Complement System The complement system, specifically through the actions of proteins C3a and C3b, destroys microbes. – Comprises inactive proteins that circulate in the blood; of these proteins, the products of C3 cleavage (C3a and C3b) have multifold functions. • Three pathways lead to C3 cleavage: – In the classical pathway, C1 is "fixed" to antibody-antigen complexes, which initiates a cascade of events that lead to C3 cleavage. – The alternative pathway is triggered by spontaneously activated C3b. – The lectin pathway is triggered when lectins, such as, mannose-binding lectin, binds microbial sugars and marks them for phagocytosis. • Effects of cleaved C3: – C3a has pro-inflammatory effects; it recruits neutrophils and macrophages. – C3b opsonizes microbes, which involves binding to pathogens and marking them for phagocytosis. – Membrane Attack Complexes (MAC): C3b combines with other complement proteins (C5b, C6, C7, C8, and C9) to form a pore in the membrane of the microbe; massive water influx through the MAC lyses the microbe.
