In this article we will discuss about:- 1. Definition of Complement System 2. History of Complement System 3. Biological Functions 4. Components.
Definition of Complement System:
The complement system consists of a series of heat-labile serum proteins that are activated in turn. The complements exist as soluble inactive precursors which once activated, a complement component may then act as an enzyme. Enzymatic chain reactions of this type are known as cascade reactions and usually require a “trigger” to initiate the reaction chain.
Complement is a chain of enzymes whose activation eventually results in the disruption of cell membranes and the destruction of cells or invading microorganisms. Complement is an essential part of the body defense system (Fig. 7.1).
History of Complement System:
The name “complement system” is derived from experiments performed by Jules Bordet.
1. Antibody (Ab) activity did not decay. Therefore Abs are heat stable.
2. Heated serum is capable of agglutinating bacteria.
3. Therefore serum with some heat labile components are capable of agglutinating bacteria. These components—are called as complement by J. Bordet.
Biological Functions of Complement System:
Complements perform different biological functions like:
3. Activation of inflammation:
4. Solubilization and phagocytic clearance and immune complex:
Mechanism of actions are as follows:
Components of Complement System:
The complement system is made up of a number (mostly 30) of distinct serum (blood plasma) and membrane proteins which mostly assist the humoral branch of the immune system. As after initial activation, the various complement components interact sequentially to generate reaction products that facilitate antigen clearance and inflammatory response.
Different pathways of complement finally generate a macro-molecular membrane- attack complex (MAC) which helps to lyse a variety of cells, bacteria and viruses.
The complement products amplify the initial antigen-antibody reaction and convert that reaction into a more effective defense mechanism. Continuous proteolytic cleavage and activation of successive complement proteins lead to the covalent bonding or fixing of complement fragments to the pathogen surface. Each precursor of complement is cleaved into two major fragments- named as larger fragment (designated as ‘b’) and smaller fragment (designated as ‘a’).
The major or larger ‘b’ fragment has two biologically active sites—one binds to cell membranes to the target cell towards the site of activation and the other for enzymatic cleavage of the next complement component. The smaller ‘a’ fragments diffuse from the site and play a role in initiating a localized inflammatory response (chemotactic activity).
1. The proteins and glycoproteins composing the complement system are synthesized largely by liver hepatocytes, some by blood monocytes, tissue macrophages and epithelial cells of the gastro-intestinal and genitourinary tracts.
2. The proteins that form the complement system are labelled numerically with the prefix C (e.g., C1 –C9).
3. Some complement components are designated by letter symbols (e.g., factor B, D, P) or by trivial names (e.g., homologous factor).
4. There are at least 19 of these components; they are all serum proteins and together they make up about 10% globulin fraction of serum.
5. The molecular weights of the complement components vary between 24 kDa for factor D and 460 kDa for C19.
6. Serum concentration in humans varies between 20 μg/ml of C2 and 1300 μg/ml of C3.
7. Complement components are synthesized at various sites like C2, C3, C4, C5; B, D, P and I are from macrophages, C3, C6, C8 and B from liver (Table 7.1 and 7.2).