2-11. CONTROL MECHANISMS
Several control mechanisms are involved in the complement system which
preclude uncontrolled activation and consumption of its protein components.
a. Labile binding sites on the activated proteins decay rapidly causing
dissociation of complexes. This decay results in failure to achieve membrane or surface
attachment of the complex, which restricts the complement activation to a local area.
b. C1 Inactivator binds to activated C1s and inhibits further activation of C4 and
C2 in the classical pathway.
c. Factor I prevents further activation of C3b by cleaving the molecule into
inactive fragments, C3c and C3d. Factor I and C4 binding protein displace C4b from
the C4b2a complex and cleaves C4b into the inactive fragments, C4c and C4d.
d. Factor H accelerates the action of factor I on C3b and also displaces the Bb
from the C3b, Bb complex of the alternative pathway, rendering it inactive.
Several substances are released to produce the biological effects of complement
a. Anaphylatoxins (C3a, C4a, C5a). Anaphylatoxins cause the release of
histamine from mast cells and basophils. Histamine in turn enhances vascular
permeability and causes smooth muscle contractions, resulting in edema and
b. Opsonins (C3b, C4b). Many cells, including polymorphonuclear cells, B
lymphocytes, and macrophages, have receptor sites for C3b and C4b. Also many of
the nonimmunological activators have receptors for C3b and C4b. These fragments
bind to their receptors and act to facilitate adherence and phagocytosis of the target
c. Chemotactic Factor (C5a). The function of the chemotactic factor is to
induce and direct the migration and accumulation of phagocytic cells at the site of the