Complement system

A collection of circulating cell membrane proteins that play an important role in host defense against microbes and Ab mediated tissue injury. Ability of protein to assist /complement antimicrobial activity of Ab May be activated in absence of Ab-innate immunity Ab mediated- adaptive immunity

Pathways of complement activation

2 major pathways Initiated by microbes in absence of AbAlternative Initiated by certain isotypes of Ab attached to antigens-Classical Most abundant C3 role in both pathways C3 sponataneous hydrolysis-products unstabledegraded

Alternative pathway
C3b-hydrolysis product of C3 is deposited on microbe Forms stable covalent bond with microbial protein or polysaccharide-prevents degradation Microbe+C3b-substrate for fragment Bb (plasma protease product Factor B)-C3bBb C3bBb breaks more C3( alternative pathway C3 convertase) Cascade of C3b and C3bBb produced to bind microbe C3bBb+C3b= C3bBb3b complex( C5 convertase) C5 convertase breaks C5 initiate late steps of complement activation

Late steps of complement cascade

Binding of C5 to C5 convertase Protelysis= C5b C6,C7,C8,C9 bind sequentially C9 polymerises(membrane attack complex) to form pore in cell membrane Water and ions enter-cell death

C5a
C6 C5

C 7 C8

Poly C9

C5 convertase
C3b C3b Bb

C5b

Cell lysis C8

Membrane attack complex

Classical pathway Triggered by IgM/IgG1/IgG3+ Ag on microbial cell surface Fc region of Ab become accessible to complement protein 2 or more Fc region come close C1 binds to 2 adjacent Fc regions C1 becomes enzymatically active-bind and cleaves C4 and C2 Forms C4b2a complex attaches to Ab coating the microbe Classical pathway C3 convertase Breaks C3 to generate C3b attach to microbe Some C3b+ C4b2a= C4b2a3b complex function as C5 convertase

Binding of complement protein to microbial cell surface or Antibody

Formation of C3 convertase

Cleavage of C3 Covalent binding of C3b to Microbial surface

Late steps of complement activation

Functional features
Sequential proteolytic cleavage of proteins Leads to genetation of effector molecules Elimination of microbes Cascade of complement activation achieves tremendous amplification Small no of complement molecules produce large no of effector molecules Activated complement protein attach to cell surface where activation occurs- limiting to correct site Complement system tightly regulated by molecules on normal host cells

Lectin pathway
Initiated by attachment of plasma mannose binding lectin(MBL) to microbe MBL activates proteins of classical pathway