THE COMPLEMENT SYSTEM

Prepared by: MOHD KHAIRUL AMRAN BIN MOHAMMAD Bsc. In Medical Laboratory Technology Faculty Of Health Science University Teknology Mara (UiTM)

THE COMPLEMENT SYSTEM

Introduction The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities of antibodies to clear pathogens from an organism.
Consist of approximately 30 serum molecules 10% of the total serum proteins One of the major defense systems of the body Defensive system of over 30 proteins Liver produces the proteins Circulated in blood plasma and tissues Cause cascade reactions Destroy microbes by causing:

Phagocytosis Cytolysis Inflammation Preventing excessive tissue damage

Major function of the complement system

Control of inflammatory reaction and chemotaxis Clearance of the immune complexes Cellular activation and antimicrobial defense It is a major effector in immuno-pathological diseases

Biologic significant of complement system:

Lysis of foreign cell ( C1 to C9 ) Increase vascular permeability ( C1,C2,C4,C3a,C4a ) Smooth muscle contraction ( C1,C2,C4,C3a,C4a ) Mast cell degranulation (C3a,C4a ) Localization of complexes in germinal centres ( C3b,C4b ) Opsonization and phagocytosis of bacteria ( C3b,C4b ) Neutrophil activation and chemotaxis ( C5a )

The role of complements:

1. C3 to C3a and C3b 2. C3b binds to microbe, phagocytes bind to C3b Opsonization attachment of phagocyte to microbe 3. C5 - C9 help form Membrane attack complex Cytolysis

4. C3a and C5a bind to mast cells release histamine Inflammation Chemotaxis

Complement components: 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

Complement activation:
1-classical pathway which is activated by Ab bound to Ag 2-the lectin pathway activated by carbohydrates 3-Alternative pathway activated in the presence of various microbial pathogen The protein of the system act in enzyme cascade

Consequences of the complement activation:

1. It generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. 2. The small fragments of some complement proteins act as chemo-attractants to recruit more phagocytes to the site of complement activation and also to activate these phagocytes. 3. The terminal complement components damage certain bacteria by creating pores in the bacterial membrane.

Overview of the main components and effector actions of complement:

Classical pathways
during an immune (specific) response, the formation of antigen-antibody complexes activates the complement system. The complement fragment C1 binds to the stem (Fc portion) of an antibody that is already attached to it specific antigen. The C1 is then activated & acts as an enzyme, initiating the sequence of reactions called the complement cascade.

Attached immunoglobulins can set off the "classical pathway" as shown above schematically. The complement cascade can generate active compounds such as C3b that functions as an opsonin, or C5a that attracts neutrophils.

If the C5-9 complex (the "membrane attack complex") is generated, the cell to which the complex is attached can be lysed by perforation of its cell membrane.

Classical pathway of complement activation:

Alternative pathways
during nonspecific responses (no antibodies present), direct contact between complement proteins & polysaccharides on the surface of a microbe activates the system. The alternative pathway begins halfway through the complement cascade with the formation of C3b. only certain microbes have the surface polysaccharides that trigger this pathway.

Complement proteins are present in circulation and can be activated by a variety of mechanisms. Bacterial products can set off the "alternative pathway" as shown above schematically. The complement cascade can generate active compounds such as C3b that functions as an opsonin, or C5a that attracts neutrophils. If the C5-9 complex (the "membrane attack complex") is generated, the cell to which the complex is attached can be lysed by perforation of its cell membrane.

Alternative pathway of complement activation:

Comparison of the classical and alternative complement pathways:

Antigen/antibody complexes C3 Microorganisms

Classical pathway

Alternative pathway (innate)

C3b

C3a

C5-C9 Terminal sequences