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Complement system

A collection of circulating cell membraneproteins that play an important role in hostdefense against microbes and Ab mediated

tissue injury. Ability of protein to assist /complement

antimicrobial activity of Ab

May be activated in absence of Ab-innateimmunity

Ab mediated- adaptive immunity

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Pathways of complement activation

2 major pathways

Initiated by microbes in absence of Ab-Alternative

Initiated by certain isotypes of Ab attached toantigens-Classical

Most abundantC3role in both pathways

C3 sponataneous hydrolysis-products unstable-degraded

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Alternative pathway

C3b-hydrolysis product of C3 is deposited on microbe

Forms stable covalent bond with microbial protein orpolysaccharide-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

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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

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C3b BbC3b

C5

C6C

7 C8

C5b

C8

Poly C9

Cell lysis

Membrane

attack complex

C5a

C5 convertase

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Classical pathway

Triggered by IgM/IgG1/IgG3+ Ag on microbial cell surface

Fc region of Ab become accessible to complementprotein

2 or more Fc region come close

C1 binds to 2 adjacent Fc regions

C1 becomes enzymatically active-bind and cleaves C4 andC2

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 C5convertase

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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

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Functional features

Sequential proteolytic cleavage of proteins

Leads to genetation of effector molecules

Elimination of microbes

Cascade of complement activation achievestremendous amplification

Small no of complement molecules produce large no ofeffector 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

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Lectin pathway

Initiated by attachment of plasma mannose

binding lectin(MBL) to microbe

MBL activates proteins of classical pathway