Chapter Seven Flashcards

1
Q

What happens once the antigen is encountered?

A

cellular reconfiguration: naive lymphocyte -> active cells

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2
Q

What happens in active cells?

A
  1. reorganize actin cytoskeleton 2. activating transcription factors 3. synthesizing a wide range of new proteins
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3
Q

What else is needed aside from receptor mediated signaling to activate naive T cell and naive B cells?

A

co-stimulatory signaling

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4
Q

Intracellular signaling proteins serve to

A

integrate incoming signals.

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5
Q

Signal transduction

A

process whereby one type of signal is converted to another

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6
Q

What do transmembrane receptors covert extracellular signal into?

A

intracellular biochemical events

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7
Q

Enzymes most commonly associated with receptor activation

A

protein kinases. How are receptors activated?

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8
Q

3 AAs in animals that protein kinases phosphorylate proteins on

A
  1. tyrosine 2. serine 3. threonine (we focus on tyrosine)
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9
Q

Intrinsic protein kinsaes

A

intrinsic part of the receptor

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10
Q

Associated protein kinases

A

kinase in noncovalently associated with the receptor

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11
Q

Receptor Tyrosine Kinases (RTK)

A

activate lymphocyte receptors

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12
Q

What is signal strength?

A

minimum threshold all factors must meet for signaling to occur

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13
Q

What do variations in signal strength determine?

A

magnitude of cellular responses

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14
Q

What does protein phosphatase do?

A

turns off signal via dephosphorylation (dephos does not alway turn off)

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15
Q

What does extent of phosphorylation of an enzyme determine?

A

its activity…represent a balance between activity of kinases and phosphatases

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16
Q

Large multiprotein signaling complexes

A

mediate intracellular signal propagation. made on unique enzymes + other components = signal it generates

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17
Q

Signaling proteins interact with each other and with lipid signaling molecules via

A

modular protein domains

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18
Q

SH2 protein domain

A

recognizes phosphorylated tyrosine (pY) and AA 3 positions away and binds in sequence specific fashion

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19
Q

Assembly of signaling complexes

A

mediated by scaffold and adaptor proteins (non-enzymatic). scaffolds can function to promote membrane localization of the signaling complex

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20
Q

Ras

A

small GTPase involved in many pathways leading to cell proliferation

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21
Q

Small G proteins

A

molecular switches in many different signaling pathways

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22
Q

Rac, Rho, Cdc42

A

small GTPases that control changes in actin cytoskeleton caused by signals received through the TCR or BCR

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23
Q

GTP binding

A

signals turns on: GDP out & GTP in

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24
Q

GTP hydrolysis

A

signal turns off: Phosphate pops off

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25
Q

Signaling by GTPA binding proteins

A

GTP binding turns on vs. GTP hydrolysis turns it off

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26
Q

Ways signaling proteins are recruited to membrane

A
  1. binding to phosphorylated site on membrane associated protein 2. recognition of activated small G proteins 3. PIP2 to PIP3 4. binding to membrane lipids
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27
Q

Phosphatases vs. Ubiquitination protein degradition

A

reversible vs. irreversible termination of signaling

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28
Q

TLR signaling ->

A

activation of transcription factor NFkB -> pro-inflammatory cytokines (IFN-alpha, IFN-beta, type I interferons)

29
Q

Small molecule 2nd messengers

A

activation of enzymes produces small-molecule biochemical mediators (e.g. calcium)

30
Q

ITAMs (immunoreceptor tyrosine-based activation motifs)

A

tyrosine phosphorylation here initiates signaling from the TCR: 2 tyrosine residues bc phosphorylated by protein tyrosine kinases making site for SH2 domains of signaling proteins

31
Q

TCR complex is made of

A

variable antigen recognition proteins and invariant signaling proteins

32
Q

BCR complex

A

cell surface Ig w/ each of the invariant signaling proteins Ig-alpha and Ig-beta (transport receptor to surface and mediate BCR signaling)

33
Q

ZAP-70

A

only in T cells and NK cells works w SH2 domains and ITAMS

34
Q

1st intracellular signal in cascade

A

phosphorylation of ITAMs by Src-family kinases

35
Q

What does Csk do?*

A

reduce Lck activity and to reduce TCR signaling

36
Q

ITAMs are also found

A

in other receptors on leukocytes that signal for cell activation

37
Q

Activated ZAP-70

A

phosphates scaffold proteins (LAT, SLP-76) and promotes PI 3-kinase activation

38
Q

Activation of PLC-gamma is important because

A

enzyme that generates 2nd messengers diacylglycerol and inositol trisphosphate that lead to transcription factor activation

39
Q

What does PLC-gamma do?

A

cleaves inositol phospholipids to generate DAG and IP3 - 2 important signaling molecules

40
Q

IP3

A

open Ca2+ channels & depletion of Ca2+ from ER leads to STIM1 aggregation

41
Q

Ca2+ entry activates

A

transcription factor NFAT (nuclear factor of activated T cells) turns on many genes needed for T cell activation such as IL-2

42
Q

What happens when calcineurin is inhibited

A

NFAT cannot form

43
Q

CsA & FK506

A

selective inhibitors of calcineurin

44
Q

Effective immunosuppressants

A

CsA & Fk506

45
Q

calcineurin

A

activates T cells

46
Q

Ras activation

A

stimulates mitogen-activated protein kinase (MAPK) relay & induces expression of transcription factor AP-1

47
Q

NFAT

A

transcription factor that turns on many genes needed for T cell activation e.g. cytokine IL-2

48
Q

AP-1

A

similar to NFAT - turns on many important T cell activation genes e.g. cytokine IL-2

49
Q

Protein kinase C - theta

A

isoform of PKC restricted to T cells & muscle that activates NFkB and AP-1

50
Q

How is IL-2 transcribed

A

need NFkB, NFAT, and AP-1

51
Q

Akt

A

aka protein kinase B (serine/threonine kinase) leads to increased cellular metabolic activity activated by PI 3-kinase

52
Q

mTOR

A

activated by Akt… is a key regulator of macromolecular biosynthesis

53
Q

mTOR pathway

A

provides raw materials needed to carry out increased gene expression

54
Q

Vav activation

A

-> actin polymerization -> activation of Cdc42 -> cytoskeleton reorganization -> immune synapse formation

55
Q

ADAP recruitment

A

-> enhanced integrin adhesiveness and clustering -> immune synapse formation

56
Q

Src family kinases

A

associated w B cell receptors & phosphorylate tyrosines in ITAMS (Ig alpha and beta) to make binding site for Syk

57
Q

Do B cells express ZAP-70?

A

no they use Syk which is activated just by binding to phosphorylated site

58
Q

BCR + co receptor ->

A

activates Akt, PLC-gamma, WASp

59
Q

B cell co receptor

A

CD19, CD21 (receptor for C3dg), CD81

60
Q

Enhance BCR signaling

A

if co receptor is bound by its ligand and cluster w the antigen receptor (CD21)

61
Q

naive t cell signal 2

A

CD28

62
Q

naive b cell signal 2

A

CD40

63
Q

inhibitory receptors

A

prevent excessive immune responses & down regulate activation signals

64
Q

CD28

A

aids antigen dependent T cell activation -> T cell proliferation, cytokine production, cell survival, max PLC-gamma activation

65
Q

CD40

A

in B cells enhances Akt activation

66
Q

OX40, 4-1BB, CD30, CD27

A

TNF receptor super family on T cells that are upregulated during activation

67
Q

inhibitory receptors

A

CTLA-4 and PD-1 on B and T cells recruit protein or lipid phosphates

68
Q

regulatory T cells

A

lots of CTLA-4 on surface