Complement

WEL COME

Dr.Mejbah UddinAhmed

Complement 

Definition:

Complement is a group of serum proteins at least 20 in number, which normally remain in inactive form and when activated they act in concert in an orderly sequence to exert their biological effects.

Complement 

Production of complement components:

Complements are synthesized by the liver, spleen, macrophage and intestinal epithelial cells.  Components of the complement system: There are more than 20 components in the complement system of which following are important: C1, C2, C3, C4, C5, C6, C7, C8, C9, Factor B, Factor D, Factor H, Factor I, Properdin, C1 inhibitor, C4 -binding protein & S protein.

Complement Activation of complement: Classic or antibody dependent pathwayWhen Ag combines with Ab (IgG, IgM), it activates this pathway. Lectin pathway- Lectin pathway is activated by the interaction of microbial carbohydrates (Mannan/ Mannose) with mannose-binding proteins in the plasma and tissue fluids. Alternate pathway - Endotoxin, cell wall of some other bacteria, cell wall of Yeasts Aggregated IgA, cobra venom can directly activate this pathway.

Complement Regulation of complement activation: The regulation of complement activation is done by various inactivators as well as by normal metabolic degradation. Examples of inactivators are C1 esterase inhibitor, C3b inhibitor, anaphylatoxin inhibitor, and C4b inhibitor, Decay-accelerating factor.

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Complement 

Final effect of activation: The final effect of each pathway is same. All complement pathways result in the formation of membrane attack complex (MAC) leading to lysis of target cells.

Complement Biological activities of complement:  Anaphylatoxins: C3a,C4a and C5a causes degranulation of mast cells or basophils and release mediators, e.g. histamine. (e.g. increase capillary permeability, contraction of smooth muscle etc.)  Opsonization: C3b promote the attachment of antigens to phagocytes.  Chemotaxis: C5a and the C5,6,7 complex attract phagocytes to the infection site. 

Complement

Complement Clinical Aspects of comlement: •C5-C8 deficiency→ Neisseria and other infection. •C3→leads to pyogenic infection. •C1 esterase inhibitor→angioedema. •Ig+Ab+complement→disease(AGN,SLE) • Decay-accelerating factor →Paroxysmal nocturnal haemoglobinuria. 

Complement Questions: 1. Define complement. What are the complements? Where they remain? 2. How complements are activated? What are the pathways for complement activation? 3. What is the final effect of complement activation? What are the other biological effects? 4. Name some complement-mediated diseases. 5. What are anaphylatoxins, chemotaxins? 6. Why complements need to be activated? 7. Why antibodies present in the blood don not activate complements? 8. Which classes of antibodies can activate complement? Which one is most efficient and why?

Thank You All