Antigen: History, Composition and Chemical Nature

In this article we will discuss about Antigens:- 1. History of Antigen 2. Composition of Antigen 3. Chemical Nature 4. General Properties.

History of Antigen:

The inhabitants of East Africa have succeeded in vaccination against the bite of poisonous snakes from time immemorial, they could immunise artificially against tick borne relapsing fever and could protect their cattle from contagious pleuropneumonia by their old method of vaccination.

In 2,000-3000 BC, children were vaccinated against small pox in South East Asia by the folk methods of direct contact of hands of the children. Only after 100 years of Jenner’s work. Immunology was enriched with his own methods built on the scientific works of Louis Pasteur.

Composition of Antigen:

Many substances (egg white, serum, milk, snake venom, dead and living bacteria, bacterial exotoxins and endotoxins, plant or animal tissue) containing proteins may act as antigen when introduced into the deeper tissues of the body.

Protein taken in the gastrointestinal tract as food may not act as antigen under normal conditions because they are rapidly destroyed by the gastric juice. To act as antigen, a protein must gain entrance to the blood and other tissues in a chemically unaltered state. Entrance is commonly by injection or infection (i.e. by routes other than the gastrointestinal tract) or by parenterally.

An antigen (Gr. anti—against, genos—genus) is a foreign protein (organic substances of colloidal structure) which, when introduced parenterally (Gr. para—beyond or outside of; enteron—intestine), by route other than the gastrointestinal tract into the human body, will provoke the lymphoid tissue of the human to produce antibodies which will react specifically with the same antigen and not with other substances.

Antigens have the following main properties:

(a) Antigenicity (the ability to cause the production of antibodies);

(b) Antigenic specificity (the ability to enter into an interaction with the corresponding antibodies).

The small portion of a molecule may be called as unit of antigen. This unit is known as antigenic determinant. This determinant is a contour which locks one molecule of antibody. As antigenic determinants have three dimensional structures, the antibody molecule can approach or can get attached to any of the wide range of possible configurations in a single determinant (Fig. 9.1).

The specificity of the antigen is dependent upon antigenic determinant (epitope) i.e. chemical groupings of the antigen molecules. When the antigen comes in contact, the animal reacts. This is known as “acquired immune response.”

The acquired immune response may be of two forms:

(a) The humoral or circulating antibody response;

(b) Cell mediated response.

An antibody directed against an antigenic determinant of a particular antigen molecule will react only with this determinant or another very similar structure. Even minor chemical changes in the determinant will reduce the ability of the original antibody to react with the altered determinant. Antigens which are capable of stimulating immune response are known as immunogens.

Antigens may be complete or partial. Complete antigens are substances which cause the production of antibodies and react with them in vivo and in vitro (e.g. foreign proteins, bacteria, toxins, rickettsiae, viruses). Partial antigens are known as haptens.

They do not produce antibodies but react with the antibodies produced by another substance. They are lipids, complex carbohydrates and other substances of low molecular weight. The addition of protein to haptens in small quantity will convert the hapten into a complete antigen. In this case, the protein carries out the function of a conductor.

The antigenic function of bacteria, rickettsiae and viruses is characterised by species and type specificity. Salmonella typhi antigen induce immunity against typhoid and it will not produce immunity against paratyphoid fever. So this antigen is species and type specific. The type specificity is associated with the presence of special polysaccharide complexes in the bacterial cell.

In the laboratory, there is cross-reaction between antisera to certain bacterial antigens and antigens present in cells such as erythrocytes. These antigens are known as heterophile antigens. Antisera to such antigens will cross-react with cells of different species of animals and various microorganisms.

Chemical groupings of heterophile antigens are not yet known. The best known of the heterophile antigens is the Forssmann antigen which is present in the red cells of many species as well as in the bacteria such as pneumococci and salmonella. Another heterophile antigen is found in Escherichia and human red cells of Group B.

Semihaptens (iodine, bromine, quinine, antipyrin, colloidal iron, azoprotein) are not antigenic themselves, but, in combination with the protein of the body, they acquire the properties of complete antigen. All natural proteins are inherited with the properties of chemical, structural and functional specificity.

Proteins of different species of animals, plants, bacteria, rickettsiae and viruses can be differentiated by immunological reactions.

Chemical Nature of Antigens:

Antigens may be proteins, polysaccharides or lipids. Antigens of cell wall of bacteria (streptococci, staphylococci, corynebacteria) are rather less well defined and appear to be complex mucopeptides, sometimes associated with lipids. Capsulated microorganisms (pneumococci) have complex high molecular weight polysaccharides in their capsules.

General Properties of Antigens:

1. Antigen should be foreign, egg albumin is an excellent antigen in the rabbit, but fails to produce an antibody response in fowl;

2. More foreign—the more powerful antigen;

3. It should have a molecular weight of 5,000. Sometimes, some substances of low molecular weight (aspirin, penicillin, sulphonamides) can act as antigen when applied to the skin;

4. The ability of antibody to form a strong bond with an antigen depends on intermolecular forces which act strongly only when two molecules come in contact in a very precise manner. The better the fit the stronger the bond.

Isoantigens:

Isoantigens are those substances which have antigenic properties and are contained in some individuals of a given species. They are found in erythrocytes of animals and man. At first it was established that there are two antigens (A and B) in the human erythrocytes and in the sera, there are two antibodies (anti-A and anti-B).

Only heterogenic antigens and antibodies (agglutinins) are found in human blood.

These combinations may be represented as:

On the basis of antigenic structure, the erythrocytes of all people can be divided mainly into four groups. Consequently, variants of antigens of erythrocytes in the second (A) and fourth (AB) groups were isolated. The Group-A consists of two sub-groups A₁ and A₂.

The AB groups containing A₁ B and A₂ B and the antigens M and N and M₂ and N₂ etc. have been revealed. At present 30 antigens are known. Besides, there is rhesus factor in the erythrocytes. All these groups are taken into account during blood transfusion.

Auto-antigens are those substances (eye lens, spermatozoa, skin, kidney, lung) which do not, under normal condition, come in contact with the immune system of the body—then the antibodies are not produced against such cells and tissues.

However, if these tissues are damaged, then the auto-antigens may be released and may cause the production of antibodies which react with the corresponding auto-antigens of the cells resulting in the development of glomerulonephritis, interstitial thyroiditis, orchitis, corneal opacity.

The cooling, radiation, drugs (amidopyrine, sulphonamides), virus infection (virus pneumonia, infectious mononucleosis, bacterial proteins, toxins of streptococci, staphylococci, tubercle bacilli and other factors may release auto-antigens from the tissues.