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complement pathways



  1. the classical complement pathway (initiated usually by binding of C1 to IgG or IgM antibody to C1) is a complex of three subunits: C1q, C1r, and C1s. After C1q is bound, C1r (an overbar indicates enzymatic activity) cleaves C1s to C1s. C1s cleaves both C4 into C4a and C4b as well as C2 into C2a and C2b. C2b combines with C4b to form C4b2b, which is a C3 convertase. C3 convertase cleaves C3 into C3a and C3b. C3b joins C4bC2b to form a C5 convertase (also known as C4b2b3b), which cleaves C5 into C5a and C5b. After C5b has been bound to the cell surface, the remainder of the complement components (C6–C9) as well as C5b form the membrane attack complex (MAC). MAC causes a hole in the cell membrane.
  2. in the alternative complement pathway, surface-bound C3b binds factor B, which is cleaved by factor D into Ba and Bb. C3bBb is an unstable C3 convertase unless properdin (P) binds to it to form C3bBbP. The stable C3 convertase generates more C3b. When a complex of C3bBbC3b is formed, this is the alternative pathway C5 convertase. From C5b through C9, the classical and alternative pathways are the same.
  3. In the lectin-binding pathway, mannose-binding protein initiates the pathway, which then uses components of the classical complement pathway. Some of the “a” components of both pathways have various biologic activities, C3a is an anaphylatoxin.

Further information

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© Copyright 2018 Wolters Kluwer. All Rights Reserved. Review date: Sep 19, 2016.