Complement system

The Complement System
The complement system is a complex system of serum proteins which interact in a cascade, many of the early components are serine proteases which activate each other sequentially.The complement system is composed of more than 30 different plasma proteins which are produced mainly by the liver ,in the absence of infection these protein circulates in an active forms > In the presence of pathogens or the antibody bound to pathogens the complement system becomes activated particular complement proteins interacte with each other to form several to form several different pathways of complement activation . There are two pathways by which complement activation is initiated. The classical pathway is activated by antibody-antigen complexes. The alternative pathway is initiated when a previously activated complement component binds to the surface of a pathogen, where it is protected. Activation of complement has a number of important biological effects.

Nomenclature: the components of the classical pathway are called C1, C2 etc. Where components are proteolytically cleaved, the products are referred to as C2a + C2b etc. Alternative Pathway specific components are given letters as names (factor B etc).

C3 is THE key component of Complement
The central component of the complement system is C3. C3 is an abundant serum protein (1.2mg/ml) which contains an unusual internal thiolester bond. In native C3 this bond is stable but this thiolester bond can become highly reactive as a result of conformational changes in the C3 protein structure. Generally the activation of C3 comes about as a result of proteolytic cleavage of the C3 molecule into 2 biologically active fragments.

C3------- vascular permeability -
Phagocyte activation-
C4------- recognition of M.O
Phagocytosis
Killing by PMNs
The Alternative Pathway

The alternative pathway(AP) is an innate immune mechanism which exploits the properties of C3.


Initiation of the AP relies on the generation of an activated C3 molecule. There are various ways in this initiating activated C3 can be generated. These include proteolysis by enzymes derived from bacteria themselves and, via blood clotting enzymes, injury. However activation of C3 can occur spontaneously. This process proceeds constitutively at a slow rate. The activated thiolester will normally be rapidly hydrolysed in solution.

But if C3 binds via its ester bond to a cell surface or protein complex, it can recruit the AP serum protein factor B. Factor B, once bound to activated C3, is cleaved by another serum protein, factor D, and the resulting complex forms an enzyme which activates further C3 molecules by cleaving them to form the activated fragment C3b (plus C3a).



At this point the Alternative Pathway becomes self-generating by a positive feedback loop, those activated C3b molecules which are not quenched by hydrolysis binding to nearby surfaces, recruiting factors B and D and generating the C3bBb complex which in turn cleaves more C3 etc. The complex C3bBb is known as the alternative C3 convertase. This complex is a short-lived one, but is stabilised on certain microbial surfaces by binding of the serum factor Properdin (P).