complement system Flashcards
How does the classical pathway make C3 convertase?
C1 binds to antibodies (IgG or IgM) or the microbial cell surface
C1r cleaves C1s into an active serine protease
C1s cleaves bound C4 into C4b and C4a
- exposes a thioester domain that covalently bonds to surface
C1s cleaves C2 into C2a (bound to C4b)
C4b2a is a C3 convertase
How does the lectin pathway make C3 convertase?
Mannose binding lectin or ficolin’s bind to mannose or acetylated compounds activates MASP-1, which cleaves MASP-2
MASP-2 cleaves C4 into C4b and C2 into C2a, both of which become bonded to the surface
How does the alternative pathway make C3 convertase? C3(H2O)
Spontaneous tick-over
C3 is spontaneously hydrolysed C3(H2O)
Factor B binds to C3
Factor D cleaves factor B into Bb
C3(H2O)Bb is a C3 convertase
c5 convertase and MAC
C4b2a3b = convertase for lectin and classical
C3b(2)Bb = convertase for alternative
cleaves C5 into C5b and C5a
C5b combines with C6, C7 and C8
C9 joins as a tube like structure
CR1 mediated phagocytosis
CR1 on macrophages bind to C3b on microbe
+ IgG bound to FcgammaR (receptor) on macrophages
both at once = enhanced phagocytosis
Removing immune complexes
CR1 binds to free flowing antigen. C3b opsonizes the complex so that it can be bound to CR1 on erythrocyte surfaces (RBC), which will be removed later by macrophages in the spleen and liver
Uses FcR and complement receptors
How does the alternative pathway make C3 convertase? C3b
Spontaneous activation ->
C3 is cleaved into C3b and C3a
conformational change in C3b exposes a thioester domain that can bond to the pathogen surface
Factor B binds to C3b
Factor D cleaves factor B into Bb
C3bBb
Must be stabilized by properdin to become a convertase
will be hydrolysed (inactivated) otherwise
C1 pathogen sensing complex
C1q: collagen tail and globular heads
C1r/s: serine proteases that need to be activated
*CR1-mediated phagocytosis is enhanced by C5a
just remember that lol
Inactivating C3b on pathogen surfaces
factor I and MCP cofactor cleaves C3f off of C3b, leaving iC3b
facto I and R1 released C3c and leaves C3dg on the surface
Regulating C1 activation ~ soluble factors
C1 inhibitor - C1 INH binds to complex and inactivates serinase complex
Regulating C3 convertase ~ membrane bound factors
DAF, MCP, CR1
Classical/lectin: one of the three receptors bind to C4b, acting as competition for C2a
alternative: same story but competition for Bb and only DAF or CR1 can bind
Regulating C5 convertase
CR1 binds to C3b that is in a C5 convertase (C4b2a3b or 3Cb(2)Bb), allowing it to be cleaved by factor I
OR
Factor H acts as cofactor, same story from there
Regulating C3b with soluble factors
- Factor I: cell bound C3b is bound by MCP or CR1, which are cofactors for Factor I
Factor I cleaves C3b, producing iC3b and C3f - Factor H binds to C3b on cell surface -> it is a cofactor for factor I, which can do its job as per normal
Regulating membrane attack complex ~ membrane bound factors
CD59 ~ inhibits poly-C9 assembly
Regulation of MAC - SOLUBLE INHIBITOR
S protein inhibits insertion of C5-7
