Microbial subversion of the immune response

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Abstract
A microbe becomes a pathogen by evading—to a greater or lesser extent—the immune defenses of its host. The mechanisms that have evolved for so doing are legion in number and striking in their diversity and ingenuity. They involve mechanisms to evade recognition by—and mechanisms to subvert the effector mechanisms of—both the innate and the adaptive immune response (see Table 1). All classes of infectious agents from the smallest viruses to helminth worms use these techniques albeit in somewhat different ways. An almost ubiquitous target for these subversion mechanisms is the complement system and it is with the subversion of complement by smallpox virus that the report in this issue of PNAS by Rosengard et al. (1) is concerned. Mechanisms for microbial subversion of the immune response An extremely simplified view of the complement system is shown in Fig. 1. There are two principal biologically important steps. The first is brought about by the activation (and subsequent fixation) of C3 by C3-converting enzymes. This step generates the bound C3 fragments (C3b and iC3b) that interact with complement receptors on inflammatory cells and the activation fragments C3a and C5a, which also activate inflammatory cells. The second important step is the formation of the membrane attack complex, which inserts a channel into cell membranes. Simplified view of …