Complement System Flashcards
what is the complement system?
system comprised of proteins that help to kill microbes, induce inflammation, increase phagocytosis by opsonization and clear soluble immune complexes
what is the lectin pathway initiated by?
lectins that bind mannose
what is the alternate pathway activated by?
cell wall of bacteria and yeast
what is the classical pathway initiated by?
antigen-antibody complex
what are the steps for activation of the complement system?
- recognition
- enzyme activation
- expression of biological activity
what are some similarities/differences on the paths?
S: end result
D: unique proteins & enzymes for first step
all three pathways make:
C3 convertase (and cleave C3)
what proteins are involved in the classical pathway?
C1-9
what makes up the C1 complex?
C1q, C1s, C1r
what is the first step of the classical pathway?
binding of C1 to antibody
the conformational change that occurs when C1 is bound activates:
C1s
what is needed for binding onto the C1 complex?
2 IgG OR 1 IgM (cause IgM so big)
what is C1s?
C1 esterase that cleaves C4 and C2
(cleaves C4 to C4a + C4B, C2 to C2a, C2b)
what steps occur to form MAC?
c6 binds to c5b
c7 binds to that
c8 binds to that
C5bc6c7c8 acts as receptor for c9
What happens after C3 cleaves C4 and C2?
C4b and C2a form a complex called C3 convertase that can cleave C3 into C3a&b
what is the largest amplification step?
C3 convertase cleaving hundreds of copies of C3, forms amplification or cascade of reactions
C4bC2aC3b forms a complex called ____
C5 convertase (cleaves C5 to C5a&b)
what does C5b do?
initiates the formation of membrane attack complex
what does c9 do?
polymerizes into tube that inserts onto membrane punching holes that allow water and ions to ender making the cell lyse (causes direct death of microorganisms)
what is a lectin?
proteins that bind to carbohydrates
mannose binding lectin bind to _______________
carbs on surface of bacteria and yeast
MBL cleaves _______
C4 and C2 (thus making C3 convertase) (picks up classical pathway from here)
In the alternate pathway PAMPS begin the pathway how?
they hydrolyze C3 to make C3 a&b
after C3bFactorB complex is formed what ccurs?
factor D cleaves factor B forming c3bBb which is C3 convertase
what binds to C3bBb and why?
properdine to make it more stable
becomes C3bBbP
after c3b binds to the cell surface what happens?
binds factor B forming C3bFactorB complex,
what does C3bBbP do?
cleaves C3 to C3b (positive feedback loop)
what does C3bBbC3b do?
cleave C5, C5b then can initiate process to make MAC
how does the complement system induce inflammation?
C3a, C4a, C5a
strongly stimulate chemotaxis for neutrophils and basophils/mast cells
what is C reactive protein?
protein produced by inflammation to tart classic pathway, used as a marker to detect inflammation in the body
how does the complement system facilitate phagocytosis?
opsonization (immune system recognizing and destroying pathogens)
what binds to the complement receptors?
C3b, iC3b, C4b
how are immune complexes cleared?
after complement cascade is activated, complex binds to complement receptors enhancing phagocytosis and destruction of antigen
deficiency in complement components C1, C4, C2 is associated with ______ because ______
Lupus
impaired ability to clear immune responses (exhausts quantities of complement proteins)
deficiency
in the alternate pathway can lead to what?
increased susceptibility to recurrent infection with pus producing bacteria
what is the first thing that inhibits the classical pathway?
Cleavage of C4 and C2 blocked by C1 inhibitor
what is the second thing that blocks a later stage of the classical pathway?
decay accelerating factor binds to C4 dissociating C4bC2a blocking formation of C3 convertase
what is associated with deficiency of C1 INH?
angioedema or uncontrolled activation of Cā
what blocks C3 convertase in the alternate pathway?
factor H (displaces Bb from C3bBb)
what forms inactive C3b?
factor I and membrane cofactor protein
what blocks C3 convertase in the alternative pathway?
DAF
what blocks C9 binding and precents MAC?
C59
what are serum carboxypeptidase inactive anaphylatoxins?
C3a, C5a, C4a
Phagocytic removal of microbes and immune
complexes from our tissues is helped by
which of the following?
a) IgG
b) C3bi
c) C3b
d) All of the above
d) All of the above
Although compliments are considered part of
the innate defense, which of the three
pathways may require time and acts with
antigen specificity?
a) Classical
b) Lectin
c) Alternate
d) C reactive protein
a) Classical
