Assignment 5 Flashcards
what is the complement system?
a family of > 30 activation and regulatory proteins found either bound to cell membrane or in circulation
what is the source of complement proteins and distribution
mainly by the liver
some by macrophages and fibroblasts
what are the general features of the complement system?
the complement proteins function as enzymes and are activated in a cascade called the complement pathway (alternative and classical pathways). each pathway generates a “C3b” which is important in host defense - after, both pathways converge into a common/terminal pathway
list 5 immunological functions of complement
- facilitate interaction of phagocytes to induce opsonin-mediated phagocytosis
- induce osmotic lysis of microbes
- enhance vascular permeability by inducing degranulation of mast cells/basophils
- induce chemotaxis of neutrophils
- facilitate immune complex elimination
describe the mechanism by which complement facilitates immune complex elimination
complement component C3b can bind to immune complexes in circulation
now the immune complexes can be eliminated by neutrophils (opsonin mediated phagocytosis)
the complexes ca also be transported to the liver and/or spleen via red blood cells. RBCs express CR1 and bind to C3b –> transport to liver and spleen where resident phagocytes strip the complex off the RBCs
what are the components for the classical pathway of complement activation?
C1 C2 C3 C4 C5
explain how the classical complement pathway is activated
occurs only after adaptive host defenses have been recruited - IgM or IgG (subclasses 1,2, or 3) antibodies specific for an antigen must be generated and bind to that antigen!
explain why IgM is more effective at activating complement than IgG
because IgM is a pentamer - even 1 molecule of IgM provides 2 Fc regions which is the minimum number required for C1 activation
about 600 IgG molecules are required to generate 2 IgG molecules that are close for binding by C1
what is the fab region on the antibody for
where the antigen binds
what is the Fc region of the antibody for
where the complement protein binds
list the components of the C3 convertase in CP and AP
CP => C4b2a
AP => C3bBb
list the components of the C5 convertase
CP => C4b2a3b
AP=> C3bBbC3b
what is the role of C3a and C5a?
- induction of histamine release
- chemotaxis of neutrophils
what is the role of C3b
- serves as an opsonin
- facilitates elimination of immune complexes
- component of C3 convertase AP
- component of C5 convertase in CP + AP
what is the role of C2b
- weak kinin
- increases vascular permeability = genesis of inflammation
what is the ole of C2a and C4b
- form the C3 convertase in CP
- components of C5 convertase in CP
what is the role of C5b
-the stimulus for the formation of membrane attack complex (MAC) = induces osmotic lysis of cells on which it forms!
what are the components of the terminal;common pathway
C5b C6 C7 C8 C9
what are the roles of the various components of the terminal pathway
AP and/or CP –> C5b which initiates the formation of MAC. Insertion of MAC into the target membrane induces osmotic lysis and death of microbe (or cell)
list the components of the AP of complement activation
C3b Factor B Factor D Properdin C3 C5
what is meant by “tick over” process? What is its role?
mobilization of the AP is based on the availability of C3b. C3b is derived from circulating C3.
explain how the alternative complement pathway is activated
when microorganisms/bacteria are around, C3b is spontaneously generated from C3 and binds to microbial surfaces = initiation step!
What is the role of properdin
stabilizes C3 convertase in AP and extends its half life 6-10 fold!
what are the regulators of the CP?
C1 INH (C1 esterase inhibitor) DAF (decay accelerating factor) C4bp Factor I AI (anaplylatoxin inhibitor)
what are the regulators for the AP?
Factor H
DAF (decay accelerating factor)
AI (anaphylatoxin inhibitor)
Factor I
what is the role of C1 INH (C1 esterase inhibitor)?
prevents spontaneous activation of CP - inhibiting C1
inactivates kallirein (protease) that links the complement and intrinsic coagulation pathways
what is the role of DAF (decay accelerating factor)
blocks formation of the AP and CP C3 convertase
when the C3 convertase are already formed, DAF binds with C3b or C4b and dissociates them!
what is the role of C4bp
- cofactor for Factor I
- binds to C4b and prevents its attachment to cells
- when C3 convertase has formed, C4bp bind with C4b and dissociated it
what is the role of Factor I
cleaves C4b (bound or soluble) to its inactive form, C4bi in the presence of one of several cofactors (CP)
in the presence of many cofactors CR1 cleaves C3b to make inactive C3bi (AP)
what is the role of AI (anaphylatoxin inhibitor)
binds to C3a, C4a and C5a (CP and AP) and inhibits their binding to receptors on mast cells and basophils
what is the role of factor H
binds with C3b and prevents C3b from binding to cell surface
when AP C3 convertase has formed, factor H binds with C3b inducing the dissociation of the convertase
what is the regulatory protein in the terminal pathway
MAC inhibitors (MAC INH)
what is the role of MAC INH
includes HRF (homologus restriction factor), S-protein and CD59 inhibit the formation of MAC on autologous cells
S-protein/vitronectin binds to (C5b, C6, C7) preventing their insertion into autologous membranes
CD59/HRF20 bind to C8 and prevent the binding and polymerization of C9 and MAC formation!
