Properties of antigens / Factors Influencing Immunogenicity

Immunogenicity is determined by –

1. Foreignness – An antigen must be a foreign substance to the animal to elicit an immune response.

2. Molecular Size – The most active immunogens tend to have a molecular mass of 14,000 to 600,000 Da. Examples: tetanus toxoid, egg albumin, thyroglobulin are highly antigenic. Insulin (5700) is either non-antigenic or weekly antigenic.

3. Chemical Nature and Composition – In general, the more complex the substance is chemically the more immunogenic it will be. Antigens are mainly proteins and some are polysaccharides. It is presumed that presence of an aromatic radical is essential for rigidity and antigenicity of a substance.

4. Physical Form – In general particulate antigens are more immunogenic than soluble ones. Denatured antigens are more immunogenic than the native form.

5. Antigen Specificity – Antigen specificity depends on the specific actives sites on the antigenic molecules (Antigenic determinants). Antigenic determinants or epitopes are the regions of antigen which specifically binds with the antibody molecule.

6. Species Specificity – Tissues of all individuals in a particular species possess, species specific antigen. Human blood proteins can be differentiated from animal protein by specific antigen-antibody reaction.

7. Organ Specificity – Organ specific antigens are confined to particular organ or tissue. Certain proteins of brain, kidney, thyroglobulin and lens protein of one species share specificity with that of another species.

8. Auto-specificity – The autologous or self antigens are ordinarily not immunogenic, but under certain circumstances lens protein, thyroglobulin and other may act as auto-antigens.

9. Genetic Factors – Some substances are immunogenic in one species but not in another. Similarly, some substances are immunogenic in one individual but not in others (i.e. responders and non-responders). The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells. They may not have the appropriate genes needed for the APC to present antigen to the helper T-cells.

10. Age – Age can also influence immunogenicity. Usually the very young and the very old have a diminished ability to elicit and immune response in response to an immunogen.

11. Degradability – Antigens that are easily phagocytosed are generally more immunogenic. This is because for most antigens (T-dependant antigens) the development of an immune response requires that the antigen be phagocytosed, processed and presented to helper T-cells by an antigen presenting cell (APC).

12. Dose of the Antigen – The dose of administration of an immunogen can influence its immunogenicity. There is a dose of antigen above or below which the immune response will not be optimal.

13. Route of Administration – Generally the subcutaneous route is better than the intravenous or intragastric routes. The route of antigen administration can also alter the nature of the response. Antigen administered intravenously is carried first to the spleen, whereas antigen administered subcutaneously moves first to local lymph nodes.

14. Adjuvant – Substances that can enhance the immune response to an immunogen are called adjuvant. The use of adjuvant, however, is often hampered by undesirable side effects such as fever and inflammation. Example: aluminum hydroxide.

Super Antigens –

When the immune system encounters a conventional T-dependent antigen, only a small fraction (1 in 104 -105) of the T-cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response). However, there are some antigens which polyclonally activate a large fraction of the T-cells (up to 25%). These antigens are called super-antigens.

Examples of super-antigens include: Staphylococcal entero-toxins (food poisoning), Staphylococcal toxic shock toxin (toxic shock syndrome), Staphylococcal exfoliating toxins (scalded skin syndrome) and Streptococcal pyrogenic exo-toxins (shock).

Although the bacterial super-antigens are the best studied there are super-antigens associated with viruses and other micro-organisms as well. The diseases associated with exposure to super-antigens are, in part, due to hyper activation of the immune system and subsequent release of biologically active cytokines by activated T-cells.