1. Complement system
Complements are protein synthesized by the liver and play a major role in defense against infections.
The components proteins are called C1, C2,…C9 (nomenclature ) depends on the discovery time.
Cleavage of any C protein into two parts will be given a/b for example C3= C3a and C3b
These proteins can be activated by three pathways: classical pathway, lectin pathway and alternative pathway.

2. Function of complements:
1- pathogen destruction through cell lysis
2- pathogen destruction through opsonization
3-chemotaxis via certain cleaved product acting as chemical signal for phagocytic cells
4- mediate anaphylaxis ( is a extreme and severe allergic reaction that rapid in onset and may cause death) through split product such as C5a and C3a promote inflammation

3. Classical pathway
Called classical because it was the first pathway has been discovered
This initiated by antigen- antibody complex (two IgG, or one IgM).
IgM>IgG3>IgG2
IgA, IgE, IgD, and IgG4 do not activate complement.
Steps:
1- antigen bind to antibody
After binding of C1 via (C1q subunit) C1s is activates C4 and C2
C4 will cleaved into C4a (small) and C4b (big)
C2 will cleaved into c2a and c2b
C2a-c4b= C3 convertase
C1=C1q+C1s +C1r

5. Lectin pathway
Mannose residues expressed by Gram pos/neg, fungi and yeast activates lectin pathway in absence of antibodies.
After binding of lectin to mannaose residues MASP (mannan binding lectin serine peptidase) activates C4/C2
C4 will be cleaved into C4a (small) and C4b (big)
C2 will be cleaved into c2a and c2b
C2b-c4b= C3 convertase
Lectin+MASP
Bacteria +mannose

7. Alternative pathway
C3b binds to protein or carbohydrates of a pathogen
Then a serum protein called factor B will combines with C3b to a form a complex called c3bB. This will ebable factor D to cleave factor B to generate a fragments called Ba and Bb.
Ba will be reslesaed into fluid where as Bb will remain attached to c3b , this is called (c3bBb) alternative pathway c3 convertase. Which cleave C3 into c3a and c3b.
Triggered by almost any foreign substances in absence of antibodies
Considered as effector arm of innate immunity
C3 undergo a spontaneous cleave to c3b. C3b found in normal circulation at low concentration, forming a sensor for immune system
C3b binds to protein& carbohydrates expressed on cell surfaces of the pathogen or even host cell (host cells has inhibitor to inhibit the C3b such as factor H) system.
Pathogen does not have these Complement inhibitors.

8. Alternative pathway

9. C5a release into fluid and has a potent anaphylactic properties
Terminal pathway
C3b binding to c3 convertase (to form c5 convertase) allows the next step to occur, that is c5 to be cleaved into c5a and c5b.
C5a release into fluid and has a potent anaphylactic properties
C5b binds to cell surfaces of the pathogen.
C5b bind to c6…c7…c8…c9….. To form membrane attack complex and causing cell lysis of the pathogen by rapturing the cell membranes.
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