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Zach- Immunology > 11. differentiation/function CD8+ cells > Flashcards

11. differentiation/function CD8+ cells Flashcards

1
Q

What marker will differentiate T cells from other cell types?

A

CD3

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2
Q

Which marker will be on and mark a helper T cell?

A 
CD3 and CD4 with MHC II class restiction
66% of cells
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3
Q

Which marker will be on and mark cytotoxic T cell?

A 
CD3, CD8, with MHC I class restiction.
33% of cells
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4
Q

Walk through the process of cytotoxic CD8+ T cell activation.

A
  1. DC present peptide antigen to naive T cells in LN
  2. CD8+ proliferate/differentiate into CTL and memory T cells
  3. CTL enter circulation and travels to the site of Ag infection
  4. CTL recognize the Ag at the site, directly kill the target cells
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5
Q

What is required for CTLs to be activated?

A
  1. signal 1, from Ag recognition
  2. Signal 2, from B7-1,-2 costimulator
  3. Signal 3, comes from cytokines
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6
Q

What will an active CTL secrete?

A
  1. granules of perforin and granzymes

2. IFN-gamma, IL-2, -15, -21

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7
Q

What is an important transcription factor that is required during CTL differentiation?

A

T-bet

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8
Q

What happens if a CTL undergoes differentiation in the absence of T-bet transcription factor?

A
  1. the perforins and granzymes and IFN-gamma would not be produced
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9
Q

What is cross-presentation?

A
  1. the presentation of an exogenous Ag that is able to be presented to an MHC I class restriction molecule
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10
Q

When would cross-presentation be most beneficial during an immune response?

A
  1. latent infection periods

2. infections that impair the function of DC

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11
Q

How does cross-presentation occur?

A
  1. Ag moved from the endosome into the cytosol in the APC
  2. Ag is processed by proteasomes into peptide fragments
  3. peptide fragments are packed back into endosomes and migrate to different areas
  4. allows peptide fragment presentation to MHC I class molecules
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12
Q

What role can CD4+ cells have with activation of CD8+ cells?

A
  1. help form CD8+ memory cells
  2. Produce cytokines for CTL differentiation (signal 3)
  3. Enhance the CD4+ ability to stimulate CTL differentiation
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13
Q

What is APC licensing?

A
  1. the use of DC to activate CD8+ cells against a variety of pathogens
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14
Q

How does APC licensing occur?

A
  1. CD40 and B7 (DC) bind with CD40L and CD28 (T cell)
  2. increases efficiency of CTL differentiation
  3. upregulates B7-1,-2 on the APC
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15
Q

When is the most likely case to have a 3rd signal, from cytokines, introduced for cell signaling?

A
  1. weak innate immune responses:
    - latent (chronic) viral infection
    - organ transplant
    - tumor growth
  2. enhance the activity of CTL
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16
Q

Which are the most commonly seen cytokines that act as 3rd stimulatory signals in CD8+ T cell activation?

A
  1. IL-2
  2. IL-12
  3. IL-15
  4. IL-21
  5. IFN-1
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17
Q

What are the effects of IL-2?

A
  1. T cell growth

2. CD8+ —> memory and CTL

18
Q

Of the three subunits in the IL-2, which is most highly expressed before and after T cell activation?

A
  1. before: beta and gamma

2. after: alpha

19
Q

IL-2 gamma has similar structure recognition as what other signaling molecules?

A
  1. IL-15, -21
20
Q

What is the function of IL-12?

A
  1. stimulate naive T cell–> CTL
  2. provides survival/developmental for optimal effector function
  3. prevents CD8+ cells from exhaustion during chronic infection
21
Q

What is the function of IFN-1?

A
  1. assist with naive T cell stimulation to CTL

2. provides survival/developmental support for optimal effector function

22
Q

What is the function IL-15?

A
  1. formed by tissue macrophage and DC
  2. promotes survival of memory CD8+ T cells
  3. costimulate production of IFN-gamma
23
Q

What is function IL-21?

A
  1. formed by active CD4+ T cell

2.

24
Q

What is IL-2?

A
  1. 15kDa polypeptide

2. autocrine function that can have paracrine effects on CD8+ cells

25
Q

What type of receptor is able to recognize IL-2?

A

type I cytokines

26
Q

What is IFN-gamma?

A
  1. 25kDa homodimer
  2. released from NK, Th1, CTL cells
  3. favors development of Th1 cells and IgG
  4. upregulates Ag presentation, meaning it’s a large anti-viral component
27
Q

What type of activating effects does IFN-gamma have?

A
  1. activates tissue macrophages
  2. activates MHC I on all cells
  3. activates MHC II on professional APC
28
Q

What is IL-12?

A
  1. formed by DC or tissue macropahges
  2. pro-inflammatory cytokine producer (IFN-gamma, TNF-B)
  3. prevents CD8+ exhaustion
29
Q

Which compound is highly expressed in hopes of controlling tumor growth?

A
  1. IL-12

2. provides much higher tumor control in terms of numbers and function compared to IFN-1 signals

30
Q

IL-15 from active CD4+ cells are able to perform what functions?

A
  1. stimulate memory CD4, CD8, and naive CD8 cells

2. costimulator for IFN-gamma production

31
Q

What role do CD8+ T cells have in acute infection?

A
  1. secretion of TNF-B, IFN-gamma, perforins, granzymes

2. undergo clonal expansion/differentiation into CTL

32
Q

What is exhaustion?

A
  1. the diminishing effect of CD8+ T cells that occurs in a chronic infection process.
33
Q

What leads to exhaustion? How do the CD8+ T cells begin to diminish when Ag are still present?

A
  1. downregulation of IFN-gamma
  2. upregulation of PD-1 receptor
    - marks for programmed cell death.
34
Q

What is the theory of HIV chronicity?

A
  1. CD8+ T cells experience exhaustion and have upregulation of PD-1 receptor.
  2. common in Hep C as well.
35
Q

What are the types of CTL mediated cytotoxicity?

A
  1. Fas-FasL mediated

2. Granzyme/perforin mediated

36
Q

What occurs in granzyme/perforin mediated cytotoxicity?

A
  1. Ca, granzyme, perforins are released from a granules
  2. attack the target cells
  3. Granzyme B activates caspase-3
  4. caspase-3 causes DNA degradation
37
Q

How do CTL only attack the target cell and not affect other surrounding cells?

A
  1. the binding creates an immunological synapse where components are secreted and maintained in that synapse to prevent accidental signaling to wrong cells
38
Q

How does Fas-FasL mediated cytotoxicity work?

A
  1. Fas and FasL binding activates signaling cascade
  2. ultimately caspase-3 is activated
    caspase-3 then degrades DNA
39
Q

Both Fas-FasL and granzyme/perforin mediated cytotoxicity activate caspase-3. What are the signals that will lead to DNA Degradation?

A
  1. caspase-3 binds and cleaves ICAD from the ICAD-CAD complex
  2. ICAD is degraded
  3. CAD moves into the nucleus to degrade DNA
40
Q

What is T cell functional polarization?

A
  1. ability to take on specific tasks to promote adaptive immune response.
    - - effector or regulatory functions depending on response
41
Q

IL-2R shares common receptor components with which other cytokines?

A

IL-4, -7, -9, -15, -21

Zach- Immunology (10 decks)

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