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Immunology > receptors and signal transduction > Flashcards

receptors and signal transduction Flashcards

1
Q

what substances bind to GCPRs

A

chemokines and prostaglandins

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2
Q

what substances bind to RTKs (or Src kinases)

A

insulin (RTK)

integrin (Src)

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3
Q

nuclear receptors are _______ receptors and can ben nuclear or

A

intracellular

translocate to nucleus after binding

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4
Q

lipid soluble ligands bind to _______ receptors

A

nuclear

(glucocorticoids/Vit D/homrones)

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5
Q

signal transduction signaling requires a ligand-induced

A

clustering or receptors (called cross-linking)

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6
Q

clustering and conformational alterations result in changes in the _______ portion of the receptor that promotes interactions with other signaling molecules

A

cytosolic

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7
Q

in the nuclear phase of signal transduction, modified ________ ________ enter the nucleus and induce the expression of target genes that have a binding site in the promoter

A

transcription factors

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8
Q

the enzymatic phosphorylation of tyrosine, serine, or threonine in the cytosolic portion of the receptor initates the

A

signal transduction

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9
Q

the covalent addition of ubiquitin molecules either target proteins for ________ or drive _______ _______ in many cells

A

degradation

signal transduction

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10
Q

protein signaling molecules can also be modifed by the covalent addition of _______ that may promote plasma membrane _______ of signaling molecules

A

lipids

localization

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11
Q

The N-terminal tails of histones can undergo _______ and _______ that modulate: gene expression, DNA replication, and DNA recombination

A

acetylation and methylation

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12
Q

moduar signaling proteins contain ______ and ______ domains

A

kinase and binding

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13
Q

all modular proteins are made of _____ , _____ , and ______ domains, or some combo of them

A

SH2, SH3, and PH

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14
Q

SH2 domains bind

A

phosphotyrosine

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15
Q

SH3 domains bind

A

proline rich peptides

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16
Q

PH domains bind

A

inositol phospholipids

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17
Q

modular signaling proteins - tyrosine kinase families:

1.

2.

3.

A
  1. Src
  2. Syk
  3. Tec
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18
Q

Src:

examples:

domains:

A

examples: lyn, fyn, lyk
domains: SH2, SH3

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19
Q

Syk:

  1. examples
  2. domains:
A
  1. examples: syk and Zap-70
  2. domains: SH2 (x2)
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20
Q

Tec:

  1. examples:
  2. domains:
A
  1. examples: Btk and Itk
  2. SH2, SH3, and PH
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21
Q

adaptor proteins are considered the ______ of the signaling complex and do not have ______ activity

A

scaffolding

catalytic

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22
Q

main job of adaptor proteins

A

link enzymes and promote assembly of signaling complex

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23
Q

main adaptor proteins

A

LAT (linker for T-cell activation) = adaptor for T-cell signaling

BLNK (B-cell linker) = adaptor for B-cell signaling

GADS

SLP-76

VAV

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24
Q

no LAT =

A

no mature T cells

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25
Q

LAT adaptor protein:

is the only ______ membrane protein

after phosphorylation, LAT recruits

A

integral

PLC-gamma and GADS

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26
Q

SLP-76 adaptor protein:

is _____ rich

binds to _____ domain on GADS → phosphorylation of ______ residue

A

is proline rich

binds to SH3 domain on GADS → phosphorylation of tyrosoine residue

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27
Q

VAV adaptor protein:

is a _____

activate _____ _____ rearrangements and _____ changes

A

GEF

actin cytoskeletal ; and transcriptional

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28
Q

ITAMs =

ITAMs are found on _____ and _____

A

ACTIVATE

CD3 and zeta chains

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29
Q

TCR complex consists of

A

the alpha-beta TCR non-covalently linked to the CD3 and zeta proteins

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30
Q

each CD3 protein has ______ ITAMs

A

2

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31
Q

each zeta protein has _____ ITAMs

A

6

32
Q

the number of ITAMs activated signals the

A

affinity of the Ag to the TCR

33
Q

weak TCR signal for self Ag = ____ selection

A

positive

34
Q

strong TCR signal for self Ag = ____ selection

A

negative

35
Q

the longer an Ag is bound to TCR, _______ number of active ITAMs

A

increased

36
Q

ITIMs =

A

INHIBIT

37
Q

ITIMs are commonly found on

A

FcgammaRIIB (found on B cells and myeloid cells)

38
Q

CD8 coreceptors interact with MHC ______

CD4 coreceptors interact with MHC ______

A

class I

class II

39
Q

CD4 coreceptor has 4 ______ - like domains

A

Ig

40
Q

CD8 coreceptors have a ____ and ____ domain, each with 1 _____ - like chain

A

alpha and beta domain,

Ig-like chain

41
Q

CD8 binds to class I MHC molecules and interacts with

A

beta2 microglobulin

42
Q

the immunologic synapse is initiated by TCR recognition of

A

peptide-MHC complex

43
Q

immunological synapse

T cell accessory molecule: Fxn: Ligand: location

A
  1. CD3 : signal transduction : none
  2. zeta : signal transduction : none
  3. CD4 : signal transduction : MHC- II - APC
  4. CD8 : signal transduction : MHC-I - all nucleated
  5. CD28 (CD80/86) : signal trans-costim : B7-1/B7-2 -APC
  6. CTLA-4 : signal transduction : B7-1/B7-2 - APC
  7. PD-1 : signal trans : PD-L1/PD-L2 - APC, tissue/tumor cells
  8. LFA-1 : adhesion : ICAM-1 : APC, endothelium
  9. CD2 : ———– : LFA-3
44
Q

TCRs of circulating CD4 T cells that recognize pMHC II form a _____ bond that is stabilized by _____ molecule via noncovalent interaction with the portion of MHC II that is not involved in _____ binding

A

weak

CD4

peptide

45
Q

the LFA-1:ICAM-1 complexes move ______ from the pMHC:TCR:CD4 complex forming the peripheral circle of molecules involved in the immunological synapse

A

away

46
Q

CD2:LFA-3 complexes and costimulatory CD28:CD80/86 move ______ the pMHC:TCR:CD4 complex

A

toward

47
Q

formation of the pMHC:TCR:CD4 comlpex provides a ______ signal

the first signal is necessary but not sufficient to stimulate:

a second signal provided by costimulatory molecules is required for:

A

first

a naive T cell to proliferate and differentiate

T cell activation

48
Q

upon Ag recognition, the ITAMs are ________ and dock other signaling molecules

A

phosphorylated

49
Q

TCR-Dependent Cascade

A
  1. TCR engages pMHC II
  2. CD4 engages pMHC II to activate Lck
  3. Lck phosphorylates ITAMs to activate ZAP-70
    1. ZAP-70 Pathway 1
      1. ZAP-70 phosphorylates LAT and activates PLC-gamma
      2. PLC-gamma cleaves PIP2 to form DAG and IP3
      3. DAG + Ca2+ activates PKC
        1. PKC phosphorylates IkBeta to migrate to the nucleus
      4. IP3 + Ca2+ activates calcineurin
        1. calcineurin activates NFAT
    2. ZAP-70 Pathway 2
      1. ZAP-70 phosphorylates LAT
      2. LAT activates ras and rac
      3. ras and rac initiate phosphyrlation cascades to activate AP-1 family transcriptional factors

*ZAP-70 autophosphorylates after interaction with active zeta chains

*AP-1 also called Jun??

50
Q

what activates NFKB pathway

1.

2.

3.

A
  1. TCR/BCR
  2. TLRs
  3. CD40
51
Q

NFKB pathway

A

PKC phosphorylates and activates IKBeta → phosphorylated IKBeta is ubiquitinated and sent to proteasome → this frees NFKB to go to nuclues and promote IL-2 transcription

52
Q

NFAT pathway

A

calcineurin activates NFAT (by dephosphorylating?) → NFAT migrates to nucleus to promote IL-2 transcription

53
Q

clonal anergy is the term that describes T cell ________ at the cellular level

A

unresponsiveness

54
Q

hyporesponsive state of T cell is characterized by a reduced capacity to synthesize

A

IL-2

55
Q

anergic T cells do not _______ in response to appropriate Ag stimulation

A

proliferation

56
Q

Co-stimulation: T cell activation:

_____ (on T-cells) → _____ (on APCs)

_____ (on T-cells) → _____ (on APCs)

A

CD28 (on T-cells) → CD80/80 (also B7) (on APCs)

CD40L (on T-cells) → CD40 (on APCs)

57
Q

Co-Stimulation: T cell inhibition

_____ (on T-cells) → _____ (on APCs)

_____ (on T-cells) → _____ (on APCs)

A

CTLA-4 (on T-cells) → CD80/86 (on APCs)

PD-1 (on T-cells) → PDL1 (on APCs)

58
Q

anergy can be induced by substimulatory levels of Ags in the absence of:

______ interactions beween costimulatory receptors on T cells and counter-receptors on APCs

a costimulatory signal provided by soluble ______

A

CD28:CD8086

cytokines

59
Q

anergy can be overcome by

A

exogenous IL-2

60
Q

if only first T cell signal is present (TCR:pMHC:CD4) , only ______ is produced which leads to decreased transcription of ______

A

NFAT

IL-2

61
Q

NFAT activation alone =

A

anergy

62
Q

naive B mature B cells express

A

IgM and IgD on their surface

63
Q

class-switched and memory B cells expess either

A

IgM, IgG, IgA, or IgE

64
Q

transmembrane signlaing componeent of BCR

A

Ig-alpha and Ig-beta

65
Q

Ig-alpha and Ig-beta contain ______ in their cytoplasmic tails

A

ITAMs

66
Q

B cell co-receptors:

1.

2.

3.

4.

5.

A
  1. CD19 functions as the dominant signaling component
  2. CD21 is also known as a complement receptor 2 (CR2) and helps to lower the activation threshold
  3. CD32 is also known as Fcgamma receptor type IIb (FCgammaRIIB) - inhibitory and contains ITIMs
  4. CD81 stabilizses CD 19
  5. CD22 is inhibitory and B cell specific (lacking can cause autoimmunity)
67
Q

BCR signaling cascade

A
  1. BCR engages epitope (signal 1)
  2. Costimulatory molecules bind (signal 2) which activates lyn, lck, blk, fyn which then phosphorylate ITAMs on Ig-alpha and Ig-beta to activate Syk
  3. Syk phosphorylates and activates PLC-gamma
  4. PLC-gamma cleavew PIP2 to form DAG and IP3
    1. DAG activates PKC
      1. PKC phosphoyrlates IkB (releasing NFkB)
        1. NFkB migrates to the nucleus to promote transcription of IL-2
    2. IP3 + Ca2+ activates calcineurin
      1. calcineurin activates NFAT
        1. NFAT migrates to nucleus to promote transcription of IL-2
68
Q

BCR signaling:

activation = _______ of ITAMs and ______ of ITIMs

deactivation = _______ of ITAMs and _______ of ITIMs

A

phosphorylation dephosphorylation

dephosphorylation phosphorylation

69
Q

B cell signaling is initiated by Ab binding and ______ of BCR receptors

A

crosslinking

70
Q

complement and CR2 activation of BCR:

  1. C3b on bacteria cleaved into _____ by factor I
  2. C3d bind to ______ receptor on B cell as Ag binding to the BCR
  3. C3d:CR2 binding brings ______ close to the BCR associated kinases; CD19 has to be stabilized with ______
  4. CD19 _____ are pohphorylated, allowing recruitment of Lyn and PI3-kinase
  5. overall effect:
A
  1. C3d
  2. CR2 (CD21)
  3. CD19 CD81
  4. ITAMs
  5. greatly enhanced signaling
71
Q

the CR2:CD19:CD81 complex is often called the B cell coreceptor complex because CR2 binds to Ags through attached ______ at the same time that BCR binds directly to the Ag

A

C3d

72
Q

B cell activation is tightly controlled to limit immune resopnses against microbes in order to avoid ______ _______ to host tissues

A

collateral damage

73
Q

inhibitory receptors typically recruit and activate _______ that counter signaling events induced by Ag receptors

A

phosphatases

74
Q

BCR inhibitory signaling:

  1. binding of the inhibitory signal → phosphorylation ofITIMs by ______ family
  2. phosphorylated ITIMs recruit ______ domain phosphatases (SHP and SHIP)
  3. SHP and SHIP removes phosphates groups from ______

(Example:)

A
  1. Src
  2. SH2
  3. ITAMs (PIP3)

(Example: binding via the CD32 (FcgammaRIIB) and CD22

75
Q

inhibitory signaling in lymphocytes is mediated primarily by inhibitory receptors and also by

A

E3 ubiquitin ligases

76
Q

B-cell and T-cell interaction (most B cell responses require CD4 T cell help):

  1. ______ on B cell will present Ag to T cell ______ complex
  2. CD28:CD80/86 provides costimulation for release of ____
  3. T cell will induce expression of _____ to bind to _____ on B cell
  4. B cell upregulates _____ and increases the signaling cascade leading to activation
A
  1. MHC II TCR:CD3:CD4
  2. IL-4
  3. CD40L CD40
  4. IL-4R

Immunology (23 decks)

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