The Pharmacological Control of Immediate Hypersensitivity

Immediate hypersensitivity is a reaction to a foreign substance and is im­ munological in nature. Initial challenge with the foreign material stimu­ lates, by interaction with T lymphocytes and macrophages, the immune system. The response is the generation of B lymphocytes which recognize the antigenic determinants of the foreign material; these B cells then differentiate into plasma cells which elaborate IgE-class antibodies directed against the antigens. The IgE antibodies so formed become fixed to tissue mast cells or circulating basophil leucocytes. In man, rat, and mouse the antibody which fixes to mast cells and basophils is of the IgE class whereas in other species such as guinea pig it appears to be a subclass of IgG antibodies. In either case the production of antibody which specifically binds to mast cells and basophils is fundamental to the immediate hypersen­ sitivity reaction. Second and subsequent challenges with foreign antigen lead to an antigen-antibody reaction on the mast cell and basophil mem­ brane. The immunological and the pharmacological control of IgE produc­ tion has been the subject of earlier reviews (1-4). Stimulation of the mast cell and basophil membranes initiates a sequence of cellular events leading to the release of the mediators of the immediate hypersensitivity reaction. The mediators have long been known to include histamine, slow reacting substance (SRS), and, in some species, 5-hydroxy­ tryptamine. Other putative mediators include prostaglandins, kinins, chemotactic factors, and platelet activating factor. The smooth muscle contraction, glandular secretion, cell accumulation, increased capillary