Flashcards in Complement Deck (47)
what is complement?
A very complex system of about 50 different proteins found either in serum
or as receptors on white cells
what does complement mediate?
wide range of functions
what does complement involve?
Describe enzyme cascades.
-all components circulate as inactive precursors
- comes into contact with appropriate stimulus
- one product of one reaction acts as an enzyme for next reaction and so on
what can the compliment system be triggered by?
- Lectin pathway
What do the 3 pathways have in common?
result in proteolytic cleavage
of C3 to C3b (large fragment) and C3a (small)
what is compliment effective at doing?
Getting rid of bacterial infection
what is the central protein of the complement system?
what does deficient in C3 lead to?
recurrent bacterial infections
where is C3b deposited to in all 3 pathways?
surface of micro-organism and marks it out for destruction (lysis/ opsonisation)
How does C3b attach to the microorganisms surface?
- C3 comes into close proximity to the membrane of the pathogen
-thioester bond between Cys and Glu on alpha chain is cleaved
-Thioester bond becomes exposed and unstable
Nucleophilic attack by electrons on OH and -NH2 groups
-covalent bond is formed
what is the first component of the classical pathway?
Describe the structure of C1q.
-“Bunch of tulips” arrangement of 18 polypeptides
-6 collagenous base and arm(stalk) regions
connected to 6 globular heads
what is the classical pathway activated by?
IgG and IgM
How does IgG activate the classical pathway?
-2 IgG molecules are adjacent and in close proximity (control measure to prevent innpaorpriate activation)
-C1q binds 2 of the 6 globular head regions to the IgG molecules
what is different about IgM?
only one molecule but C1q only binds when it goes through a conformational change
what binds to C1q (CP)?
C1r and C1s (2 each)
what do C1r and C1s become (CP)?
what is cleaved by C1r and C1s (CP)?
C4 and C2
what is formed by classic pathway?
C3 convertase (C4bC2a)
-cleaves C3 into active products
what does proteolyally active C1s cleave C4 into?
C4a and C4b
what does C4b bind to and what does it recruit?
microbial surface and recruits C2 protein
what else can active C1s enzymes cleave?
C2 into C2a and C2b
what is the first component of the lectin pathway?
Mannose binding lectin
what is the structure of mannose binding lectin reminiscent of?
what does mannose binding lectin bind?
Binds sugars molecules found in repeating arrays on microbial surfaces
Describe lectin pathway activation.
-MBL and MASP-2 together act on C4 and C2 (same classical pathways)
-A C3 covertase is formed
-C3 is cleaved
-C3b fragments bind to surface
what is different between the classic pathway and the lectin pathway?
Same outcome from classic pathway- difference is the lectin pathway does not need an antibody i.e its part of the innate system
what does the alternative pathway produce?
C3 convertase but uses different proteins