312 art 1 Immune effector mechanisms TABLE 13-3 Summary of biological effects mediated by complement products Effect Complement product mediation Cell lys C5b-9, the membrane-attack complex(MAC) Inflammatory response Degranulation of mast cells and basophils T : 3a, C4a, and C5a(anaphylatoxins) Degranulation of eosinophils 3a, C5a, c5b67 Aggregation of platelets Inhibition of monocyte/macrophage migration and induction of their spreading Release of neutrophils from bone marrow Release of hydrolytic enzymes from neutrophil Increased expression of complement receptors CR3)on neutrophil Opsonization of particulate antigens, increasing their phagocytosis 33b Viral neutralization C3b, C5b-9(MAC) Solubilization and clearance of immune complexes Boldfaced component is most important in mediating indicated effect. 'Degranulation leads to release of histamine and other mediators that induce contraction of smooth muscle and increased permeability of vessels. gonorrheae resistant to complement-mediated killing have Gram-positive bacteria are generally resistant to comple- been associated with disseminated gonococcal infections in ment-mediated lysis because the thick peptidoglycan layer in humans. Some evidence suggests that the membrane pro- their cell wall prevents insertion of the MAC into the inner teins of resistant Neisseria strains undergo noncovalent in- membrane. Although complement activation can occur on teractions with the MAC that prevent its insertion into the the cell membrane of encapsulated bacteria such as Strepto- resistant gram-negative bacteria are the exception; most C3b deposited on the membrane and the Cri on phagocytic gram-negative bacteria are susceptible to complement- cells. Some bacteria possess an elastase that inactivates C3a mediated lysis and C5a, preventing these split products from inducing an TABLE 13-4 Complement-binding receptors Receptor Major ligands Activity Cellular distribution CR1(CD3 C3b. C4b Blocks formation of c 3 Erythrocytes, neutrophils, convertase binds immune monocytes, macrophages, complexes to cells eosinophils, follicular dendritic cells. B cells some t cells CR2(CD21) C3d. cda Part of B-cell coreceptor; B cells, follicular dendritic binds Epstein-Barr virus cells CR3(CD11b/18) Bind cell-adhesion molecules Monocytes, macrophages, C3b on neutrophils, facilitating their neutrophils, natural killer CR4(CD11c/18) extravasation bind immun cells. some T cells complexes, enhancing their C3a/C4a receptor C3a, C4a Induces degranulation of mast Mast cells, basophils, granulocytes Is and basophils C5a receptor Induces degranulation of mast Mast cells, basophils, granulocytes. Is and basophils monocytes, macrophages, platelets, endothelial cells Cleavage of C3dg by serum proteases generates C3d and C3g.312 PART III Immune Effector Mechanisms TABLE 13-3 Summary of biological effects mediated by complement products Effect Complement product mediating* Cell lysis C5b–9, the membrane-attack complex (MAC) Inflammatory response Degranulation of mast cells and basophils† C3a,C4a, and C5a (anaphylatoxins) Degranulation of eosinophils C3a, C5a Extravasation and chemotaxis of leukocytes at inflammatory site C3a, C5a, C5b67 Aggregation of platelets C3a, C5a Inhibition of monocyte/macrophage migration and induction Bb of their spreading Release of neutrophils from bone marrow C3c Release of hydrolytic enzymes from neutrophils C5a Increased expression of complement receptors C5a type 1 and 3 (CR1 and CR3) on neutrophils Opsonization of particulate antigens, increasing their phagocytosis C3b, C4b, iC3b Viral neutralization C3b, C5b–9 (MAC) Solubilization and clearance of immune complexes C3b *Boldfaced component is most important in mediating indicated effect. † Degranulation leads to release of histamine and other mediators that induce contraction of smooth muscle and increased permeability of vessels. TABLE 13-4 Complement-binding receptors Receptor Major ligands Activity Cellular distribution CR1 (CD35) C3b, C4b Blocks formation of C3 Erythrocytes, neutrophils, convertase; binds immune monocytes, macrophages, complexes to cells eosinophils, follicular dendritic cells, B cells, some T cells CR2 (CD21) C3d, C3dg,* Part of B-cell coreceptor; B cells, follicular dendritic iC3b binds Epstein-Barr virus cells, some T cells CR3 (CD11b/18) Bind cell-adhesion molecules Monocytes, macrophages, iC3b on neutrophils, facilitating their neutrophils, natural killer CR4 (CD11c/18) extravasation; bind immune cells, some T cells complexes, enhancing their phagocytosis C3a/C4a receptor C3a, C4a Induces degranulation of mast Mast cells, basophils, granulocytes cells and basophils C5a receptor C5a Induces degranulation of mast Mast cells, basophils, granulocytes, cells and basophils monocytes, macrophages, platelets, endothelial cells *Cleavage of C3dg by serum proteases generates C3d and C3g. } gonorrheae resistant to complement-mediated killing have been associated with disseminated gonococcal infections in humans. Some evidence suggests that the membrane pro￾teins of resistant Neisseria strains undergo noncovalent in￾teractions with the MAC that prevent its insertion into the outer membrane of the bacterial cells. These examples of resistant gram-negative bacteria are the exception; most gram-negative bacteria are susceptible to complement￾mediated lysis. Gram-positive bacteria are generally resistant to comple￾ment-mediated lysis because the thick peptidoglycan layer in their cell wall prevents insertion of the MAC into the inner membrane. Although complement activation can occur on the cell membrane of encapsulated bacteria such as Strepto￾coccus pneumoniae, the capsule prevents interaction between C3b deposited on the membrane and the CR1 on phagocytic cells. Some bacteria possess an elastase that inactivates C3a and C5a, preventing these split products from inducing an