Presentation 1 Flashcards
Complement
cascade consists of interactions between several complement proteins resulting in activation of 3 pathways
zymogen cascade
detection of proteins activates zymogen
triggers cascade of proteolysis
zymogens are sequentially activated to = active proteases, cleave and continue cascade
zymogen
an inactive protein precursor of an enzyme secreted by living cells and converted (as by a kinase or an acid) into an active form. called also proenzyme.
cascade result
amplifies signal resulting in activation of phagocytosis, MAC, inflammatory response
three pathways
The classical pathway
The alternative pathway
the lectin pathway
all 3 result in production of C3 convertase that cleaves C3 to release C3a and C3b which
classical complement
activated via anitbody binding
CC effector function
opsonization
leukocyte/microglial recruitment
target
membraneoltyic pore in pathogen cell membrane = death
mechanism of action
clearing of target antigen
CDC pathway - complement dependent cytotoxicity
complement receptor CR dependent phago. cyto
C1q complex
six globular heads helped together by collagen like tails
C1r and C1s composed
initiation of CC
binding C1q surface = conformational change to R and S complexes = activation of autocatalytic activity in R, R then cleaves S = active serine protease
formation C3 convertase
activated S binds C4 and cleaves = C4a and C4b
4b binds covalently to surface of protein and bindi C2, cleaved by C1 into C2a and b
C2a and C4b remain on surface acting as C3 convertase, C3 convertase cleaves C3 into C3a and C3b
C3a=local inflammatory response
C5 convertase and MAC
C3b binds C4bC2B complex = C5 convertase