effector mechanisms of humoral immunity: elimination of extracellular microbes and toxins Flashcards
Effector functions of Abs
- neutralize - microbial toxins
- opsonize - tags pathogens for ehancing phagocytosis (IgG)
- sensitize - enhances NK cell kiling of target
- mediation of phagocytosis (IgG)
- activation of complement (IgM and IgD)
effector functions of Abs are mediated via
Fc (heavy chain contant region) of Ig molecules
neutralization
- blocks the binding of microbes and toxins to cellular ____
- prevents ____ of microbes from infected to healthy cells
- receptors
- spread
virulence factors refer to the properties of bacterial gene ____ that enable a microorganism to cause disease
products
FcgammaRI has a ____ affinity
high
FcgammaRII has a ____ affinity
low
FcgammaRIII has a ____ affinity
low
FcepislonRI has a ____ affinity
high
FcbgammaRIIB:
- found on ___ cells
- can bind ____ complexes via Fc portion
- activates ____ → inhibits signaling in B cell
- ____ affinity receptor meaning in works later in immune response
- B cells
- Ag-Ab
- phosphatases
- low
isotypes ____ and ____ are the most effiient opsonins for promoting phagocytosis via high-affinity FcgammaRI
IgG3 and IgG1
due to its ____ affinity, FcgammaRI works ____ in immune responses
high
early
due to its ____ affinity, FcgammaRIIB works ____ in immune responses when large amounts of immune complexes are formed
low
later
FcepsilonRI:
- found on ____ cells and ____
- bind Fc portion of ____
- useful in protection against ____
- when bound to Fc portion of IgE → release cationic protein ( ____ ____ ____ ) that is toxic to worms
- this happens in immediate reactions due to its ___ affinity
- mast cells and eosinophils
- IgE
- helminths
- major basic protein (MBP)
- high
antibody dependent cellular cytotoxicity (ADCC):
- Ab binds to microbe, then Fc portion bind to ____ on ____
- activates NK cells to kill Ab-coated cells via ____ and ____
- ____ affinity → works later in immune response
- FcgammaRIII on NK cells
- perforin and granzymes
- low
alternative complement pathway:
- C3 spontaneously celave to ____ on cell surface
- Factor ____ binds to C3b
- Factor ____ binds to and cleaves Factor B
- Factor B is cleaved into ____ and Ba
- Bb is bound to C3b, forming ____ (C3 alternative convertase)
- C3 convertase cleaves C3 into ____ and C3a
- C3b combines with C3bBb forming ____ (C5 convertase)
- C5 convertase cleaves C5 into ____ and C5a
- formation of ____
properdin:
- C3b
- B
- D
- Bb
- C3bBb
- C3b
- C3b3bBb
- C5b
- MAC
Properdin: stabilizes the interactions of the alternative pathway
classical complement pathway:
- ____ or ____ bind to the surface of bacterial pathogen
- ____ binds to staple formation of IgM (sometimes IgG) (bind to Fc portin)
- C1q activates ____ which activates ____
- C1s cleaves ____ (into C2a and C2b) and ____ (into C4a and C4b)
- C4b combines with C2a to form ____ (C3 convertase) (which is deposited on surface)
- C3 convertase cleaves C3 into ____ and C3a
- C3b combines with C4b2a to form ____ (C5 convertase)
- C5 convertase cleaves C5 into ____ and C5a
- formation of ____
- IgM or IgG
- C1q
- C1r C1s
- C2. C4
- C4b2a
- C3b
- C4b3b2a
- C5b
- MAC
lectin complement pathway:
- ____ ____ ____ binds to the surface of mannose on bacterial walls
- ____ is bound to the MBL
- MASP2 cleaves ____ (into C2a and C2b) and ____ (into C4a and C4b)
- C4b combines with C2a to form ____ (C3 convertase)
- C3 convertase cleaves ____ into C3b and C3a
- C3b combines with C4b2a to form ____ (C5 convertase)
- C5 convertase cleaves ____ into C5b and C5a
- formation of ____
- mannose binding lectin
- MASP2
- C2 C4
- C4b2a
- C3
- C4b3b2a
- C5
- MAC
MAC formation:
- after C5 convertase activity, ____ has binding site for C6
- when C5b-C6 complex have formed, ____ binds
- C5b67 complex is bound to membrane via ____
- ____ binds (allowing for complex to be inserted into the membrane
- C8 initiates the polymerization of ____
- ____ polyemizes to form the pore
- C5b
- C7
- C7
- C8
- C9
- C9
CR1 functions:
- promote ____ of C3b and C4b coated particles
- ____ of immune complexes
- activates ____ mechanisms of phagocytes
phagocytosis
clearance
killing
CR 2:
on ____ lymphocytes
____ affinity for cleavage products of C3b
enhances response of B cell to ____ when bound
associated with ____ infections
B
high
Ag
EBV
CR3:
- can bind ____ (necessary for recruitment of leukocytes
- binds iC3b to induce ____
- ICAM-1
- phagocytosis
C1 INH inhibits ____ activation
classical
DAF:
- ____ convertase decay
- inhibits ____ pathways
C2:C4
classical or alternative
CR1
C3 convertase decay – inhibits ____ pathways
all
MCP:
____ convertase decay
inhibits ____ pathways
C3
all
CD59:
inhibits ____ formation by blocking the addition of ____
MAC
C9
complement function: induction of inflamation:
inflammation via ____ , ____ , ____
these proteins active:
C5a, C3a, C4a
mast cells, NPs, and endothelial cells
by binding to Ag-Ab complexes, complement promotes ____ of these complexes and their clearance by phagocytes
solubilization
____ deficiency is the most common human complement dificiency
C2
systemic lupus erythematosus:
- complement deficiency:
- effect:
- C1q, C2, C4
- failure of clearing immune complexes; will be deposited on blood vessels and lead to inflammation
pyogenic bacterial infections:
- complement deficiency:
- effect:
- C3
- can be fatal, inability to produce complement activities
deficiencies in ____ and ____ result in increased susceptibility to infection with pygoenic bacteria
properdin and factor D
neisseria bacteria:
complement deficiency:
C5-C9
pathologies of complement:
- complement system can cause sigificant tissue ____
- complement activation is associated with intravascular ____ and can lead to ____ injury to tissues
- can lead to ____ (MAC mediated)
- damage
- thrombosis ischemic
- neuropathies
evasion of complement of microbes:
- microbes can evade the complement system by recruiting host:
- many pathogens express ____ acids which can inhibit the alternative pathway of complement by recruiting factor ____ which displaces C3b from Bb
- example: HIV incorporate host regulatory proteins ____ and ____ when it buds from an infected cell
- complement regulatory proteins
- sialic H (which removes C3b from Bb)
- DAF and CD59
neonatal immunity:
- transport of maternal ____ across the placenta and across the neonatal intetinal epithelium is mediated by ____
- maternal ____ in breast milk in ingested by infant
- Abs in breast milk are transported across the gut epithelium by a process known as ____
- IgG FcRn
- IgA
- transcytosis
