Functions of complement, proteins of classical pathway, amplifying loop, alternative pathway, proteins of alternative pathway, membrane-attack complex, complement regulation

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Colorado State University
Microbio, Immun, Pathology
MIP 342
Alan Schenkel

6 FebruaryFunctions of complementC3a and C5a recruit phagocytic cells to the site of infection and promote inflammationPhagocytes with receptors for C3b engulf and destroy the pathogenCompletion of the complement cascade leads to formation of a membraneattack complex MAC which disrupts cell membrane and causes cell lysisThe newly synthesized C3 protein is cleaved to generate a chain and an chain held together by disulfide bondsBefore cleavage by C3 convertase the thioester bond within TED is protected from reactingCleavage of C3 releases C3a and a change in conformation of C3b allows the thioester bond to react with a chemical group usually hydroxyl or amine on the pathogen surfaceNlinked glycoproteins of yeasts contain many terminal mannose residues whereas glycoproteins of vertebrates have terminal sialic acid residuesMBL binds sugar expressed highly on microbesActivated MASP2 associated with MBL or ficolin cleaves C4 to C4a and C4b which binds to the microbial surfaceC4b then binds C2 which is cleaved by MASP2 to C2a and C2b forming the C4b2b complexC4b2b is an active C3 convertase cleaving C3 to C3a and C3b which binds to the microbial surface or to the convertase itselfone molecule of C4b2b can cleave up to 1000 molecules of C4 to C3bMany C3b molecules bind to the microbial surfaceClassical pathwaysame but C1q instead of MBLMASP similar to C1rC1scleave C4C1q binds IgM antibody already bound to pathogens serine protease activity activated
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