Ambivalent effect of immunoglobulins on the complement system: Activation versus inhibition

Pathogen and self-specific antibodies are known for their ability to trigger generation of active complement fragments that then serve as effectors of cell damage. The remainder of the immunoglobulin pool of the host has the capacity to quench harmful effects of activated complement cascade by preventing active complement fragments from binding to their specific receptors. This scavenging function is mediated by different acceptor sites within the immunoglobulin molecule. Large fragments, such as C3b and C4b are preferentially bound to the Fc region, while biologically potent C3a and C5a anaphylatoxins get neutralized by low-affinity interaction with the constant domain of the F(ab)′2F(ab)′2. The ambivalent effect of immunoglobulins on the complement system implies their role in homeostasis as well as expansion of use of high-dose intravenous immunoglobulins in diseases and states mediated by inappropriate complement activation.