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Transcript
KA 4: Active immunisation and vaccination and
the evasion of specific immune response by
pathogens
(a) Active
immunity,
Vaccinations,
Herd
Immunity
KA 4
(b)
Pathogenic
evasion:
antigenic
variation,
direct attacks
KA 4a: Active Immunity, Vaccinations and Herd
Immunty
By the end of this section you will
be able to …..
•
•
•
•
•
State how active immunity can be achieved
Describe what a vaccine is
State the 4 types of antigens found in vaccines
State the function of an adjuvant
Describe the effect of a vaccine on the immune
system (how do vaccines work):
– a) immediately after vaccination
– b) when the body comes into contact with the same
pathogen in later life
Active Immunity
• Immunisation is the process by which a
person develops immunity to a pathogen.
• Active Immunity is when the protection
is gained as a result of a person
producing antibodies.
• There are 2 types of active immunity:
Immunity
Naturally Acquired
Active Immunity
Artificially Acquired
Active Immunity
Antibodies produced in
response to infection /
re-infection
Antibodies
produced after a
vaccination
Vaccinations
• Vaccination is the method of achieving
immunisation.
• Vaccinations are designed to initiate an
immune response without producing the
full blown infection, by deliberately
introducing the pathogen into the body by:
– Injection
– Ingestion
– Nasal spray
• The vaccine is prepared with antigens from
infectious pathogens.
Antigens in Vaccines
1. Dead pathogens (the pathogen is
destroyed and cannot replicate itself)
–
Hepatitis A, Polio
–
Rubella, Mumps, Measles
–
Hepatitis B and HPV
–
Diphtheria, Tetanus
2. Weakened pathogens (the pathogen
has been altered so it cannot cause
the disease)
3. Parts of pathogens (only the protein
coat of the pathogen is used)
4. Inactivated pathogen toxins (the
toxins produced by the pathogen are
injected)
Adjuvants
• Vaccines containing antigens from
infectious pathogens are usually mixed
with an adjuvant.
• This is a chemical that enhances the
immune response.
• Adjuvants promote the activity of the
antigen in order to:
– Induce B cells to produce antibodies and cause
the primary immune response.
– Produce memory cells so that they remain to
give a faster secondary immune response if we
ever come across the pathogen again.
VIDEO: How vaccines work
(simplified)
NHS definition:
• Adjuvants work to boost our immune
response to a vaccine and make it more
effective and long-lasting.
• Using an adjuvant makes it possible to
reduce the amount of antigen used in a
vaccine, and sometimes the number of
doses that need to be given.
Meningitis
• Meningococcal bacteria can cause
meningitis and septicaemia.
• There are 6 groups; Men A, Men B, Men C, Men W, Men X
and Men Y.
• While meningococcal disease affects all age groups,
babies and young children, and teenagers and young adults
are at a higher risk
• They are also more likely to carry meningitis causing
bacteria in the back of their throats and the bacteria is
transmitted by coughing and sneezing and close contact.
• The bacteria is completely harmless most of the time.
However, in a susceptible person, these bacteria can
cause a wide range of diseases.
• Real Story (scroll to bottom of page)
Meningitis Vaccines in the UK
• Men C: 12-13 months and 3 years
– Since the introduction in 1999, cases have fallen by over
90% in all age groups
• Men B: new vaccine introduced Sep 2015 – 3 doses to
be given at 2, 4 and 12 months old
– babies under 1 are most at risk
– Most common strain
• Men W: from August 2015 1 dose offered by GPs to
17-18 year olds and 1 dose to older university
entrants (aged 19 – 25)
– Aggressive strain (ST-11)
– Historically rare, but cases of meningitis and septicaemia
have been increasing in England from 22 cases in 2009 to
117 in 2014.
– An increase in all age groups, but there has been a
significant increase in university students.
Men ACWY
• Introduced as a routine vaccine in Aug
2015
• From Spring 2016 it will replace the Men C
dose which is currently offered to 13/14
year olds.
• The introduction of the Men ACWY for 13
– 18 year olds will improve protection for
this high risk group and also help stop the
bacteria spreading to the wider population.
What’s in your vaccine?
The vaccine only contains the sugar
coating on the surface of the four
groups of meningococcal bacteria and
works by triggering the body’s immune
system to develop antibodies against the
sugar coating without causing disease.
http://www.medicines
.org.uk/emc/search
But what was the
first vaccination?
The Smallpox Story video
Smallpox Exercise
• Read the passage and answer the
questions that follow
• (in folder)
Answers
1. When was the first vaccination carried out? (1 mark)
1796
2. What made Jenner think that inoculating people with cowpox would make them immune to smallpox? (1 mark)
Folklore suggested that milkmaids who suffered from cowpox never caught smallpox.
3. Why is it preferable to catch cowpox rather than smallpox? (2 marks)
Cow-pox is a mild disease. Smallpox was one of the biggest killers of the period, especially of children.
4. How long did it take from the first vaccination to the publication of Jenner’s work? (1mark)
2 years
5. Where does the word ‘vaccine’ come from? (1 mark)
From the Latin word for cow – vacca.
6. What evidence from the passage suggests that Jenner truly believed in his work? (1 mark)
He tested his theory on his 11-month-old son.
7. Why were Jenner and his discovery mocked? (1 mark)
Critics thought it was repulsive and ungodly to inoculate someone with material from a diseased animal.
8. How old was Jenner when he died? (1 mark)
73
9. What would Jenner have had to do to ensure that James Phipps was immune to smallpox? (2 marks)
Deliberately expose James to smallpox. Observe to see if he became ill
10. What might have happened to Jenner if his theory had been incorrect? (2 marks)
James might have died. Jenner would have been considered a murderer.
Quick Questions
1. Describe what is meant by “active
immunity” When a person develops immunity
against a disease because they have
produced antibodies
2. What name is given to the chemical
added to vaccine to enhance the
immune response? Adjuvant
3. Name 2 types of antigens found in a
vaccine Dead pathogen / weakened pathogen /
part of a pathogen / inactivated toxin
KA 4a: Active Immunity, Vaccinations and Herd
Immunty
By the end of this section you will
be able to …..
State why clinical trials are important
Describe what is meant by a
randomised, double blind, placebocontrolled protocol.
How does a new drug make it your
cabinet?
Clinical Trials Video
• As you watch the video, write down the
6 essential steps to a successful clinical
trial
Answers…
1.
2.
Design should be approved by an ethics committee
The people taking part should be split into groups
– 1 group should receive the experimental treatment
– The 2nd group should receive a placebo, but if there is already
an effective treatment, they should receive that, to allow
comparison
•
3.
4.
5.
6.
A placebo is identical to the experimental treatment, but is inactive (will
NOT cause any side effects)
– Groups should be randomised
Double blind research carried (both groups AND the testers
should not know who is receiving which treatment)
Results should be analysed by unbiased researchers
Procedure must be replicated in other independent trials
Benefits and risks of experimental treatment must be carefully
evaluated before approval can be given (not enough that the
treatment is as effective as the old treatment or placebo).
Clinical Trials
• Vaccines are subjected to clinical trials
in the same way as other pharmaceutical
medicines to establish their safety and
efficacy (capable of producing the
intended result) before being licensed
for use.
• Clinical Trials protocols MUST be:
1. Randomised
2. Double-blind
3. Placebo-controlled
• Randomised
– Subjects are split into groups in
randomised way to eliminate bias
• Double Blind
– Neither the subjects nor the researchers
know who is receiving the active treatment
(vaccine). This also eliminates bias.
• Placebo controlled
– One group of subjects receives the active
treatment (vaccine), while the second group
receives a placebo control (no medical
value) to ensure valid comparisons.
• The Power of the Placebo Effect video
• Big bang theory Placebo effect
Food unwrapped: The power of
Beetroot!
• 18.30 – 23.15
• Placebo / blind trial
• http://www.channel4.com/programmes/
food-unwrapped/on-demand/61830-025
Large Scale Studies
• The 2 groups must be of a suitable size to
reduce the magnitude of experimental error
– For example: one group may have an atypically
large number of older people who are overweight
and more seriously ill. Thus their health conditions
will impact results
• 9 out of 14 compared to 41 out of 250
• At the end of the trial, results from the two
groups are then compared to determine
whether there are any statistically significant
differences between the groups, i.e:
– Group 1: 50 out of 250 showed improved
– Group 2: 224 out of 250 showed improvement
KA 4a: Active Immunity, Vaccinations and Herd
Immunty
By the end of this section you will
be able to …..
• State what is meant by herd immunity
• Describe the benefit of herd immunity to nonimmune individuals
• Describe the importance of herd immunity in
reducing the spread of disease
• State that the herd immunity threshold depends on
a number of factors
 Give examples of barriers to herd immunity in the
developing world
 Give examples of barriers to herd immunity in the
developed world
What is Herd Immunity?
• http://www.immunisationscotland.org.uk/w
hy-immunise/benefits-for-you.aspx (watch
the video on “Benefits for you” and also on
“Benefits for s all”
• https://www.youtube.com/watch?v=CPcC4o
GB_o8 (detailed)
• https://www.youtube.com/watch?v=UqKPETVvrc (simple)
What is Herd immunity?
• Herd immunity occurs when a large
percentage of a population are
immunised.
• Non-immune individuals are therefore
protected as there is a lower
probability they will come into contact
with infected individuals
• This herd immunity is important in:
– Reducing the spread of diseases and
– Protecting vulnerable and non-vaccinated
individuals.
Herd immunity threshold
Disease
Transmission
Average number of
secondary infections
resulting from single
index case
Diptheria
Saliva
6–7
85%
Measles
Airborne
12 – 18
83 – 94 %
Mumps
Airborne
droplet
4–7
75 – 86 %
Whooping
cough
Airborne
droplet
12 – 17
92 – 94 %
Polio
Faecal-oral
route
5–7
80 – 86 %
Rubella
Airborne
droplet
5–7
83 – 85 %
Smallpox
Social
contact
6–7
83 – 85 %
Herd
immunity
threshold
Drop in immunisation rates…
Herd immunity threshold
• This is the percentage of the population
who need to be immunised by the
vaccine to offer protection for people
who are not vaccinated.
• Herd Immunity threshold varies as it
depends on:
– The disease
– The efficacy of the vaccine and
– The contact parameters for the population.
Snakes & Ladders
• Sort the cards into 2 piles – a snake card pile
and a ladder card pile
• Play the game like you NORMALLY would do
EXCEPT…
• If you go up a ladder you must read a ladder
card out loud AND say if the card relates to
the developed world or developing world.
• If you go down a snake, you must read a snake
card out loud AND say if the card relates to
the developed world or developing world.
Think…
• What colour cards do you think are
relevant to the:
– Developing world?
– Developed world?
• Use the cards to make notes on:
– Barriers to herd immunity in the developing
world
– Barriers to herd immunity in the developed
world
Barriers to herd immunity
• In most countries, the policy in public
health medicine is to establish herd
immunity to a number of diseases.
• Difficulties can arise when widespread
vaccination is not possible due to
malnutrition and poverty (the developing
world) or when vaccines are rejected by
a percentage of the population (the
developed world).
House md clip - no vaccine
MMR and autism
• Example of inadequate research
– Sample size
– Bias
• Example of development of vaccine
rejection (barrier to herd immunity)
– Led to a series of outbreaks and epidemics
in the UK
• Example of media influence
The MMR Scare
• Autism is a condition which affects 1 or
2 people in every 1000, affecting neural
development and causing restricted and
repetitive behaviour.
• It affects social behaviour and
language; its causes are unknown.
• It is usually diagnosed from the age of
three onwards.
The MMR Scare
• In Britain, as in many countries, the
majority of children are vaccinated against
measles, mumps and rubella using a
combined vaccine (MMR).
• A British doctor (Andrew Wakefield)
wrote a report on 12 children who had been
vaccinated with the MMR vaccine and were
subsequently diagnosed as autistic.
• The result of this report was that media
interest was raised; many anti-MMR
stories appeared and there was a
significant fall in the number of children
given the MMR vaccine.
Importance of large scale
studies
• The Madsen study in Denmark.
• Because Denmark tracks patients and the care they
receive they have been able to study the
correlation between vaccination and illness; the
data clearly shows that there is no correlation
between MMR vaccination and the incidence of
autism.
Why is this study more reliable than Dr Wakefields?
• The study was based on data from over half a
million children
• Over 440,000 had been vaccinated and there was
no greater incidence of autism amongst children
vaccinated as amongst those not vaccinated.
• What
happened to
the MMR
vaccination
rates of
children?
• What
happened to
the
incidence of
measles?
• Is there a
causal link?
NO Herd immunity to protect those who were not
vaccinated, so incidence of measles increases!
So… is there a correlation?
There
is
of course
a correlation
(similar
Did the
pollen
count
cause
the cream
ice cream
sales toover
rise?
•• One
graphs
shows
ice
sales
• Did
the sale of ice cream cause the pollen count to
pattern)
year
and IS
theNO
other
showsTOpollen
• arise?
BUT
THERE
EVIDENCE
SUGGEST
• count.
Is
thereONE
any link?
THAT
CAUSES THE OTHER
No effect of MMR withdrawal on the incidence
of autism: a total population study. H Honda et
al. Journal of Child Psychology and Psychiatry
2005
COMMENT:
The increase in autism
and autistic spectrum
disorders in this part
of Yokohama displays
the same increase over
time seen in other
parts of the world.
Here, though, the
increase occurred even
when the MMR vaccine
was withdrawn. This
destroys any possible
causative link between
use of the vaccine and
autism
The MMR Scare
• It was subsequently established beyond
reasonable doubt that there is no causal
link between MMR vaccination and autism.
The doctor had a commercial interest in
the alleged link and was subsequently
struck off.
• The scare affected no other countries;
MMR vaccination rates are rising again.
Watch the following video on the effect of adverse
publicity on the MMR vaccination
http://www.youtube.com/watch?v=jfheO9H8CD4
• This is how
the paper
now appears
on the
journal
website…
RETRACTED
Quick Questions
1. During clinical trials, one group of test
subjects receive the vaccine, but the other
group do not. Describe what the 2nd group
receive instead. Placebo (has no medical value)
2. What term is used to describe a trail where
neither the researchers nor the test Double-blind
subjects know who has received the vaccine.
3. Describe how herd immunity is achieved
By immunising a large percentage of the population
4. Give one advantage of establishing herd
immunity
Reduces the transmission rate
KA 4a: Active Immunity, Vaccinations and Herd
Immunty
By the end of this section you will
be able to …..
• describe the process of antigenic variation
• give examples of pathogens that use antigenic
variation
• describe why antigenic variation poses a
problem to public health
• Describe how to set up an experiment to view
the antibody-antigen interaction
 describe how HIV overcomes the immune
response
 describe how TB can avoid the immune response
Evasion of specific immune
responses
• Not all diseases can be eradicated by
vaccines.
• Some pathogens have evolved mechanisms
that evade the immune system. This has
great consequences for vaccination
strategies.
• Pathogens can either:
1. Undergo antigenic variation
•
Malaria, Influenza, Trypanosomiasis (sleeping
sickness)
2. Directly attack the immune system
•
HIV and TB
Re-cap
• What is antigen?
• Describe the specific immune response
• Describe the role of memory cells
Let’s play Chinese Whispers!
Malaria
To prevent the red blood cells, which the malaria
protozoa hide in, from being destroyed they present
a protein on the cell’s surface which causes it to
stick to a blood vessel wall.
It is also able to
switch between many
genes for this
protein preventing
the immune system
producing
appropriate
antibodies in time.
Evolution of the FLU virus
• In this
diagram, the
antigens can
change in two
ways, but
importantly, it
means that the
antibodies
produced by
memory cells
cannot bind to
them and
inactivate the
pathogen.
Trypanosomiasis
• A protozoa called Trypanosoma
brucei causes the fatal disease
called trypanosomiasis or ‘sleepingsickness’.
• It has a glycoprotein coat which can
contain one of many different
antigens. About 1% of them can vary
the antigen and replace the whole
‘coat’ when the immune system
attacks.
• The new coat has different antigens
so the immune system has to start
again, giving it time to reproduce
before destroying another 99%.
Survive and
change
Survive and
change
Meningitis B has also evaded our
immune system
• https://www.theguardian.com/science/o
ccams-corner/2015/sep/01/why-is-thenhs-vaccination-for-meningitis-b-notprovided-to-everyone
Videos 
• Malaria:
http://www.youtube.com/watch?v=qvlTOhC
mxvY
• Trypanosomiasis:
• http://www.youtube.com/watch?v=4aVUrG
O97Zg&list=PLXfKWnjanUc3He0aOwo7Uw
0MuG0jlQjci
• Influenza:
• http://www.youtube.com/watch?v=ugM1nIhfIA
1. Antigenic variation
• Some pathogens can change their antigens,
avoiding the effect of immunological
memory (memory cells).
• Antigenic variation occurs in diseases like
malaria and trypanosomiasis, and is one of
the reasons why they are still so common
in many parts of the world.
• Antigenic variation also occurs in the
influenza virus, explaining why it remains a
major public health problem and why atrisk individuals require to be vaccinated
every year.
Antibody and Antigen interaction
– using agar gel (Experiment)
• Agar gel can be used to observe
antibodies reacting with antigens.
• The agar allows the proteins to diffuse
towards each other
• When they meet they bind together.
This is indicated by a white line in the
agar.
Antibody and Antigen interaction
– using agar gel (Experiment)
Antigen X placed in
centre well
Blood plasma
of Pupil A
Blood plasma
of Pupil B
AIM: To observe the presence
of antibodies against antigen X
in various pupils
RESULTS
Blood
plasma
of
Pupil F
Blood
plasma of
Pupil E
Blood
plasma of
Pupil D
Blood
plasma of
Pupil C
What conclusion can be drawn
from these results?
Antigen X placed in
centre well
Blood plasma
of Pupil A
Blood plasma
of Pupil B
Blood
plasma
of
Pupil F
Blood
plasma of
Pupil E
Blood
plasma of
Pupil D
Blood
plasma of
Pupil C
More Questions!
1. Pupil C wanted to
investigate what other
antibodies she had.
Explain how she could do
this.
Antigen X placed in
centre well
Blood plasma
of Pupil A
Blood plasma
of Pupil B
Blood
plasma
of
Pupil F
Blood
plasma of
Pupil E
Blood
plasma of
Pupil D
Blood
plasma of
Pupil C
More Questions!
2. Antigen X is actually
from an Influenza virus.
All the pupils have
suffered from influenza.
Explain why a line did not
form between ALL the
pupils and antigen X.
3. Explain why a line DID
form between 3 of the
pupils and antigen X.
Antigen H placed in
centre well
Blood plasma
of Pupil A
Blood plasma
of Pupil B
Blood
plasma
of
Pupil F
Blood
plasma of
Pupil E
Blood
plasma of
Pupil D
Blood
plasma of
Pupil C
More Questions!
4. Antigen X was replaced
with an antigen from a
different virus (antigen
H). Only Pupils A and E
have been vaccinated
against this virus.
Predict the results that
would be observed from
this experiment.
2. Direct attack on the Immune
System
• The absence or failure of some
component of the immune system
results in increased susceptibility to
infection.
Direct attacks on the immune system
HIV infection
• https://www.youtube.com/watch?v=ng2
2Ucr33aw
Symptoms of HIV infection
• Oral candida is a common symptom
• Body cannot defend against the fungus that
causes oral thrush
• Lesions form on the chest and develop all
over the skin
Human Immunodeficiency Virus
• AIDS is a deficiency disease caused by the HIV virus.
• The glycoproteins on the HIV attach to the receptors
on the T-helper lymphocytes.
• The virus infects the T-helper cell, replicates, leaves
by budding and infects more T-helper cells.
• The membrane of the T-helper cell becomes punctured,
leaving the cell destroyed.
• As the number of T-cells decrease, the person becomes
more susceptible to infections (pneumonia, rare forms
of cancer)
Remember, helper T cells are of
critical importance to the immune
system – they activate B cells and
cytotoxic T cells
Direct attacks on the immune system
TB
• http://www.youtube.com/watch?v=IGZLkRN76Dc
• http://www.youtube.com/watch?v=gruBIZ0Bm-I
• http://www.youtube.com/watch?v=f5uq-ta4km0 –
call me maybe version!
Symptoms of Tuberculosis
TB disease symptoms may include:
• A bad cough that lasts 3 weeks or longer.
• Pain in the chest.
• Coughing up blood or sputum (phlegm from deep
inside the lungs)
• Weakness or fatigue.
• Weight loss.
• No appetite.
• Chills.
• Fever.
Tuberculosis Bacteria
• TB is an example of where a pathogen
hijacks the immune system for themselves.
• They allow themselves to be engulfed by
phagocytes but prevent the lysosomes
fusing with the vacuole they are in. They
also have a waxy coat to prevent them
being digested even if they did come into
contact with it.
• The pathogen remains alive inside the
phagocyte and avoids immune detection
and destruction.
How to eradicate a disease?
• https://www.youtube.com/watch?v=oBS
andHijDc
Don’t forget you can do the Key Area 1,2,3 Questions again! Yey 
Key Area 4: Past Papers
Yellow Booklet
Paper (new
higher human biology)
Section
Question
2015
1
2
17,20
12,13
specimen
1
2
1
2
19,20
11,12,13
19,20
12
exemplar
Don’t forget you can do the Key Area 1,2,3 Questions again! Yey 
Key Area 4: Past Papers
Red Booklet
Paper (revised higher human
biology)
2014
2013
2012
Section
Question
1
2
1
16,28,29,30
12
28,29
2
14
2
13a-f