Complement was first discovered because of its activity in helping or complementing the action of antibodies in clearing pathogens from an organism. The Complement system consists of a number of small plasma proteins which normally circulate as inactive precursors capable of being activated upon cleavage by proteases. Several Complement proteins are themselves proteases which when activated by one of several possible mechanisms, can go on to activate other Complement components in a sequential cascade. The end result is a massively amplified response ultimately leading to the formation of the Membrane Attack Complex (MAC) which creates a pore in the cell membranes of certain pathogens causing their death.

There are three pathways to Complement activation, the Classical pathway, the Alternative pathway and the Mannose Binding Lectin (MBL) pathway which all lead to a common final pathway, forming of MAC. The Classical pathway is triggered by the binding of the first protein in the Complement cascade, C1q which is part of the C1 complex, to the Fc portion of immunoglobulin bound to antigen or by C1q binding directly to target antigens on the pathogen surface. This leads to activation of C1s, which in turn leads to cleavage of C4 into C4a and C4b. This in turn leads to cleavage of C2 into C2a and C2b. A complex of C4b2a then leads to cleavage of C3 into C3a and C3b. C3b can act as an opsonising agent for phagocytes and/or can initiates the common final pathway to the formation of MAC.

The Alternative pathway, which is antibody independent, depends on C3 undergoing spontaneous cleavage and assembly with other factors to form C3 Convertase which is a highly efficient C3 cleaving enzyme. Cleavage of C3 into C3a and C3b and is part of the common final pathway to the formation of MAC.

The Mannose Binding Lectin pathway is similar to the Classical pathway and activates many of the components of the Classical pathway. MBL binds to mannose on bacterial cell surfaces leading to activation of serine proteases which lead to the cleavage steps of C4 and C2 of the classical pathway leading to cleavage of C3 into C3a and C3b is part of the common final pathway to the formation of MAC.

Multiple regulatory molecules act on various stages of these complement pathways either enhancing or inhibiting Complement activity. These include Complement Receptors which can bind C3 and inhibit its action and Decay Accelerating Factor (DAF or CD55) which accelerates the disassembly of C3 Convertase, thus blocking the formation of MAC.