complement cascade Flashcards
3 complement paths
- classical
- alternative
- lectin
role of complement in innate immune response
-opsonin, inflammation, cytolysis, eliminates Ag-Ab complex
lysis
-lyse cells, bacteria, & viruses
-major effector of the humoral branch of immune system
-MAC
opsonization
promotes phagocytosis of particulate Ags
binding to specific complement receptors on cells of immune system
-trigger specific cell functions (inflammation)
-secretion of immunoregulatory molecules
immune clearance
-removes immune complexes from circulation
-deposits immune complexes in the spleen & liver
anaphylatoxin
-C3a, C4a, & C5a
-bind to complement receptors on mast cells & basos to induce degranulation
-induce smooth muscle contractions, increase vascular permeability, extravasion & chemoattraction (C3a, C5a & C5b67)
main osponin of complement
C3b binds surface of microbes
-C4b & iC3b can also osponize
viral neutralization
-formation of viral aggregates reduces the net number of infectious particles
-deposits of Ab & complement on viral particles neutralizes infectivity by blocking viral attachment
source & atomic location
-soluble proteins produced by the liver
-present in blood, lymphatics, & ECM
complement activation
cascade of enzymatic reactions where each protease cleaves & activates the next protease in the pathway
role of RBCs in complement
deliver the Ag-Ab complex to the liver & spleen for consumption by phagocytes
classical pathway
-starts with C1q (18 peptides that can form trimers)
-C1 & C1r/C1s make dimeric pairs
-C1qr2s2 binds 2 immunoglobulins
-once 1 IgM binds, C1qr2s2 folds to bind more
-must have high IgG concentrations
-C1qr2s2 is bound, C1r converts to C1[r]
-C1[r] converts C1s to C1[s]
-C1[s] cleaves C2 & C4
-C4 cleaved into C4a & C4b (C4b + C2)
-C2 gets cleaved by C1[s] = C[4b2a], a C3 convertase
-C3b can join C[4b2a] and make C[4b2a]3b, a C5 convertase
classical pathway activation
formation of Ag-Ab complex
alternative pathway activation
-inhibited by cell surface constituents that are foreign to host
-Ab-independent
lectin pathway activation
-binding of mannose binding lectin (MBL) to mannose residues on glycoproteins or carbs on microorganisms surface
-Ab-independent
has
no
spleen
haemophiles- mostly in kids prior to H. flu vaccine
neisseria - you’re dead
strep pneumonia- most infectious, 57% sepsis, 59% death
alternative pathway
-does not depend on pathogen binding for activation
-C3bBb convertase
-initiated through spontaneous hydrolysis of C3
-C3 exists in high concentrations & contains thiolester with spontaneous cleavage
-C3b can bind bacteria & enhance phagocytosis
-C3 convertase contains C3b & creates positive feedback
-factor H displaces B, inactivating the convertase
4 fates of C3b
-bind microbial surface
-associate with factor B
-associate with factor H
-bind another C3b
MAC formation in alternative pathway
-C5 convertase cleaves C5 into C5a and C5b.
-C5b is unstable and is stabilized by C6.
-C5b6 allows C6 and C7 to associate and penetrate a membrane.
-The C5b67 recruits C8 which organizes C9 to form a “membrane attack complex” (MAC).
MBL pathway
MBL: acute phase protein which binds mannose residues on glycoproteins or carbs. increases during inflammation
MASP-1 & MASP-2: MBL associated serine proteases
-Has no spleen organisms can activate
-resembles classical: C4 & C2 to produce activated proteins
-works the same as C1q
-MASPs cleave C4 & C2 forming C3 convertase
-continues to form C5 convertase & MAC
lectin definition
proteins that bind to carbs
protecting normal cells from complement
-MCP or CD46 accelerates C3b, CD46, Factor H & Factor I to prevent excess alternative pathway activation
-DAF accelerates destruction of C3 convertase
-CD59 (protectin) prevents incorporation of C9 to inhibit MAC formation
iC3b
inactive form of C3b
-opsonin
