The Complement System:
The complement system is a collection of circulating and cell membrane proteins that play important roles in host defence against microbs and in antibody- mediated tissue injury. The term complement refers to the ability of these proteins to assist, or complement, the antimicrobial activity of antibodies. Complement system includes more than 25 soluble and cell-bound proteins. The biological activities of this system affect both innate and acquired immunity. The complement system includes several components that exist in a nonactive state in the plasma. When these complement components are converted to their active form, a sequential, rapid, cascading sequence ensues. Most of the complement glycoproteins are synthesized predominantly by the liver cells, but macrophages and many other cell types are also sources of various complement components, especially at sites of infection and/or inflammation. All normal individuals always have complement components in their blood. The synthetic rates for the various complement glycoproteins increase when complement is activated and consumed during an infection. The increased rates appear to be under several regulatory mechanisms.
Major biologic activities of complement:
1-opsonization: 2-cytolisis: 3Anaphylatoxins: 4-Chemotaxis: 5-Clearance of immune complexs
Complement activation:
Most of complement proteins are present in the circulation in inactive form .These proteins undergo sequential activation to cause their immunologic functions.
There are three pathways of activation:
I-Classical pathway:
It is an Ab-dependent pathway (IgM,IgG1,IgG2,IgG3,but not IgG4).
II-Alternative pathway: It is an Ab-independent pathway .Surface constitutents of microbial cells or their products such as endotoxins(LPS)can activate the complement system via alternative pathway .
III-Lectin pathway(mannan binding lectin (MBL)pathway: MBL protein in circulation can bind to terminal sugar (mannose)residues found in microbial surfaces .
The final steps in all pathways is the formation of membrane attack complex(MAC)which makes holes and destroys the membrane of target cells.
Regulation of complement activation:
Fluid –phase proteins and cell- bound proteins have evolved to regulate complement activation: Fluid phase proteins are: C1 inhibitor regulates the classical pathway Factor I and H regulate the alternative pathway
Cell bound proteins: Decay accelerating factor(DAF):regulate C3 and C5 convertase Protectin (CD59):regulates MAC formation
Deficiencies of Complement components
Hereditary deficiencies of C-components especially C3 results in an increased susceptibility to infection with pyogenic bacteria. -Deficiencies of the other components of the classical pathway C5-C9 result in recurrent neisserial infections. -patients with severe liver diseases cannot synthesize sufficient complement proteins ,are predispose to pyogenic infections.