The complement system

The complement system composed of 22 glycoproteins molecules normally present in serum as an inactive enzymes, produced mainly from Hepatocytes and macrophages,

Fight infection by :

1-Lysis of microorganisms

2-Opsonizing pathogens,

3-Inducing inflammatory responses,

4-Role in humoral immunity by enhancing antibody responses.

Classified whether numerically C1,C2,C3 or alphabetically CB,CI,Cp

Act in a cascade manner

Three pathways which can activate the complement system are outlined below

1-Classical pathway ( in the presence of AB)

C1 only complement consists of 3 subunits C1q, C1r, C1s

C1q has 6 whipples that catch FC portion of an AB (bind to specific antigen) that activate          C1r activate         C1s       

C1s activate         C4 then C2

C4 undergo fragmentation C4a and C4b

C4b attached to the antigen antibody complex then

C2 activated and defragmented into C2a and C2b

C2b attached to C4b and antigen and antibody complex---- C4bC2b complex acting as convertase to C3

NB; convertase is the molecule that activate the next molecule

C3 activated and defragmented into C3a and C3b

C3b is convertase for C5

C5 activated and defragmented into C5a and C5b

C5b is convertase for C6

C6 activated then C7 the C8 then C9

C9 make perforation (hole) and lysis of m.o

This process occur under strict control as if it started from C9 it will destroy body cells

Cumulative effect start from C6

MAC: membrane attack complex (combine complement from C6:C9) that destroy certain pathogens by disrupting their membrane integrity

2-Alternative pathway (in the absence of of AB)

Only C3 spontaneously cleavages in the serum to C3b which is convertase for C5,

If this spontaneous cleavage left uncontrolled will destroy body cells

As a protection mammalian cells contain Sialic acid how?

When C3 cleavage to C3b and attached to sialic acid on mammalian cell surface, activation of 2 complement factor occurs

Factor H and factor I which bind to C3b and inactivating it by forming IC3b complex which undergo hydrolysis and phagocytosis.

When pathogen enter without sialic acid on its surface, C3 cleavage to C3a and C3b

C3b (in presence of factor D) activated and activate B

B defragmented into Ba and Bb

C3b+Bb             C3bBb + Properidin

C3bBbP is convertase for C3

C3 activated and defragmented into C3a C3b

C3b is convertase for C5

C5 activated and defragmented into C5a and C5b

C5b is convertase for C6

C6 activated then C7 then C8 then C9

C9 make perforation (hole) and lysis of m.o

Thus, the alternative complement pathway is able to distinguish self from non-self on the basis of the surface expression of complement regulatory proteins.

3-Mansoe Lectin Binding (MLB) pathway ( in the absence of of AB)

Serum Lectins are carbohydrate-binding proteins secreted in case of infection as acute phase protein,

The catch the mannose part of microorganisms whether can be bacteria or fungi

This pathway is activated by :

Binding of Lectin to mannose residues on the pathogen surface, which activates the Mannose-associated serine proteases, P-1, and P-2 (very similar to C1r and C1s, respectively),

P2 activate          C4 then C2

C4 undergo fragmentation C4a and C4b

C4b attached to the antigen antibody complex then

C2 activated and defragmented into C2a and C2b

C2b attached to C4b form complex---- C4bC2b acting as convertase to C3

NB; convertase is the molecule that activate the next molecule

C3 activated and defragmented into C3a and C3b

C3b is convertase for C5

C5 activated and defragmented into C5a and C5b

C5b is convertase for C6

C6 activated then C7 the C8 then C9

C9 make perforation (hole) and lysis of m.o

C3a and C5a ar 2 important fractions act as anaphylactic toxins initiate inflammatory process activate mast cells release Histamin increase permeability extravasation.