Flashcards in 4. Complement Deck (59)
what are the 5 important immune functions of complement?
1. opsonization (C3b and iC3b)
2. Cell Lysis (MAC)
3. Inflammation (C3a, C5a)
4. limiting immune complex-mediated destruction (complement receptors)
5. alert the adaptive immune system to pathogen invasion (C3d and C5a)
where are complement proteins (inactive) produced?
liver (and some blood cells, aka monocytes)
complement is activated by _____, which cleaves each C' protein into a and b components that do what?
one acts as a protease itself, activating the next step of the cascade
one will be inactive, or perform other immune functions
who are the susbtrate-binding molecules of complement?
C1q (bdins to antigen:Ab complexes and pathogen surfaces)
C3, C4, MBL (MBL binds to carb structures like mannose)
who are the serine proteases in complement?
C1r, C2s, C2a, Factor B (Bb), Factor D, MASP
what proteins make up the MAC?
C5b, C6, C7, C8, C9
who are the bioactive fragments in complement?
C3a, C5a, C3b, iC3b, (C4a)
who are the regulators in complement?
properidin (only positive regulator mentioned)
C1 inhibitor (C1INH)
Factor I (the only PROTEASE mentioned)
C4-binding protein (C4BP)
membrane cofactor protein (MCP = CD46)
decay accelerating factor (DAF = CD55)
who are the complement receptors?
who are the homologues of C3?
C4, and C5 (and alpha 2 macroglubulin)
who are the homologues of Factor B (Bb)?
who are the homologues of C1r?
C1s and MASP1&2
who are the homologues of CR3?
CR4 (Beta2 integrins)
who are the homologeus of Factor H?
CR1 (CD35) and C4BP
who are the homologes of C3aR?
what makes C3 (and C4) molecules unique?
they ar ethe only defense molecules known to bind covalently to the surface of pathogens via a THIOESTER BOND
which pathways generate the significant biologically active molecs (C3a, C3b, C5a, and MAC)?
all of them
The thioester bond in intact C3 is...
concealed - exposed in C3b following cleavage of C3a chain by C3 convertase
what happens to C3b in the fluid phase?
inactivated by hydrolysis
what are the serine proteases in unique to the classical pathway?
C1r, C1s, C2a
what are the unique substrate-binding molecules in the classical pathway?
C1q and C4
what is required to initiate the classical pathway cascade?
IgM or IgG ( IgG1 or IgG3) antibodies
what comprises the C1 complex?
6 C1q molecules and a tetramer of covalently associated C1r and C1s (two each: 2 C1r&s)
C1q binds to ______ of Ig with C1q's globular head regions, leading to what?
leading to the activation (via conformational change) of C1r enzyme that then cleaves and activates C1s enzyme
what does activated C1s do?
cleaves soluble C4 into C4a and C4b, exposing a thioester site on C4b to allow it to covalently bind in the vicinity of the Ab/C1 complex and exposing another site on C4b, permitting non covalent association wht the potential enzyme C2.
C1s then cleaves C2 into C2b and the next active protease, C2a
what is the C3 convertase?
the C4a, C2b complex
what does C3 convertase do?
cleaves C3 into C3a and C3b
C3b then associates with the C4b, C2a dimer and a C4b, C2a,C3b tripartite complex forms, changing the protease specificity of C2a so that it becomes C5 convertase
what does C5 convertase do?
cleaves C5 into C5a and C5b
what does C5b/C5a production lead to?
C5b: initiation of the lytic cascade
C5a: promotes inflammation