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8/13/2019 (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.
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