ABSTRACT

Throughout the ages, man has been fascinated and, at times, obsessed by the marvelous, mysterious and even baffling qualities of the blood. A ferment of research activity in the latter 1800s was designed to elucidate mechanisms of host immunity against infectious disease agents. Elie Metchnikoff’s demonstration that blood cells could phagocytize (ingest) invading microorganisms led to the ‘cellular theory’, the first of two opposing concepts of bacteriolysis. The other, the ‘humoral

theory’ was based on Fodor, Nuttall and Buchner’s detection of the heat-labile constituent of fresh, cell-free serum, which could include bacteriolysis. Hans Buchner named this principle ‘alexin’ (Greek without a name) (Figure 1). In 1889, Buchner1 (Figure 2) described a heat-labile bactericidal principle in the blood, which he termed alexine. This was later identified as the complement system. In 1894, Pfeiffer discovered specific in vivo lysis of bacteria by observing that cholera vibrios injected

into the peritoneum of immune guinea pigs were lysed. In 1895, Jules Bordet2 (Figure 3), working at the Institut Pasteur in Metchnikoff’s laboratory, extended this finding by demonstrating 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 Ehrlich3 called Bordet’s alexine ‘das Komplement’. In 1901, Bordet and Gengou4 developed the complement fixation test to measure antigen-antibody reactions (Figures 4-6). von Wassermann applied this principle to the serologic diagnosis of syphilis.