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IDM2003 Exam 2 > Lecture 12: Signaling through immune receptors > Flashcards

Lecture 12: Signaling through immune receptors Flashcards

1
Q

signal transduction is the process of _____ from outside source that activate ________ that are converted into ____ singals/responses

A

input signals; biochemical pathways; output

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2
Q

there are often _____ requirements since some outputs can be dangerous to a cell

A

threshold

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3
Q

the receptor/ligand is the ____

A

input

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4
Q

an example of an input threshold requirement is ________

A

receptor cross-linking or clustering; F(ab)2 BCR

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5
Q

Trimeric _____ released by NK and cytotoxic T cells binds to FAS and ______ it. Death domains cluster so Fas can recruit FADD. _______ recruit procaspase 8.

A

FasL; trimerizes; DED

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6
Q

Receptor signaling can be distributed to _____ or ______

A

cytoskeleton or nucleus

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7
Q

Signals to cytoskeleton impact ________, including ___, _____, and ____

A

cell morphology: cell shape, size, and mobility

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8
Q

Signals to the nucleus impact ______

A

gene expression: synthesis of new proteins, inducing cell division, proliferation, cell death

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9
Q

Protein kinases are enzymes that

A

catalyze attachment of phosphate

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10
Q

Protein phosphatases ______ phosphate group

A

remove

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11
Q

kinases add phosphate to 1 of 3 aa residues:

A

tyrosine, serine, threonine

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12
Q

______ catalyze attachment of a phosphate to a phospholipid

A

Phospholipid kinases

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13
Q

an example of phospholipid kinase

A

PI3K converts PIP2 -> PIP3

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14
Q

_____ carry kinase activity in the cytoplasmic tail of the surface receptor. They have an ____ activity. An example is FLT3 which is involved in hormone differentiation of CD34 cells to produce DC

A

Receptor tyrosine kinases; intrinsic

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15
Q

_____ noncovalently associate with intracellular tyrosine kinases on T and B cells

A

Nonreceptor kinases

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16
Q

propagation of intracellular signaling is mediated by ______

A

multiprotein signaling complexes

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17
Q

multiprotein signaling complexes can be common to several pathways and have distinct binding domains such as ___ and ___, which are generally found in _____ molecules

A

SH2/SH3; adaptor

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18
Q

SH is part of ____ homology (a nonreceptor tyrosine kinase)

A

Src

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19
Q

______ proteins (ex: LAT) are like power strip - many things can bind

A

scaffolding

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20
Q

______ proteins (ex: Grb2) link one protein to another (like a wall block)

A

Adaptor

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21
Q

_____ binds to SLP76. It makes a docking site complex for _____ during TCR signaling. It allows this molecule to be activated by phosphorylation by Itk

A

LAT; PLC-gamma

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22
Q

adaptor protein ____ recruits Sos via its ____ domain to an activated receptor that is tyrosine phosphorylated via its ___ domain

A

Grb2; SH3; SH2

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23
Q

Sos does activity on Ras as ____

A

GEF (guanine-nucleotide exchange factor)

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24
Q

SH2 binds in ___ format

A

pYXXZ (three aa away from phosphorylated tyrosine)

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25
Q

SH3 binds in ___ format

A

XPPXP (proline in 2nd and 5th position)

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26
Q

____ is a small G protein associated with pancreatic cancers

A

Ras

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27
Q

GTPases act as ______, triggered by GEF

A

on/off switch

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28
Q

Ras bound to ____ is inactive and is active when bound to _____.

A

GDP; GTP

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29
Q

___ helps to open up Ras bound to GDP so that it can be exchanged for GTP

A

GEF

30
Q

_____ are recruited to the site of receptor activation

A

GEFs

31
Q

The active receptor molecule is

A

GTP:Ras

32
Q

activity of small G proteins will lead to shutdown/feedback conversion of ___ to ____. Alterations in this regulatory process lead to cancer.

A

GTP to GDP

33
Q

_____ is the process of a kinase cascade

A

Amplification

34
Q

_____ is example of kinase cascade (adding a kinase to a kinase). The higher the number = further upstream from the outcome

A

MAP (mitogen-activated protein)

35
Q

Ras/MAP kinase

A

TCR signaling produces DAG, which recruits RasGRP where it activates Ras at the membrane. Ras binds to Sos - enhances Sos activity and amplifies Ras activation. Ras activates Raf (MAP3K), which phosphorylates Mek (MAP2K), which phosphorylates Erk (MAPK). Erk enters nucleus and activates TF like Elk-1

36
Q

second messengers are small molecule biochemical _____ that diffuse through the cell

A

mediators

37
Q

calcium ion influx from the ER to the cytosol is an example of ______. Ca2+ modifies _____ to act on effector protein that activates _______ which dephosphorylates and activates NFAT and transcription of IL2

A

second messenger; calmodulin; calcineurin

38
Q

Regulation: kinase activity is often modulated by _____ activity

A

phosphatase

39
Q

Signaling can be regulated by ______ and tagged for proteasomes

A

ubiquination

40
Q

____ can turn on the proteasome that targets for MHC I

A

IFN-gamma

41
Q

receptors and ligands can be directly ______ by antibodies, soluble receptors, and non-activating ligands

A

inhibited

42
Q

what is signal 1?

A

antigen specific interaction between MHC and TCR (this is the antigen you need to interact with)

43
Q

what is signal 2?

A

other info from APC regarding how serious the infection is, guiding the response

44
Q

CD3 is made up of

A

delta, epsilon or gamma, epsilon

45
Q

there are 2 _____ (homodimers) in cytoplasm underneath TCR

A

zeta chains

46
Q

ITAMs (immunereceptor tyrosine based activation motifs) have 2 ___ domains and are present on cytoplasmic tail of ___

A

SH2; CD3 (4 total) and zeta (3 on each)

47
Q

Phosphorylated ITAMs recruit _____ with tandem SH2 domains

A

ZAP70

48
Q

______ is an example of ITIM on NK cell that stops NK cell from killing a self cell (recognizes MHC)

A

NKG2A

49
Q

_____ is an example of ITIM that stops T cells from killing. Blocking the receptor would allow T cells to keep killing (cancer drug)

A

PD-1

50
Q

ITIMs are _____ and recruit inhibitory phosphatases that ______ signaling pathways

A

phosphorylated; deactivate

51
Q

____ helps TCR if its engaged to MHC II and enhances the signal to TCR

A

CD4

52
Q

___ (on tail of CD4) adds phosphate to ITAMs (especially __ chains)

A

Lck; zeta

53
Q

phosphorylation of TCR ITAMs by Lck, recruits _____ through tandem _____ domain

A

ZAP70; SH2

54
Q

____ phosphorylates ZAP70

A

Lck

55
Q

Lck on CD4/8 is _______ when phsophorylated on terminal tyrosine that binds the ___ domain and linker region binds ___ domain

A

inactive; SH2; SH3

56
Q

_____ removes phosphate from Lck to activate it. TCR co-localize and polarize, pushing away ___. Physical contact between ____ and TCR removes phosphate group.

A

CD45

57
Q

Lck is active when _____ is removed and _____ domain releases linker region

A

phosphate; SH3

58
Q

Lck and ___ are both invovled in phosphorylated ITAMs and recruiting ZAP70

A

Fyn

59
Q

ZAP70 is an early factor in 4 downstream signaling pathways. It begins by recruiting ____ and ____.
____ activation leads to metabolic activity
_____ activation leads to transcription of cytokines
___ activation leads to cytoskeletal (actin) reorganization
____ activation leads to adhesiveness clustering

A

LAT and SLP76;
Akt
Plc-gamma
Vav
ADAP

60
Q

_______ phosphorylates and recruits scaffolding proteins LAT and SLP-76. Adaptor protein ______ holds LAT and SLP-76 together to create docking site.

A

ZAP70; Gads

61
Q

____ costimulation (signal 2 from APC) recruits and activates PLC-gamma

A

CD28

62
Q

DC have costimulatory molecules ____ and ___. Both signals binding to CD28 induce phosphorylation and activate _____ kinase to produce PIP3.

A

CD80 and CD86 (or B7.1 and B7.2);
PI3

63
Q

PIP3 role

A
  • recruits PLC-gamma
  • Recruits Itk to membrane
64
Q

____ is recruited by PIP3 and phosphorylates PLC-gamma

A

Itk

65
Q

How do signal 1 and 2 work together?

A

signal 1: TCR leads to ZAP-70 activation, resulting in LAT/SLP76 complex, where PLC-gamma can dock
signal 2: CD28 costimulation activates PI3 kinase which converts PIP2 to PIP3. PIP3 recuits Itk and PLC-gamma, PLC-gamma can dock and be activated by Itk

66
Q

PLC-gamma function

A

cleave PIP2

67
Q

PIP2 is cleaved into

A

IP3 and DAG

68
Q

IP3 function

A
  • diffuses from membrane and allows for calcium influx from ER to cytoplasm and from outside cell
  • Ca2+ leads to activation NFAT
69
Q

DAG function

A
  • PKC activator (activates NF-kappaB)
  • recruits Ras-GRP (GEF) to activate RAS, MAP kinase cascade, and TF AP-1 (IL-2 cytokines)
70
Q

in the lab, _____ is a DAG mimic and ______ is IP3 mimic

A

PMA;
ionomycin

IDM2003 Exam 2 (7 decks)

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