There are 3 distinct pathways of complement activation. The classical system is antibody dependent whereas the other 2 pathways, lectin and alternative, are antibody independent and are initiated by reaction of complement proteins with surface molecules of microorganisms rather than antibody. All 3 pathways generate C3, and C5 convertases and bound C5b, which is converted into a membrane attack complex (MAC). The MAC complex forms a large channel through the membrane of the target cell, enabling ions and small molecules to diffuse freely across the membrane. Hydrolysis of C3 by C3 convertase enzymes of the classical, lectin and alternative pathways is the major amplification step, generating large amounts of C3b, which forms part of the C5 convertase. C3b also can diffuse away from the activating surface and bind to immune complexes of foreign cell surfaces, where it functions as an opsonin by phagocytic cells bearing C3b receptors.

Nomenclature: Classical pathway components are labeled with a C and a number (e.g., C1, C3). Because of the sequence in which they were identified, the first four components are numbered C1, C4, C2 and C3. Alternative pathway components are lettered (e.g., B, P, D). Cleavage fragments are designated with a small letter following the designation of the component (e.g., C3a and C3b are fragments of C3). Inactive C3b is designated iC3b. Polypeptide chains of complement proteins are designated with a Greek letter after the component (e.g., C3alpha and C3beta are the alpha and beta chains of C3. Cell membrane receptors for C3 are abbreviated CR1, CR2, CR3, and CR4.

(1) classical pathway See outline

(2) lectin pathway see outline

(3) alternative pathway (AP):  See outline