Lecture 8: Immune Receptors and Signal Transduction I Flashcards

1
Q

Activation of NF-kB pathway

A

Activated IKK phosphorylates IkB and induces poly-ubuiquination of IkB
IkB is then degraded and cytoplasmic NF-kB dimers are released and translocated to nucleus

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2
Q

Adaptor protein domains

A

May contain several SH2 and SH3 domains
May have tyrosine residues for docking sites for proteins with SH2 domain
May have proline-rich sequence for binding proteins with SH3 domain

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3
Q

Number of ITAMs phosphorylated represents

A

The # of phosphorylations is a cytosolic interpretation of Ag affinity to TCR
The stronger/prolonged binding of Ags to TCR results in increasing # of phosphorylated ITAMs

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4
Q

Covalent addition of lipids may promote

A

Plasma membrane localization of signaling molecules

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5
Q

FcyRIIB

A

Inhibitory receptor found on B cells and myeloid cells

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6
Q

Strong TCR signals are required for

A

Negative selection of T cells and their death by apoptosis

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7
Q

TCR complex consists of

A

alpha/beta TCR non-covalently linked to CD3 and Zeta proteins
Both a/b chains have carboxyl terminal cytoplasmic tails 5-12 AAs long
CD3 and zeta proteins serve as signal-transducing subunits

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8
Q

VAV

A

Guanine nucleotide exchange factor

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9
Q

No expression of LAT in a cell causes

A

Defective in TCR mediated signaling

No mature a/b T cells would be found

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10
Q

SH3 domain

A

50 amino acids that bind to proline-rich stretches

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11
Q

Formation of pMHC/TCR/CD4 complex provides

A

First signal through TCR associated CD3 complex to T cell

  • this signal is necessary but not sufficient to stimulate naïve T cell to proliferate and differentiate
  • also requires group of costimulatory molecules
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12
Q

Tyr416 site on Src

A

Can be auto-phosphorylated, opening pocket and allowing substrate to gain access

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13
Q

Result when TCR engagement occurs in the absence of CD80/28 co-stimulation

A

Calcium mediated signals induce the activation of NFAT only
NFAT elicits expression of Anergy inducing genes which inhibit T cell function and induce status of T cell unresponsiveness

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14
Q

CD8 structure

A

Two related chains called CD8a and CD8b

  • both have a single extracellular Ig domain
  • both have highly basic cytoplasmic tail about 25 AAs long
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15
Q

Tyr527 site on Src

A

Phosphorylation of Tyr527 inactivates Src through interaction of Tyr527 with SH2 domain, which folds Src into a close, inaccessible bundle
-dephosphorylation at this site activates it

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16
Q

Ras-MAP kinases, activation of AP-1 events

A

Ag recognition- CD4/CD8 associated Lck is activated
Lck phosphorylates ITAMs of z-chain
ZAP-70 binds z-chains and self-phosphorylate to activate
ZAP-70 activates adaptor protein LAT
LAT binds GADS adaptor (Grb2) that docks GTP/GDP exchange factor SOS
SOS converts Ras-GDP to Ras GTP which activates MAP kinase and ERK
The cascade activates AP-1

17
Q

Anergy can be induced by

A

Substimulatory levels of Ags in the absence of:

  • CD28:CD80 interactions between costimulatory receptors on T cells and counter receptors on APCs
  • A costimulatory signal provided by soluble cytokines
18
Q

LFA-1:ICAM-1 complex and pMHC:TCR:CD4 complex and CD2:LFA3 and CD28L:CD80/86 complex

A

LFA/ICAM complex move away from MHC/TCR/CD4 complex while CD2/LFA3 and CD28/CD80/86 complexes move toward the MHC/TCR/CD4 complex

19
Q

Clonal anergy

A

Describes T cell unresponsiveness at cellular level
Hyporesponsive state characterized by reduced capacity to synthesize IL-2
Anergic T cells do not proliferate in response to Ag

20
Q

SH2 domain

A

100 amino acids that bind to phophotyrosine-containing peptides
-Present in Syk and ZAP-70 tyrosine kinases

21
Q

Which terminus of histones is modified

A

The N terminus

22
Q

Weak TCR signals are required for

A

Positive selection of T cells in the thymus

23
Q

LAT

A

Integral membrane protein that functions as adaptor

24
Q

CD4 structure

A

4 extracellular Ig-like domains

Highly basic cytoplasmic tail 38 AAs long

25
SH4 domain
Contains myristic acid moiety, essential for its localization to the inner surface of cell membrane
26
PH domain
Found in Tec family kinases and recognize specific phospholipids -Btk tyrosine kinase
27
Cytoplasmic tails of CD3 domain contain ____ | Compare to cytoplasmic tails of TCR
Cytoplasmic domain of CD3 contain ITAMs, while those of the TCR do not
28
GADS
Cytosolic adaptor protein
29
Adaptor protein catalytic activity
They have no catalytic activity
30
Immunologic synapse is imitated by
TCR recognition of pMHC
31
SLP-76
Adaptor protein with proline rich domain and SH2 binding domains
32
SH1 domain
Catalytic domain
33
TCR complex contains __ signaling chains and __ ITAMs
6 signaling chains | 10 ITAMS