Studies on the Mechanism of Hypersensitivity Phenomena

Abstract

The interaction of fresh rat and guinea pig serum with washed preformed immune aggregates has been studied with respect to the loss in hemolytic potency of the serum, diminution of the C'3; activity, and appearance of anaphylatoxin. It has been found that the formation of anaphylatoxin, as judged by its effect on capillary permeability and smooth muscle contraction, is coincident with or subsequent to the fixation of all the known C' components. Less anaphylatoxin is formed by aggregates formed with excess antigen than those in equivalence ratio combination. C' fixation, as well as anaphylatoxin production, may be inhibited by chelation of the divalent cations, presumably by interfering with the fixation of C'1, C'4, and C'2. Phlorizin suppresses the utilization of C'3 in immune hemolysis, C' fixation by antigen-antibody aggregates, and the production of anaphylatoxin. The biological activities associated with the fixation of C' are not manifest unless C'3 participates in this process at 37°C. It is concluded that the formation of anaphylatoxin may be regarded as a product of C' fixation.

Properties of Guinea Pig 7s Antibodies

“…It is increasingly recognized that in different mammalian species, the liberation of these amines can be triggered by several mechanisms. One of the mechanisms appears to require the intervention of C' and the formation of serum anaphylatoxin, as demonstrated in the rat (18,19); other mechanisms, more efficient in terms of antibody requirements, best demonstrated in the guinea pig and man, involve the selective fixation of certain types of antibody globulins to specific tissue receptors. Only this last property is lacking in the guinea pig 7S'y2 globulins (6)(7)(8).…”

The history of mast cell and basophil research – some lessons learnt from the last century

“…Following this general trend, research on mast cells and basophils, since the exciting discoveries of IgE and its receptors, had also focussed on the adaptive effector arm studying allergy and to a lesser extent parasite immunology. Yet, as mentioned above, mast cell tissue passive cutaneous anaphylaxis responses could be induced by IgG but also anaphylatoxins, providing early hints regarding mast cells' ability to respond to signals other than immunoglobulins (14). Furthermore, it became clear that mast cells express numerous receptors and produce many inflammatory products with potential effects in tissue responses, host defense mechanisms, and immunoregulation advocating a role of these cells well beyond allergy.…”

“…E. Friedberger proposed in 1909 (13) that the serum contains a reactive substance called anaphylatoxin that results as a cleavage product after introducing the toxin. However, it was not until 1959 that Zolt an Ovary had identified such anaphylatoxins as cleavage products of complement proteins (14). These peptides can induce an anaphylactic reaction by mast cells and basophils, which bear receptors for these peptides on their surface.…”

Studies on Circulating Immune Complexes

“…Rabbits producing both "light" and "heavy" complexes were found to have marked depletion of hemolytic complement activity, suggesting that both types of complexes possessed pathogenic qualities. Two such qualities known to be dependent upon complement activation by antibody are the formation of anaphylatoxin (21)(22)(23) and the accumulation of leukocytes (24). The latter of these qualities is undoubtedly fundamental to the development of serum sickness lesions (16,20).…”