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Clinical Immunology > T Cell Activation > Flashcards

T Cell Activation Flashcards

1
Q

What is the first signal of T cell activation?

A

Bind Ag with MHC via TcR

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2
Q

What do accessory molecules strengthen? And what are the accessory molecules?

A

Accessory molecules strengthen the association of T cells with APC/TC by providing additional linkages

CD4 to class II MHC (dendritic cells, macrophages, B cells etc)
CD8 to class I MHC (all nucleated cells)
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3
Q

Do accessory molecules provide an activating signal?

A

NO, they only help the activation process

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4
Q

What is ‘I ate it’?

What is ‘To call for help’?

A

I ate it - CD8 to MHC class I - Tc

To call for help - CD4 to MHC class II - Th

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5
Q

Are TcR, Ag and MHC accessory?

A

No - it is signal 1

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6
Q

What does the crosslinking of membrane molecules do?

A

Translocation of co-receptors (CD4/8)

Which brings INTRAcellular domains in contact

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7
Q

What happens if a T cell only receives signal 1?

A

It will switch off = anergy

Antigen binding signal isn’t enough on its own

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8
Q

What type molecules are involved in signal 2?

A

Co-stimulatory molecules

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9
Q

How do signalling events occur in signal 2?

A

B7 on APC binds to CD28 on T cell

Ie. Convey a signal from the cell surface via the cytosol into the nucleus to give rise to specific gene transcription

= signal transduction, an amplification process

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10
Q

What are the common intracellular signals?

A
  • Phosphorylation
  • Hydrolysis of inositol phosphates
  • Alteration of intracellular calcium and protein kinase C (PKC) activities
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11
Q

What does signal 2 involve? And what do these do?

A

2nd messengers eg Ca2+, IP3

Activation of transcription factors

Gives an increase in the cytokine IL-2 (& others) & receptors for growth

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12
Q

How is signal 2 inhibited?

A

CTLA-4 is an alternative high affinity ligand for B7

Interaction of B7 (on APC) with CTLA-4 (on ACTIVATED T cells) results in INHIBITION of activation

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13
Q

How are T helper cells activated?

A

By binding to an antigen

Th + ag —> gene activation

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14
Q

What is encoded <1/2hr after ag recognition?

A

Transcription factors

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15
Q

What is encoded 1-2hrs after ag recognition?

A

Cytokines & their receptors regulate growth & differentiation (IL-2, -2R, -3, -6, IFNγ)

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16
Q

What is encoded > 2 days after ag recognition?

A

Adhesion molecules

17
Q

Where does superantigen-induced T helper activation bind? And what does this activate?

A

Outside groove of MHC molecule

Polyclonal activation

18
Q

What happens during polyclonal activation? Leading to what?

A

Overproduction of Th cytokines

Systemic toxicity

19
Q

What is a superantigen?

A

Massive immune response not specific to any particular epitope

20
Q

What happens to IL-2 after 2nd signal?

A

100x increase in IL-2 (transcription and stable mRNA) production and presence of IL-2 receptors (autocrine/paracrine)

21
Q

What do the 2 subsets of Th depend on?

A

The cytokines that they secrete

22
Q

What are the two subsets of Th?

A

Th1 and Th2

23
Q

What cytokines are involved in Th1?

A

IL-2,IFNγ and TNFβ

Classic CMI: Delayed-Type Hypersensitivity, activate Tc

24
Q

What cytokines are involved in Th2?

A

IL-4, -5, -6, -10

Help B cell activation

25
Q

What does the apoptosis of activated Th do?

A

Eliminates cells producing high levels of cytokines that are no longer needed?

26
Q

What do patients with Canale-Smith syndrome fail to do?

A

Tcell apoptosis - a severe life threatening disease

27
Q

What is the third signal for the generation of Tc?

A

Interaction of IL-2 (Th) with new IL-2R (IL-2 Receptor)

28
Q

What is required for the destruction of Target cells by Tc?

A

Close membrane contact

29
Q

What do Tc granules contain? And what do they induce?

A

Perforin (pore-forming protein)
Granzymes (= fragmentins which are proteases)

Induce apoptosis

30
Q

What activates Fas on target cell?

A

FasLigand on Tc

Clinical Immunology (5 decks)

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