Fig. 2.15 gives a highly simplified preview of the initiation mechanisms and outcomes of complement activation. The three pathways of complement activation are initiated in different ways. The lectin pathway is initiated by soluble carbohydrate-binding proteins—mannose-binding lectin (MBL) and the ficolins—that bind to particular carbohydrate structures on microbial surfaces. Specific proteases, called MBL-associated serine proteases (MASPs), that associate with these recognition proteins then trigger the cleavage of complement proteins and activation of the pathway. The classical pathway is initiated when the complement component C1, which comprises a recognition protein (C1q) associated with proteases (C1r and C1s), either recognizes a microbial surface directly or binds to antibodies already bound to a pathogen. Finally, the alternative pathway can be initiated by spontaneous hydrolysis and activation of the complement component C3, which can then bind directly to microbial surfaces.
These three pathways converge at the central and most important step in complement activation. When any of the pathways interacts with a pathogen surface, the enzymatic activity of a C3 convertase is generated. There are various types of C3 convertase, depending on the complement pathway activated, but each is a multisubunit protein with protease activity that cleaves complement component 3 (C3). The C3 convertase is bound covalently to the pathogen surface, where it cleaves C3 to generate large amounts of C3b, the main effector molecule of the complement system; and C3a, a small peptide that binds to
The complement system and innate immunity.
C3a and C5a recruit phagocytic cells to the site of infection and promote infammation C3a infected tissue Phagocytes with receptors for C3b engulf and destroy the pathogen Completion of the complement cascade leads to formation of a membrane-attack complex (MAC), which disrupts cell membrane and causes cell lysis factor D factor B properdin C3 C1q, C1r, C1s C4 C2 MBL/fcolin, MASP-2 C4 C2 C3a C3 complement receptors All pathways generate a C3 convertase, which cleaves C3, leaving C3b bound to the microbial surface and releasing C3a C3b C6 C5b C8 C7 C9 MAC C3b Phagocyte