IMMUNOLOGY AND PUBLIC HEALTH
Teacher’s notes
Introduction
Mammals have well-developed immune systems. As a consequence of living
in densely populated groups humans are particularly liable to transmitted
diseases. To manage these hazards humans have developed public health
measures and immunisation programmes.
A key function of the immune system is to recogni se pathogens, some toxins
and cancer cells as foreign and to create a response to them. The immune
system may also produce allergic responses to harmless foreign materials.
Defence responses include general non-cellular and cellular responses,
including phagocytosis and natural killer cells. Key aspects of the specific
cellular immune response include immune surveillance and clonal selection
theory. Emphasis should be placed on the role of cytokines, antigenpresenting cells and memory cells in the function of T - and B-lymphocytes.
Emphasis is placed on the control of infectious disease by public health
measures. Control of transmission of infectious diseases depends on an
understanding of disease biology and the epidemiology of disease. The
principles of active immunisation and vaccination should be considered ,
using appropriate examples. A study of clinical trials for vaccines should be
used to consider the design of such trials to ensure the elimination of bias,
valid comparisons and minimisation of experimental error by using
randomised, double-blind, placebo-controlled protocols. A study of herd
immunity and public health policy allows aspects of population biology to be
considered. Students should have the opportunity to consider evidence-based
decision making on public health policy issues related to the challenges to
disease control presented by antigenic variation (eg annual influenza
vaccination programme) and pathogens that attack the immune system (eg
HIV and tuberculosis).
Students should already have a clear understanding of the following areas of
content:
 defences against disease (phagocytosis, antibodies, vaccination)
 diseases (viruses, bacteria, fungi, parasite s)
 hygiene (personal, sexual, food, water).
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
1
IMMUNOLOGY AND PUBLIC HEALTH
Infectious diseases and immunity
Because of its role in maintaining health and combating infectious diseases
on a global level, the immune system is at the centre of much of the research
in public health.
(a) The transmission of infectious diseases
Infectious diseases are caused by pathogens such as viruses, bacteria, fungi,
protozoa and multicellular parasites. Infectious diseases are transmitted by
direct physical contact, water, food, body fluids, inhaled air or vector
organisms. The transmission of infectious disease can be controlled by
quarantine, antisepsis, individual responsibility (good hygiene, care in sexual
health and appropriate storage/handling of food), community responsibility
(quality water supply, safe food webs and appropriate waste disposal
systems) and the control of vectors.
See the WHO website for further information on infectious diseases:
http://www.who.int/topics/infectious_diseases/en/
Transmission
Transmission is the passing of a communicable disease from an infected host
individual or group to an individual or group, regardless of whether or not the
other individual was previously infected.
The term usually refers to the transmission of microorganisms directly from
one person to another by one or more of the following means:
 droplet contact – coughing or sneezing on another person
 direct physical contact – touching an infected person, including sexual
contact
 indirect physical contact – usually by touching soil contamination or a
contaminated surface
 airborne transmission – if the microorganism can remain in the air for long
periods
 fecal–oral transmission – usually from contaminated food or water
sources.
Transmission can also be indirect, via another organism – either a vector (eg
a mosquito) or an intermediate host (eg tapeworm in pigs can be transmitted
to humans who ingest improperly cooked pork).
2
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
IMMUNOLOGY AND PUBLIC HEALTH
Control
Quarantine is compulsory isolation, typically to cont ain the spread of
something considered dangerous, often but not always disease.
Antisepsis is prevention of infection by inhibiting or arresting the grow th and
multiplication of infectious agents. This can be done through sterilising
equipment, washing hands, wearing gloves, wearing surgical masks etc...
Individual responsibility – good hygiene, care in sexual health and
appropriate storage/handling of food.
Community responsibility – quality water supply, safe food webs and
appropriate waste disposal systems.
Control of vectors – any method to limit or eradicate the mammals, birds,
insects or other arthropods that transmit disease pathogens. The most frequent
application is mosquito control, which is done using a variety of strategies:
 habitat control, where stagnant water is avoided, for example by removal
of old tyres, empty cans etc, or better management of used water (an
approach that is recommended whenever possible for its cost effectiveness)
 use of insecticides, which are spread over mosquito breeding zones,
sprayed in houses, or impregnated in bednets
 introduction of sterilised male mosquitoes in order to reduce the breeding
rate
 use of larvicides, as has been done worldwide in mosquito abatement
programmes since 1965, with temephos the standard chemical used.
Suggested activities – see Lesson plans 12 and 13.
(b) Epidemiology of infectious diseases
Epidemiologists study the outbreak and pattern of infectious diseases to
determine the factors that affect the spread of infectious disease. The s pread
of infectious diseases is classified as: sporadic (occasional occurrence),
endemic (regular cases occurring in an area), epidemic (unusually high
number of cases in an area) or pandemic (a global epidemic). Based on
epidemiological studies, control measures can be considered, including
preventing transmission, drug therapy, immunisation or a combination of
these.
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
3
IMMUNOLOGY AND PUBLIC HEALTH
Epidemiology is the study of the distribution and determinants of health related states or events (including disease), and the application of this study
to the control of diseases and other health problems. Various methods can be
used to carry out epidemiological investigations: surveillance and descriptive
studies can be used to study distribution, while analytical studies are used to
study determinants.
The classification of infectious diseases is as follows:
 sporadic – occurring occasionally, singly or in scattered instances
 endemic – restricted or peculiar to a locality or region
 epidemic – affecting or tending to affect an atypically la rge number of
individuals within a population, community or region at the same time
 pandemic – prevalent throughout an entire country, continent or the whole
world; epidemic over a large area.
Suggested activities – see Lesson plan 14.
Active immunisation and vaccination
Active immunity can be developed by vaccination with antigens from
infectious pathogens. Antigens from infectious pathogens, usually mixed with
an adjuvant to enhance the immune response, include inactivated pathogen
toxins, dead pathogens, parts of pathogens and weakened pathogens. These
agents induce an initial primary immune response and immunological
memory in the individual, but not disease symptoms.
Vaccines include inactivated bacterial toxins, killed microbes, parts of
microbes and viable but weakened microbes. These agents can no longer
cause disease but they retain the ability to act as antigens, stimulating an
immune response and, more importantly, immunological memory. The most
common method of administering vaccines is by in jection, but some are given
by mouth or nasal spray. A vaccinated person who encounters the actual
pathogen will have the same quick secondary response based on memory cells
as a person who has had the disease. Routine immuni sation of children and
infants has dramatically reduced the incidence of infectious diseases such as
measles and whooping cough and has led to the eradication of smallpox.
Suggested activities – see Lesson plans 15, 16 and 17.
4
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
IMMUNOLOGY AND PUBLIC HEALTH
Vaccine clinical trials
Vaccines are subjected to clinical trials in the same way as other
pharmaceutical medicines in order to establish their safety and efficacy
before being licensed for use. Clinical trials use randomised, double -blind,
placebo-controlled protocols. Subjects are split into groups in a rando mised
way, in which neither the subjects nor the researchers know which group they
are in to eliminate bias. One group of subjects receives the vaccine, while the
second group receives a placebo control to ensure valid comparisons. At the
end of the trial, results from the two groups, which must be of a suitable size
to reduce the magnitude of experimental error , are compared to determine
whether there are any statistically significant differences between the groups.
Before treatments can be tested on humans, they will usually have undergone
extensive investigation in the laboratory and testing on cells grown in the
laboratory or on animals. These are usually called pre -clinical trials, and they
look at things such as how the treatment works and what sort o f side effects
might occur. If the results from these studies are positive, the next step is to
seek approval to begin trials in humans.
Approval has to be sought from the regulatory authority of the member state
in which the trial is to be conducted. In the UK, this is the Medicines and
Healthcare products Regulatory Agency (MHRA).
The researchers conducting the trial must draw up a plan or protocol for it,
which will include information such as:




who and how many will take part in the trial
what question the trial aims to answer
what treatments will be compared and how this will be done
how the results will be collected.
The protocol then undergoes an independent scientific review and must also
be approved by an ethics committee before the trial can go ahead. These
checks are to ensure that the trial design is sound and that the research will
respect the rights, dignity, safety and well -being of the participants.
Since May 2004, all trials have been required by UK law to meet the
standards set by the European Union Clinical Trials Directive. This is
designed to ensure that all trials will be carried out to the same standard
wherever they take place in Europe.
Advice and guidance on good practice in clinical trials is available from
bodies such as the Medical Research Council.
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
5
IMMUNOLOGY AND PUBLIC HEALTH
Clinical trial stages
Once the relevant scientific, regulatory and ethical bodies have approved the
protocol, testing in humans can go ahead.
The first step, known as phase I, is to check that the treatment is safe. The
treatment is tested in small doses on a very small number of people, usually
healthy volunteers, to check for any side effects.
Phase II trials test the treatment in a larger number of people, typically a few
hundred, who have the illness that the therapy aims to treat. The purpose of
these tests is to ensure both that the treatment is safe and that it works.
Treatments only move into a phase III trial if phases I and II have been
successful. Phase III trials involve many more patients with the illness, often
several thousands. The treatment under investigation is pitted against the
treatment currently in use or a dummy drug, known as a placebo, to see how
well it compares.
Often the study is designed so that neither the participants nor the
investigators know which treatment each person is getting. This is called a
‘double-blind’ trial and it produces more reliable results. To further reduce
the risk of bias – when incorrect conclusions are drawn due to prejudices –
the participants can be allocated at random to the two treatments being
compared. If both these rules are applied, the study is called a randomised
double-blind trial. The researchers will also check for any side effects.
Once a drug has been through all of these stages of testing, which can tak e
10–12 years, it can be considered for licensing by the relevant body. When a
licence application is submitted, the researchers must provide all results from
the trial, both positive and negative. If a medicine is granted a licence by the
MHRA it can then be sold in the UK.
Sometimes phase IV trials are carried out after a treatment has been granted a
licence. These trials aim to find out more about the long-term risks, benefits
and use of the treatment, or to test the product in different populations, su ch
as children. These are called post-marketing studies and they are also
important because some side effects are quite rare and may only show up
once a drug has been used by thousands or hundreds of thousands of people.
Suggested activities – see Lesson plan 18.
6
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
IMMUNOLOGY AND PUBLIC HEALTH
Herd immunity
If a large percentage of a population are immunised, non -immune individuals
are protected as there is a lower probability that they will come into contact
with infected individuals. This herd immunity is important in reducing the
spread of diseases and in protecting vulnerable and non -vaccinated
individuals. The herd immunity threshold depends on the disease, the efficacy
of the vaccine and the contact parameters for the population.
In immunology, herd immunity refers to a situation in which a high
percentage of a population is immune to a disease, essentially stopping the
disease in its tracks because it cannot find new hosts. You may also hear this
concept referred to as ‘community immunity’. The threshold for herd
immunity varies, depending on the disease, with more virulent agents
requiring vaccination of a higher percentage of the population to cr eate the
desired herd immunity. In addition to being used in disease prevention,
community immunity is also used to fight ongoing outbreaks.
Most vaccination policies are focused on creating herd immunity. Many
countries require vaccinations in childhood, for example , to protect children
from common diseases. This ensures that when these diseases enter the
population, they cannot prey on children or adults since they have been
previously vaccinated or exposed to the disease. The creation of herd
immunity is especially important in crowded environments that facilitate the
spread of disease, such as schools.
Immunologists try to prevent the outbreak of diseases by creating herd
immunity, but they are not always successful. Sometimes a disease mutates or
is entirely new, or a batch of vaccinations is faulty, or a large percentage of
the population fails to get vaccinated, creating a situa tion in which an
outbreak can occur because much of the population is vulnerable. In the event
of an outbreak of a major disease, agencies like the World Health
Organization can dispatch teams within days to determine the cause of the
outbreak and develop a vaccine, in the hopes of creating herd immunity to
halt the outbreak in its tracks.
For some diseases, herd immunity thresholds are as low as 50%, especially
when combined with good hygiene. In other instances, up to 90% of the
population may need to be vaccinated to create the desired herd immunity. It
is also extremely important to receive regular boosters, as some vaccines lose
their efficacy over time, leaving people vulnerable to an outbreak. Herd
immunity led to the eradication of smallpox, and it explains why diseases
such as polio and diphtheria are rare in developed nations with established
vaccination policies.
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
7
IMMUNOLOGY AND PUBLIC HEALTH
The concept of herd immunity is often used to encourage reluctant parents to
vaccinate their children. In addition to ensuring that t heir children are
protected from fully preventable diseases, childhood vaccinations also benefit
society at large by creating herd immunity. Likewise, adults may be reminded
to receive boosters to help protect their communities.
Suggested activities – see Lesson plans 19 and 20.
Public health medicine
In most countries, the policy of 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 pove rty (the developing
world) or when vaccines are rejected by a percentage of the population (the
developed world).
The focus of a public health intervention is to prevent rather than treat a
disease, through surveillance of cases and the promotion of healt hy
behaviours. In addition to these activities, in many cases treating a disease
can be vital to preventing its spread to others, for example during an outbreak
of infectious disease or contamination of food or water supplies. Vaccination
programmes and the distribution of condoms are examples of public health
measures.
Most countries have their own government public health agencies, sometimes
known as ministries of health, to respond to domestic health issues. In the
USA, the front line of public health initiatives are state and local health
departments. The US Public Health Service (PHS), led by the Surgeon
General of the USA, and the Centres for Disease Control and Prevention,
headquartered in Atlanta, are involved with several international health
activities, in addition to their national duties.
There is a vast discrepancy in access to health care and public health
initiatives between developed nations and developing nations. In the
developing world, public health infrastructures are still forming. The re may
not be enough trained health workers or monetary resources to provide even a
basic level of medical care and disease prevention. As a result, a large
majority of disease and mortality in the developing world results from and
contributes to extreme poverty. For example, many African governments
spend less than USD$10 per person per year on health care, while in the U SA
the federal government spends approximately USD$4,500 per capita in 2000.
Many diseases are preventable through simple, non -medical methods. For
example, research has shown that the simple act of hand -washing can prevent
many contagious diseases.
8
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
IMMUNOLOGY AND PUBLIC HEALTH
Public health plays an important role in disease prevention efforts in both the
developing world and developed countries, through local healt h systems and
through international non-governmental organisations.
Suggested activities – see Lesson plan 21.
(e)
Evasion of specific immune responses by pathogens
Many pathogens have evolved mechanisms that evade the specific immune
system. This has consequences for vaccination strategies.
Antigenic variation
Some pathogens can change their antigens , avoiding the effect of
immunological memory. Antigenic variation occurs in diseases like malaria
and trypanosomiasis, and is one of the reasons why these conditions 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 at-risk individuals must be vaccinated every year.
The term ‘antigenic variation’ refers to the mechanism by which an infectious
organism alters its surface proteins in order to evade a host immune response.
This change in antigenic profile may occur as the pathogen passes through a
host population (also called ‘antigenic diversity’) or may take place in the
originally infected host. The strategy is particularly important for organisms
that:
 target long-lived hosts
 repeatedly infect a single host, and
 are easily transmitted.
Pathogens that express these characteristics and und ergo antigenic variation
have a selective advantage over their more genetically stable counterparts.
Antigenic variation can occur through three broadly defined genetic
processes: gene mutation, recombination and switching. In all cases,
antigenic variation results in pathogens that are immunologically distinct
from the parental strains.
Viruses
The process of antigenic variation occurring in viruses is categori sed as either
antigenic drift or antigenic shift. Antigenic drift, which is exhibited by a wi de
range of viruses, is a result of genetic point mutations accumulated by the
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
9
IMMUNOLOGY AND PUBLIC HEALTH
viral genome over an extended period of time. This drift produces small
antigenic changes in the pathogen population , which ultimately reduce the
efficacy of B and T cell memory during the host immune response.
Antigenic drift has been well characterised in the influenza virus, and is
becoming more and more evident in the rapid evolution of rhinoviruses and
enteroviruses. The human immunodeficiency virus (HIV) exhibits antigenic
drift within the particular host due to its high rate of replication.
Antigenic shift refers to a more immediate and extensive change in genetic
information. This can occur when two strains of the pathogen recombine, a
process exemplified by influenza A. In this instance of genetic
recombination, whole segments of the virus genomes are swapped when
human and avian strains dually infect a single host. The immunological
challenges posed by the newly produced influenza strain are the cause of
widespread influenza epidemics.
Bacteria
Bacteria in general are phenotypically hypermutable, a characteristic that
allows the pathogen to evade the host immune system and develop resistance
to therapeutic drugs. Examples of bacteria that undergo high genetic mutati on
rates and therefore phenotypic variation include Escherichia coli and
salmonella.
Processes of antigenic variation that lead to a more sophisticated mechanism
of immune evasion can be seen in Borrelia recurrentis and Neisseria
gonorrhoeae. In these bacteria, gene switching and phase variation allow for
a high level of epitope variation.
Protozoa
Protozoa represent the most biologically complex pathogens presented to the
human immune system. In Plasmodium falciparum, an etiological agent for
malaria, gene switching results in the variable expression of surface proteins
produced on infected red blood cells during the erythrocytic asexual phase.
Trypanosomes exhibit unique processes of gene conversion, whereby any one
of hundreds of genes coding for variable surface glycoproteins can be
expressed. These protozoan processes of antigenic variation lead to a gradual
exhaustion of the host immunity in the terminal stages of disease.
Suggested Activities – see Lesson plan 22.
10
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
IMMUNOLOGY AND PUBLIC HEALTH
Direct attack on the immune system
The absence or failure of some components of the immune system results in
increased susceptibility to infection. HIV attacks lymphocytes and is the
major cause of acquired immunodeficiency in adults. Tuberculosis (TB)
survives within phagocytes and avoids immune detection.
HIV
Human immunodeficiency virus (HIV) is a lentivirus (a member of the
retrovirus family) that causes acquired immunodeficiency syndrome (AIDS),
a condition in humans in which the immune system begins to fail, leading to
life-threatening opportunistic infections. The four major routes of
transmission are unsafe sex, contaminated needles, breast milk and
transmission from an infected mother to her baby at birth. Screening of blood
products for HIV has largely eliminated transmissio n through blood
transfusions or infected blood products in the developed world.
HIV primarily infects vital cells in the human immune system such as helper
T cells (specifically CD4 + T cells), macrophages and dendritic cells. HIV
infection leads to low levels of CD4 + T cells through three main mechanisms:
 direct viral killing of infected cells
 increased rates of apoptosis in infected cells
 killing of infected CD4 + T cells by CD8 cytotoxic lymphocytes that
recognise infected cells.
When CD4 + T cell numbers decline below a critical level, cell-mediated
immunity is lost and the body becomes progressively more susceptible to
opportunistic infections.
Most untreated people infected with HIV eventually develop AIDS. These
individuals mostly die from opportunistic infections or malignancies
associated with the progressive failure of the immune system. HIV progresses
to AIDS at a variable rate affected by viral, host and environmental factors;
most of those infected will progress to AIDS within 10 years of HIV
infection: some will progress much sooner and some will take much longer .
Treatment with anti-retrovirals increases the life expectancy of people
infected with HIV. Even after HIV has progressed to diagnosable AIDS, the
average survival time with antiretroviral therapy was estimated to be more
than 5 years as of 2005. Without antiretroviral therapy, someone who has
AIDS typically dies within a year.
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
11
IMMUNOLOGY AND PUBLIC HEALTH
TB
Tuberculosis (TB) is a bacterial infection. It is spread by inhaling tiny
droplets of saliva from the coughs or sneezes of an infected person.
Mycobacterium tuberculosis is the bacteria responsible for TB, it is an
intracellular pathogen – it grows and persists within phagocytic cells .
Mycobacterium tuberculosis are very slow moving, so a person may not
experience any symptoms for many months, or even years, after becoming
infected.
TB primarily affects the lungs (pulmonary TB). However, the infection is
capable of spreading to many different parts of the body, such as the bones or
nervous system. Typical symptoms of TB include a persistent cough, weight
loss and night sweats.
Types of TB
There are three possibilities that can occur after becoming infected by TB.
These are listed below.
 Your immune system kills the bacteria, and you experience no further
symptoms. This is what happens in the majority of cases.
 Your immune system cannot kill the bacteria, but manages to build a
defensive barrier around the infection. This means that you will not
experience any symptoms, but the bacteria will remain in your body. This
is known as latent TB.
 Your immune system fails to kill or contain the infection and it slowly
spreads to your lungs. This is known as active TB.
There is also the possibility that a latent TB infection could develop into an
active TB infection at a later date, particularly if your immune system
becomes weakened.
Countries with high numbers of HIV cases also often have high numbers of
TB cases. This is because HIV weakens a person’s immune system, which
means that they are more likely to develop a TB infection.
Vaccination
It is thought that between 70 and 80% of people who are given the Bacillus
Calmette–Guérin (BCG) vaccine are protected against TB.
However, BCG vaccinations are not routinely given as part of the childhood
immunisation schedule, unless a baby is thought to have an increased risk of
coming into contact with TB compared to the general population.
12
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
IMMUNOLOGY AND PUBLIC HEALTH
For example, babies born in areas of inner -city London, where TB rates are
higher than in the rest of the country, will probabl y be given the BCG
vaccination.
Vaccinations may also be recommended for people who have an increased
risk of developing a TB infection, for example health workers, people who
have recently arrived from countries with high levels of TB and people who
have come into close contact with somebody infected with TB.
Suggested activities – see Lesson plan 23.
IMMUNOLOGY AND PUBLIC HEALTH (H, HUMAN BIOLOGY)
© Learning and Teaching Scotland 2011
13