Gamma Globulin and Molecular Mechanisms in Hypersensitivity Reactions (Part 1 of 2)

Abstract

Pre-formed antigen-antibody complexes can induce allergic reactions. Induction of skin reactive properties and C[image]-fixing potency by the formation of these complexes is dependent on 2 factors: their composition with respect to antigen/antibody ratio and the species of origin of the antibody concerned. 2 or more antibody molecules appear to be required for the formation of a skin reactive complex. With regard to the mechanism for the induction of these biological activities, it was suggested that an interaction between antibody molecules brought into apposition by antigen and possibly consequent structural changes in the antibody molecules might be involved. This hypothesis was supported by the fact that nonspecifically aggregated normal gamma-globulins from the human and the rabbit have the ability to induce increased permeability of skin capillaries, Arthus-like reactions in normal guinea pigs and erythema wheal reactions in humans. The aggregated gamma-globulin inactivated C[image], agglutinated human erythrocytes and rabbit platelets in vitro and released histamine and 5-hydroxytryptamine from rabbit blood. Evidence was presented that aggregated gamma-globulin and antigen-antibody complexes induced these reactions through similar mechanisms. Induction of the biological activities (skin reactivity and the ability to fix C[image]) upon aggregation was characteristic for the gamma-globulin of certain animal species. Possibly induction of the allergic reactions as well as immunochemical reactions in which C is involved is not characteristic of antigen-antibody system per se but of the interaction between gamma-globulin molecules and therefore that some allergic diseases might be induced by molecular changes in globulin without the participation of any antigen. As anaphylactic reactions are probably caused by the formation of active antigen-antibody complexes in vivo, the molecular bases of the reactions may be as follows. In the sensitized state, antibody molecules are fixed on certain tissue cells by a region of the antibody surface corresponding to Fr. III. As the result of antigen-antibody combination, antigen-antibody complexes form on the cells and antibody molecules combining with the same antigen may interact with each other. A structural alteration in the Fr. HI segment may occur as the result of the antibody-antibody interaction. The final structure in the molecule may give the complexes biological activities such as the capacity to liberate vasoactive amines which may play an important role in anaphylactic reactions.