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Flashcards in Complement Deck (28):

What are the results of activation of complement system? (5)

cell lysis, increased phagocytosis, increased vascular permeability, enhanced leukocyte chemotaxis, stimulation of macrophages


What is the end result of either classical or alternate pathway?

cleavage of C3 to C3b and C3a


What complements form the MAC? How does it form?

C5b binds 6, then 7, then 8 (first to insert into the membrance) and 9 causes pore to form leading to cell lysis


What is the bigger fragment, C5a/C5b, C2a/C2b?

C5b, C2a


Which pathway is first to act? How?

alternative pathway, pathogen surface creates local environment conducive to complement activation


How does C1 act?

C1 (with three subunits r, q, s) binds pentameric IgM or 2 IgGs on surface with C1q.
C1r cleaves C1s to activate it.
Activated C1s cleaves C2 and C4.


How does C4b2a complex form?

Both C2 and C4 cleaved by activated C1s. C4b binds bacterial surface and C2a binds it.


What cleaves C3 in the classical pathway?

C4b2a complex is C3 convertase.


How is the alternate pathway activated?

C3b is at a low concentration in bloodstream, binds pathogen surface. Factor B binds C3b. Factor D cleaves Factor B to Bb and Ba to form C3bBb complex, an active protease that cleaves more C3 to C3b.


What function does properdin have?

stabilizes C3 convertase C3bBb complex on pathogen surface


What function does Factor H have?

Binds C3b to let Factor I clip it to iC3b (inactive form)


How are human cells nonpermissive to the alternate pathway?

DAF and MCP inhibit production of an active C3bBb complex. DAF knocks Bb off C3b. MCP knocks Bb off C3b and allows Factor I to inactivate C3b to iC3b.


What receptor on macrophages bind C3b?



Does iC3b have a function?

Yes, it can still stimulate phagocytosis.


What two stimuli are needed for engulfment of pathogen by neutrophil?

-Ab (Fc receptor) and C3b (complement receptor)


How is C5 activated by the alternative pathway? classical?

for alternative, C3bBb binds C3b, which cleaves C5
for classical, C4b2a binds C3b, which cleaves C5


What do C5a and C5b do?

C5a- critically important chemotactic factor
C5b- starts lytic path


How is MAC prevented in human cells?

CD59 binds C5b678 to prevent C9 from joining and forming a pore


What complements are anaphylatoxins? How do they act?

C3a, C5a
-act on blood vessels to increase vascular permeability for extravasation of complement, plasma proteins, and leukocytes into tissue


What is a C1 inhibitor?

C1INH inhibits C1 by removing C1r or C1s


What is C4BP?

disrupts the classical C3 convertase (C4b2a) by kicking off C2a and allowing Factor I to inactivate C4b


What does a deficiency of C1, C2, C4 cause?

immune-complex disease, no greater rate of bacterial infection


What does a deficiency of C3 cause?

susceptibility to capsulated bacteria


What does a deficiency of C5-C9 cause?

susceptibility to Neisseria


What does a factor I deficiency cause?

susceptibility to capsulated bacteria like C3 because if you don't have an inhibitor, all of C3 gets used up and isn't there when you need it


What do DAF or CD59 deficiencies cause?

autoimmune conditions


Which is the more important function of complement: opsonization or MAC?

opsonization is more important for clearing more bacteria


How do you determine the amount of complement deficiency?

Expose patient serum to sheep RBCs that have previously been coated with rabbit anti-sheep Ab.
The presence of complement determined by the lysis of Ab-coated RBCs and expessed as CH50, the dilution of a patient's serum that gives 50% lysis of RBCs