Immune complexes trigger activation of which complement pathway?

• A. Lectin pathway
• B. Alternative pathway
• C. Classical complement pathway
• D. Terminal pathway

Answer: (C)

Immune complexes activate the classical complement pathway. When antibodies such as IgG or IgM bind a pathogen or antigen, their Fc regions are recognized by the C1 complex (C1q with associated C1r and C1s). This recognition starts the proteolytic cascade: C1s cleaves C4 and C2 to form the C4b2a C3 convertase, which then cleaves C3 into C3a and C3b. C3b helps opsonize the invader and leads to further activation that eventually forms the membrane attack complex (C5b-9). In contrast, the lectin pathway is triggered by mannose-binding lectin binding to microbial sugars, and the alternative pathway is activated directly on microbial surfaces without antibodies. The terminal steps to form the membrane attack complex can be reached from any initial pathway, but immune complexes specifically initiate the classical route.