IMS - Complement

COMPLEMENT  

collective term designating a complex series /mixtures of plasma proteins that have functions of zymogen. Group of non Ig circulating in the blood in biologically inactive form

to C3a & C3b ,allowing C3b or C4b to form covalent bond with protein and carbohydrate Classical Pathway

Complement System  C was discovered several years ago as a heat labile of normal plasma that augment opsonization of bacteria by Ab complement the antibacerial activity of Ab  Consist of approximately 30 serum molecules  10% of the total serum proteins  One of the major defense system of the body Major functions 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 immune pathological diseases Complement Activation  classical pathway which is activated by Ab bound to Ag  the lectin pathway activated by carbohydrates  Alternative pathway activated in the presence of various microbial pathogen  The protein of the system act in enzyme cascade The Mannose Binding Lectin Pathway  The MB-lectin pathway uses a protein very similar to C1q to trigger the complement cascade  MB-lectin binds specifically to mannose residues on pathogens surfaces  It is present at low conc. in normal plasma and during acute phase reaction its production increase by liver  MB-lectin forms a complex with two protease : MBL associated serine protease; MASP-1 and MASP-2  Closely homologous to C1r and C1s and activated to cleave C4 and C2

Consequences of Complement Activation  it generate large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement  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  the terminal complement components damage certain bacteria by creating pores in the bacterial membrane C1 Complex  C1q bind to Ab complexed with Ag  C1q can also bind directly to the surface of some pathogenes  C1q bind to 2C1r and 2C1s zymogene  Binding of C1q heads to the pathogen surface cause enzymatic activity of C1r, then cleave C1s to generate serine protease C3 and Thioester Bond  The α chain of C3 and C4 contain a thioester bond between cystein and a glutamine, fallowing cleavage

Hydrolysis of C3 causes initiation of Alternative Pathway  Spontaneous hydrolysis of plasma C3  C3b is produced at a significant rate by spontaneous cleavage (C3 tick over) through spontaneous hydrolysis of the thioester in the C3 to form C3(H2O), allowing binding factor B. factor D plasma protease cleave factor B to form C3(H2O)Bb a fluid C3 convertase, and can cleave C3 to C3a and C3b. Most of these C3b inactivated by H2O C5 Convertase  C5 convertase are formed when a large number of C3b on the surface of pathogene bind to C4b2b or C3bBb  C5a is the most anaphylatoxine  C5b initiate the assembly of the terminal complement component Anaphylatoxins: C3a, C4a, C5a (local inflammation)  C5a is more active than C3a which is more active than C4a  C5a is a potent mast cell activation, degranulate mast cell mediators; histamine and TNFα induce inflammation  C5a can enhance phagocytosis of opsonised microorganism