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Term Paper on Complement System
Term Paper # 1. Introduction to Complement System:
The complement system is an enzyme cascade that helps to defend against an infection. Many complement proteins are present in serum as zymogens (inactive enzyme) and others reside on cell surfaces. The interaction of antibodies and antigens is sometimes useful by itself. For example, coating of a virus/bacterium prevents it from binding and invading a host cell. But most of the time, this binding performs no useful function until and unless it can activate an effector mechanism.
The complement system serves several effector roles. Therefore, the complement system provides the actual protection from the response and the antibodies and antigen interaction provides the specificity of the response. We can also say that antibodies “finger” the target and complement destroys it.
The complement system acts as a bridge between innate and acquired immunity by:
i. Augmenting antibody responses and immunologic memory.
ii. Lysing the foreign cells.
iii. Clearing immune complexes and apopiotic cells.
Term Paper # 2. Functions and Features of Complement System:
Complement system components have many biologic functions which are as follows:
The lysis of cells, bacteria, and viruses is the major effector response of the humoral branch of the immune system. The polymerization of specific activated complement components on a foreign cell leads to the formation of pores. The lipid bilayer of the cell is then disrupted.
Some complement proteins bind to virions. Phagocytic cells with receptors for such complement proteins then engulf the virus particles and destroy them which are known as opsonization. It promotes phagocytosis of particulate Ags.
3. Activation of Inflammatory Response:
The proteolytic cleavage of complement proteins produces peptides which bind to specific complement receptors on cells of the immune system and triggers specific cell functions like inflammation and enhances responses to foreign antigens.
4. Immune Clearance:
Sometimes there is accumulation of antibody-virus complexes. If these immune complexes lodge in blood vessels they can cause damage. For example, glomerulo-nephritis. Some complement proteins disrupt such complexes and facilitate their clearance from the circulatory system.
Features of the Complement System:
Following are the characteristic features of complement system:
1. The complement system consists of approximately 30 proteins which circulate in blood plasma.
2. Most of components are inactive until they are cleaved by a protease which further converts them into a protease.
3. Many components serve as the substrate of a prior component and then as an enzyme to activate a subsequent component.
4. The pattern of sequential activation produces an expanding cascade of activity.
The complement system comprises an assembly of liver-manufactured, soluble and cell-bound proteins that participate in innate and adaptive immunity, although significant amounts are also produced by blood monocytes, tissue macrophages, and epithelial cells of the gastrointestinal and genitourinary tracts. These components constitute 5% (by weight) of the serum globulin fraction. The complement components are C1 (C1q, C1r, C1s), C2(C2a, C2b), C3(C3a, C3b), C4(C4a, C4b), C5(C5a, C5b), C6, C7, C8, C9, factor B, factor D, DAF, CD55, CR1, CD35, factor H, factor I.
Term Paper # 3. Regulation of the Complement System:
The complement system is strictly regulated by:
(i) Discrimination between micro-organisms and self,
(ii) Passive mechanisms of regulation where highly labile components undergo spontaneous inactivation if they are not stabilized by reaction with other components, and
(iii) A series of specific regulatory proteins which inactivate various components.
The complement control proteins that regulate the activity of the complement system are:
i. C1 inhibitor (C1INH)—eliminates the proteolytic activity of activated C1r and C1s.
ii. Factor I—which inactivates C3b.
iii. Factor H—removes Bb and interrupts the C3 convertase feedback loop within the alternative pathway.
iv. CD59—inhibits C9 polymerization during assembly of the membrane attack complex.
Dys-regulation of the complement system manifests as immune complex disorders (C2 deficiency), susceptibility to bacterial infections (C3 deficiency), the autoimmune disorder SLE (early component or C2. deficiency), and hereditary angioneurotic edema (HANE, C1INH deficiency).