Fig. 2.32 The cleavage products of C3b are recognized by different complement receptors. After C3b is deposited on the surface of pathogens, it can undergo several conformational changes that alter its interaction with complement receptors. Factor I and MCP can cleave the C3f fragment from C3b, producing iC3b, which is a ligand for the complement receptors CR2, CR3, and CR4, but not CR1. Factor I and CR1 cleave iC3b to release C3c, leaving C3dg bound. C3dg is then recognized by CR2.
When only C3b binds to CR1, bacteria are not phagocytosed nonsignaling receptor that acts as a decoy receptor for C5a and may regulate activity of the C5a receptor. Proteins associated with the extracellular matrix, such as fibronectin, can also contribute to phagocyte activation; these are encountered when phagocytes are recruited to connective tissue and activated there.
Four other complement receptors—CR2 (also known as CD21), CR3 (CD11b:CD18), CR4 (CD11c:CD18), and CRIg (complement receptor of the immunoglobulin family)—bind to forms of C3b that have been cleaved by factor I but that remain attached to the pathogen surface. Like several other key components of complement, C3b is subject to regulatory mechanisms that cleave it into derivatives, such as iC3b, that cannot form an active convertase. C3b bound to the microbial surface can be cleaved by factor I and MCP to remove the small fragment C3f, leaving the inactive iC3b form bound to the surface (Fig. 2.32). iC3b is recognized by several complement receptors—CR2, CR3, CR4, and CRIg. Unlike the binding of iC3b to CR1, the binding of iC3b to the receptor CR3 is sufficient on its own to stimulate phagocytosis. Factor I and CR1 cleave iC3b to release C3c, leaving C3dg bound to the pathogen. C3dg is recognized only by CR2. CR2 is found on B cells as part of a co-receptor complex that can augment the signal received through the antigen-specific immunoglobulin receptor. Thus, a B cell whose antigen receptor is specific for an antigen of a pathogen will receive a strong signal on binding this antigen if it or the pathogen is also coated with C3dg. The activation of complement can therefore contribute to producing a strong antibody response.
The importance of opsonization by C3b and its inactive fragments in destroying extracellular pathogens can be seen in the effects of various complement deficiencies. For example, individuals deficient in C3 or in molecules that catalyze C3b deposition show an increased susceptibility to infection by a wide range of extracellular bacteria, including Streptococcus pneumoniae. We describe the effects of various defects in complement and the diseases they cause in Chapter 13.
The complement system and innate immunity.
2-14  The small fragments of some complement proteins initiate a local inflammatory response.