Complement Cascade Flashcards
what systems does complement “complement”?
humoral and innate immunity
C’
complement
complement is central to what?
inflammatory reactions
triggering and amplifying inflammation, attraction of phagocytes, clearance of immune complexes, cellular activation, direct microbial killing, and important in development of the humoral responses
larger and smaller fragment of complement?
a - smaller
b - larger
b binds and a diffuses
anaphylotaxins
a fragments of complement
are chemotactic peptides
role of anaphylatoxins
play a role in initiating a localized inflammatory response
all pathways of complement end where?
formation of the MAC
classical pathway
activated by antigen binding to antigen
assists in the humoral response
alternative pathway
not necessary for a prior exposure
-doesn’t need antibody
plays a role in surveillence
more primitive than classical
lectin pathway
activated by binding of mannose binding protein in bacteria
initiation of classical pathway?
IgG or IgM antibody is bound and results in the binding of C1
-C1 binds to Fc portion of antibodies
overview of classical complement pathway
most efficient and fast
1) IgG and IgM antibodies bind antigen and Fc portion binds C1
-binds to C1q domains (cleavage of C1r and C1s)
enzymatically active C1qrs
structure of C1
one hexamer C1q subunit, two C1r, and two C1s subunits
forms a large complex
what activates C1?
cleavage of C1r and C1s
-yields active C1qrs
*the C1 is a C1q hexamer, two C1r, and two C1s subunits
how many of each antibody to activate classical pathway?
IgM is a pentamer
-only requires one to initiate cascade
IgG is a monomer
-requires at least two to initiate cascade
activity of enzymatically active C1qrs?
cleaves C4
-release C4a and C4b
C4b attaches to the cell membrane which form clusters around the area of the antibody interaction
C4a diffuses away
also cleaves C2
activity of C4b?
recruits C2, which is also cleaved by C1qrs
-C2a diffuses away and C2b binds to C4b
what is the C3 convertase of classical pathway?
C4b2b
-cleaves C3
C3b will opsonize and also associate with the C3 convertase
-forms the C4b2b3b (C5 convertase)
importance of C3
responsible for the distinction between self and non-self
self surfaces limit the deposition of C3b
-C3b rapidly associates with non-self surfaces
C5 convertase of the classical pathway?
C4b2b3b
initiates the formation of the MAC complex
C5b associates with C6 and C7 which inserts into the membrane
-forms pore - which will lead to slow lysis
C8 then bind the C5b67 which
-forms C5b678 which recruits 10-16 copies of C9
forms the MAC
what is the MAC complex?
C5b6789
creates large pores in the membrane
-results in more rapid osmotic lysis of the cell
alternative pathway of complement?
slow and less efficient
surveillence system
initiation of alternative pathway?
spontaneous conversion of C3 to C3b
-important in recognizing self from non-self
how is C3b involved in the recognition of self membrane?
sialic acid levels are high on the self membranes
-result in the inactivation of C3b
bacterial and viral envelopes have low sialic acid
-C3b remains associated with membrane