Complement system Department of Microbiology Complement system A

Complement system Department of Microbiology

Complement system • A group of heat labile serum proteins that complements / assists antibody molecule in lysis of bacteria. • Complement proteins. system consists of approximately 30 serum • Many a components of complement remain in inactive form. • The components of complement system undergo activation in a cascade manner.

Major function of the complement system • Activation of complement leads to formation of “Membrane attack complexes” which forms pores in the cell wall/ membranes. • Some complement components act as chemotactic agents. • Some complement components act as opsonin clearance of the immune complexes. and help in • Some complement components also play role as “anaphylotoxins”.

Complement components • • • C 1(C 1 q, C 1 r, C 1 s ) C 2(C 2 a, C 2 b) C 3(C 3 a, C 3 b) C 4(C 4 a, C 4 b) C 5(C 5 a, C 5 b) C 6 C 7 C 8 C 9 factor B factor D DAF, CD 55 CR 1, CD 35 factor H factor I

Complement activation Complement pathways can be initiated by any one of the following three mechanisms: 1 -Classical pathway: activated by Ab bound to Ag 2 -Alternative pathway: activated in the presence of various microbial pathogen 3 -Lectin pathway: activated by carbohydrates

Complement activation

Classical Pathway: • • Sequence of Events: Ag+Ab+C 1 qrs+C 4 b+C 2 b+C 3 b+C 5 b+C 6+C 7+C 8+ C 9 Classical pathway is triggered only after binding of antigen and antibody molecule i. e. , activation of classical pathway requires Ab molecule. The binding of C 1 qrs to the Ag+Ab complex is Ca++ dependent. C 4 b+C 2 b (C 4 b 2 b) is the C 3 Convertase of Classical Pathway. C 4 b+C 2 b+C 3 b (C 4 b 2 b 3 b) is the C 5 Convertase of Classical Pathway. C 5 b+C 6+C 7+C 8+C 9 (C 5 b 6789) forms the Membrane Attack Complex (MAC).

Classical pathway of complement activation

Alternative • • Pathway: “Properdin Pathway” Sequence of Events: Bacterial surface+C 3 b+Bb+C 3 b+C 5 b+C 6+C 7+C 8+ C 9 This pathway doesn’t require antigen antibody reaction i. e. , this pathway is independent of antibodies. A small amount of C 3 b, formed by autolysis of C 3, is always present in the serum. This component could bind directly to the bacterial surfaces. The binding of C 3 b to bacterial surface allows Factor B to bind to this C 3 b. The factor B bound to C 3 b+B complex is cleaved by Factor D, thus forming C 3 b. Bb complex. This C 3 b. Bb has enzymatic activity and acts as C 3 Convertase in Alternative Pathway. But this complex is extremely labile. The binding of Properdin (factor P) stabilizes this complex. C 3 b. Bb 3 b acts as C 5 Convertase in Alternative Pathway.

Alternative pathway of complement activation

Lectin Pathway: • • Sequence of Events: Ag+MBL+MASP 1+MASP 2+C 4 b+C 2 b+C 3 b+C 5 b+C 6+C 7+C 8 + C 9 This is quite similar to Classical pathway. The only difference lies with the use of MBL, MASP 1 and MASP 2 in place of C 1 q, C 1 r and C 1 s components of Complement, respectively. C 4 b+C 2 b acts as C 3 Convertase in Lectin pathway. C 4 b+C 2 b+C 3 b acts as C 5 Convertase in Lectin pathway.

The mannan binding lectin pathway is homologous to the classical pathway • The MB-lectin pathway uses a protein very similar to C 1 q 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

Lectin pathway • MB-lectin forms a complex with two protease : MBL associated serine protease; MASP-1 and MASP-2 • Closely homologous to C 1 r and C 1 s and activated to cleave C 4 and C 2

Terminal Event: • The membrane attack complex thus formed at the end of each Pathway inserts itself into a microbial cell membrane and thus causes their lyses by osmotic imbalance.

Membrane attack complex

Overview of three pathways of complement activation

The terminal complement components

Anaphylatoxins : C 4 a, C 3 a and C 5 a causes local inflammation • C 5 a is more active than C 3 a which is more active than C 4 a • C 5 a is a potent mast cell activation, degranulate mast cell mediators; histamin and TNFα induce inflammation • C 5 a can enhance phagocytosis of opsonised microorganism

THANKS