Complement system Complements are protein synthesized by the

Complement system § Complements are protein synthesized by the liver and play a major role in defense against infections. § The components proteins are called C 1, C 2, …C 9 (nomenclature ) depends on the discovery time. § Cleavage of any C protein into two parts will be given a/b for example C 3= C 3 a and C 3 b § These proteins can be activated by three pathways: classical pathway, lectin pathway and alternative pathway.

Function of complements: • 1 - pathogen destruction through cell lysis • 2 - pathogen destruction through opsonization • 3 -chemotaxis via certain cleaved product acting as chemical signal for phagocytic cells • 4 - mediate anaphylaxis ( is a extreme and severe allergic reaction that rapid in onset and may cause death) through split product such as C 5 a and C 3 a promote inflammation

Classical pathway • Called classical because it was the first pathway has been discovered • This initiated by antigenantibody complex (two Ig. G, or one Ig. M). • Ig. M>Ig. G 3>Ig. G 2 • Ig. A, Ig. E, Ig. D, and Ig. G 4 do not activate complement. Steps: 1 - antigen bind to antibody C 1=C 1 q+C 1 s +C 1 r After binding of C 1 via (C 1 q subunit) C 1 s is activates C 4 and C 2 C 4 will cleaved into C 4 a (small) and C 4 b (big) C 2 will cleaved into c 2 a and c 2 b C 2 a-c 4 b= C 3 convertase

Lectin pathway • Mannose residues expressed by Gram pos/neg, fungi and yeast activates lectin pathway in absence of antibodies. Lectin+MASP Bacteria +mannose After binding of lectin to mannaose residues MASP (mannan binding lectin serine peptidase) activates C 4/C 2 • C 4 will be cleaved into C 4 a (small) and C 4 b (big) • C 2 will be cleaved into c 2 a and c 2 b • C 2 b-c 4 b= C 3 convertase

Alternative pathway • Triggered by almost any foreign substances in absence of antibodies • Considered as effector arm of innate immunity • C 3 undergo a spontaneous cleave to c 3 b. C 3 b found in normal circulation at low concentration, forming a sensor for immune system • C 3 b binds to protein& carbohydrates expressed on cell surfaces of the pathogen or even host cell (host cells has inhibitor to inhibit the C 3 b such as factor H) system. • Pathogen does not have these Complement inhibitors. C 3 b binds to protein or carbohydrates of a pathogen Then a serum protein called factor B will combines with C 3 b to a form a complex called c 3 b. B. This will ebable factor D to cleave factor B to generate a fragments called Ba and Bb. Ba will be reslesaed into fluid where as Bb will remain attached to c 3 b , this is called (c 3 b. Bb) alternative pathway c 3 convertase. Which cleave C 3 into c 3 a and c 3 b.

Alternative pathway

Terminal pathway • C 3 b binding to c 3 convertase (to form c 5 convertase) allows the next step to occur, that is c 5 to be cleaved into c 5 a and c 5 b. • C 5 a release into fluid and has a potent anaphylactic properties • C 5 b binds to cell surfaces of the pathogen. • C 5 b bind to c 6…c 7…c 8…c 9…. . To form membrane attack complex and causing cell lysis of the pathogen by rapturing the cell membranes. Google images