T Cell Activation and Generation of Effector T Cells Flashcards

1
Q

MHC class 1 presents {?} antigen but MHC class 2 presents {?} antigen

A

MHC class 1 presents endogenous antigen but MHC class 2 presents exogenous antigen

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2
Q

Upon leaving the Thymus what do Naiive T celle enter lymph nodes via?

A

Naiive T cells upon leaving the thymus enter lymph nodes via a high endothelial venule which is a specialised blood vessel

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3
Q

T cells use {?} lymphatic vessels to move between lymph nodes

A

T cells use efferent lymphatic vessels to move between lymph nodes

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4
Q

Dendritic cells presenting an antigen can move from a site of infection through an {?} to the lymph node to present to naiive T cells

A

Dendritic cells presenting an antigen can move from a site of infection through an afferent lymphatic vessel to the lymph node to present to naiive T cells

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5
Q

Activated T cells move into the circulation through the {?}. And move to sites of infection due to {?} instead of circulating.

A

Activated T cells move into the circulation through the thoracic duct (vena cava). And move to sites of infection due to chemokines instead of circulating.

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6
Q

Explain why a T cell would recirculate and what this means?

A

If a naiive T cell does not encounter its specific antigen (being presented by a dendritic cell) in either of the lymph nodes it travels through (only 2 LNs?). Then it will recirculate and go back into the first lymph node again.

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7
Q

Naiive T cells are activated in {?} lymphoid organs such as {?}

A

Naiive T cells are activated in secondary lymphoid organs such as lymph nodes and spleen

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8
Q

How do naiive T cells encounter their antigen in a LN when the antigen would likely be at the site of infection (where the pathogen is)?

A

As dendritic cells presenting the antigen move into LNs by afferent lymphatic vessels

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9
Q

Explain how there are 2 stages of activation from a naiive T cell

A
  • There is activation of the naiive T cell to an effector cell
  • And there is activation of the effector T cell (can happen in periphery at sites of infection) which is functional differentiation of the cell
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10
Q

Name 3 cells that can activate naiive T cells

A
  • Dendritic cells
  • Macrophages
  • B lymphocytes (can pick up soluble antigen with their BCR on surface and present to T cells)

Only activated professional APCs such as the ones above present high levels of MHC class 2

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11
Q

Professional APCs express {?} and high levels of {?} when activated

A

Professional APCs express co-stimulatory molecules and high levels of MHC2 when activated

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12
Q

Name the 3 signals needed for a T cell to be fully activated and differentiated into an effector or memory T cell

A
  • Signal 1: Antigen recognition
  • Signal 2: Co-stimulation
  • Signal 3: Cytokines - Part 3
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13
Q

Which of the 3 professional APCs is the costimulatory signal mostly found on

A

Dendritic cells
- but also found on macrophages and B cells

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14
Q

The co-stimulatory signal for a T cell involves the binding of {?} from a T cell to {?} on the APCs

A

The co-stimulatory signal for a T cell involves the binding of CD28 from a T cell to B7 on the APCs

  • B7 is a common term for B7-1 (CD80) and B7-2 (CD86)
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15
Q

Dendritic cells that have been activated in the presence of PAMPs upregulate {?} and {?}

A

Dendritic cells that have been activated in the presence of PAMPs upregulate B7-1 (CD80) and B7-2 (CD86)

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16
Q

Name 2 important cyctokines in the activation of T naiive T cells by an APC

A

IL12 released by the APC
IL-2 released by the T cell (paracrine)

  • also IL-6 IL-4 and TGf-beta
17
Q

T cells recognise antigen with or without costimulators, causing the expression of {?} on T cells

A

T cells recognise antigen with or without costimulators, causing the expression of CD40L on T cells

18
Q

Explain what CTLA-4 is and what it binds to

A

This is a signal on the T cell that can overide the signal of CD28 and can stop the T cell from being activated - also binds to B7-1 (CD80) and B7-2 (CD86) and so in a way it competes with CD28

19
Q

Name a negative T-cell co-stimulator that has been exploited for cancer immunotherapy

A

PD-1 (programmed death protein 1)

20
Q

CTLA-4 is expressed aproximately {?} days post stimulation of the T cell

A

CTLA-4 is expressed aproximately 2-3 days post stimulation of the T cell

21
Q

CTLA-4 has {?} affinity than CD28 for B7-1 (CD80)

A

CTLA-4 has higher affinity than CD28 for B7-1 (CD80)

  • Even though the peak levels of expression are lower than CD28, affinity is higher
22
Q

Describe HOW detection of PAMPs can help to induce T cell activation (this is the mechanism of the danger hypothesis)
- this is also how a cd4+ cell choses between TH1 and TH2

A
  • Dendritic cells with their MHC bound to a TCR and CD80/86 bound to CD28 (and also other co-signals such as CD40L) may detect some PAMPS by their PRRs.
  • These PRRs will cause signalling which can allow for cytokine release to affect the T cell and drive it to activate.
  • These cytokines can push the cell become either TH1 or TH2.
  • So PRR binding stimulates:
    • B7 (CD80/CD86) increase
    • Polarising cytokine release
23
Q

So what is an important function of this 3rd signal of cytokines on T cells?

A

Induction of T cell polarisation - so cytokine environment (from the APC) causes the cell to decide what it will differentiate into, do not know if this is for CD8+ cells also but CD4+ is below

24
Q

When cytokines bind to T cells, what happens to induce their polarisation?
- is signal 3

A

In response to certain cytokines, each effector T cell will express a master controller transcription factor which controls the expression of the cytokines expressed by that T cell

25
Q

IL-2 is an important {?} chemokine for T cells. (describe the mechanism of action in one word)

A

IL-2 is an important autocrine chemokine for T cells

26
Q

Without IL-2 T cells can’t {?}.

A

Without IL-2 T cells can’t proliferate.

27
Q

Name a way that IL-2 function on T cells is regulated (decreased)

A
  • Treg cells have more IL-2 receptors than the naiive T cell so the IL-2 binds to the T reg instead
28
Q

Describe the functions of the below surface receptors - these are expressed one after the other over time

A
  • CD69 (on tissue resident cells) allows for retention in the lymph node so they can be fully activated
  • CD25 is receptor for IL-2
  • CD40L is needed for further activation by denderitic cells
  • CTLA-4 is expressed days after to calm/regulate the response
29
Q

Upon activation, what does a T cell do and what choice does it need to make

A
  • Proliferation by IL-2
  • Differentiation
  • Choice to become effector or memory cell
30
Q

What are effector cytokines?

A

These are the cytokines that are produced by fully differentiated T cells such as IL-10 to reduce inflammation by a Treg cell

31
Q

What are polarising cytokines?

A
  • Are cytokines that polarise a T cell instead of having a distinct effect.
  • So they cause the naiive T cell to differentiate. (are signal 3).
  • Are generated by the APC.
32
Q

What is the brief function of:

  • TH1 cells
  • TH2 cells
  • TH7 cells
  • Treg cells
A
  • TH1 cells: activate macrophages to enhance their ability to destroy intracellular pathogens
  • TH2 cells: recruit cells for anti-parasitic responses
  • TH7 cells: recrutment of neutrophils particularly in an antibacterial response
  • Treg cells: decrease/regulate immune response
  • TFH cells: signal to B cells to differentiate and produce antibodies
33
Q

TH1 polarisation occurs in response to the presentation of {?} by an APC

A

TH1 polarisation occurs in response to the presentation of intracellular pathogens such as viruses and bacteria by an APC

  • Remember that TH1 cells are for removing intracellular pathogens
34
Q

Important transcription factors that regulate TH1 polarisation are {?} and {?}

A

Important transcription factors that regulate TH1 polarisation are STATs (STAT1 and STAT4) and T-bet

35
Q

TH1, via the release of {?}, causes enhanced action of macrophages and stimulates B cells to release antibodies that opsonise bacteria and activate complement.

A

TH1, via the release of IFγ, causes enhanced action of macrophages and stimulates B cells to release antibodies that opsonise bacteria and activate complement.

36
Q

TH2 cell polarisation occurs in response to {?} as well as other conditions such as {?}.

A

TH2 cell polarisation occurs in response to parasites as well as other conditions such as asthma and allergies

37
Q

The main TH2 polarising cytokine is {?}. Which os produced by eosinophils, basophils and mast cells.

A

The main TH2 polarising cytokine is IL4. Which os produced by eosinophils, basophils and mast cells.

38
Q

The main polarising cytokine in TH2 cells (IL4) causes activation of the transcription factors {?} and {?}. {?} promotes activation of IL4 and IL13 genes.

A

The main polarising cytokine in TH2 cells (IL4) causes activation of the transcription factors STAT6 and GATA3. GATA3 promotes activation of IL4 and IL13 genes.

  • So the IL4 is an autocrine response
39
Q

Describe the functions of TH2 cells fully

  • Which cytokines do they secrete?
  • Which class switching do they initiate?
A