How is the alternative complement pathway activated?

• A. Antibody-antigen complex
• B. Spontaneous C3 hydrolysis and C3b deposition on microbial surfaces
• C. Mannose-binding lectin activation
• D. C5 convertase formation via classical

Answer: (B)

Activation of the alternative pathway is driven by spontaneous, antibody-independent events on microbial surfaces. In plasma, C3 undergoes a low level of spontaneous hydrolysis to C3(H2O), which can bind factor B. Factor D then cleaves B to form C3bBb, the C3 convertase. When C3b is deposited on a microbe, it helps assemble more C3 convertase and creates a positive feedback loop that rapidly amplifies C3 cleavage on the surface. Properdin can stabilize this C3bBb complex, extending its activity. This pathway operates as part of innate immunity and does not require antibodies, distinguishing it from pathways activated by antibody-antigen complexes or by lectin binding. Eventually, the amplification leads to formation of C5 convertase and the membrane attack complex, enhancing pathogen lysis.