Role of the Classical Complement Pathway in Immune Response Against Pathogens

The classical complement pathway is activated when

C1 binds to the antibody in an antigen-antibody complex

The classical complement pathway is activated when certain antibodies, mainly IgM or IgG, bind to specific antigens on the surface of pathogenic microorganisms (e.g. bacteria, viruses, fungi) or other foreign particles (e.g. toxins). This binding, which is part of the specific immune response, triggers a series of enzymatic reactions involving C1 complex consisting of C1q, C1r, and C1s proteins. C1q binds to the antibody-antigen complex and activates C1r, which cleaves C1s into its active form. Activated C1s then cleaves other complement proteins, starting with C4 and C2, to form the C3 convertase enzyme. C3 convertase cleaves C3 into its active fragments – C3a and C3b. C3b can then bind to the surface of the pathogen or foreign particle, marking it for destruction by various mechanisms including phagocytosis and formation of the membrane attack complex (MAC). The classical complement pathway is one of three main pathways that lead to complement activation and is particularly important for clearance of infections caused by extracellular pathogens.

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