part 1 review Flashcards
1
Q
B cells are attracted to follicles by:
A
CXCR5
2
Q
T cells are attracted to paracortex by:
A
CCR7
3
Q
PAMPs assoc with-
DAMPs assoc with-
A
PAMPs- micobes
DAMPs- damaged/necrotic cells
4
Q
typically, extracellular TLRs recognize ____ and intracellular recognize ___, exception?
A
extracellular- bacterial
intracellular- viral
exception- TLR9 is present in endosomes, recognized CpG DNA which is bacterial
5
Q
2 things that are activated by TLRs
A
- NFkB = acute inflammation/adaptive immunity
- interferon reg factors=IFN a/b (antiviral defense)
6
Q
NOD-like receptors are present in the ____ and form ____ upon activation
A
cytosol; inflammasome
7
Q
what is the action of NLRP-3?
A
cleaves Pro-IL-1B to IL-1B = inflammation and acute fever
8
Q
what is the exception in NLRs?
A
NOD2 is specific for bacterial peptides and does not trigger formation of inflammasome
9
Q
gd T cells
A
lymphs with limited diversity, recognize microbial lipids in CD1
10
Q
neutrophil production in bone marrow is stimulated by-
A
GM-CSF
11
Q
M1- formed by, actions
A
formation via signaling from TLRs and IFNg
promote inflammation, phagocytose/kill bacteria and fungi
12
Q
M2- formed by, actions
A
formation via signaling from IL-13, 14
release IL-10, TGFb and promote anti-inflam and wound healing
13
Q
2 main functions of NK cells
A
- kill virus infected cells by ADCC
- secrete IFNg to activate M1s to kill phagocytksed microbes
14
Q
what is NKG2D?
A
activating receptor on NK cell that recognizes MHC-I proteins expressed during cell stress
15
Q
what is CD16?
A
activating receptor on NK cell that recognizes IgG on cell surface and kills cell via ADCC
16
Q
responsible for the development and maturation of NK cells
A
IL-15
17
Q
stimulates NK cells to release IFNg
A
IL-12
18
Q
NK T cells
A
in epithelia and lymph organs, recognize microbial lipids
19
Q
B1 cells
A
in peritoneal cavity and mucosa, produce IgM specific to microbial cell wall - “natural antibodies”
20
Q
marginal zone B cells
A
present in lymph follicle border, produce rapid antibody response against polysaccharide rice microbes in blood
21
Q
CRP targets ___ on microbe surface
A
phosphorylcholine
22
Q
how does CRP help fight infection? (2)
A
- activates complement via classical pathway
- targets microbe for phagocytosis by macrophages
23
Q
movement of WBCs into tissues is mediated by:
A
first selectins (weak) then integrins (stronger)
24
Q
antiviral defense substances
A
type 1 IFN (a/b) and NK cells
25
what triggers the production of IFNs by virus-infected cells?
activation of TLRs
26
IL-10
anti-inflammatory, inhibits M1 activation
27
main "player" in mucosal immunity
MALT
28
effect of commensals on paneth cells
commensals will regulate the composition of antimicrobial peptides released from paneth cells
29
why are commensals not eliminated from the intestine?
- IECs express low levels of TLR 2, 4
| - IECs express high levels of tollip (inhibitory)
30
effect of commensals on dendritic cells
commensals result in immature DCs that will only given eek costimulatory signals in the LN and lead to the formation of Tregs
31
effect of commensals on NFkB
commensals will block NFKB from binding to promoter through PPARg and IKB
32
how do paneth cells "sense" microbes?
via TLRs
33
what cells regulate paneth cells?
NK T cells
34
2 genetic programs that are responsible for the antimicrobial peptides of paneth cells
MyD88 and NOD2-dependent
35
IEL locations
CD8- closer to surface
| CD4- in lamina propria
36
"type a" activity of IELs
virus infected cell presents on MHC-I
| IEL kills with perforin/granzyme and Fas-dependent path
37
"type b" activity of IELs
stressed cells express MIC-A and MIC-B
IELs bind MIC via NKG2D
kill via perforin/granzyme path
38
M cells are:
conduits for antigen sampling; targeted by some pathogens
39
FcRn dependent transport =
IgA binds antigen and carries across cell via FcRn to DC
40
apoptosis dependent transport=
IEC undergoes apoptosis and fragments released to DC
41
antigen capture=
DC squeezes between 2 IECs to grab antigen
42
2 types of IgA
IgA1- planar, proteins
| IgA2- kinked, LPS/carbs
43
functions of secretory IgA (2)
- bind and neutralize pathogens or toxins in gut lumen or inside endosomes
- export toxins/pathogens from the lamina propria into gut lumen for excretion
44
what will compensate in the case of SIgAD?
IgM will compensate
45
what is released by DCs in mesenteric LN to trigger formation of Tregs?
IL-10
46
oral tolerance is induced only by
mesenteric LN
47
what is MHC restriction?
T cells can only recognize peptides when they are displayed on MHC molecules
48
plasmacytoid DCs are directed against-
viruses
49
genes for MHC-I
HLA-A,B,C
50
structure of MHC-I
binding cleft made of a1/a2, conserved b2 region
51
which cells express MHC-I?
all nucleated cells
52
how are antigens processed for presentation by MHC-I?
degraded in proteasome to fragments
| fragments then pumped into ER by TAP
53
genes for MHC-II
HLA-DQ, DP, DR
54
structure of MHC-II
binding cleft made of a1 and b1 subunits
55
MHC-II expressed on:
dendritic cells, macrophages, B cells only
56
how are antigens processed for presentation by MHC-II?
taken into cell by endocytosis, broken into fragments by proteases, ER produces MHC-II+CLIP and releases in vesicle, vesicles fuse, HLA-DM removes CLIP to leave IL and peptide binds MHC-II
57
codominant expression of MHC genes increases-
| polymorphism of MHC genes increases-
individual survival
| population survival
58
what causes bare lymphocyte syndrome?
MHC molecules do not form stably due to mutations in TAP or CLIP
59
B cell antigen recognition differ from T cells: (4)
- not limited to peptides
- uses antibodies
- no processing of antigen needed
- antigens presented by FDCs or complement
60
describe a thymocyte
```
double positive (CD4, CD8)
expressing novel TCR ab
```
61
thymocytes interact with ____ in the thymic ____
thymic epithelial cells
| cortex
62
end result of T cell maturation in thymus=
mature, naive T cells
63
what will ingest the thymocytes that undergo apoptosis?
thymic macrophages (tingible macrophages)
64
peptides used in T cell selection process are:
self peptides
65
structure of TCR
1 a chain, 1 b chain
| each chain with variable region (3CDRs) and constant region (anchors to membrane)
66
TCR lacks
effector functions
67
combinatorial diversity
different VDJ combinations
68
junctional diversity
inaccurate gene splicing results in random insertion or cleavage of nucleotides
69
Erk kinase
Erk kinase signaling influences development of gd T cells
strong Erk = gd T cell forms
weka Erk= ab T cell forms
70
TNF family is located-
in the middle of MHC thus alteration in MHC = alteration in TNF
71
2 states of Lck
inactive- phosphorylated
| active- unphosphorylated, reveals kinase domain
72
T cell structures involved in signal transduction
CD3, zeta
73
T cell costimulator interaction
CD28 (t cell)
| C7-1/B7-2 (activating cell)
74
action of CD45
phosphatase that dephosphorylates/activated Lck
75
where does ZAP70 bind?
double phosphate docking sites present on CD3 and zeta
76
what are the actions of active ZAP70?
phosphorylation and activation of PLC, Ras/Rac, Pl-3 kinase = up regulation of transcription factor and protein synthesis
77
what TFs are increased via T cell activation?
NFAT, NKkB, AP-1 (jun, fos)
78
why is IL-2 important?
regulates clonal expansion of T cells
79
effect of rapamycin
blocks IL-2R
80
x-linked SCID caused by
mutation in Yc chain of IL-2R - causes failure to recruit JAK3
81
what is CD25?
CD25 = IL-2Ra = high affinity
82
what is the first molecule to be up regulated on the T cell surface following activation?
CD69
83
how do cyclosporin/tacrolimus cause immune suppression?
PLC will increase calcineurin levels in cell
| calcineurin inhibitors= NFAT remains phosphorylated and is unable to move into nucleus
84
CD40L is expressed by:
CD4 T cells
85
CD40/CD40L is the second signal for (3)
macrophages- phagocytosis, cytokine expression
B cells- isotope switching
Dendritic cells- costimulation, cytokine expression
86
3 ways that CD8 T cell can kill a cell
initiate apoptosis via:
- perforin/granzyme
- fas/fas ligand
- produce IFNg/TNK to activate NFKB = NO production
87
mediators of migration of naive T cells through HEVs (3)
L-selectin, LFA-1 and CCR7
88
present in efferent lymph vessel to lead T site to infection
S1P (that attracts S1PR1 on T cell surface)
89
resistance of mycobacteria to cell mediated immunity=
inhibits phagolysosome
90
resistance of HSV to cell mediated immunity=
interferes with TAP
91
resistance of CMV to cell mediated immunity=
interferes with proteasome
92
resistance of EBV to cell mediated immunity=
interferes with proteasome, secreted IL1-0 to block M1 activation
93
resistance of Pox virus to cell mediated immunity=
secretes soluble receptors to IL-1 and IFNg to block their actions
94
b cells use ___ for signal transduction
Iga and Igb
95
affinity of B cells vs. T cells for antigen
B cells have a higher affinity and can also INCREASE their affinity as part of the maturation process
96
most abundant Ig
IgG
97
type of cell that dictates B cell selection
bone marrow stromal cells
98
expressed by naive, mature B cells
IgM and IgD
99
how are plasmacytes formed?
naive mature B cells interact with antigens on their surface, endocytose the antigen, process it and express it on MHC-II; CD4 T cell binds MHC-II and secretes cytokines to active B cell = plasmacyte that travels to germinal center of LN
100
what attracts B cells to LN
SLC and MIP3B from dendritic cells
101
what attracts B cells to follicles
BLC from FDCs
102
what is somatic hypermutation?
b cell editing that yields daughter cells with varied affinity for antigen, daughter cells will interact with FDC and only those with high affinity will survive
103
what enzymes are used in somatic hypermutation?
cytodine deaminase
| uracil glycosylase
104
what is isotope switching?
changing type of antibody from changes to Fc region
105
what enzymes are used in isotope switching?
cytodine deaminase, uracil glycosylase, APE1
106
what is meant by "thymus dependent"?
thymus dependent antigens are those that require T cell activation- peptide antigens are thymus dependent
107
what signals class switching to IgG?
IFNg
108
what signals class switching to IgE?
IL-4
109
what signals class switching to IgA?
TGF-b and IL-10
110
which Ig crosses placenta?
IgG
111
which Ig activate complement?
IgM>IgG
112
functions of IgG (6)
- neutralization
- opsonization
- activate complement (classical)
- activate NK cells for ADCC
- neonatal Ig transfer
- feedback inhibition of B cell activation
113
function of IgM
-activate complement via classical pathway
114
functions of IgA (2)
- mucosal immunity
| - neutralization
115
functions of IgE (2)
- granulocyte degranulation
| - defense against helminths
116
what helps to increase the half-life of IgG?
FcRn by protecting IgG from catabolism
117
what is "opsonization"?
IgG coats the outside of microbe, then IgG binds to FcgRI or FcgRIIA on phagocytes and microbe is phagocytosed and killed
118
what are the clinical implications of splenectomy?
spleen is reservoir for macrophages, thus if spleen is removed, pt is at risk for bacterial infections (encapsulated)
119
FcgRI and FcgRIIA
located on phagocytes for phagocytosis of opsonized microbes
120
FcgRIIB
for feedback inhibition of B cells and attenuation of inflammation
121
FcgRIII
on NK cells for ADCC activation
122
FceRI
on granulocytes, binding will signal degranulation
123
alternative pathway C3 convertase
C3b+Bb
124
alternative pathway C5 convertase
C3b+Bb+C3b+C5
125
function on C3b, C4b on microbes
acts as opsonin (signals IgG to bind)
126
functions of C5a, C3a, C4a
trigger inflammation
127
initiator of classical pathway
C1 binds to antibody on microbe surface
128
initiator of lectin pathway
mannose-binding lectin binds mannose on microbe surface
129
C3 convertase in classical and lectin pathways
C4b+2a
130
C5 convertase in classical and lectin pathways
C4b+2a+C3b+C5
131
what triggers the late stages of complement cascade?
C5b
132
properdin
stabilizes C3 convertase in alternative pathway
133
3 end actions of the complement cascade
1-opsonization (C3b)
2- cytolysis via MAC formation (late steps triggered by C5b)
3- inflammation (C5a, C3a, C4a)
134
DAF
decay accelerating factor
| inactivates C3 convertase in alt pathway by displacing Bb
135
MCP
prevents assembly of C1 to block activation via classical pathway
136
C1 inhibitor
blocks protolytic activity of C1 (inhibits classical and MBL pathways)
137
patients deficient in C1, C2 or C4 have increased risk to develop-
SLE
138
complement def that is typically fatal in early life
C3
139
def in C9 or MAC = increased susceptibility to
neisserial infections
140
paroxysmal nocturnal hemoglobinuria
RBCs lack DAF and CD59 = susceptible to complement mediated attack/lysis, treat with anti-C5 antibody
141
hereditary angioedema
def in C1 inhibitor causing accumulation of kallikrien/bradykinin, not "really" complement mediated disease
142
C50 test will gauge
amount of serum required to lyse 50% of RBCs
| increased C50 = decreased complement activity
143
what surface markers are expressed by Tregs? transcription factors?
surface- CD4, CD25, CTLA-4
| TF- FoxP3
144
mutation in FoxP3 will cause
IPEX (deficiency of Tregs)
145
what is AIRE?
present in thymic medullary cells, allows for expression of distant-tissue specific proteins
146
absence of AIRE causes
APECED (autoimmune polyendocrine syndrome)
147
clinical manifestations of autoimmunity depend on
antigen targeted
148
NOD2 contributes to
crohn's disease
149
HLA-B27 is assoc with
ankylosing spondylitis (90%)
150
what is the molecular mimicry hypothesis?
autoimmune diseases develop after exposure to antigen that is very similar to self
