TCR signalling Flashcards

1
Q

what is signal transduction?

A

conversion of energy or information from one form into another

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2
Q

what are the steps in signal transduction?

A
  1. extracellular molecule activates a cell surface molecule
  2. this receptor alters intracellular molecules
  3. amplification of the signal
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3
Q

what is the result of signal transduction?

A

ultimately, get gene transcription and protein production

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4
Q

what are the first messengers in signal transduction?

A

-natural inter-cellular ligand that bind and activate receptors
- need receptors in the membrane

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5
Q

what is the role of the second messengers in signal transduction?

A

-enter the cytoplasm and trigger response within the cell
- chemical relays from plasma membrane tp cytoplasm
- intracellular signal transduction

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6
Q

what determines what happens inside a target cell?

A

external influences,
need receptors in the membrane

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7
Q

what is the function of downregulation?

A

avoid persistent activation

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8
Q

what is affinity?

A

strength of binding

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9
Q

what is avidity?

A

strength of interaction

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10
Q

what is the structure of the T cell receptor?

A

Two chains- alpha and beta
Variable region and constant region
Membrane bound only

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11
Q

what molecules are involved in signal one of T cell activation?

A

Antigen-specific
- TCR and MHC

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12
Q

what molecules are involved in co-receptor during T cell activation?

A

CD4/8
MHC

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13
Q

what molecules are involved in adhesion during T cell activation?

A

LFA-1
ICAM

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14
Q

what molecules are involved in signal two of T cell activation?

A

CD28
CD80

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15
Q

what molecules are involved in inflammatory signals in T cell activation?

A

APC
IL-12

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16
Q

what is antigen specific binding in T cell activation?

A

TCR and MHC bind
- T cell recognizes specific antigen

17
Q

what is the co-receptor stage in T cell activation?

A

CD4 MHCII
CD8 MHCI
stabilise low-affinity interaction between TCR and MHC

Co-receptor stabilizes cell-to-cell binding

18
Q

what is the adhesion stage in T cell activation?

A

LFA-1 on T cells
ICAM-1 on APC
stabilise interaction between T cells and APCs

Adhesion molecules further stabilise cell-to-cell binding

19
Q

what is the co-stimulation stage in T cell activation?

A

Signal 2
-CD28-CD-80 interaction

Costimulatory receptor sends extra activation signal

20
Q

What are the intracellular signalling stages in T cell activation?

A
  1. Phosphorylation of ITAMs
  2. co-receptor signal
  3. activation of ZAP-70
  4. involvememt of scaffold proteins and adaptor molecules
  5. activation of PLC-y
  6. activation of transcription factors
21
Q

how are ITAMs phosphorylated?

A

Two tyrosine kinases phosphorylate ITAMS

22
Q

what happens when ITAMs are phosphorylated?

A

It exposes their active sites
- Lck becomes constitutively associated with cytoplasmic domains of CD4 and CD8
- Fyn associates weakly with cytoplasmic chains of x and CD3 chains

23
Q

what is the co-receptor signal in intracellular T cell activation?

A

CD4 and CD8 involved
- brings Lck associated with co-receptor together with ITAMs

24
Q

how id ZAP-70 activated?

A

Phosphorylated ITAMs provide a binding site for ZAP 70

ZAP 70 gets phosphorylated by Lck

25
Q

what is the role of phosphorylated ZAP-70?

A

activated ZAP-70 phosphorylated scaffold proteins LAT and SLP76
These recruit phospholopase PLC-g

26
Q

what is the role of LAT and SLP76 scaffold proteins?

A

recuit PLCg to the membrane

It is recruited to the signalling complex and then phosphorylated by Lck

27
Q

what is the role of activated PLCg?

A

PLC activation leads to three pathways that activate distinct transcription factors

28
Q

what is the outcome of activating transcription factors in intracellular T cell activation?

A

Transcription factors regulate gene expression
IL-2= T cell proliferation and survival
Performin/granzyme= T cell cytotosic function
Cytokines= activate other cells depending on type of infection