10. Lymphocyte receptor signalling Flashcards

1
Q

a primary response to an antigen causes:

A

clonal expansion of antigen-reactive T or B cells

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2
Q

what is the function of signal transduction pathways

A

control transcriptional and metabolic pathways
determine lymphocyte function

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3
Q

membrane receptors have 3 domains:

A
  1. extracellular domain: binds ligand
  2. transmembrane domain: span the PM
  3. cytoplasmic domain: participate in signal transduction
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4
Q

ligands for TCR and BCR

A

TRC: peptide + MHC
BCR: antigen

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5
Q

what is the immunological synapse

A

the space between the T cell and APC where receptor-ligand binding occurs in order for signal transduction to happen

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6
Q

T cells are activated through 2 signals…

A

signal 1: MHC + peptide on APC binds TCR
signal 2: B7 on APC binds CD28 on naive T cell (costimulatory signal)

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7
Q

what is the costimulatory signal in T cell activation

A

B7 binds CD28
B7 is only expressed if infection is present

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8
Q

what makes up the immunological synapse

A

TCR and MHC:peptide complex
co-stimulatory molecules
co-receptor and MHC:peptide complex
cell-adhesion molecules

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9
Q

what is CD3

A

the cytoplasmic domain of the TCR that relays the signal from the synapse so that signal transduction can start

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10
Q

what are ITAMs

A

immunoreceptor tyrosine-based activation motifs
cytoplasmic aa sequences containing tyrosine that are targets of phosphorylation
docking sites for other proteins
mediate interactions with cytoplasmic protein-tyrosine kinases

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11
Q

what are the protein-tyrosine kinases in TCR signal transduction

A

Lck and ZAP-70

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12
Q

what is the key event in TCR signal transduction

A

the phosphorylation of ZAP-70 by Lck
induces 3 signal transduction pathways

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13
Q

1st signal transduction pathway of TCRs: NFAT actiavtion

A
  1. phosphorylation and activation of PLCy
  2. cleavage of PIP into IP3 and DAG
  3. IP3 signals calcium stores to open
  4. Ca2+ diffuses through the cell
  5. calcineurin is activated and dephosphorylates NFAT
  6. NFAT acts as a TF and activates genes for T-cell expansion and differentiation
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14
Q

2nd signal transduction pathway of TCRs: NFkB activation

A
  1. phosphorylation and activation of PLCy
  2. cleavage of PIP into IP3 and DAG
  3. DAG activates PKC
  4. PKC activates the NFkB through destruction of associated IkB protein
  5. NFkB acts as a TF and activates genes for T-cell expansion and differentiation
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15
Q

3rd signal transduction pathway of TCRs: AP-1 activation

A
  1. phosphorylation and activation of PLCy
  2. cleavage of PIP into IP3 and DAG
  3. DAG associates with RAS
  4. RAS triggers MAP kinase cascade to activate Fos
  5. Fos interacts with Jun to produce AP-1
  6. AP-1 acts as a TF and activates genes for T-cell expansion and differentiation
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16
Q

what is the most important gene for T-cell activation

A

IL-2

17
Q

what activates the Jun proteins in TCR signalling

A

a co-stimulatory signal provided by CD28

18
Q

multiple signalling pathways for TCR signalling converge on the…

A

IL-2 promoter
- TCR and CD28 activate PLC-y which leads to activation of TFs on the IL-2 gene

19
Q

what is the role of Ig-B and Ig-a in the B-cell receptor

A

signal transduction during B-cell activation (similar to CD3 of the TCR)

20
Q

what is required for BCR signal transductions to be activated

A

clustering of BCR complexes on the B-cell surface

21
Q

what proteins are part of the Src family kinases

A

Blk, Fyn, Lyn

22
Q

what makes up the BCR co-receptor

A

CR2
CD19
CD81

23
Q

B-cell coreceptor binding for signal transduction activation

A
  • CR2 binds to iC3b and C3d (required for costimulatory signal
  • CD19 has a cytoplasmic domain for signalling events
  • CD81 stabilizes the coreceptors
24
Q

signalling at the Ig receptor complex

A

Syk (similar to ZAP 70) is a kinase which induces 3 signal transduction pathways: NFkB, NFAT, AP-1
GEFs catalyze the exchange of guanine nucleotides on binding proteins Ras and Rac so that AP-1 can be produced

25
Q

inhibitory receptors on lymphocytes down-regulate immune responses by…

A

interfering with co-stimulatory signalling pathways

26
Q

inhibitory vas acitvating receptors of T cells

A

naive = activating = CD28: one dimer engages with one B7 (stronger adhesion)
activated = inhibitoy = CTLA4: 2 dimers bind to 2 B7s (higher affinity)