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
IL-15 costimulates innate immune ____ production
IFN-y
26
IL-21 role with B cells and T follicular help cells
Key role in B cell differentiation to plasma cells and in development of T follicular helper cells
27
IL-21 effect on CD8+ T cells
Induces a functional program that leads to enhanced survival, antiviral activity and antitumor activity
28
IL-21 role with Th17 cells
Key role in development of Th17 cells
29
IL-21 promotes a range of _____ diseases
Autoimmune diseases, including lupus, type I diabetes, MS, IBD and psoriasis Clinical trials using IL-21 inhibitors are in progress
30
What happens after DCs present viral Ags to CD8+ T cells
They differentiate into CTLs and release TFN-b, IFN-y, perforins and granzymes
31
Exhausted CD8+ T cells show what
Reduced expression of IFN-y and increased expression of PD-1 inhibitory receptors
32
Fas ligand is expressed on what cells
Activated CTLs, and engages Fas on the surface of target cells, inducing apoptosis
33
Perforin and granzymes
Released from CTLs and enter target cells. Granzymes are delivered into cytoplasm of target cells by a perforin-dependent mechanism
34
Fas ligand process in type I cells
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
Fas ligand process in type II cells
- 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
Granzyme mediated apoptosis
``` 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
Granzyme B
Only granzyme shown to be required for CTL cytotoxicity in vivo It activates Caspase-3 which triggers apoptosis
38
Perforin is homologous to
C9 complement protein