Introduction of Antigen
- In 1899 Ladislas Deutsch (Detre) (1874–1939) named the hypothetical substances halfway between bacterial constituents and antibodies “substances immunogens or antigens”.
- He originally believed those substances to be precursors of antibodies, just like zymogen is a precursor of zymase.
- But by 1903 he understood that an antigen induces the production of immune bodies (antibodies) and wrote that the word antigen was a contraction of “Antisomatogen.
Definition of antigen
The antigen is a substance which when introduced parentally into the body stimulates the production of an antibody with which it reacts specifically and in an observable manner.
Classification of antigen
Based on Immunogenicity
1. Complete antigen: Substances that can induce antibody formation by themselves and can react specifically with these antibodies
2. Incomplete antigen (haptens): substances unable to induce antibody formation on their own but can become immunogenic when covalently linked to proteins, called carrier proteins. They are of two types:
a) Simple and
b) Complex.
Based on origin
1. Exogenous antigens: Exogenous antigens are those antigens that enter the host body from their surroundings or external environments. These are basically pollutants, microorganisms, pollens, drugs, etc.
2. Endogenous antigens: They are again classified onto –
a. Xeno-genic or Heterogenic antigens
b. Allogenic or Idiotypic antigens
c. Autologous antigens
a. Xeno-genic or Heterogenic antigens: Foreign items which are related to tissue transplantation and serology.
b. Allogenic or Idiotypic antigens: Foreign items which enter when an individual receives a blood transfusion or undergoes transplantation operation
c. Autologous antigens: This group of antigens is very rare and unnatural. In normal conditions, self-components are non-immunogenic in nature, but in an abnormal condition, self-body components are started to be considered as non-self or antigenic components.
Immunogenicity Vs Antigenicity
Immunogenicity: Ability to induce a humoral or cell-mediated immune response.
Antigenicity: Ability to combine specifically with the final products of the humoral or cell-mediated immune response.
- All molecules possessing the property of immunogenicity also possess the property of antigenicity.
- Some molecules that possess the property of antigenicity but lack immunogenicity are known as haptens.
Factor of antigenicity
1. Foreignness
The antigen must be foreign to the immune system: What substances are foreign to the immune system? According to Burnnet’s clone selection theory, foreignness ( non-self) means substances that are never in contact with lymphocytes during the embryo period.
2. Size
- Larger molecules are highly antigenic
- Lower molecular weights are either nonantigenic or weakly antigenic
3. Chemical Nature
- Most naturally occurring antigens are either proteins or polysaccharides.
- Lipids and nucleic acids are less antigenic on their own but do so when combined with proteins
4. Susceptibly to tissue enzymes
Substances that can be metabolized and are able to the action of tissue enzyme behave as antigen.
5. Antigenic specificity
- It depends upon the epitope.
- The position of the epitope in the antigen molecule is important for specificity.
6. Species specificity
The tissue of all individuals in species possesses species-specific antigens.
7. Isospecificity
It depends on isoantigens which may be found in some but not all members of species.
8. Auto specificity
Self-antigens are generally non-antigenic but in some cases such as lens protein and sperm, these are not recognized as self-antigen because they are absent during the embryonic life and develop later.
9. Organ specificity
Some organs such as the brain, kidney, and lens protein of different species share the same antigens, and such antigens are the characteristics of an organ or tissue found in different species and are known as organ-specific antigens.
10. Heterogenic specificity
- The same or closely related antigen may sometimes occur in different biological species, classes and kingdoms are know as heterophile antigens.
- Antibodies to these antigens produced by one species cross-react with antigens of other species. e.g. Forssman Ag, Weil-Felix reaction, Paul-Bunnell test.
Adjuvants
- Substances that are mixed with an antigen and injected with it, serve to enhance the immunogenicity of the antigen.
- They are often used to boost the immune response when an antigen has low immunogenicity or when only small amounts of an antigen are available, limiting the immunizing dosage.
Epitope
- Epitopes are antigenic determinants.
- B and T cells recognize different epitopes on the same antigenic molecule.
Superantigens
- They are the most potent T-cell mitogens known.
- Note: Mitogens are agents capable of inducing cell division in a high percentage of T or B cells.
- Superantigens bind to residues in the V(variable) domain of the T-cell receptor and to residues in Class II MHC molecules outside of the antigen-binding cleft.
- In this way a superantigen can cross-link a T cell to a Class II MHC molecule even when the TCR does not recognize the bound antigenic peptide, leading to activation of the T cell.
- Thus a superantigen can activate all T cells expressing the V domain to which that superantigen binds.
- Common superantigens include the staphylococcal enterotoxins(Ses) and toxic shock syndrome toxin(TSS1), which is produced by the gram-positive bacterium Staphylococcal aureus.
Tests for antigen detection
- Direct Enzyme-Linked Immunosorbent Assay ( ELISA)
- Direct Immunofluorescence
- Radioimmunoassay (RIA)
- Neutralization test
Complement Fixation Test (CFT)
Immunohistochemistry
Further Reading
- Essential immunology-Third Edition -Ivan M. Roitt
- Kuby Immunology –Sixth Edition-Thomas J. Kindt, Richard A. Goldsby, Barbara A. Osborne
- Basic Immunology –Second Edition -Abdul K. Abbas, Andrew H. Lichtman
- Immunology-Seventh Edition-Donald M. Weir, John Stewart
- Advances in Immunology- Volume-29 -F. J. Dixon, Henry G. Kunkel
- Fundamental Immunology-William E. Paul