Complement in Infections

The complement system provides a fundamental component of the body's immune response to invading microorganisms. This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. Complement is activated by three pathways: the classical pathway, the alternative pathway, and the lectin pathway. The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage, inflammation, and depletion of complement components. A deficiency in any component of the classical pathway is associated with an increased risk of immunological disease and recurrent bacterial infections. Pneumolysin is a potent virulence factor produced by all serotypes of S. pneumoniae. Pneumolysin is released as a 52 kDa soluble monomer. It binds cholesterol-containing membranes and the monomeric subunits oligomerize to form a pore in the target cell membrane that leads to cell death. Pneumococcal surface protein C (PspC) is a major virulence factor of Streptococcus pneumoniae and contributes to many different biological functions.