The Complement System
Throughout the ages man has been fascinated and at times obsessed by the marvelous, mysterious and even baffling qualities of the blood. In 1889, Hans Buchner described a heat-labile bactericidal principle in the blood which was later identified as the co
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Throughout the ages man has been fascinated and at times obsessed by the marvelous, mysterious and even baffling qualities of the blood. In 1889, Hans Buchner described a heat-labile bactericidal principle in the blood which was later identified as the complement system. In 1894, Jules Bordet working at the Pasteur Institute in Metchnikoff's laboratory discovered that the lytic or bactericidal action of freshly drawn blood, which had been destroyed by heating, was promptly restored by the addition of fresh, normal, unheated serum. Paul Ehrlich called Bordet's "alexine" das Komplement. In 1901, Bordet and Gengou developed the complement fixation test to measure antigen-antibody reactions. Ferrata in 1907 recognized complement to be a multiple component system, a complex of protein substances of mixed globulin composition present in normal sera of many animal species.
Multiple plasma proteins may be activated during inflammation. Immune complexes activate the classic pathway of complement whereas bacterial products activate the alternative pathway without participation by specific antibody. Many antimicrobial effects are produced by complement. C5a, C5b67 and C3a induce chemotaxis of leukocytes. C3b has opsonic properties. The membrane attack complex leads to lysis of bacterial cells. Complement also facilitates the antimicrobial effects of PMNs and macrophages through the alternative pathway (Figure 1).
The classical pathway of complement activation was described first by investigators using sheep red blood cells sensitized with specific antibody and lysed with guinea pig or human complement. In addition to immune lysis, complement has many other functions and is important in the biological amplification mechanism that is significant in resistance against infectious disease agents. Complement's mechanism of action in the various biological reactions in which it participates has occupied the attention of a host of investigators. In 1954, Pillemer et al. suggested the existence of a nonantibody-dependent protein in the serum which is
Complement (C) is a system of 20 soluble plasma and other body fluid proteins together with cellular receptors for many of them and regulatory proteins found on blood and other tissue cells. These proteins play a critical role in aiding phagocytosis of immune complexes, which activate the complement system. These molecules and their fragments resulting from the activation process are significant in the regulation of cellular immune responsiveness. Once complement proteins identify and combine with target substance, serine proteases are activated. This leads ultimately to the
Classic Pathway
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Figure 1. The classical and alter
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