Lecture 5: Complement Flashcards
What are the three complement pathways?
lectin, classical, alternative
What are the three main effector functions of the complement system?
- inflammation
- phagocytosis
- membrane attack complex
What activates the complement system?
pattern recognition trigger
What will pattern recognition trigger?
protein cascade amplification/C3 convertase
Lectin: what are the key proteins involved?
Mannose binding lectin, MASP-1,2,3
Lectin: What is the C3 convertase?
C4b2a
Detail lectin pathway
MBL binds pathogen -> activates MASP-1 -> MASP1 activates/cleaves MASP2 -> cleaves C2 and C4 to make C4b2a the C3 convertase
Classical: What are the key proteins involved?
C1 (subunits C1q,r,s)
Classical: What is the C3 convertase?
C4b2a
Detail classical pathway
C1q binds pathogen with at least 2/6 globular heads -> activate C1r-> activates C1s -> cleaves C4 and C2 to make C4b2a the C3 convertase
Alternative: What are the key proteins?
C3b, Factor B, Factor D
Alternative: How is C3b generated?
From classical/lectin pathway, product of itself, can be hyrdolyzed spontaneously
What are 3 C3 convertases?
C3bBb, C3(H2o)Bb, C4b2a
What stabilizes C3bBb and C3(H2O)Bb?
properdin (factor P)
What makes factor P?
neutrophils
Detail alternative pathway
C3b binds Factor B -> Factor B cleaves bound Factor B to Bb and Ba -> C3bBb is C3 convertase
Which proteins mediate inflammation?
C3a and C5a activate vascular endothelium
How does phagocytosis occur via complement system?
C3b is bound to pathogen and phagocytes with C3b receptors can engulf it. C5a can help to regulate this process
What are the C5 convertases?
C4b2a3b and C3b2Bb
How is C5 cleaved?
C5 binds to C3b and is cleaved by Bb or C2a
How does membrane attack complex form?
A C5 convertase generates C5a and C5b. C5b binds C6 to form C5b6. C5b6 binds C7 to attach to lipid bilayer. C5b67 binds C8(beta) and C8alpha-gamma will insert itself into lipid bilayer. C9 binds and polymerizes to form pore in the membrane
What are regulators of complement system?
C1INH
DAF (CD55)
C4BP
CR1(CD35)
Factor H
Factor I
CD59
What is mechanism of regulation for C1INH?
C1 inhibition - binds to C1r:C1s so they dissociate from C1q and cannot cleave C2 or C4
How does DAF act?
competes with Factor B (or displaces it) from C3b
_____ cleaves C3b to form iC3b and C3f
Factor I
iC3b can bind to these receptors
CR2,3,4 and CRIg
iC3b can be cleaved by ____ and ____ to form C3c and C3dg
Factor I and CR1
DAF, C4BP, and CR1 work to regulate complement system by
displacing C2a from C4b2a, then C4b and C4BP will by cleaved by protease I to form C4d and C4c
_____ will prevent assembly of MAC by binding C5b678
CD59
___ and ___ will displace C3b from C5 convertase
CR1 and Factor H
