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Immunology - Unit 3 - Zach H. > Differentiation and Functions of CD8 T Cells > Flashcards

Differentiation and Functions of CD8 T Cells Flashcards

1
Q

Which cell type make up 70% of all lymphocytes in the blood?

A

T cells

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2
Q

Which cell type make up 30% of all lymphocytes in the blood?

A

B cells

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3
Q

What is signal 1 in the activation of naive CD8 cells?

A

Ags

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4
Q

What is signal 2 in the activation of naive CD8 cells?

A

CD28-CD80 costimulation

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5
Q

Activated CTLs contain numerous granules called lysosomes. What do lysosomes contain?

A

> perforin
granzymes

used to kill other cells

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6
Q

What do activated CTLs secrete?

A

Cytokines, mostly IFN-gamma, that potently activate macrophages.

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7
Q

What transcriptional factor does CTL differentiation involve?

A

T-bet

similar to activation of Th1 cells

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8
Q

What does the transcriptional factor, T-bet, regulate?

A

Transcription of genes encoding:
> perforin
> granzymes
> IFN-gamma

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9
Q

What is the “magic of cross-presentation”?

A

Extracellular Ags are processed and presented within class II MHC (classical), but they are also presented in association with class I MHC.

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10
Q

Extracellular Ags are processed and presented within class II MHC (classical), but they are also presented in association with class I MHC. HOW??

A

Ag CROSS-PRESENTATION -> some viral Ags are released from phagosome in cytoplasm of DC and then presented within class I MHC.

The same cross-presenting APC also display microbial peptides within class II MHC for CD4+ helper T cells.

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11
Q

Are CD4 helper T cells more important for generation of CD8 memory T cells or the differentiation of naive CD8 T cells into effector CTLs?

A

More important for the generation of CD8 memory T cells.

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12
Q

When does licensing of the APC occur?

A

When the CD4 T cell recognizes Ag presented by an MHC class II APC and delivers activating signals through CD80/CD86 and CD40.

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13
Q

What happens when the CD4 T cell recognizes Ag presented by an MHC class II APC and delivers activating signals through CD80/CD86 and CD40?

A

LICENSING of the APC

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14
Q

Which activated cell type expresses CD40L?

A

Activated CD4 Th cells express CD40L.

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15
Q

What does the interaction of CD40-CD40L upregulate the expression of?

A

Expression of CD80/CD86 on professional APCs which makes them more efficient at stimulating the differentiation of CD8 T cells.

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16
Q

What does the expression of CD80/CD86 on professional APCs make them more efficient at?

A

More efficient at stimulating the differentiation of CD8 T cells.

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17
Q

Does the mechanisms of APC licensing require that CD4 and CD8 T cells be in contact with the APC at the same time?

A

No - it does not require that CD4 and CD8 T cells be in contact with APC at the same time.

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18
Q

What is signal 3 to enhance activation of CTLs?

A

CD4 helper T cells provide signal 3 in form of cytokines which enhance activation of CTLs.

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19
Q

True of False:

CD4 helper T cells are required for CD8 T cell responses when relatively weak innate immune reactions are evoked by latent viral infections, organ transplants, and tumors.

A

True

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20
Q

What is the role of IL-2 in CTL activation?

A

promotes PROLIFERATION and DIFFERENTIATION of CD8 T cells into CTLs and MEMORY CELLS.

CD8 T cells may express high levels of the alpha subunit of IL-2R after activation. Shares a common receptor component (the gamma chain) with IL-15 and IL-21.

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21
Q

What is the role of IL-12 and type I IFNs in CTL activation?

A

stimulate the DIFFERENTIATION of naive CD8 T cells into effector CTLs.

Haive CD8 T cells proliferate in response to TCR and CD28 signals, but require IL-12 or type I IFN for SURVIVAL and DEVELOPMENT of optimal effector functions.

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22
Q

What is the role of IL-15 in CTL activation?

A

Produced by DCs and tissue macrophages.
Important for the SURVIVAL OF MEMORY CD8 T CELLS.

mice lacking IL-15 show a significant loss of memory CD8 T cells.

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23
Q

What is the role of IL-21 in CTL activation?

A

produced by activated CD4 T cells play a role in the induction of CD8 T cell memory and the prevention of CD8 T cell exhaustion.

24
Q

What is a major feature of IL-2 in how it operates?

A

autocrine loop

25
Q

What other cytokines does IL-2 share a common receptor component (the gamma-chain)?

A

IL 4, 7, 9, 15, and 21

26
Q

True of False:

Local release of IL-2 can lead to activation of nearby CD8 T cells in a paracrine fashion.

A

True

27
Q

Is CD4 T cell-derived IFN-gamma a homodimer?

A

Yes

28
Q

What cell types release IFN-gamma?

A
  • Th1 cells
  • CTLs
  • activated NK cells
29
Q

What is IFN-gamma a potent activator of?

A

Potent activator of macrophages inducing an increase in metabolic, phagocytic, and killing activity.

30
Q

What does IFN-gamma have the ability to do?

A

Increase class I MHC molecule expression on a range of cell types and induce expression of class II MHC molecules on professional APCs.

This may be an important component of antiviral protection, since it up-regulates Ag presentation of viral targets by infected cells.

31
Q

What does IFN-gamma favor the development of?

A

Th1 cells and B cell differentiation biasing the production of immunoglobulin in favor of IgG and away from IgE.

32
Q

What cell types produce IL-12?

A

DCs and macrophages

33
Q

What does IL-12 do?

A

Profound effect of inducing naive CD4 T cells to differentiate into Th1 effector cells.

34
Q

The balance between which cytokines determines whether cells become Th1 or Th2?

A

IL-12 and IL-4

35
Q

What does IL-12 promote the production of?

A

IFN-gamma and TNF-beta by CD4+ and CD8+ T cells.

36
Q

Does IL-12 assist in the prevention of CD8 T cell exhaustion?

A

Yes

37
Q

Does IL-12 activate NK cells?

A

Yes

38
Q

Which cells produce the primary soruce of IL-15?

A

Activated tissue macrophages and mature DCs.

39
Q

What other cytokine does IL-15 share a similar biologic properties with?

A

IL-2 - have shared receptor signaling components.

40
Q

What does IL-15 simulate the proliferation of?

A

Memory CD4+ and CD8+ and naive CD8+ T cells.

41
Q

Can IL-15 costimulate innate immune IFN-gamma production?

A

Yes

42
Q

In vitro, what type of T helper cell does exogenous IL-15 favor?

A

Th1 T-cell

43
Q

Once a CTL is activated by presentation of a viral Ag via a DC, what does the CTL secrete?

A
  • TNF-beta
  • IFN-gamma
  • cytotoxic perforn and granzymes
44
Q

After viral clearance, what happens to CD8+ T cells?

A

Undergo an extensive contraction phase, mediated by apoptosis.

45
Q

What do exhausted CD8+ T cells show?

A

Reduced production of IFN-gamma and increased expression of PD-1 inhibitory receptor.

46
Q

What do inhibitory signals from PD-1 block the activation of?

A

CTLs

PD-1 mediated T cell exhaustion may contribute to the chronicity of HIV and hepatitis C virus

47
Q

True or False:

Anti-PD-1 Abs are effective in the immuno-therapy of tumors.

A

True

48
Q

True or False:

CTLs are injured during the killing of target cells.

A

False - CTLs are not injured during the killing of targets.

49
Q

What are the two major mechanisms of killing by CTLs?

A

> Fas-FasL-Mediated Apoptosis

> Granzyme-Mediated Apoptosis

50
Q

Threre are granzymes A, B, and C, which are serine proteases. Which is the only one shown to be required for CTL cytotoxicity in vivo?

A

Granzyme B

51
Q

What complement protein is perforin homologous to?

A

C9 complement protein.

52
Q

What is the function of the sulfated proteoglycan serglycin that is also contained in granules released by CTLs?

A

Assembles a complex containing granzymes and perforin.

53
Q

By what mechanism does perforin and granzymes enter the target cell to kill it?

A

Perforin insertion into the target cell membrane elicits a membrane repair process in the target cell that lead to internalization of both the perforin and granzymes in to endosomes.

When in the target cell, GRANZYME B activates caspase-3 that triggers apoptosis.

54
Q

Draw out the Fas-FasL -Mediated Apoptosis mechanism.

A

Keep working hard!!

55
Q

What is the mechanism of CD8+ CTLs in host defense against intracellular bacteria?

A

> CD8 T cells cooperate with CD4 T cells and in defense against intracellular microbes.

> Intracellular bacteria such as L. monocytogenes are phagocytized by macrophages and may survive in phagosomes and escape in the cytoplasm.

> CD4 T cells respond to class II MHC-associated peptide Ag derived from the intravesicular bacteria nad produce IFN-gamma and IL-2.

> CD8 T cells respond to class I-associated peptides derived from cytosolic Ags and kill the infected cells.

Immunology - Unit 3 - Zach H. (4 decks)

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