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The following basic properties are known to be essential to make a antigens: 1. Foreign Nature 2. Molecular Size 3. Antigenic Determinants and Cross-Reactivity 4. Molecular Rigidity and Complexity 5. Genetic Factors in the Individual.
Property # 1. Foreign Nature:
The prerequisite for immunogenicity is that the substance should be foreign to the body of recipient. As a 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.
Property # 2. Molecular Size:
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It is not always true that a substance should have to be of foreign origin to make it an antigen. 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.
Property # 3. Antigenic Determinants and Cross-Reactivity:
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.
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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.
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.
Property # 4. Molecular Rigidity and Complexity:
The rigidity 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.
Property # 5. 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. In a comprehensive study of the familial predisposition towards allergic rhinitis, atopic eczema and asthma, Cooke and Vander Veer (1916) confirmed and considerably extended Wyman’s observations.
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 (Table 10.1).
The highest frequency (72.2%) of atopy among children is observed where both parents are atopic and with same manifestation (Table 10.1). 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.
With the invent of IgE it was suspected that some specific genetic factors involved in atopic allergy. The overall regulation of atopic diseases include at least one antigen-nonspecific gene that is not HLA-linked.
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Now the major antigen specific control appears in HLA-linked genes. Hopkins (1990) suggested the non-MHC linked genetic control of IgE synthesis, in which the inheritance of atopy is related to a gene on chromosome 11q.
Method of administration and dosage:
It is evident that the method of administration and the dose of antigen are very much important. The immune response against a certain substance can be enhanced by administering an adjuvant together with the antigen.
