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Figure 4 | Arthritis Research & Therapy

Figure 4

From: Parietal and intravascular innate mechanisms of vascular inflammation

Figure 4

The complement system. Effectors: Irrespective of the activation pathway, three families of molecules are generated during the complement cascade: complement opsonins (C3b and C4b), complement anaphylotoxins (C3a and C5a) and the terminal complement complex (TCC). The key common step in the progression of the complement cascade is the generation of a C3-convertase, which cleaves inactive C3 into C3a and C3b. The latter binds to the C3-convertase to generate a C5-convertase, which generates C5a and C5b from inactive C5. C5b interacts with factors 6 to 9 to establish the TCC, which induces cell lysis by acting as a membrane attack complex or accumulates in the fluid phase or in extravascular spaces as an inactive moiety (iTCC). It can also bind to cell membranes as a sublytic membrane attack complex. Activators: Both in the classical and the lectin pathway, cleaving enzymes (namely component C1r and C1s of the C1 factor in the classical pathway and mannose binding lectin (MBL)-associated serine proteases in the MBL pathway) are destabilized and activated by antigen–antibody interactions (either directly in the case of MBL or with the intermediation of component C1q in the classical pathway) to process C4 to C4a, C4b and C2a, C2b respectively. The C4bC2a complex corresponds to the first variant of C3-convertase. Moieties expressed on the bacterial surface determine in the alternative pathway the spontaneous generation of the C3bBb complex, which acts as the second solid phase variant of C3-convertase. This atypical form of C3-convertase develops when partial spontaneous activation of C3 (tickover) is accompanied by binding of C3 with factor B, which in turn is cleaved to factor Ba and Bb by factor D to generate the C3(H2O)Bb complex or fluid-phase C3-convertase.

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