2. INTRODUCTION
Antigens are large molecules of proteins
Present on the surface of the pathogen- such as bacteria, fungi viruses, and
other foreign particles.
When these harmful agents enter the body, it induces an immune response
in the body for the production of antibodies.
For example: When a common cold virus enters the body, it causes the
body to produce antibodies to prevent from getting sick.
3. Specificity will be regulated due to recognition of antigenic
determinants or epitopes on the surface of the Antigen
Epitopes = immunologically active regions that bind to:
Ag-specific membrane receptors on lymphocytes
Already secreted antibodies
Many epitopes can be found on single molecule
INTRODUCTION
4. PROPERTIES OF ANTIGENS
The antigen should be a foreign substance to induce an immune response.
The antigens have a molecular mass of more than 5000 Da.
They are mainly proteins and polysaccharides.
The more chemically complex they are, the more immunogenic they will be.
Antigens are species-specific.
The age influences the immunogenicity.
Very young and very old people exhibit very low immunogenicity.
5. TYPES OF ANTIGENS
BASED ON ORIGIN
Exogenous Antigens
Endogenous Antigens
Autoantigens
Tumour Antigens
6. EXOGENOUS ANTIGENS
Exogenous antigens are the external antigens that enter the body from
outside.E.g. inhalation, injection, etc.
This include food allergen, pollen, aerosols, etc. and are the most
common type of antigens.
ENDOGENOUS ANTIGENS
Endogenous antigens are generated inside the body due to viral or bacterial
infections
7. AUTO ANTIGENS
Autoantigens are the ‘self’ proteins or nucleic acids that due to some genetic or
environmental alterations get attacked by their own immune system causing
autoimmune diseases.
TUMOUR ANTIGENS
It is an antigenic substance present on the surface of tumour cells that induces
an immune response in the host.
Many tumors develop a mechanism to evade the immune system of the body.
Native Antigens
An antigen that is not yet processed by an antigen-presenting cell is known as
native antigens.
8. ATTRIBUTES OF ANTIGENECITY
INDUCTION OF IMMUNE RESPONSE – IMMUNOGENECITY
SPECIFIC REACTION WITH ANTIBODIES - IMMUNOLOGICAL REACTIVITY
An antigen introduced in the body specifically reacts with those particular
immunocytes (B or T Lymphocytes) which carry unique markers which produce
specific antibodies or complementary cells.
Antibody such produced will react with only that particular Antigen.
9. BASED ON IMMUNE RESPONSE
Antigens can be classified as:
IMMUNOGEN OR COMPLETE ANTIGEN
These may be proteins or polysaccharides and can generate an immune response
on their own.
Ability to produce observable and specific activity with the antibody
HAPTEN
These are non-protein, foreign substances that require a carrier molecule to
induce an immune response.
10. Immunogenicity = ability to induce humoral and/or cell- mediated immune response
Antigenicity = ability to combine specifically with the final products of the above
responses (i.e., antibodies and/or cell-surface receptors).
Haptens, small molecules, are antigenic but incapable of inducing specific immune
response
Immunogenicity and Antigenicity
11. ANTIGENS VS IMMUNOGENS
An immunogen refers to a molecule that is capable of producing an immune
response by the immune system.
An antigen refers to a molecule that is capable of binding to the product of
that immune response.
So, an immunogen is necessarily an antigen, but an antigen may not
necessarily be an immunogen.
Vaccines are examples of antigens in an immunogenic form, which are
intentionally administered to a recipient to induce the memory function
towards antigens of the pathogen invading that recipient
12. STRUCTURE OF ANTIGENS
The epitopes or antigenic determinants are the components of antigen.
Every antigen has several epitopes.
An antibody has at least two binding sites that can bind to specific epitopes on antigens.
The antigens combine with the antibody according to the lock and key mechanism.
The ability of the body to act against the disease-causing agents and antigens by the
immune system is termed as the immunity. This immunity may be either inborn or
acquired from vaccinations.
13. EPITOPE
SMALLEST AREA ON THE ANTIGEN
MOSTLY CONSIST OF 4 OR 5 AMINOACIDS OR A MONOSACCHARIDE
POSSESS A SPECIFIC CHEMICAL STRUCTURE
ELECTIRCAL CHARGE
SPATIAL CONFIGURATION
CAPABLE OF SENSITISING AN IMMUNOCYTE AND REACT WITH THE
COMPLIMENTARY SITE ON THE ANTIBODY OR T CELL RECEPTOR
IT MAY BE LINEAR SEQUENTIAL SEGMENT OR
BRINGING TOGETHER RESIDUES FROM DIFFERENT SITES OF THE PEPTIDE MAKING
A CONFORMATIONAL EPITOPE.
14. IMMUNE CELLS DO NOT INTERACT WITH, OR RECOGNIZE, ENTIRE IMMUNOGEN MOLECULE
LYMPHOCYTES RECOGNIZE DISCRETE SITES ON IMMUNOGEN MOLECULE CALLED EPITOPES, OR
ANTIGENIC DETERMINANTS.
EPITOPES ARE THE IMMUNOLOGICALLY ACTIVE REGIONS OF AN IMMUNOGEN THAT BIND TO
ANTIGEN-SPECIFIC MEMBRANE RECEPTORS ON LYMPHOCYTES OR TO SECRETED ANTIBODIES
STUDIES WITH SMALL ANTIGENS REVEAL THAT B AND T CELLS RECOGNIZE DIFFERENT EPITOPES
ON SAME ANTIGENIC MOLECULE
EPITOPE
15. RECOGNITION OF EPITOPES
T CELL RECOGNISES SEQUENTIAL EPITOPE
B CELL RECOGNISES TERTIARY STRUCTURE OF THE CONFORMATIONAL EPITOPE
THE COMBINING AREA ON THE ANTIBODY CORRESPONDING TO THE EPITOPE IS CALLED THE
PARATOPE
EPITOPE AND THE PARATOPE DETERMINE THE SPECIFICITY OF THE IMMUNOLOGICAL REACTIONS
ANTIGENS ON THE BACTERIA AND VIRUSES CARRY DIFFERENT TYPES OF EPITOPES PRESENTING
AN ANTIGENIS MOSAIC.
PRESENCE OF THE SAME OR DIFFERENT EPITOPES ON DIFFERENT ANTIGENS ACCOUNTS OF
ANTIGENIC CROSS REACTIONS.
19. BASIC PROPERTIES ARE KNOWN TO BE ESSENTIAL TO
MAKE A ANTIGENS
Foreign Nature
Molecular Size
Antigenic Determinants and Cross-Reactivity
Molecular Rigidity and Complexity
Genetic Factors in the Individual.
20. FOREIGN NATURE
The important requirement for immunogenicity is that the substance should be foreign to the body of
recipient.
With result the immune system must be able to distinguish between normal body components and foreign
substances.
Normally the body has no tendency to recognize its own components as antigens, therefore does not
initiate an immune response against these.
For example, if serum albumin from a mouse is injected back into the same mouse or into another
mouse, no antibody production will occur. On the other hand, if the albumin is infected into an animal of
another species, antibody may be produced.
21. MOLECULAR STRUCTURES
The substance or molecule must have certain physio-chemical properties, where molecular
size is an important factor.
It is established that a molecule must have a minimum size (generally > 5000 Da) before it
can be considered as antigen.
Hence small molecules like amino acids or monosaccharides are usually not antigenic.
However, low molecular substance can demonstrate immunogenicity, if coupled to a suitable
carrier molecule like protein.
These low molecular substances are called haptens which are considered as ‘partial
antigens’ that contain at least one of the determinant groups of an antigen. Hapten can thus
reacts with specific antibody but is not immunogenic in absence of a carrier molecule.
Example of Haptens: Drugs, peptide hormones, and steroid hormones
23. ANTIGENIC DETERMINANTS
Only limited parts of the large antigen molecule are involved in the binding to
antibodies.
These parts are called antigenic determinants. It is established that a molecule must
have at least two antigenic determinants in order to stimulate antibody production.
For this reason a small molecule does not function as antigen. Because it is not
possible for a small molecule to have more than one antigenic determinant.
The number of antigenic determinants on a small molecule varies with molecular
size. Say for example, human serum albumin (Mol. wt.70 KDa) has at least six
different antigenic determinants, that means at least six antibodies of different
specificities can be produced after immunization.
It is established that antibodies recognize the three dimensional structure of the
antigen rather than their primary amino acid sequence.
24. CROSS-REACTIVITY
In some cases antibodies can bind to an antigen other than one which initiated antibody
production. This is known as cross-reactivity.
For example, the homologous ‘antigen a’ has induced
production of the antibody specific for antigen a and
cross-reacts with non-identical ‘antigen b’ (Fig.10.2).
Through cross-reactivity an allergic reaction can be
initiated by a substance with which the individual has
never been in contact before.
25. RIGIDITY AND COMPLEXITY
The firm and stiff nature and complexity of the molecule are the important factors for
immunogenicity.
A rigid molecule is a good antigen, probably because it is easier to raise antibodies to
certain structures than to others.
The immunogenicity is very much dependent on the complexity of the antigens.
For example, a molecule containing a repeating unit of only one amino acid is generally
poor immunogen, even if the molecule is large; while a molecule with two or three
repeating amino acids can, however, function well as an immunogen.
26. GENETIC FACTORS IN THE INDIVIDUAL
Genetic factors are of prime importance for the immunogenicity.
It was Wyman (1872) who for the first time reported that allergy runs in
families and some families suffer more than others.
All individuals within a species need not show the same allergic response
against a particular antigen.
Anyone can develop an allergy but the probability is increased if one or both
the parents suffer from some kind of allergic condition.
The highest frequency of hypersensitivity among children is observed where
both parents are atopic and with same manifestation.
So the frequency of allergy among children is progressively increased
according to the nature and intensity of allergy in parents.
It is evident that about 10-20% of the population suffer from aeroallergens
such as pollen grains and spores.