Chapter 3
Immunity and how vaccines work
A Practical Guide to Immunisation
3.1 Objectives:
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To understand and describe the immune system and how vaccines produce immunity
To understand the differences between Passive and Active immunity
To understand what Antigens and Antibodies are and how they contribute to immunity
To understand how vaccines work
To understand the importance of different components of vaccines including suspension
fluids, preservatives, stabilisers and antimicrobial agents and thiomersal
To understand the differences between inactivated vaccines, toxoids and live vaccines
To understand what is meant by the term “vaccine failure”
To understand why it is necessary to leave time intervals between vaccinations.
3.2 The immune system
Immunity can be defined as the ability of the human body to protect itself from infectious disease.
The body has its own specific mechanism for protection e.g. physical barriers (skin and mucous
membranes), chemical barriers (gastric and digestive enzymes) and immunological barriers
(phagocytes, macrophages and complement system) that help to protect us. The characteristic
feature of these mechanisms of protection is that no “memory” of protection exists afterwards.
3.3 Active and Passive Immunity
Immunity to illness can be acquired through passive or active mechanisms.
Passive immunity is the mechanism whereby protection is provided by the transfer of antibodies
from people who have immunity to those that do not. The most common form of passive immunity
is the transfer of antibodies from mother to baby across the placenta. Other less common forms
of passive immunity include transfer of antibodies through transfusion of blood or blood products
including immunoglobulin. This protection is temporary.
Active immunity can be acquired through contact with a disease and the development of
antibodies to that disease or through vaccination. Vaccines are designed to provide immunity
similar to natural disease but without the side effects or complications of the disease. Vaccination
helps to stimulate and strengthen the immune system and generate long lasting immunity.
Active immunisation involves the administration of all, or part of, a micro-organism or a modified
product of that micro-organism (e.g. toxoid, purified antigen, or an antigen produced by genetic
engineering) to provoke an immune response in the recipient. Some vaccines provide life long
protection against disease, some provide partial protection and some must be re-administered at
regular intervals to provide protection.
3.4 What do antibodies contribute to the immune system?
Antibodies neutralise toxins, block adhesion/cell entry of the antigen and kill the antigen by
producing complement. Different types of antibody are produced at different time periods and
by different body systems. Antibodies are antigen specific and cannot cross protect e.g. measles
antibody cannot protect against meningococcal disease etc.
There are five different types of antibodies namely IgM, IgG, IgA, IgD and IgE antibodies, of which
IgM and IgG are the most important (Figure 3.1).
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Chapter 3: Immunity and how vaccines work
A Practical Guide to Immunisation
Figure 3.1: Immune Response following exposure to antigen.
The primary immune response develops in the weeks following exposure to an antigen and is
mainly IgM antibody. It is made by cells in lymph nodes, spleen and bone marrow and circulates in
the blood and lymphatic system. IgM antibodies activate the complement system. IgM antibodies
have a short half-life (5 days).
The secondary immune response is faster and more powerful and is predominantly IgG antibody.
It is made in lymph nodes, spleen and bone marrow. The IgG antibody is smaller than IgM and its
half life is about 3 weeks. It also passes through the placenta from mother to baby giving the baby
antibodies to which the mother is immune.
Active immunity can be divided into antibody and cell mediated responses.
3.4.1 Antibody mediated immunity
Antibody mediated responses are produced by B lymphocytes (B cells) and plasma cells. When a
B cell encounters an antigen that it recognises, the B cell is stimulated to proliferate and produce
large numbers of lymphocytes, secreting antibody to the antigen. Replication and differentiation
of B cells into plasma cells is regulated by contact with the antigen and by interactions with T cells,
macrophages and complement. The antibodies produce immunity through neutralising toxins,
blocking adhesion and cell entry by organisms, neutralising and preventing viral replication or
complement-mediated killing.
3.4.2 Cell mediated immunity
Cell mediated immunity is controlled by a subset of lymphocytes called T lymphocytes or T cells.
T cells stimulate B cells to produce antibodies and play an inhibitory role and control the level and
quality of the immune response. Cytotoxic T cells recognise and destroy infected cells and activate
phagocytes to destroy pathogens that they have taken up.
3.5 How do vaccines work?
Vaccines work by inducing active immunity and by providing immunological memory.
Immunological memory allows the immune system to recognise and respond rapidly to natural
infection when exposed at a later stage and to prevent or modify the effect of that disease.
Antibodies can be detected in blood or serum but, even if undetectable, memory usually still exists.
Vaccines are made from inactivated (killed) or attenuated live organisms, secreted products,
recombinant components or components of cell walls. Vaccines must contain sufficient antigenic
mass to stimulate a desired response. The components of vaccines are listed in Table 3.1.
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A Practical Guide to Immunisation
Table 3.1: Types of Vaccines
Vaccine Name
Type
BCG
Live attenuated
Diphtheria
Toxoid
Tetanus
Toxoid
Pertussis
Inactivated bacteria
Polio
Inactivated virus
MMR
Live attenuated
Meningococcal
Conjugate
Hib
Conjugate
Hepatitis B
Conjugate
Pneumococcal
Conjugate
3.6 Vaccine components
Other components of vaccines include:
3.6.1 Conjugating agents
There are carrier proteins which when combined with antigens enhance the type and magnitude
of the immune response. Examples include Haemophilus influenzae B (Hib) and Meningococcal C
vaccine.
3.6.2 Suspension fluid
The suspension fluid could simply be water for injection or saline solution. It may also be a tissueculture mixture containing proteins or other components from which the vaccine is produced (e.g.
egg antigen, gelatine or cell culture derived antigens).
3.6.3Preservatives, stabilisers and antimicrobial agents.
Trace amounts of preservatives and antimicrobial agents (e.g.neomycin or streptomycin sulphate)
may be included in some vaccines and immunoglobulin products to maintain stability. An allergic
reaction can occur if the recipient is sensitive to one or more of these additives.
3.6.4 Thiomersal
Thiomersal (also known as thimerosal) is a mercury-containing compound added to some
vaccines to prevent bacterial and fungal growth. Thiomersal has been used since the 1930s in
the manufacture of some vaccines and other medical products. Thiomersal is also used as an
inactivating agent in the very early stages of production of some killed vaccines. Only minuscule
amounts of thiomersal used for this purpose remain after the manufacture is completed.
Recently there was concern that thiomersal could be associated with neurological problems. There
is now strong evidence to show that thiomersal in vaccines does not cause adverse neurological
effects. As part of a global goal to reduce exposure to mercury from avoidable sources in general,
European and American regulators recommended in 1999 that vaccine manufacturers phase out use
of thiomersal wherever possible as a precautionary measure.
Manufacturers are actively developing research programmes to eliminate, substitute or reduce
thiomersal in vaccines, following the European recommendations. Further information is available
on the National Immunisation Office website www.immunisation.ie.
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Chapter 3: Immunity and how vaccines work
A Practical Guide to Immunisation
3.6.5 Adjuvants
An aluminium salt is used in varying concentrations to increase immunogenicity for vaccines
containing inactivated micro-organisms or their products. Examples include Hepatitis B vaccine,
and diphtheria and tetanus toxoids.
3.7 Live attenuated vaccines
Live attenuated vaccines usually are created from the virus or bacterium itself. Viruses and
bacteria are weakened (or attenuated) by growing them over and over again in a laboratory under
nourishing conditions called cell culture. The process of growing a virus repeatedly serves to lessen
the disease-causing ability of the virus. Vaccines are made from viruses whose disease-causing
ability has been weakened from multiple passages.
Live attenuated viral vaccines produce a long lasting immune response after one or two doses. The
live organism grows in the body and stimulates the immune system to react as it does to natural
infection.
As the vaccine is an attenuated live vaccine it does not cause the
disease itself but can cause a mild form of the disease (e.g. fever
and rash 6-10 days after MMR).
3.8 Inactivated vaccines and toxoids
Inactivated vaccines and toxoids injected into a person who does not have prior exposure to the
antigen produce a primary antibody response. IgM antibody is produced initially followed by IgG
antibody. Two or more injections are usually required initially with the need for booster doses at
longer time intervals. Even if antibody levels are undetectable immunological memory will persist
and will be called upon in response to antigen exposure. Inactivated vaccines cannot cause the
disease that they have been designed to protect against.
Polysaccharide vaccines are not as effective in stimulating the immune system as toxoids. This
means that the polysaccharide vaccines do not provide life long immunity and the response in
children can be poor. The vaccines can be made more effective by conjugation as described above.
Some inactivated vaccines contain adjuvants such as aluminium phosphate or aluminium hydroxide
to enhance the immune response.
3.9 What is vaccine failure?
When a person who has been fully vaccinated develops the disease against which they have been
vaccinated, it is referred to as vaccine failure. In the vast majority of cases, however, it is not the
vaccine that has failed, but an inadequate immune response to the vaccine has occurred.
Vaccine failure can be primary or secondary
Primary vaccine failure occurs when the recipient does not produce enough antibodies when first
vaccinated. Infection can therefore occur at any time post vaccination. This can occur in about 10%
of those who receive the MMR vaccine.
Secondary vaccine failure occurs when an adequate number of antibodies are produced
immediately after the vaccination, but the levels fall over time. The incidence of secondary vaccine
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A Practical Guide to Immunisation
failure therefore increases with time after initial vaccination and booster doses are required. This is
a feature of many of the inactivated vaccines.
3.10 Why it is necessary to leave time intervals between vaccinations?
Gaps between deliveries of vaccines are needed to allow the immune response to develop. If
another live vaccine is given whilst the immune system is making a primary immune response, the
activation of the immune system may neutralise the second live vaccine so that it does not work. A
gap of four weeks is therefore required between the administration of any two live vaccines.
If immunoglobulin has been given, it is necessary to leave a gap of three months before a live
vaccine can be administered. The antibodies in the immunoglobulin could neutralise any live
vaccines.
3.11 Useful resources
American Academy of Paediatrics. 2006 Report of the Committee on Infectious Diseases – The Red
Book http://aapredbook.aappublications.org/
Department of Health UK. November 2006. Immunisation against infectious disease. http://www.
dh.gov.uk/en/Policyandguidance/Healthandsocialcaretopics/Greenbook/DH_4097254
Health Protection Surveillance Centre, Ireland. www.hpsc.ie
Irish Pharmaceutical Healthcare Association Medical Compendium. http://www.medicines.ie.
Irish Medicines Board. http://www.imb.ie
National Immunisation Office. Health Service Executive, Ireland. http://www.immunisation.ie.
Royal College of Physicians of Ireland. Immunisation Guidelines for Ireland. Available at www.hpsc.ie
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Chapter 3: Immunity and how vaccines work