310 art 1 Immune effector mechanisms Cell membrane NH CRI or MCP Factor I Cell membrane C3f O=C SH Factor h or CRi or MCP Factor I v C3dg Bound c3b iC3b FIGURE 13-10 Inactivation of bound C4b and C3b by regulatory pathway, factor H, CRl, or MCP bind to Ccb and act as cofactors proteins of the complement system. (a)In the classical pathway, for factor I-mediated cleavage of C4b. Free diffusible fragments C4bBP( C4b-binding protein), CR1(complement receptor type 1), are shown in dark shades: membrane bound components in light or MCP(membrane cofactor protein) bind to C4b and act as cofac. shades tors for factor I-mediated cleavage of C4b. (b)In the alternative Biological Consequences of The Membrane- Attack Complex Can Lyse a Broad Spectrum of Cells Complement Activation The membrane-attack complex formed by complement acti- Complement serves as an important mediator of the hu- vation can lyse gram-negative bacteria, parasites, viruses, moral response by amplifying the response and converting erythrocytes, and nucleated cells. Because the alternative and it into an effective defense mechanism to destroy inad- lectin pathways of activation generally occur without an ini ing microorganisms. The MAC mediates cell lysis, while tial antigen-antibody interaction, these pathways serve as im other complement components or split products participate portant innate immune defenses against infectious micro- in the inflammatory response, opsonization of antigen, organisms. The requirement for an initial antigen-antibody viral neutralization, and clearance of immune complexes reaction in the classical pathway supplements these nonspe- (Table 13-3, page 312) cific innate defenses with a more specific defense mecha Many of the biological activities of the complement sys- nism. In some instances, the requirement for antibody in the tem depend on the binding of complement fragments to activating event may be supplied by so-called natural anti- complement receptors, which are expressed by various cells. bodies, which are raised against common components of In addition, some complement receptors play an important ubiquitous microbes role in regulating complement activity by binding biologi The importance of cell-mediated immunity in host cally active complement components and degrading them fense against viral infections has been emphasized in previ into inactive products. The complement receptors and their ous chapters. Nevertheless, antibody and complement do primary ligands, which include various complement compo- play a role in host defense against viruses and are often ents and their proteolytic breakdown products, are listed in crucial in containing viral spread during acute infection Table 13-4 (page 312) and in protecting against reinfection. Most-perhapsBiological Consequences of Complement Activation Complement serves as an important mediator of the hu￾moral response by amplifying the response and converting it into an effective defense mechanism to destroy invad￾ing microorganisms. The MAC mediates cell lysis, while other complement components or split products participate in the inflammatory response, opsonization of antigen, viral neutralization, and clearance of immune complexes (Table 13-3, page 312). Many of the biological activities of the complement sys￾tem depend on the binding of complement fragments to complement receptors, which are expressed by various cells. In addition, some complement receptors play an important role in regulating complement activity by binding biologi￾cally active complement components and degrading them into inactive products. The complement receptors and their primary ligands, which include various complement compo￾nents and their proteolytic breakdown products, are listed in Table 13-4 (page 312). The Membrane-Attack Complex Can Lyse a Broad Spectrum of Cells The membrane-attack complex formed by complement acti￾vation can lyse gram-negative bacteria, parasites, viruses, erythrocytes, and nucleated cells. Because the alternative and lectin pathways of activation generally occur without an ini￾tial antigen-antibody interaction, these pathways serve as im￾portant innate immune defenses against infectious micro￾organisms. The requirement for an initial antigen-antibody reaction in the classical pathway supplements these nonspe￾cific innate defenses with a more specific defense mecha￾nism. In some instances, the requirement for antibody in the activating event may be supplied by so-called natural anti￾bodies, which are raised against common components of ubiquitous microbes. The importance of cell-mediated immunity in host de￾fense against viral infections has been emphasized in previ￾ous chapters. Nevertheless, antibody and complement do play a role in host defense against viruses and are often crucial in containing viral spread during acute infection and in protecting against reinfection. Most—perhaps 310 PART III Immune Effector Mechanisms FIGURE 13-10 Inactivation of bound C4b and C3b by regulatory proteins of the complement system. (a) In the classical pathway, C4bBP (C4b-binding protein), CR1 (complement receptor type 1), or MCP (membrane cofactor protein) bind to C4b and act as cofac￾tors for factor I–mediated cleavage of C4b. (b) In the alternative pathway, factor H, CR1, or MCP bind to Ccb and act as cofactors for factor I–mediated cleavage of C4b. Free diffusible fragments are shown in dark shades; membrane bound components in light shades. (a) Factor I Cell membrane Cell membrane C NH O S S S S S S S S C4d C4c S S S S S S S S C4c S S S S S S S S Bound C4b SH C4bBP or CR1 or MCP S S S S Bound C3b (b) Factor I Factor H or CR1 or MCP C O SH R O S S S S iC3b C3f Factor I S S S S C3c S S S S C3c C NH O C O SH R O C O SH R O C3dg