CIS Complement System Flashcards
Functions of the complement system
complement and regulatory proteins kill microbes induce inflammation recruit phagocytosis opsonize and facilitate phagocytosis
Main function of C3a and C5a
inflammation
C3b is the main
opsonizer
it is rate limiting Not factor D
steps of the complement pathway
microbe is recognized by complement pathway
C3 convertase cleaves C3 to C3a and C3b
C3 convertase binds C3b and forms protease complex C5 convertase
C5 convertase cleaves C5 inot C5a and C5b
C5a is a chemoattractant and makes BV more permeable
C5b initiates MAC
complement activation involves proteolytic cascades where a
zymogen is altered to become an active protease to cleave the next complement protein
the complement enzyme cascades ____ the amount of proteolytic products that are generated
amplifies!
the complement system works in conjunction with
the blood coagulation pathway and the kinin-kallikrein ststem
The alternative pathway
“autoactivated” due to tickover of C3
occurs spontaneously, 1% pf total C3 per hour, making C3a and C3b
C3b bidns to Factor B which is cleaved to Ba and Bb by Factor D
Bb binds to C3b and C3 convertase forms
C3 convertase cleaves ,pre C3 making more C3b
these steps are enhanced by properidin which stabilizes C3bBb interactinos
AP can also be initiated as an amplification loop when C3b is generated by the complement pathway or lectin pathway
MAC formation
C5b binds with C6 and 7
C5b67 bind to membrane via C7 and then C8 adds on and the many C9s
form a little pore into the cell membrane
same for all three pathways
The classical pathway is
antibody mediated
plasma protein C1q reconizes and binds to the Ag-Ab complex first
C1q binds to the Fc portion of the antibody and two serine proteases called C1r and C1s become active
C1r activates C1s so that it can activate C2 and C4
Complex C4bC2a is the classical C3 convertase
Complex C4bC2aC3b is the classical C5 convertase
The lectin pathway is initiated by
the binding of mannose binding lectin to bacterial surfaces and the activtion of MASP1 and MASP2
MBL has a hexametric structrue and after binding MASP1 and 2 are activated
analogous to C1r and C1s and initate a downstream proteolytic cascade (identical to classical cascade)
FI mediated inactivation of C3b and C4b
the cleavage of C3b and C4b by Factor I prevents them from forming active convertases and requires cofactro activity
the cofactros include the membrane bound membrane cofactor protein and complement receptr Cr1, factor H, and C4b binding protein
inactivation of C3 and C5 convertases
protein decay acclerating factor DAF, CRw, and C4BP inhibit assembly of new C3 convertases and shorten the half life of the preformed convertases, limting their ability to participate in complement activation
classical-DAF, CRI, and C4BP
Alternative pathway-DAF, Factor H, and CR1
INactivation of MAC
the MAC is the lytic complex of complement and its assembly can be inhibted by the membrane-bound MAC-inhibitory protein (CD59) and the fluid phase vitronectin and S protein
Complement is not activated on the surface of mammalian cells because those cells express
regulatory proteins that inhibit, disassemble or cleave the convertases
