Immune Receptors and Signal Transduction Part I (Lec 8)

Question 1

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

Answer 1

lipid-soluble ligands that can cross the plasma membrane

Question 2

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

Answer 2

cross-linking

Question 3

Clustering and conformation alterations result in what?

Answer 3

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

Question 4

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

Answer 4

initiates the signal transduction

Question 5

Phosphotases usually play what type of role in signal transduction?

Answer 5

inhibitory

Question 6

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

Answer 6

target proteins for degradation or drive signal transduction

Question 7

What does the addition of lipids do to signal transduction?

Answer 7

promotes plasma membrane localization signaling molecules

Question 8

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

Answer 8

modulates gene expression, DNA replication, and DNA recombination events

Question 9

What are the tyrosine kinase families?

Answer 9

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

Syk family (Syk and ZAP-70)

Tec family (Tec, Btk, and Itk)

Question 10

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

Answer 10

phosphotyrosine

Question 11

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

Answer 11

proline-rich peptides

Question 12

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

Answer 12

PIP3

Question 13

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

Answer 13

adaptor proteins

Question 14

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

Answer 14

docking sites for other signaling molecules with SH2 domains

Question 15

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

Answer 15

integral membrane Adaptor protein

Question 16

GADS and SLP-76 are adaptor proteins found where?

Answer 16

cytosol

Question 17

Where is the inhibitory receptor FcyRIIB found?

Answer 17

B cells and myeloid cells

Question 18

True or false?

TCR and BCR signaling is very different.

Answer 18

false; similar

Question 19

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

Answer 19

Src

Question 20

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

Answer 20

Syk

Question 21

Recruited and activated Syk family kinase phosphorylates what?

Answer 21

adaptor proteins and enzymes that activate distinct signaling pathways

Question 22

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

Answer 22

6 signaling chains; 10 ITAMS

Question 23

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

Answer 23

increasing

Question 24

Weak TCR signals are required for positive selection of what?

Answer 24

T cells in the thymus

Question 25

Strong TCR signals in the thymus results in what?

Answer 25

thymocyte death by apoptosis

Question 26

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

Answer 26

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

Question 27

What is the coreceptor on B cells?

Answer 27

complement receptor type 2 (CR2/CD21)

Question 28

CTLA-4 is what kind of T cell receptor?

Answer 28

inhibitory

Question 29

CD22 is what kind of B cello receptor?

Answer 29

inhibitory

Question 30

CD28-CD80/86 do what?

Answer 30

costimulation in activation of T cells

Question 31

Compare the components of TCRs to Igs

Answer 31

TCR - alpha and beta chain | Ig- H and L chain

Question 32

What are the associated signaling molecules of TCRs and Igs?

Answer 32

TCR - CD3 | Ig - Ig alpha and Ig beta

Question 33

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

Answer 33

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

Question 34

``` 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 ```

Answer 34

``` 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 ```

Question 35

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

Answer 35

CD4 or CD8

Question 36

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

Answer 36

ITAMs and CD3

Question 37

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

Answer 37

phsophorylated; active

Question 38

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

Answer 38

LAT

Question 39

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

Answer 39

Ras and MAP

Question 40

What does PI3 kinase do?

Answer 40

recruited to TCR complex and generates PIP3 from PIP2

Question 41

What is PDK1 and what does it do?

Answer 41

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

Question 42

What doe activated Akt do?

Answer 42

contributes to cell survival by inactivating pro-apoptotic proteins

Question 43

What converts Ras-GDP to Ras-GTP?

Answer 43

SOS

Question 44

Ras-GTP activates what?

Answer 44

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

Question 45

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

Answer 45

hydrolyzes PIP2 to generate IP3 and DAG

Question 46

Produced IP3 stimulates what?

Answer 46

increase in cytosolic Ca ions released from the ER

Question 47

Released DAG activates what enzyme?

Answer 47

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

Question 48

True or False? | TCR and CD28 induce the same signaling pathways

Answer 48

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

Question 49

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

Answer 49

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