Lecture 13: Differentiation and Functions of CD8+ T Cells

Question 1

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

Answer 1

66% Helper T cells

33% Cytotoxic T cells

Question 2

Activated CTLs contain

Answer 2

Lysosomes that contain perforin and granzymes

Question 3

T-bet regulates what

Answer 3

Transcription of genes encoding perforin, granzymes and IFN-y

Question 4

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

Answer 4

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)

Question 5

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

Answer 5

Because DCs need “education” which takes time.

Question 6

Licensing of APC occurs when

Answer 6

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

Question 7

Activated CD4+ T cells increase expression of

Answer 7

CD40L

Question 8

Effect of CD40L/CD40 and IFN-y interactions

Answer 8

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

Question 9

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

Answer 9

IL-15R and IL-21R

Question 10

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

Answer 10

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

Question 11

IL-15 produced by what and is required for

Answer 11

DCs and tissue macrophages

Survival of memory CD8+ T cells

Question 12

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

Answer 12

Activated CD4+ T cells

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

Question 13

Key feature of IL-2

Answer 13

Autocrine loop through which it operates

15kDa peptide

Question 14

Local release of IL-2 can lead to

Answer 14

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

Question 15

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

Answer 15

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

Question 16

IFN-y is a ___dimer

Answer 16

Homodimer of 25kDa

Question 17

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

Answer 17

Increase MHC I expression on many cells

Induce expression of MHC II on professional APCs

Question 18

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

Answer 18

Favors development of Th1 cells and B cell differentiation

Production towards IgG and away from IgE

Question 19

IL-12 promotes production of pro-inflammatory cytokines

Answer 19

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

Question 20

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

Answer 20

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

Question 21

IL-12 also assists in prevention of ___ and activates

Answer 21

Prevents exhaustion of CD8+ T cells

Activates NK cells

Question 22

Primary source of IL-15

Answer 22

Activated tissue macrophages and mature DCs

Question 23

Exogenous IL-15 favors human ____ differentiation

Answer 23

Th1 T cell differentiation

Question 24

IL-15 stimulates proliferation of ____ and ___

Answer 24

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

Question 25

IL-15 costimulates innate immune ____ production

Answer 25

IFN-y

Question 26

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

Answer 26

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

Question 27

IL-21 effect on CD8+ T cells

Answer 27

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

Question 28

IL-21 role with Th17 cells

Answer 28

Key role in development of Th17 cells

Question 29

IL-21 promotes a range of _____ diseases

Answer 29

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

Question 30

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

Answer 30

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

Question 31

Exhausted CD8+ T cells show what

Answer 31

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

Question 32

Fas ligand is expressed on what cells

Answer 32

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

Question 33

Perforin and granzymes

Answer 33

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

Question 34

Fas ligand process in type I cells

Answer 34

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

Question 35

Fas ligand process in type II cells

Answer 35

• 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

Question 36

Granzyme mediated apoptosis

Answer 36

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

Question 37

Granzyme B

Answer 37

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

Question 38

Perforin is homologous to

Answer 38

C9 complement protein