IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

STRUCTURE AND FUNCTIONAL PRINCIPLES OF THE IMMUNE SYSTEM

Regulatory idiotypes

An idiotype is a set of unique determinants within the antigen-binding site of IMMUNOGLOBULINS, characteristic of each B-lymphocyte clone. Each immunoglobulin molecule contains two identical antigen-binding sites. This bivalency enables Antibodies to cross-link Antigens possessing two or more antigenic determinants. Anti-idiotypic immunoglobulins react with a specific antibody, recognizing private idiotypes. Antibodies belonging to various idiotypes are produced within each Organism. Certain antibody molecules with similar Amino acid sequences share the same idiotype, in which case we refer to "public" or "cross-reactive idiotypes." Cross-reactive idiotypes are frequently occurring idiotypes common to a multitude of antibodies with diverse specificities. These cross-reactive idiotypes serve as targets for anti-idiotypic antibodies. Such network interactions provide an additional mechanism for controlling the Immune Response.

Early antibodies bearing a dominant, cross-reactive idiotype induce the generation of regulatory T-helper Cells that recognize this idiotype. These T-helper cells, in turn, select and stimulate those cells among B-lymphocyte populations—heterogeneous in their Specificity and activated by various antigen epitopes—that carry the dominant idiotype on their receptors.

Evidently, the idiotypic network serves to sustain the immune response over a prolonged period and maintain memory cells. Furthermore, the presence of these aforementioned T-helper cells, specific for the shared idiotype of memory B cells, significantly accelerates antibody production during a secondary immune response.

It is likely that anti-idiotypic memory T-helper cells are responsible for the phenomenon wherein re-infection with a strain of Influenza virus that is antigenically related—yet not identical—to the strain that caused the primary infection stimulates higher antibody titers than re-infection with the original viral strain. In this case, antigen- and idiotype-specific T-helper cells act synergistically; specifically, the latter stimulate the proliferation of B-lymphocyte clones bearing this idiotype.

The idiotypic network allows for the manipulation of the immune response, particularly in autoimmune diseases, allergies, and transplant rejection syndromes. At the same time, the polyclonal B-Cell response is so diverse in its idiotypes that its anti-idiotypic suppression is difficult to achieve. Even when a public idiotype dominates, its suppression leads to the compensatory proliferation of other clones lacking this idiotype, meaning the drop in antibody titer is modest. Perhaps future research will yield ways to limit this compensatory reaction, especially if the number of idiotypes is small, as is typically the case for IgE synthesis in patients with IgE-mediated allergies. It is believed that T-helper cells express a narrow spectrum of idiotypes and are therefore sensitive to suppression induced by idiotypic autoimmunization, the application of which could enhance the Treatment efficacy of autoimmune diseases. On the other hand, anti-idiotypic antibodies are known to stimulate antibody production. Consequently, monoclonal anti-Ig antibodies bearing an "internal image of the antigen" can be utilized as antigen "surrogates" for immunization when obtaining the native antigen in sufficient quantities is challenging. The Use of anti-idiotypic antibodies as antigen substitutes also represents a promising therapeutic avenue for treating autoimmune diseases and preventing transplant rejection.

In Conclusion, the primary Functions of The Immune System are to protect the organism against pathogenic microbes and provide tumor surveillance. Both non-specific defense mechanisms and specific immune responses directed against specific infectious or tumor antigens participate in executing these functions. The specific immune response enhances non-specific defense mechanisms, making them more targeted.