Lecture 13: Differentiation and Functions of CD8+ T Cells Flashcards

1
Q

% of helper T cells and % of cytotoxic T cells out of T lymphocyte population

A

66% Helper T cells

33% Cytotoxic T cells

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2
Q

Activated CTLs contain

A

Lysosomes that contain perforin and granzymes

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3
Q

T-bet regulates what

A

Transcription of genes encoding perforin, granzymes and IFN-y

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4
Q

How do some EC antigens get presented in association with MHC I molecules?

A
Cross presentation- some viral Ags are released from phagosome in cytoplasm of DC and then presented with class I MHC
(The same cross-presenting APC can display microbial peptides within class II MHC for CD4+ T cells)
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5
Q

Why does generation of CD4+ T effector cells precede appearance of CD8+ T cells

A

Because DCs need “education” which takes time.

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6
Q

Licensing of APC occurs when

A

CD4+ T cell delivers activating signals through CD40L/CD40 signaling and release of IFN-y to DC after it recognizes Ag presented by an MHC class II APC

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7
Q

Activated CD4+ T cells increase expression of

A

CD40L

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8
Q

Effect of CD40L/CD40 and IFN-y interactions

A

Upregulates expression of CD80/86 on DC and stimulates Ag cross presentation which makes them more efficient at inducing differentiation of CD8+ T cells

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9
Q

IL-2R shares the same y chain with what cytokines

A

IL-15R and IL-21R

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10
Q

Naïve CD8+ T cells proliferate in response to ___ and ___ signals, but also require ___ or___ for survival and development of optimal effector functions

A

Proliferate in response to TCR and CD28 signals, but also require IL-12 or IFN-y

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11
Q

IL-15 produced by what and is required for

A

DCs and tissue macrophages

Survival of memory CD8+ T cells

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12
Q

IL-21 is produced by what and plays a role in

A

Activated CD4+ T cells

Induction of CD8+ T cell memory and prevention of CD8+ T cell exhaustion

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13
Q

Key feature of IL-2

A

Autocrine loop through which it operates

15kDa peptide

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14
Q

Local release of IL-2 can lead to

A

Clonal expansion of T cells, which upon recognition of Ag presented by APC express a-subunit of IL-2R

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15
Q

Local release of IL-2 by activated CD4+ T cell leads to

A

Activation of nearby Ag-activated CD8+ T cells in a paracrine fashion

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16
Q

IFN-y is a ___dimer

A

Homodimer of 25kDa

17
Q

IFN-y has ability to increase __________ expression on a range of cell types and induce expression of ______ on professional APCs

A

Increase MHC I expression on many cells

Induce expression of MHC II on professional APCs

18
Q

IFN-y favors development of ___ and ___ cells and biases production of Ig ___ and away from Ig___

A

Favors development of Th1 cells and B cell differentiation

Production towards IgG and away from IgE

19
Q

IL-12 promotes production of pro-inflammatory cytokines

A

IFN-y and TNF-b by CD4+ and CD8+ T cells

20
Q

IL-12 stimulated CD8+ T cells compared to IFN-y stimulated T cells

A

IL-12 stimulated are more effective in controlling tumor and they maintain high numbers and function as compared to IFN-y stimulated cells

21
Q

IL-12 also assists in prevention of ___ and activates

A

Prevents exhaustion of CD8+ T cells

Activates NK cells

22
Q

Primary source of IL-15

A

Activated tissue macrophages and mature DCs

23
Q

Exogenous IL-15 favors human ____ differentiation

A

Th1 T cell differentiation

24
Q

IL-15 stimulates proliferation of ____ and ___

A

Memory CD4+ and CD8+ and naïve CD8+ T cells

25
Q

IL-15 costimulates innate immune ____ production

A

IFN-y

26
Q

IL-21 role with B cells and T follicular help cells

A

Key role in B cell differentiation to plasma cells and in development of T follicular helper cells

27
Q

IL-21 effect on CD8+ T cells

A

Induces a functional program that leads to enhanced survival, antiviral activity and antitumor activity

28
Q

IL-21 role with Th17 cells

A

Key role in development of Th17 cells

29
Q

IL-21 promotes a range of _____ diseases

A

Autoimmune diseases, including lupus, type I diabetes, MS, IBD and psoriasis
Clinical trials using IL-21 inhibitors are in progress

30
Q

What happens after DCs present viral Ags to CD8+ T cells

A

They differentiate into CTLs and release TFN-b, IFN-y, perforins and granzymes

31
Q

Exhausted CD8+ T cells show what

A

Reduced expression of IFN-y and increased expression of PD-1 inhibitory receptors

32
Q

Fas ligand is expressed on what cells

A

Activated CTLs, and engages Fas on the surface of target cells, inducing apoptosis

33
Q

Perforin and granzymes

A

Released from CTLs and enter target cells. Granzymes are delivered into cytoplasm of target cells by a perforin-dependent mechanism

34
Q

Fas ligand process in type I cells

A

FasL binds Fas and recruits procaspase 8 through the FADD adaptor, then converts it to active caspase 8

  • In Type I cells caspase 8 can directly cleave caspase 3, independent of mitochondria
  • Activated Caspase 3 activates CAD via degradation of ICAD
  • CAD causes DNA degradation in nucleus
35
Q

Fas ligand process in type II cells

A
  • FasL binds Fas, procaspase 8 is activated
  • Caspase 8 cleaves Bid which stimulates release of Cytochrome C from mitochondria
  • Cytochrome C, along with Apaf-1 and ATP, activate caspase 9, which activates caspase 3
  • Caspase 3 activates CAD via degradation of ICAD
  • CAD destroys DNA in nucleus
36
Q

Granzyme mediated apoptosis

A
TCR recognizes specific Ag within class I MHC
CTL and target cell form immunologic synapse and perforins/granzymes are released, killing only the infected cell
37
Q

Granzyme B

A

Only granzyme shown to be required for CTL cytotoxicity in vivo
It activates Caspase-3 which triggers apoptosis

38
Q

Perforin is homologous to

A

C9 complement protein