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|Year : 1972 | Volume : 20 | Issue : 2 | Page : 42-44 |
Haffkine Institute, Bombay-12, India
S S Rao
Haffkine Institute, Bombay-12
|How to cite this article: |
Rao S S. Antigenicity. Indian J Ophthalmol 1972;20:42-4
The term 'antigenicity' has been used to describe both the ability of the antigen to combine with the antibody and also its ability to induce antibody formation. In recent years however, the first property of the antigen is called antigenicity and the second immunogenicity. This is because some small molecules for which the immunologists use the term 'haptens' are capable of combining with antibody but are unable to elicit antibody formation. The combining group of the antigen is called the "determinant group". The haptens can however be made immunogenic by attaching them to certain immunogenic carrier molecules. Antibodies reacting with penicillin can be produced by tagging it to serum albumin. Antibodies can thus be produced to any simple substance. There are substances called "adjuvants" which are not immunogenic by themselves but can enhance antibody production of weakly immunogenic substances. These are important in vaccinations to enhance antibody reponse. Aluminium hydroxide used in alum precipitated vaccines is an example of an adjuvant. There are also substances called immunosuppressors which suppress the immune response. They are important in autoimmune disease and in preventing rejection of homograft. Hydrocortisone is an important immuno supressor.
In the last few years immunogenicity has been studied using synthetic polypeptides of known structure and interesting facts have come to light. It was the prevailing belief among immunologists that only large macromolecules of molecular weight over 6.000 could be immunogenic. This was because insulin and gelatin which have a molecular weight of about 6000 are not immunogenic normally. Recent work has shown that polypeptides of single aminoacids say poly-L-lysine even though they may have molecular weight of over 50.000 are still not antigenic in any species of animals. However, polylysine with only 7 or 8 units to which is attached a single dinitrophenyl group is immunogenic in guinea-pigs giving rise to both antibody production as well as cellular immunity as indicated by the delayed skin sensitization to the polypeptide. The smallest substance which can elicit antibody production in guinea-pigs is N-acetyl-L-Tyrosine-azo-phenyl arson ate which has a molecular weight of only 450.
A large immunogenic molecule may have one or more determinant groups which have structures foreign to the host. In such a case specific antibodies are formed to each of the determinant groups which are on the surface and therefore accessible. Hidden determinant groups may not be immunogenic.
The nature of the antigen and its dosage are also important for immunogenicity. Polymerised antigens are more immunogenic than their monomers. Repeated administration of very low doses or very high doses can produce immunoparalysis while intermediate doses may be immunogenic. For example. Mitchison has reported that bovine serum albumin is immunizing when injected in dose of 10 -7 to 10 -6 moles in mice but is paralysing when low doses of 10 -8 moles or below or high doses of 10 -5 or below or high doses of 10 -5 moles and above are injected. No detectable antibodies are produced when injected with a paralytic dose. Introduction of the unnatural D-amino acids in the molecule reduces immunogenicity and even small doses may lead to paralysis. The optical configuration of the amino acids is therefore important.
The three dimentional structure is most important both for antigenicity and immunogencity. The antibodies produced are specific to the three dimentional structure. Antibodies produced to a short linear (straight chain) sequence of amino acids are different in their specificity or combining activity to antibodies produced to the same sequence of amono-acids but having a helical structure. Very slight changes in the position of individual groups in a molecule or its spacial conformation alter profoundly the specificity of the antibody formed.
The immunogenicity depends also on the species and the strain of the animal used. For example, purified pneumococcal polysaccharides, prepared from the capsular material of pneunuococci, are not at all immunogenic in rabbits. Intact pneunococci nave to be injected to produce the antibodies which will then react with the purified polysaccharide. However, purified polysaccharides are highly immunogenic in mice, rats and men and antisera will show strong agglutination with the whole organisms also. When pure inbred strains of mice or guinea pigs were immunized with synthetic polypeptides of known structure, certain interesting facts emerged. Some strains of animals responded to particular structure and other strains did not respond. For example, strain 2 of guinea-pigs produced antibodies when immunized with dinitrophenyl poly-L-lysine (DNP-PLL) while strain 13 did not produce any antibody. Breeding experiments showed that response to DNP-PLL is due to the so called PLL gene which is present in strain 2 and not in strain 13. Cross breeding experiments showed that this gene is autosomal and dominant. Later, it was found that the response to copolymer of L-glutamic acid and L-tyrosine (GT) is the property of the strain 13 and not of the strain 2. Thus the GT gene is present in strain 13 and not in strain 2. Very recent work indicates that the genes controlling immunogenicity in any given species or strain may be fairly large and some of them may be linked to histocompatibility genes of these strains. Similar work has been done with the immune response genes in the different strains of mice. Vigorous work is going on at present to identify the genes controlling the immune response and map them on particular chromosomes.
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