(4) the Complement System

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The omplement System

Prof. Dr. Mohammad Al-Sweify

2010


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Activation of the Complement system

1) Classic pathwayis activated by: Antigen-antibody complexes (IgG, IgM)

2) Lectin Pathway: When serum lectin bind to

bacterial surface receptors that contain sugars. Lectin is a large serum protein that binds to non-reduced mannose,

fructose, and glucosamine on bacterial and other cell surfaces.

Lectin resembles and replaces C1q, and on binding to bacteria itactivates a serine protease which in turn cleaves C4 and C2 to produceC3 convertase, and so on.

2)Alternate pathwayis activated by: PGs in cell wall (techoic acid and PGs fragments)

LPS of gram -ve bacterial cell wall.


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C3 is a central component of complement system.

C3b is protein that contains unusual Thio-esterbond.That bond enables C3b to tagthe bacteria by attaching to itssurface, and anchoring the whole bacteria-complementcomplex to macrophage because the latter has C3b receptors.

This function of C3b is called opsonization; so C3b is an

opsonin


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C3- activation process


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Sequence of Events in Alternate pathway: PlasmaProperdinfactor Bbinds to C3b and then

with properdin factor D, which splits factor B in the

complex, yielding Baand Bb.

Bb is an active fragment that remains linked to C3b

(forming the complement activation unit).

C3b sticks to bacterial surface and anchor the

complex to it !! Inactive Bais split from its complex leading to

activation of many C3 molecules (augmentation).


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But if C3 binds via its ester bond to a cell

surface or protein complex, it can recruit the

Properdin serum protein factor B.

Activated C3 initiates Alternate

pathway:

Various ways can activate C3, like:1) proteolysis by bacterial enzymes,

2) clotting enzymes,

3) injury.


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The membrane attack

unit is formed at the

terminal stage of classicpathway..

This lytic unit

(C5b,6,7,8)1

(C9)n

drills a

hole in the membrane

hypotonic lysis of cells.

C9 component is similar

to perforin, which isproduced by Tc and NK

cells..!


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Bio-Effects of activated complement on bacterialinvaders and host cells:

1. Complement activates inflammatory responsesand can directly

kill G-ve bacteriaand, to a much lesser extent, gram-positivebacteria(the thick PG of gram+ve shields them from lysis !!).

2. Activation of the complement cascade by gram-+ve or gram-ve

bacteria provides the following protective factors:

Chemotactic factors(C5a) to attract neutrophils andmacrophages to the site of infection

Anaphylotoxins(C3a and C5a) to stimulate mast cell

release of histamineincrease vascular permeability,

allowing access to the infection site. Opsonins (C3b),which anchor itself into bacterial cell

membrane and promote their phagocytosis(how ?)

Activationof B lymphocyte byC3b.

(4) the Complement System

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