Immune Receptors and Signal Transduction Part I (Lec 8) Flashcards

1
Q

Nuclear receptors are intracellular transcription factors that are activated by what?

A

lipid-soluble ligands that can cross the plasma membrane

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2
Q

Signaling requires a ligand-induced clustering of receptors called what?

A

cross-linking

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3
Q

Clustering and conformation alterations result in what?

A

changes in the cytosolic portion of the receptor that promotes interactions with other signaling molecules

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4
Q

The enzymatic phosphorylation of tyrosine, serine, or threonine, in the cytosolic portion does what?

A

initiates the signal transduction

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5
Q

Phosphotases usually play what type of role in signal transduction?

A

inhibitory

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6
Q

What does the covalent addition of ubiquitin molecules do to signal transduction?

A

target proteins for degradation or drive signal transduction

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7
Q

What does the addition of lipids do to signal transduction?

A

promotes plasma membrane localization signaling molecules

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8
Q

What does acetylation and methylation of the N-terminal tails of histones do to signal transduction?

A

modulates gene expression, DNA replication, and DNA recombination events

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9
Q

What are the tyrosine kinase families?

A

Src family (c-Src, Lyn, Fyn, and Lck)

Syk family (Syk and ZAP-70)

Tec family (Tec, Btk, and Itk)

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10
Q

What do SH2 domains found in all the Tyrosine kinase families bind?

A

phosphotyrosine

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11
Q

What do SH3 domains found in the (Src and Tec) Tyrosine kinase families recognize?

A

proline-rich peptides

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12
Q

What do PH domains found in the (only Tec) Tyrosine Kinase family recognize?

A

PIP3

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13
Q

molecular hubs that physically link different enzymes and promote the assembly of complexes of signaling molecules are called what?

A

adaptor proteins

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14
Q

In regards to adaptor proteins, what do phosphorylated tyrosine residues serve as?

A

docking sites for other signaling molecules with SH2 domains

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15
Q

LAT (linker protein for T cell activation) is what type of protein?

A

integral membrane Adaptor protein

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16
Q

GADS and SLP-76 are adaptor proteins found where?

A

cytosol

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17
Q

Where is the inhibitory receptor FcyRIIB found?

A

B cells and myeloid cells

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18
Q

True or false?

TCR and BCR signaling is very different.

A

false; similar

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19
Q

Ag binding and clustering results in activation of an associated ___ family kinase

A

Src

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20
Q

The two phosphorylated tyrosine’s in a single ITAM are recognized by a __ family tyrosine kinase that has tandem SH2 domains that each bind to an ITAM phosphotyrosine

A

Syk

21
Q

Recruited and activated Syk family kinase phosphorylates what?

A

adaptor proteins and enzymes that activate distinct signaling pathways

22
Q

How many signaling chains and ITAMs does the TCR complex have?

A

6 signaling chains; 10 ITAMS

23
Q

Stronger or prolonged binding of Ag to the TCR results in increasing or decreasing numbers of phosphorylated ITAMs?

A

increasing

24
Q

Weak TCR signals are required for positive selection of what?

A

T cells in the thymus

25
Q

Strong TCR signals in the thymus results in what?

A

thymocyte death by apoptosis

26
Q

Can a coreceptor with its signaling enzymes increase ITAM phosphorylation and activation of the antigen receptor?

A

yes

CD4 and CD8 are coreceptors on T helper and cytotoxic T cells

27
Q

What is the coreceptor on B cells?

A

complement receptor type 2 (CR2/CD21)

28
Q

CTLA-4 is what kind of T cell receptor?

A

inhibitory

29
Q

CD22 is what kind of B cello receptor?

A

inhibitory

30
Q

CD28-CD80/86 do what?

A

costimulation in activation of T cells

31
Q

Compare the components of TCRs to Igs

A

TCR - alpha and beta chain

Ig- H and L chain

32
Q

What are the associated signaling molecules of TCRs and Igs?

A

TCR - CD3

Ig - Ig alpha and Ig beta

33
Q

In regards to APC-T cell interaction, give the receptor that matches with the interaction:
signal transduction
antigen recognition
Adhesion

A

signal transduction: CD4, CD3, ITAM, CD28
antigen recognition: TCR
Adhesion: LFA-1

34
Q
In regards to accessory molecules of TCR, give the ligand that matches with the receptor
CD28
CD3
CD4
CD8
CTLA-4
PD-1
LFA-1
A
CD28: B7-1/B7-2
CD3: none
CD4: Class II MHC
CD8: Class I MHC
CTLA-4: B7-1/B7-2
PD-1: PD-L1/PD-L2
LFA-1: ICAM-1
35
Q

In regards to early events in T cell activation, on Ag recognition, TCR complexes cluster with what?

A

CD4 or CD8

36
Q

In regards to early events in T cell activation, CD4-associated Lck becomes active and phosphorylates what?

A

ITAMs and CD3

37
Q

In regards to early events in T cell activation, Zap-70 binds to phosphotyrosines and is itself ___ and ___

A

phsophorylated; active

38
Q

In regards to early events in T cell activation, active Zap-70 then activates (phosphorylates) various adaptor proteins such as?

A

LAT

39
Q

In regards to early events in T cell activation, the adaptors become docking sites for PLCy1 and exchange factors that activate what two kinases?

A

Ras and MAP

40
Q

What does PI3 kinase do?

A

recruited to TCR complex and generates PIP3 from PIP2

41
Q

What is PDK1 and what does it do?

A

PIP3-dependent kinase which phosphorylates and activates a downstream Akt kinase

42
Q

What doe activated Akt do?

A

contributes to cell survival by inactivating pro-apoptotic proteins

43
Q

What converts Ras-GDP to Ras-GTP?

A

SOS

44
Q

Ras-GTP activates what?

A

MAP kinase and ERK; cascade activates AP-1 - regulates gene expressionR

45
Q

Activated LAT binds PLCy1 and is activated by ZAP-70. What does the activated PLCy1 do?

A

hydrolyzes PIP2 to generate IP3 and DAG

46
Q

Produced IP3 stimulates what?

A

increase in cytosolic Ca ions released from the ER

47
Q

Released DAG activates what enzyme?

A

PKC which is important in activating NF-kB - regulates gene expression

48
Q

True or False?

TCR and CD28 induce the same signaling pathways

A

false; different pathways that result in the activation of several transcription factors

49
Q

When TCR engagement occurs in the absence of co-stimulation, calcium-mediuated signals induce the activation of what?

A

NFAT only

note: NFAT alone elicits expression of a distinct set of anergy-inducing genes that inhibit T cell function