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Bactericidal systems in normal serum from month-old rabbits and guinea pigs were characterized in terms of activity against rough- and smooth-phase species of gram-negative bacteria. Killing of the rough strains in the absence of natural antibody required complement and at least one additional nonspecific component exhibiting lability to freezer storage and to heating at 52 degrees C. Bactericidal action against the smooth-phase organisms, on the other hand, appeared to require natural antibody in addition to complement and the labile component. Both nonspecific and specific bactericidal systems were also functional in normal serum from adult animals. In immune systems, the labile nonspecific component was not essential for bactericidal activity. Whereas immune systems were subject to inhibition by homologous endotoxins, the normal serum bactericidal systems were not, indicating that the natural antibodies in normal serum were specific for surface antigens other than the O-somatic polysaccharides. The significance of these observations is discussed in relation to probable complement pathways that mediate killing in each of the systems described.
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