Which statement correctly describes the classical, lectin, and alternative pathways of complement activation?

• A. All three pathways are identical in trigger and progression.
• B. Classical is triggered by antibody-antigen complexes; lectin is triggered by mannose-binding lectin binding to pathogens; alternative is spontaneous activation on microbial surfaces; all converge to C3 convertase.
• C. Classical triggered by pathogens direct; lectin by antibodies; alternative by C-reactive protein.
• D. Classical pathway only operates in the presence of C-reactive protein and cholesterol.

Answer: (B)

Three complement pathways are activated by different triggers but converge on a common sequence that amplifies the immune response. The classical pathway starts when antibodies (IgM or IgG) bound to antigens form immune complexes and are recognized by the C1 complex, leading to cleavage of C4 and C2 to form the C3 convertase C4b2a. The lectin pathway is initiated when mannose-binding lectin binds to carbohydrate patterns on microbial surfaces; MASP-1 and MASP-2 then cleave C4 and C2 to also form the C3 convertase C4b2a. The alternative pathway is initiated spontaneously on microbial surfaces through tickover of C3 to C3b, which binds factor B and, after cleavage by factor D, forms the C3 convertase C3bBb; this pathway does not require antibodies or lectins and is stabilized by properdin. All three pathways generate C3 convertases, setting off downstream steps that lead to inflammation, opsonization, and the membrane attack complex.