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Complement System On Attack

Complement components have immunologic activity both individually and in an activation cascade leading to a polymer formed by C5, C6, C7, C8, and C9 (the membrane attack complex, or MAC), which results in lysis of target cell membrane.

Early classic complement components (especially C3 products) act as opsonins and assist in the phagocytosis of bacterial particles by neutrophils and macrophages.

Certain complement split products (C3a and C5a) are chemotactic for phagocytic neutrophils and also act as “anaphylatoxins,” which directly stimulate mast cells and basophils to release histamine resulting in increasedvascular permeability.

Deficiency of early complement components is associated with increased pyogenic infections (C3 deficiency) and an increased incidence of autoimmune diseases, possibly owing to impaired clearance of immune complexes. The MAC appears especially important in host defense against Neisseria infection. Deficiency of any one of the terminal complement components can result in recurrent infections with Neisseria.

The complement system can be activated by three pathways:

Classical-IgM and IgG binding to antigen forming immune complexes that can bind Clq activating Clr and Cls to cleave c4. other proteins including c-reactive protein (binds Clq), serum amyloid P, and C4 nephritic factor can activate this pathway.

Alternative-activated by lipopolysaccharide on microbial cell surfaces in the absence of antibody. C3 and factor B bind to cell surface forming C3bBb, which functions to cleave more C3 molecules. This is part of the innare immune system. IgA complexes and C3 nephritic factor can also activate this pathway.

Lectin-mannan-binding lectin is secreted by the liver and binds to microbial ligands. This activates mannan-binding lectin-associated proteases that are related to Clr and Cls and can cleave C4 resulting in complement activation.