COMPLEMENT SYSTEM Dr Mohit Bhatia Assistant Professor Department

COMPLEMENT SYSTEM Dr. Mohit Bhatia Assistant Professor Department of Microbiology AIIMS, Rishikesh

COMPLEMENT BASICS Cooperate with antibodies to eliminate bacteria, viruses, and other pathogens A complex group of about 16 different plasma proteins that work together to lyse their targets Prevent the lysis of normal host cells by pathogens It operates as a cascade mechanism, just like the blood-clotting system This sequential activation usually occurs by proteolysis

COMPLEMENT BASICS Amplification Factors produced by liver as zymogens Different pathways converge onto C 3 is complement factor of highest serum concentration (1. 2 mg/ml) • Complement proteins account for 10% of serum proteins(3 -4 g/l) • •

It ensures a substantial amplification of an initial response. • Since each successive component of the complement system is an enzyme that can act on many different substrates, this system of successive enzymatic steps gives a great increase in the size of the response. This pathway can be fairly easily controlled in its early stages by inhibitors of enzymatic activity. • This is essential because the C (complement) system is, as we’ll see, very destructive, and if it could be activated easily and spontaneously, it would cause considerable harm to the organism.

Three complement activation pathways

CLASSICAL PATHWAY

C 1 qr 2 s 2 COMPLEX

ALTERNATIVE PATHWAY

SUMMARY OF COMPLEMENT PATHWAYS

ELECTRON MICROSCOPIC VIEW OF COMPLEMENT MEDIATED LYSIS OF BACTERIA

REGULATION OF COMPLEMENT SYSTEM

FATE OF BOUND C 3 b & C 4 b

BIOLOGICAL ACTIVITIES OF COMPLEMENT SYSTEM

PHAGOCYTOSIS

SOLUBILIZATION OF IMMUNE COMPLEXES

MICROBIAL EVASION OF COMPLEMENT MEDIATED LYSIS

COMPLEMENT DEFICIENCIES

Hereditary angioneurotic edema v Deficiency of C 1 INH v Autosomal dominant v Recurrent episodes of edema in the skin, GI tract, UG tract, and larynx v Abdominal, pelvic pain, suffocation v Type I AND Type II

Paroxysmal nocturnal hemoglobinuria ü Intermittent intravascular hemolysis ü Defect of both CD 59 and DAF (Glycosyl phosphatidyl inositol anchored proteins) ü Pig-A gene on X chromosome is involved ü Alternate pathway is activated on host erythrocytes which leads to hemolysis ü Characterized thrombosis by hemolysis, pancytopenia and venous ü Death occurs due to hepatic vein thrombosis and bone marrow dysfunction

COMPLEMENT FIXATION TEST

OTHER DIAGNOSTIC TESTS EMPLOYING COMPLEMENT • Treponema pallidum Immobilization test (TPI) • Sabin-Feldman dye test • Vibriocidal antibody test