The complement system (Chap. 308) consists of a group of serum proteins functioning as a cooperative, self-regulating cascade of enzymes that adhere to— and in some cases disrupt—the surface of invading organisms. Some of these surface-adherent proteins (., C3b) can then act as opsonins for destruction of microbes by phagocytes. The later, "terminal" components (C7, C8, and C9) can directly kill some bacterial invaders (notably, many of the neisseriae) by forming a membrane attack complex and disrupting the integrity of the bacterial membrane, thus causing bacteriolysis. Other complement components, such as C5a, act as chemoattractants for PMNs (see below) | Chapter 113. Introduction to Infectious Diseases Host-Pathogen Interactions Part 5 The complement system Chap. 308 consists of a group of serum proteins functioning as a cooperative self-regulating cascade of enzymes that adhere to and in some cases disrupt the surface of invading organisms. Some of these surface-adherent proteins . C3b can then act as opsonins for destruction of microbes by phagocytes. The later terminal components C7 C8 and C9 can directly kill some bacterial invaders notably many of the neisseriae by forming a membrane attack complex and disrupting the integrity of the bacterial membrane thus causing bacteriolysis. Other complement components such as C5a act as chemoattractants for PMNs see below . Complement activation and deposition occur by either or both of two pathways the classic pathway is activated primarily by immune complexes . antibody bound to antigen and the alternative pathway is activated by microbial components frequently in the absence of antibody. PMNs have receptors for both antibody and C3b and antibody and complement function together to aid in the clearance of infectious agents. PMNs short-lived white blood cells that engulf and kill invading microbes are first attracted to inflammatory sites by chemoattractants such as C5a which is a product of complement activation at the site of infection. PMNs localize to the site of infection by adhering to cellular adhesion molecules expressed by endothelial cells. Endothelial cells express these receptors called selectins CD62 ELAM-1 in response to inflammatory cytokines such as tumor necrosis factor a and interleukin 1. The binding of these selectin molecules to specific receptors on PMNs results in the adherence of the PMNs to the endothelium. Cytokine-mediated upregulation and expression of intercellular adhesion molecule 1 ICAM 1 on endothelial cells then take place and this latter receptor binds to ß2 integrins on PMNs thereby facilitating diapedesis into the extravascular
