Читать книгу Immunology - Richard Coico - Страница 120

Since macromolecular antigens contain several distinct epitopes, some of these antigens can be altered without totally changing the immunogenic or antigenic structure of the entire molecule. This concept is important in relation to immunization against highly pathogenic microorganisms or highly toxic compounds. Obviously, immunization with the pathogenic toxin is unwise. However, it is possible to destroy the biological activity of such toxins and a broad variety of other toxins (e.g., snake venoms) without appreciably affecting their immunogenicity.

A toxin that has been modified to the extent that it is no longer toxic but still maintains some of its immunochemical characteristics is called a toxoid. Thus we can say that a humoral immune response to a toxoid cross‐reacts immunologically with the toxin. Accordingly, it is possible to immunize individuals with the toxoid and thereby induce immune responses to some of the epitopes that the toxoid still shares with the native toxin because these epitopes have not been destroyed by the modification. Although the molecules of toxin and toxoid differ in many physicochemical and biological respects, they nevertheless cross‐react immunologically; they share enough epitopes to allow the immune response to the toxoid to mount an effective defense against the toxin itself.

An immunological reaction in which the immune components, either cells or antibodies, react with two molecules that share epitopes but are otherwise dissimilar, is called a cross‐reaction. When two compounds cross‐react immunologically, the compounds will have one or more epitopes in common, and the immune response to one of the compounds will recognize one or more of the same epitope(s) on the other compound and react with it. Another form of cross‐reactivity is seen when antibodies or cells with specificity to one epitope bind, usually more weakly, to another epitope that is not quite identical but has a structural resemblance to the first epitope.

To denote that the antigen used for immunization is different from the one with which the induced immune components are then allowed to react, the terms homologous and heterologous are used. Homologous denotes that the antigen and the immunogen are the same; heterologous denotes that the substance used to induce the immune response is different from the substance that is then used to react with the products of the induced response. In the latter case, the heterologous antigen may or may not react with the immune components. If reaction does take place, it may be concluded that the heterologous and homologous antigens exhibit immunological cross‐reactivity.

Although the hallmark of immunology is specificity, immunological cross‐reactivity has been observed on many levels. This does not mean that the immunological specificity has been diminished but rather that the substances that cross‐react share antigenic determinants (epitopes). In cases of cross‐reactivity, the antigenic determinants of the cross‐reacting substances may have identical chemical structures, or they may be composed of similar but not identical physicochemical configurations. In the example described above, a toxin and its corresponding toxoid represent two molecules: the toxin is the native molecule and the toxoid is a modified molecule, the response to which cross‐reacts with the native molecule.

There are other examples of immunological cross‐reactivity, wherein the two cross‐reacting substances are unrelated to each other except that they have one or more epitopes in common, specifically, one or more areas that have similar three‐dimensional characteristics. These substances are referred to as heterophile antigens. For example, human blood group A antigen reacts with antiserum raised against pneumococcal capsular polysaccharide (type XIV). Similarly, human blood group B antigen reacts with antibodies to certain strains of Escherichia coli. In these examples of cross‐reactivity, the antigens of the microorganisms are referred to as the heterophile antigens (with respect to the blood group antigen).