Which complement pathway is initiated by antibody binding to antigen?

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

Answer: (A)

Antibody-bound antigen activates the classical complement pathway. When antibodies such as IgM or IgG coat a pathogen or form immune complexes, their Fc regions are recognized by C1q in the C1 complex. This recognition activates C1r and C1s, which cleave C4 and C2 to form the C4b2a complex, the classical pathway’s C3 convertase. This convertase cleaves C3 into C3a and C3b, with C3b contributing to opsonization and helping generate the C5 convertase that drives downstream steps toward the membrane attack complex. Other pathways are triggered differently: lectin pathway begins when mannose-binding lectin binds to carbohydrates on microbes, and the alternative pathway starts from spontaneous C3 hydrolysis on surfaces. The terminal pathway refers to the final assembly of the membrane attack complex, not the initiation. So, antibody binding to antigen starts the classical pathway.