complement cascade

Classification: Classical Pathway: - under most conditions, initiation of the classical pathway of complement requires the interaction of antigen with C1-fixing antibody - not all classes of immunoglobulin activate the classical pathway - IgM & IgG subclasses IgG1, IgG2, & IgG3 bind & activate C1. Alternative Pathway: - the alternative pathway of complement activation does not have an absolute requirement for antibody & does not use C1, C2, or C4 - it is of particular importance before the appearance of antibody during the course of an infection Mannan-binding lectin pathway: - third early pathway of host defense also important before the appearance of antibody during the course of an infection Classical Pathway Alternative Pathway Ag:Ab || || C3 / || C1 Ag || --> C3a | / | || || | || || C14b Ag-C3b | | || || | || || C14b2b2a Ag-C3bBb | | || || | || || C14b2b2a3b Ag-C3bBbP ----------------------- ___ _/ C5 ___ _/ C5 -------> ___ /__/ C5b ------> C5a C5a C6,C7 || ---------> || / C5b67 C8,C9 || ---------> || / C5b6789 (Membrane Attack Complex) * also see figure A & figure B which shows regulatory interactions Pathology: - increased susceptibility to infection with Neisseria with: a) defects the terminal components of the classical complement pathway C5-C9 & formation of the membrane attack complex b) defects in the complement alternative pathway (P & D) c) defects in the mannan-binding lectin pathway Comparative biology: - West Nile virus infection of neurons triggers activation of the complement cascade within the hippocampus of mice [3] - microglia then trim presynaptic terminals in response to complement activation (neurons remain viable)