Cell Signaling Flashcards

1
Q

shared gamma common subunit

A

JAK1 & JAK3
STAT5a & STAT5b

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2
Q

cytokines activated gamma common subunit

A

2, 4, 7, 9, 15, 21

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3
Q

shared gp130

A

JAK1, JAK2, & TYK1
STAT3

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4
Q

cytokines activated by shared gp130

A

IL-6, 11, OSMR, LIFR

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5
Q

STAT3 activates what hormones

A

prolactin and growth

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6
Q

CD45

A

immune synapse; negative regulation STAT

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7
Q

SOCS1 inhibits

A

STAT1

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8
Q

SOCS3 inhibits

A

STAT3

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9
Q

a mutation in KIR

A

diables SOCS from downregulating signaling

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10
Q

KIR inhibits JAK by functioning as

A

a psuedo stubstrate

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11
Q

High SOCS1 causes

A

high M2 polarization

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12
Q

High SOCS3 causes

A

high M1 polarization

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13
Q

Ruxolitinib

A

inhibits JAK1 and JAK2

treats myelofibrosis by reducing spleen size

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14
Q

Tofacitinib

A

inhibits JAK 3

interferes with IL4 and IL2 signaling, RA treatment

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15
Q

Myd88 dependent pathway

A

fast, rapid production of inflammatory cytokines

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16
Q

Myd88 independent pathway (TRIF)

A

slow, production of INF-a and INF-b

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17
Q

NFkB activation

A

TLR4 binds LPS –> activates TAP–>TAP phosphorylates IKK complex–> IKK phosphorylates IkB –> NFkB translocates to the nucleus

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18
Q

Proximal T cell signaling

A

MHC presents antigen to TCR
CD45 phosphatase disassociates
Lck associates w/ CD 4 or 8
phosphorylates 10 ITAMs on CD3z
allows Zap70 to dock to zeta
Lck phosphorylates Zap70
Zap70 autophorylates

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19
Q

Distal T cell signaling

A

Zap70 phosphorylates LAT and SLP76
—this activates 4 pathways

  1. PLC-y mediated increases calcium
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20
Q

PLC-y increases

A

calcium and IL-2

**also produces IP3 and DAG7 (required for NFkB activation)

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21
Q

calcium pathway

A

calcium binds to calmodulin
calmodulin binds to calineurin

that whole complex goes and phosphorylates NF-AT
NF-AT translocates to the nucleus to drive IL-2

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22
Q

cyclosporine inhibits

A

NF-AT

suppresses IL-2, no T cells —> graft survival

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23
Q

CTLA4 down regulates T cell activity by

A

outcompeting CD28

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24
Q

PD-1:PDL1/2
BTLA: HVEM
down regulate T cell activity via

A

ITIMs

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25
Pembrolizuab acts as cancer therapy through
PD-1
26
Ipilimuab acts as cancer therapy though
CTLA4
27
T reg cell markers
CD4, FOXP3, CD25
28
Tregs express
high CTLA4 TGF-b, IL-10, IL-35
29
Tregs requires
IL-2
30
mutations in FOXP3 cause
IPEX
31
anergy
signal 1 is received, but no costimulatory signal
32
BCR signaling
similar to TCR bind antigen --> acativated SrC kinases --> ITAMs-->Syk docks at SH2 --> phosphorylates PLC-y --> NF-AT, NFkB, etc
33
main goal of B cell signaling
get B cell ready for terminal differentiation into plasma cell
34
Arp2/3 provides
nucleation site for actin molecules to bind
35
Arp2/3 dramatically improves
actin filament polymerization
36
Arp complex is used to create the _____ for cell movement
actin web
37
TCR: MCH activation activates:
PLCy VAV
38
Vav activation leads to
actin polymerization and cytoskeletal reorganization
39
Rac
lamellpodia
40
Rho
stress fibers
41
cdc42
filopodia, microspikes
42
Rho Family GTPases are key to
topography formation of immune synapse cell migration
43
activation by cdc42 by Vav is required for
WASp mediated actin filament mucleation by Arp2/3
44
WAS triad
recurrent viral infections eczema thrombocytopenia
45
WASp pathway
TCR activation --> recruitment of cdc42 to GTP binding domain --> orients WAS to signaling platform --> WAS pops open --> stabilized by Fyn --> VCA can bind to Arp2/3 --> actin polymerization
46
classic WAS
absent/truncated proteins due to premature terminations LOF
47
X linked thrombocytopenia WAS
mutated, nonfunctional protein due to missense mutation no autoimmunity LOF
48
x linked neutropenia WAS
uncontrolled actin polymerization mutation in GTPase binding domain GOF
49
Proinflammatory cytokines
6, 2, 12, 17, 23, TNF-a
50
Anti-inflammatory cytokines
IL 4, ,5, 10, 13
51
What cytokine drives Th1 differentiation?
IL-12
52
What cytokine drives Th2 differentiation?
IL-4
53
What cytokine drive Treg differentiation?
TGF-b
54
What cytokine drives T17 differentiation?
TGF-b, IL-6 (IL-1, IL-23)
55
IFN-y STAT4 T-bet
Th1
56
IL-4 STAT6 GATA3
Th2
57
TGF-b FOXP3
Treg
58
IL-17 STAT3 RORyt
Th17
59
When TCR binds to CD80/86 this drives
actin filament rearrangement IL-2 production NFkB production
60
when CTLA4 binds CD80/86
prevents cytoskeletal rearrangement decreases IL-2 induces apoptosis or anergy
61
STAT binds to
GAS
62
what do SH2's two binding sites do?
1 weakly binds phosphotyrosine 1 provides a specific binding site for an amino acid side chain
63
a cell exits G0 and enters
G1
64
G1: CD4/6 binds to
cyclin D
65
S: CDK2 binds to
cyclin E
66
G2: CDK binds to
cyclin A
67
M: CDK1 binds to
cyclin B
68
what cyclin would be upregulated for multiple rounds of division?
D
69
a proinflammatory dual-producing Th17 cell expresses
IL-17 and IFN-y
70
a proinflammatory dual-producing Th17 cell has what markers
Tbet RORyt
71
a anti inflammatory dual-producing Th17 cell expresses
IL-17 and IL-10
72
a anti inflammatory dual-producing Th17 cell has what markers
FOXP3 RORyt
73
keratinocytes express ______ causing a feedback loop with Th17
IL-23
74
When a Th17 is in a proinflammatory environment, what cytokine is upregulated?
IL-23
75
fibroblasts release _______ after exposure to TNF-a
keratinocyte growth factor
76
TYK mutation: Homozygous Pro1104/Pro1104
increased risk for inflammatory disease decreased risk of infection
77
TYK mutation: heterozygous Pro1104/Ala1104
lower risk of inflammatory disease lower risk of infection
78
TYK mutation: homozygous Ala1104/Ala1104
very low risk of inflammatory disease very high risk of infection (TB)
79
How innate cells activate adaptive
1. MHC-TCR 2. CD28 engagement 3. cytokine activation
80
where does priming of the adaptive immune cells occur?
secondary lymphoid organs thymus spleen lymph node
81
Th1 cells protect against
viruses
82
Th2 cell protect against
helmiths
83
Th17 cells protect against
extracellular toxins, bacteria, fungi
84
Treg
anti-inflammatory
85
Why is IL-23 bad for IBD?
created a positive feedback loop into Th17
86
SNPs that affect Th17
IL23R STAT3 JAK2 TYK
87
phosphotases turn signaling
off
88
Why is Th17 proliferation a good thing?
Seals barrier
89
why is diet thought to play a role in Th17 regulation?
RORyt **mechanism unknown but regulates something with fatty acids/cholesterol, ratio gets out of whack, activates RORyt --> Th17 activation
90
a mutation in SH2 causes
loss of RTK binding
91
why don't STAT inhibitors work?
the STAT family can heterodimerize, other STATs will fill in
92
JAK inhibs induce
anergy, no cytokine signaling
93
CD154
aka CD40/CD40L
94
a mutation in Zap 70 would cause
no granzymes to be expressed