A number of properties that make a substance antigenic have been identified but the exact basis of antigenicity is still not clear.

1. Size: Antigenicity is related to molecular size. Very large molecules, such as hemocyanins (MW 6.75 million).

are highly antigenic and particles with low molecular weight (less than 5000) are non antigenic or feebly so. Low molecular weight substances may be rendered

antigenic by adsorbing them on large inert particles such as bentonite or kaolin. Some low molecular weight substances (such as picryl chloride, formaldehyde and penicillin) may be antigenic when applied on the skin, probably by combining with tissue proteins. They are

haptens of low immunogenicity, effective in some persons only and related to hypersensitivity.

2.Chemical nature: Most naturally occurring antigens are proteins and polysaccharides. Lipids and nucleic acids are less antigenic. Their antigenicity is enhanced by combination with proteins. A certain degree of structural diversity is required for antigenicity. That

probably explains why proteins, which are composed of about 20 different amino acids, are better antigens than polysaccharides, which have only four or five monosaccharide units. However, not all proteins are

antigenic. A well-known exception is gelatin, which is nonimmunogenic because of its structural instability

3.Susceptibility to tissue enzymes: Only substances which are metabolised and are susceptible to the action of tissue enzymes behave as antigens. Antigens introduced into the body are degraded by the host into fragments of appropriate size containing the antigenic determinants. Phagocytosis and intracellular of enzymes appear to play an essential role in breaking or down antigens into immunogenic fragments.Substances not susceptible to tissue enzymes such as a polystyrene latex are not antigenic. Substances

very rapidly broken down by tissue enzymes are also not antigenic Synthetic polypeptides, composed of D-amino acids which are not metabolised in the body, are not antigenic, while polypeptides consisting of

L-amino acids are antigenic.

4.Foreignness: Only antigens which are 'foreign' to the individual (nonself) induce an immune response. The animal body contains numerous antigens that induce an immune response when introduced into another individual or species. An individual does not normally mount an immune response against his or her own normal constituent antigens. This was first

recognised by Ehrlich who proposed the concept of 'horror autotoxicus' (which means fear of self poisoning). Tolerance of self-antigens is conditioned by contact with them during the development of the immune apparatus. Breakdown of this homeostatic

mechanism results in auto immunization and

autoimmune disease.