differentiation and effector functions of CD8 T cells

Question 1

naive CD8 T cells recognize ____ Ags presented by DCs in the LNs

Answer 1

peptide

Question 2

CD8 CTLs enter the circulation and ____ to the site of Ag acquistition by DCs

Answer 2

migrate

Question 3

activation of CD8 CTLs requires 3 signals

1.

2.

3.

Answer 3

1. antigen presentation
2. co-stimulation
3. cytokines

Question 4

activation of CTLs (Signal 1 Ag Presentation):

1. virally infected cell phagocytosed by ____
2. DC migrates to T-cell zone in LN via ____ ____
3. through ____ , DC will present the intracellular/viral Ag to CD8 and CD4 T cells

Answer 4

1. DC
2. afferent lymphatics
3. cross-presentation

Question 5

activation of CTLs (signal 2 co-stimulation):

____ (on T-cell) engages ____ (on DC)

Answer 5

CD28 engages CD80/86 (B7)

Question 6

activation of CD8 CTLs (signal 3 cytokines):

1. peripheral ____ : required for expansion of CD8
2. CD8 cells alone ____ produce sufficient amounts of IL-2

Answer 6

1. IL-2
2. do not

Question 7

activated CTLs contain numerous granules called lysosomes that contain ____ and ____ used by the cells to kill other cells

Answer 7

perforin and granzymes

Question 8

activated CTLs secrete cytokines, mostly ____ that potently activate macrophages

Answer 8

IFN-gamma

Question 9

similar to activation of Th1 cells, the molecular events in CTL differentiation involved trascriptional factor ____

Answer 9

T-bet

Question 10

the magic of cross-presentation:

1. cells infected with intracellular microbes, such as viruses, are ingested by ____
2. extracellular Ags are processed and presented within class II MHS, but they are also presented in association with ____
3. the mechanism called Ag cross-presentation - some viral Ags are relased from ____ in cytoplasm of DC and then presented with ____
4. the same cross-presenting APC also display microbial peptides within ____ for CD4 helper T cells

Answer 10

1. DCs
2. MHC I
3. phagosome MHC I
4. MHC II

Question 11

what happens first, the generation of CD4 T effector cells or the appearance of CD8 T cells

Answer 11

CD4

Question 12

why do CD4 T effector cells appear before CD8 T cells

Answer 12

because DC needs “education” or “licensing” by CD4 cells

Question 13

dendritic cell licensing/education:

1. to reach full capacity of CD8 proliferation, DC has to first activate ____ (in LN)
2. once CD4 T cell is activated it will express ____ → ____ on DC and releases ____ to DC
3. ____ is then upregulated on DC which amplifies ____ and co-stimulation to CTLs
4. DC release ____

Answer 13

1. CD4
2. CD40L → CD40 IFN-gamma
3. CD80/86 cross-presentation
4. IL-12

Question 14

key cytokines in CD8 differentiation: IL-2 (from T cells)

promotes proliferation and differentiation of ____

Answer 14

CD8

Question 15

key cytokines in CD8 differentiation: IL-12 (from DC and MØ) and IFN-gamma:

1. key cytokines for directing towards ____ T cell differentiation
2. these cytokines are necessary for ____/____ functions

Answer 15

1. CD8
2. surviva/effector

Question 16

key cytokines in CD8 differentiation: IL-15 (from DC and MØ):

important for ____ of memory CD8 T cells

Answer 16

survival

Question 17

key cytokines in CD8 differentiation: IL-21 (from activated CD4 , CD8 , and NKT)

1. ____ CD8 memory T cell formation
2. prevents CD8 T cell ____
3. enhances ____

Answer 17

1. initaties
2. exhaustion
3. cytotoxicity

Question 18

most potent activator of macrophages

Answer 18

IFN-gamma

Question 19

functions of IFN-gamma:

1. increases ____ expression
2. favors development of ____ cells
3. promotes ____ Ab class switch
4. decreases ____ Ab class switch

Answer 19

1. MHC
2. Th1
3. IgG
4. IgE

Question 20

what cells release IFN-gamma

Answer 20

CD8

CD4

Th1

activated NK, gamma-delta T cells, NKT cells

Question 21

what releases IL-12

Answer 21

DC and macrophages

Question 22

what release IL-15

Answer 22

DC and macrophages

Question 23

IL-12

released by:

functions:

Answer 23

DCs and macrophages

differentiates naive CD4 to Th1

promotes IFN-gamma and TNF-b production from CD4/CD8

promotes tumor control via CD8 function

activates NK cells

Question 24

IL-15:

released by:

functions:

Answer 24

DCs and macrophages

simillar to IL-2

favors Th1 differentiation

chemoattractant for T cells in blood

proliferation for memory CD4 and CD8 cells

increases IFN-gamma production

Question 25

what cells produce IL-21

Answer 25

CD4 , NKT , CD8

Question 26

functions of IL-21 on CD4

Answer 26

proliferation Th17 differnentiation inhibits Treg generation

Question 27

function of IL-21 on NKT

Answer 27

proliferation enhances cytotoxicity

Question 28

functions of IL-21 on CD8

Answer 28

proliferation memory cell formation enhances cytotoxicity enhanced antiviral and antitumor activity

Question 29

functions of IL-21 1. conventional DC 2. bone marrow-derived DC 3. NK 4. B cells 5. macrophage

Answer 29

1. apoptosis 2. inhibits function 3. enhances cytotoxicity 4. proliferation, apoptosis, Ig class-switching, plasma cell differentiation 5. enhances phagocytosis, M2 → M1 transition

Question 30

IL-21 promotes a range of ____ diseases

Answer 30

autoimmune

Question 31

activated CTLs secrete proinflammatory cytokine ____ and ____ and cytotoxic ____ and \_\_\_\_

Answer 31

IFN-gamma and TNF-b perforin and granzymes

Question 32

after viral clearance, the CD8 cells undergo an extensive ____ phase mediated by \_\_\_\_

Answer 32

contraction apoptosis

Question 33

in some chronic viral infections, the responses of CD8 cells may be initiated but gradually extinguished, this is called \_\_\_\_

Answer 33

exhaustion

Question 34

exhausted CD8 cells show reduced proudction of ____ and increased expression of \_\_\_\_

Answer 34

IFN-gamma PD-1 inhibitory receptor

Question 35

\_\_\_\_ - mediated T cell exhaustion may contribute to teh chronicity of HIV and hepatitis C virus (HCV)

Answer 35

PD-1

Question 36

anti \_\_\_\_/\_\_\_\_ are effective treatments in immunotherapy of tumor

Answer 36

PD-1/CTLA-4

Question 37

_CD8 cells kill via apoptosis:_ 1. \_\_\_\_-mediated apoptosis 2. \_\_\_\_-mediated apoptosis

Answer 37

1. Fas-FasL 2. granzyme

Question 38

binding of FasL (on CD8) to Fas (on target cell) recruits ____ through the FADD adaptor and converts it into the active enzyme \_\_\_\_

Answer 38

procaspase-8 capsase 8

Question 39

_FasL - Fas:_ 1. in type I cells (thymocytes), caspase 8 → ____ cleaves caspase-3 (mitochondria independent) 2. in type II cells (virus-infected hepatocytes), caspase 8→ cleaves ____ → relase of ____ → cytochrome c + ____ + ATP → activates ____ → activates ____ → degrades ____ → activated ____ → degrades \_\_\_\_ (mitochondria dependent)

Answer 39

1. in type I cells (thymocytes), caspase 8 → directly cleaves caspase-3 2. in type II cells (virus-infected hepatocytes), caspase 8→ cleaves Bid → relase of cytochrome c → cytochrome c + Apaf-1 + ATP → activates caspase 9 → activates caspase 3 → degrades ICAD → activated CAD → degrades DNA

Question 40

_granzyme-mediated apoptosis:_ 1. TCR recognizes specific Ag with ____ molecules 2. this interaction brings CTL and target cell in close contact which results in formation of ____ \_\_\_\_ which ensures that normal bystander cells are not injured by CTLs 3. CTLs are not ____ during the killing of targets

Answer 40

1. MHC I 2. immunological synapse 3. injured

Question 41

immunological synapse formation is crucial to prevent

Answer 41

collateral damage

Question 42

perforin is a membrane-perturbig molecule that is homologous to the ____ complement protein

Answer 42

C9

Question 43

perforin insertion into the target cell membrane elicits a compensatory membrane repair process in the target cell that leads to ____ of both the ____ and ____ into endosomes

Answer 43

internalization perforin and granzymes

Question 44

granzymes are

Answer 44

serine proteases

Question 45

what granzyme is required for cytotoxicity

Answer 45

granzyme B

Question 46

CD4 T cell can activate DCs by interaction of ____ with ____ on the DC

Answer 46

CD40 CD40L

Question 47

activation of DCs results in upregulation of maturation markers \_\_\_\_

Answer 47

CD80/86

Question 48

_CD4 and CD8 and intracellular bacteria:_ 1. ____ (from CD4) can improve phagolysosomal killing intracellular bacteria 2. intracellular bacteria are phagocytized by macrophages and may survive in phagosome and escape into the ____ , in which CD8 can initiate \_\_\_\_ 3. this ____ up reservoirs of pathogen/bacteria to be cleared by other means

Answer 48

1. IFN-gamma 2. cytoplasm apoptosis 3. frees