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Figure 1. The classical and terminal complement pathway cascades. C1q is part of the C1 complex, which comprises a single C1q molecule bound to two molecules (each of the serine proteases C1r and C1s). C1q is a calcium-dependent protein belonging to the collectin family of proteins, which contains both collagen-like and lectin domains, hence the name collectin. C1q has six globular heads, linked together by a collagen-like tail, which surrounds the (C1r-C1s)2 complex. Binding of more than one of the C1q heads to the Fc portion of antibodies (binding on the pathogen surface) causes a conformational change in the (C1r-C1s)2 complex, which leads to activation of an autocatalytic enzymatic activity in C1r; the active form of C1r cleaves its associated C1s to generate an active serine protease. Once activated, the C1s enzyme acts on the next two components of the classical pathway, cleaving C4 and then C2 to generate two large fragments, C4b and C2a, which together form the C3 convertase of the classical pathway. The C4b molecules also acts as opsonins, they bind covalently to the pathogen and immune complexes, thereby targeting them for destruction by phagocytes and epuration, respectively. The most important activity of the C3 convertase is to cleave large numbers of C3 molecules to produce C3a and C3b molecules. C3a initiates a local inflammatory response, whereas C3b molecules opsonize the pathogen surface as well as immune complexes. C3b also binds the C3 convertase to form a C5 convertase that produces the most important small peptide mediator of inflammation, C5a, as well as a large active fragment, C5b, which initiates the common complement pathway. This comprises a sequence of polymerization reactions in which the terminal complement components interact to form a membrane-attack complex, which creates a pore in the cell membranes of some pathogens that can lead to their death.
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Figure 2. C4A and C4B interactions with immune complexes and pathogen surfaces. C4A proteins interact more efficiently with immune complexes, and C4B proteins are more important in the defense against microbes.
(Figure omitted. See article PDF.)
Figure 3. Suggested roles for complement in the pathogenesis of systemic lupus erythematosus. IC: Immune complex.
(Figure omitted. See article PDF.)
Complement was discovered in the late 19th Century as...