Which pathway of the complement system is activated by antibody-antigen complexes?

• A. Classical pathway is activated by antibody–antigen complexes; lectin and alternative pathways also exist.
• B. Lectin pathway is the only one that activates complement.
• C. Alternative pathway begins with immune complex formation.
• D. All pathways are activated by T cell signals.

Answer: (A)

Antibody–antigen complexes primarily trigger the classical pathway of the complement system. When antibodies bind to an antigen, the C1q component of the C1 complex recognizes and binds to the Fc portions of those antibodies. This activates C1r and C1s, which then cleave C4 and C2 to form the C4b2a C3 convertase. This enzyme cleaves C3 into C3a and C3b, driving the cascade forward to promote inflammation, opsonization, and, ultimately, the assembly of the membrane attack complex.

There are two other pathways, but they do not rely on antibody-antigen immune complexes: the lectin pathway is initiated when mannose-binding lectin binds carbohydrate patterns on pathogens, and the alternative pathway is continuously activated at low levels and amplifies the response on microbial surfaces via C3bBb, without needing antibodies. The statements that place the trigger on lectin alone, or on immune complexes starting the alternative pathway, or that rely on T cell signals to activate all pathways, do not reflect how complement activation is organized.