep looking forward and I know I will keep doing
so with love and support from family, friends and work
colleagues … and having a greater acceptance of my
complete self, whatever its shape or form.
Figure 8.40 Rachel preparing for class
IMMUNITY: DEFENCE AGAINST DISEASE
277
Core
Capsid
RNA molecules
carrying virion’s
genetic code
Enzymes
Figure 8.41 Drawing of a model
Envelope of fat
molecules
of the human immunodeficiency virus
(HIV) that causes acquired immune
deficiency syndrome (AIDS)
Glycoprotein
molecules
embedded in
the envelope
It is now known that lipids make up about 30 per cent by weight of the HIV-1
virus (figure 8.42a). Disruption of the HIV-1 lipid surface by certain chemical
agents reduces the infectivity of the virus. Researchers at the Macfarlane Burnet
Institute for Medical Research and Public Health are investigating ways of developing new antiviral strategies with drugs that would prevent the spread of HIV-1
(figure 8.42b).
(a)
lipid
bilayer
membrane
HIV
Figure 8.42 (a) Disruption of the HIV lipid
surface by certain chemical agents reduces
the infectivity of the virus. (b) Electron
micrograph of HIV-1 being released
from an infected host
surface
proteins
disrupt the
lipid bilayer
(b)
Do plants have an immune system?
unsuccessful infection
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NATURE OF BIOLOGY BOOK 2
Plants have no distinct immune system of the kind found in humans and many
other animals. However, most plants are resistant to pathogens. Plants have
evolved over years in situations in which they were exposed to pathogens. Only
those plants which had appropriate structural and physiological characteristics
to resist infection survived, and their genetic material was transmitted to future
generations.
ODD FACT
Many antibiotics
used with animals, including
humans, are extracted from
plants and fungi.
Mechanical barriers
The cuticle and epidermal cells form an outer barrier for plants in much the same
way as skin does in humans. The silicon content of some leaves makes them
particularly resistant to the degrading enzymes of pathogens. If a disease-causing
organism penetrates the outer layers, and the stomata in particular can be a point
of entry, layers of thickened cells (called cork) form in many cases. This gives
rise to abnormal swellings at the infection site. These swellings are called galls
and limit the distribution of the parasite in the plant. Galls are caused by pathogenic organisms, including insects and nematode worms.
Chemical barriers
Figure 8.43
Some plants resist disease by producing chemicals that act as antibiotics. Lemon
trees, Citrus limonia (figure 8.43), and mint plants, Mentha spp., produce oils
that repel some insect pests. Stone fruit trees, such as plum and peach, secrete
gum around an infected area to ‘seal it off’ from the rest of the plant. Other
chemicals that have a defence role in plants include resins, tannins and phenolic
substances.
New methods of plant breeding are being developed to produce plants that are
resistant to specific diseases. These include cell and tissue culture and recombinant DNA technology (see chapter 12).
KEY IDEAS
• Any part of the immune response can be faulty.
• Cells of the immune system are involved in allergic reactions.
• An immune system can lose the ability to distinguish ‘self’ from ‘nonself’.
• The action of the immune system can be reduced by treatment with
certain drugs.
• Antibodies are sometimes injected to inhibit an immune response.
• Most plants resist infection by mechanical and chemical means.
QUICK-CHECK
24 Explain why treatment of transplant patients with the drug
cyclosporin reduces the chance of transplant rejection.
25 Explain why a person suffering from an allergy may be treated with an
antihistamine.
26 Explain what is meant by an auto-immune disease.
27 Explain why some women are given an injection of immunoglobulin
shortly after the birth of a baby.
28 Explain why a person with AIDS is particularly susceptible to a range
of infections.
29 A baby is born with a defective thymus. Comment on the baby’s
ability to resist infection — immediately after birth and at six months
of age.
30 Why are galls effective in reducing the spread of infection in some
plants?
IMMUNITY: DEFENCE AGAINST DISEASE
279
BIOCHALLENGE
Autocrine
1
Cytokines are protein molecules that act as messengers between cells of the immune system.
An immune cell may communicate with itself, an autocrine effect, with a cell nearby, a
paracrine effect; or with a cell some distance away, an endocrine effect.
You will recall from chapter 5 that this is similar to communication by hormones. One
difference is that hormones are more likely to act on distant cells than close ones while
Paracrine
cytokines are more likely to act on close cells than on distant ones.
Explain why this difference is biologically logical, given the organs and cells involved in the
immune and hormonal systems of the body.
Endocrine
Ovary
2
IgY from
blood
Oviduct
IgA locally
secreted
Immunoglobulins pass from a mother hen into a developing egg. IgY immunoglobulins are
found in the yolk of an egg, and IgM and IgA are found in the white. The white forms a watery
liquid, the amniotic fluid, in which a chick develops, and the yolk becomes nutrient for the
developing embryo. In a newly hatched chick, IgY is found in its serum and IgM and IgA in its
intestine.
a Why would it be important for a chick to have some immunity immediately after hatching?
b Suggest an explanation for the different positions of the immunoglobulins in a newly
hatched chick.
c Given that immunoglobulins are present in the chick, explain whether any immunity they
give would be passive or active immunity.
d Explain whether the immunity in a chick is likely to be long lasting or temporary.
IgA in albumin
IgY in the yolk
3
Non-identical twin calves are genetically equivalent to non-twin siblings.
They share some proteins but many are different. Sometimes, the two
placentas of twin calves fuse and chimeric calves develop. A chimera
is an animal that contains cells from two or more genetically different
individuals. Stem cells from each calf travel in the bloodstream, enter the
body of the other calf and colonise the bone marrow of the other calf. In
effect, the result is that both calves have their own cells as well as cells
identical to those of their non-identical twin.
a What conclusion could you reasonably make about the ability of fetal
cells to distinguish between self and non-self cells?
b Skin from calf A was grafted onto calf B. Explain whether you would
expect rejection of the skin graft or not.
c Explain whether you would expect the same result if skin from calf B was
grafted onto calf A.
d Tests were carried out on the calves when they were six months old.
Would you expect the antibodies in each calf to be identical to those in
the other calf? Explain your answer.
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NATURE OF BIOLOGY BOOK 2
Fused placentas
A
B
Chimeric calves
CHAPTER REVIEW
Key words
acquired immune
deficiency syndrome
(AIDS)
acquired immunity
active immunity
acute myeloid leukaemia
agglutination
allergic responses
antibodies
antigen
attenuated
auto-immune diseases
B cells
B-memory cells
bone marrow
cellular immunity
class 1 markers
class 2 markers
clone
colony stimulating factor
(CSF)
complement proteins
cytokines
CROSSWORD
cytotoxic T cells (Tc)
galls
helper T cells (Th)
histamine
humoral immunity
immune deficiency
immune system
immunoglobulins
inflammation
interferons
lymph
lymphocytes
macrophages
major histocompatibility
complex (MHC)
mast cells
monocytes
natural killer
(NK) cells
neutrophils
Nobel Prize
non-self receptors
non-specific immunity
opportunistic infection
passive immunity
phagocytes
plasma cells
primary antibody response
pus
secondary antibody
response
self antigens
self receptors
specific immunity
sub-clinical infection
T cells
toxoids
vaccination
vaccines
Questions
▲
▲
▲
▲
Figure 8.44
1 Making connections between concepts ➧ Make a concept map using at least
eight key words from the list at the end of this chapter. In making your map,
you may add other concept labels.
2 Analysing information and applying understanding ➧ Bacteria of the kind
shown in figure 8.44 infect a skin wound.
a Explain the immune response that takes place at the wound site.
b Explain how many different kinds of B cells would react to the bacteria.
Draw one of them.
c Explain how many different kinds of antibodies would be produced in
response to the bacteria.
d Draw a macrophage cell that has ingested a bacterium of this kind.
e How will T cells respond to the infection by these bacteria?
3 Analysing information and drawing conclusions ➧ Di George’s syndrome
is a disease of the immune system in which B cells are produced but not
T cells.
a Explain whether a person with Di George’s syndrome would be able to
produce antibodies.
b Explain to what extent you think a person with Di George’s syndrome is
likely to accept or reject a tissue transplant.
4 Analysing information and applying understanding ➧ The ‘Mantoux’ test is
designed to determine whether a person has antibodies against the bacillus
IMMUNITY: DEFENCE AGAINST DISEASE
281
responsible for tuberculosis. When the test is carried out a small amount of
‘test’ solution is injected under the skin on the arm. If the test is positive, a
red area appears around the site of injection.
a What material must be in the ‘test’ solution to react with antibodies in the
blood?
b What do you think causes the redness around the injection site?
c Explain the various ways in which a person might have obtained antibodies against tuberculosis.
5 Analysing information and applying understanding ➧ Look at table 8.3 on
page 268. The injections of triple antigen ‘DTP’ and Sabin vaccine ‘OPV’
that are given to babies at four and six months are called ‘booster shots’.
Given that the baby has been immunised at two months, explain why booster
shots are given.
6 Analysing and interpreting data and communicating information and
ideas effectively ➧ A person can be classified into one of four groups in the
ABO blood group system on the basis of the antigen found on the red blood
cells and the antibodies in the plasma. The four groups are:
Blood group
Antigen on red blood cell
Antibody in plasma
A
A
anti-B
B
B
anti-A
A and B
neither anti-A nor anti-B
neither A nor B
anti-A and anti-B
AB
ODD FACT
In 2004 in a
Sydney hospital, a patient died
after two nurses gave type A+
blood to a woman whose blood
group type was O+.
q
Antibody preparations are made so that blood can be tested and typed. The
first column in figure 8.45 contains a test sample of blood that has been
tested with anti-A and anti-B antibodies.
How would you ‘type’ or classify this blood? Because the test blood has
reacted with anti-B, the cells must have antigen B. There is no reaction with
anti-A. The unknown blood must be from a group B person.
a Draw the test panels you would expect to obtain when testing blood of
groups B, AB and O. Explain why you predict each result.
b Fresh blood was found on a broken window at the scene of a crime. Blood
from four suspects was compared with blood from the window. The
results obtained are shown in figure 8.45.
Test
blood
sample
Blood
+
anti-A
Blood
+
anti-B
Figure 8.45
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NATURE OF BIOLOGY BOOK 2
Control
blood
+
saline
Suspect
1
Suspect
2
Suspect
3
Suspect
4
Blood from
broken
window
i What was the blood group of each of the samples tested?
ii Explain which suspect could have been at the scene of the crime.
iii What is the purpose of the control panels?
c Write a short mystery story involving blood testing. See if other class
members can solve the mystery.
7 Analysing information and applying understanding ➧ The red blood cells
of a Rhesus positive (Rh +ve) person have Rhesus protein (antigen) on their
surfaces. A person with Rhesus negative (Rh −ve) blood has neither Rhesus
antigen on the cells nor Rhesus antibody in the plasma. Sometimes, when
a blood bank runs short of Rh −ve blood, Rh +ve blood may be given to a
male who has never before had a transfusion.
a Why can such a transfusion be given without danger to the recipient?
b Explain the immune response in a male who receives such a transfusion.
c If the male required a transfusion two years later, what kind of Rhesus
blood could he be given and why?
d Explain why young women who are Rhesus negative are not given
Rh +ve blood even though it would be a safe transfusion the first time it
was given.
Antigen
Hinged
region
Light
chain
Heavy chain
Figure 8.46
8 Analysing and synthesising data and communicating ideas effectively ➧
a Briefly explain the role of antibodies.
b Briefly explain the role of antigens.
c Explain why the two ‘arms’ of an antibody are shown with identical
antigens (see figure 8.46). Would you ever expect the two antigens to be
different?
d What is the function of the hinged region of an antibody?
e By what means do cells of the immune system communicate with other
cells of the body?
9 Interpreting data and communicating ideas effectively ➧ Thymocytes are
developing T lymphocytes in the thymus. At different stages of development
they have different amounts of surface molecules called CD4 and CD8.
Thymocytes can be separated into four different groups on the basis of their
surface molecules:
Group 1 low CD4 and low CD8
Group 2 low CD4 and high CD8
Group 3 high CD4 and low CD8
Group 4 high CD4 and high CD8
IMMUNITY: DEFENCE AGAINST DISEASE
283
(a)
(b)
Figure 8.47
To separate the groups, different coloured fluorescent markers are attached
to molecules that will bind specifically with either CD4 or CD8 surface
molecules. The cells are then passed through a machine that can sort
and count cells with different fluorescent markers. The number of cells
separated into each group is shown in a form similar to a contour map (see
figure 8.47a), where each height above the baseline is shown in a different
colour.
These data can also be used to produce a three-dimensional image (see
figure 8.47b).
a What general term is used to describe molecules on cell membranes?
b To what kind of molecules would the fluorescent markers be attached?
Explain your choice.
c Note the four coloured spots in figure 8.47a. To which group of thymocytes does each coloured spot correspond?
d Examine figure 8.47b. Which group of thymocytes contained the greatest
number of cells? Which group contained the least cells?
10 Using the web ➧ Go to www.jaconline.com.au/natureofbiology/natbiol2-3e
and click on the ‘Avian influenza’ weblink for this chapter. Select ‘Avian
influenza’ and then ‘Frequently asked questions — Avian influenza’, and
answer the following questions.
a Why is a name such as A H5N1 given as well as the more general name
of avian influenza?
b What prohibitions on imports exist that reduce the chance of avian flu
being introduced into Australia?
c What is the latest information about infections and deaths attributable to
avian flu?
d How do symptoms of avian influenza compare with normal influenza?
e Are vaccines against avian flu being developed?
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