the complement system Flashcards
what is the complement system?
a family of plasma and cell associated proteins
consists of a series of inactive precursor proteins
a cascade of proteins
what are the 3 proteolytic cascades of the complement system?
classic
alternative
lectin
what does complement activation lead to?
proinflammatory mediators
opsonisation
cell lysis by the membrane attack complex
what binds to the Fc region of antibodies during the classical pathway?
C1
what does C1 consist of? (classical pathway)
C1q
C1r
C1s
what does the binding of C1q to the Fc region activate?
proteases C1r and C1s
what does C1s cleave C4 into? (classical pathway)
C4a
C4b
what happens to C4a and C4b after C4 has been cleaved?
C4b binds to target cell membrane
also binds C2
C4a diffuses away and has inflammatory properties
what is C2 cleaved by and what is it cleaved into?
cleaved by C1s
into C2a and C2b
what happens to C2a and C2b after cleavage of C2?
C2a remains bound to C4b forming C4b2a
C2b diffuses away
what cleaves C3 and what are the products of the cleavage?
C4b2a cleaves it
producing C3a and C3b
what happens to C3a and C3b after cleavage of C3?
C3a diffuses away and has inflammatory properties
C3b binds to target cells and acts as an opsonin enhancing phagocytosis by macrophages via complement receptors
what is formed when some C3b binds to C4b2a and what does it cleave?
forms C4b2a3b
cleaves C5 into C5a and C5b
what happens to the products of C5 cleavage?
C5a diffuses away and has inflammatory properties
C5b binds to target cell
what forms the membrane attack complex?
C5b binding C6, C7, C8 and C9
what is the membrane attack complex?
a pore that allows water to enter the cell resulting in cell lysis
what bind to PAMPs in the lectin pathway?
mannose binding proteins and ficolins
what are PAMPs and where are they found?
pathogen associated molecular patterns
found on microorganisms
what binds to mannose binding lectin on cell surface in the lectin pathway? what does this complex cleave?
MBL associated serine proteases 1,2 and 3
cleaves C4 into C4a and C4b
and C2 into C2a and C2b
what happens after the formation of C4b in the lectin pathway?
allows events to proceed as in the classical pathway
what happen to C3 in the alternative pathway?
it is unstable and so undergoes spontaneous hydrolysis to form C3a and C3b
what is the fate of C3b in the alternative pathway?
some binds to self cells and is inactivated by regulatory proteins on the cell surface
also able to bind to microbial cells and in turns binds to Factor B
can act as an opsonin or can bind with C3bBb to form C3bBb3b
what is Factor B which is bound to C3b cleaved by and what does it form?
cleaved by Factor D
forms Ba and Bb
what happens to Ba and Bb in the alternative pathway?
Ba diffuses away
Bb binds C3b forming C3bBb
what can C3bBb cleave and what does it form?
can cleave further C3 forming an amplification loop
what can C3bBb3b act as?
as a C5 convertase
what occurs once C5a and C5b has been formed in the alternative pathway?
classical pathway is followed to form the MAC
