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Immunology > differentiation and effector functions of CD8 T cells > Flashcards

differentiation and effector functions of CD8 T cells Flashcards

1
Q

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

A

peptide

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2
Q

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

A

migrate

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3
Q

activation of CD8 CTLs requires 3 signals

1.

2.

3.

A
  1. antigen presentation
  2. co-stimulation
  3. cytokines
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4
Q

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
A
  1. DC
  2. afferent lymphatics
  3. cross-presentation
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5
Q

activation of CTLs (signal 2 co-stimulation):

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

A

CD28 engages CD80/86 (B7)

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6
Q

activation of CD8 CTLs (signal 3 cytokines):

  1. peripheral ____ : required for expansion of CD8
  2. CD8 cells alone ____ produce sufficient amounts of IL-2
A
  1. IL-2
  2. do not
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7
Q

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

A

perforin and granzymes

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8
Q

activated CTLs secrete cytokines, mostly ____ that potently activate macrophages

A

IFN-gamma

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9
Q

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

A

T-bet

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10
Q

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
A
  1. DCs
  2. MHC I
  3. phagosome MHC I
  4. MHC II
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11
Q

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

A

CD4

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12
Q

why do CD4 T effector cells appear before CD8 T cells

A

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

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13
Q

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 ____
A
  1. CD4
  2. CD40L → CD40 IFN-gamma
  3. CD80/86 cross-presentation
  4. IL-12
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14
Q

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

promotes proliferation and differentiation of ____

A

CD8

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15
Q

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
A
  1. CD8
  2. surviva/effector
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16
Q

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

important for ____ of memory CD8 T cells

A

survival

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17
Q

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 ____
A
  1. initaties
  2. exhaustion
  3. cytotoxicity
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18
Q

most potent activator of macrophages

A

IFN-gamma

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19
Q

functions of IFN-gamma:

  1. increases ____ expression
  2. favors development of ____ cells
  3. promotes ____ Ab class switch
  4. decreases ____ Ab class switch
A
  1. MHC
  2. Th1
  3. IgG
  4. IgE
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20
Q

what cells release IFN-gamma

A

CD8

CD4

Th1

activated NK, gamma-delta T cells, NKT cells

21
Q

what releases IL-12

A

DC and macrophages

22
Q

what release IL-15

A

DC and macrophages

23
Q

IL-12

released by:

functions:

A

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

24
Q

IL-15:

released by:

functions:

A

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

25
Q

what cells produce IL-21

A

CD4 , NKT , CD8

26
Q

functions of IL-21 on CD4

A

proliferation

Th17 differnentiation

inhibits Treg generation

27
Q

function of IL-21 on NKT

A

proliferation

enhances cytotoxicity

28
Q

functions of IL-21 on CD8

A

proliferation

memory cell formation

enhances cytotoxicity

enhanced antiviral and antitumor activity

29
Q

functions of IL-21

  1. conventional DC
  2. bone marrow-derived DC
  3. NK
  4. B cells
  5. macrophage
A
  1. apoptosis
  2. inhibits function
  3. enhances cytotoxicity
  4. proliferation, apoptosis, Ig class-switching, plasma cell differentiation
  5. enhances phagocytosis, M2 → M1 transition
30
Q

IL-21 promotes a range of ____ diseases

A

autoimmune

31
Q

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

A

IFN-gamma and TNF-b

perforin and granzymes

32
Q

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

A

contraction

apoptosis

33
Q

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

A

exhaustion

34
Q

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

A

IFN-gamma

PD-1 inhibitory receptor

35
Q

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

A

PD-1

36
Q

anti ____/____ are effective treatments in immunotherapy of tumor

A

PD-1/CTLA-4

37
Q

CD8 cells kill via apoptosis:

  1. ____-mediated apoptosis
  2. ____-mediated apoptosis
A
  1. Fas-FasL
  2. granzyme
38
Q

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

A

procaspase-8

capsase 8

39
Q

FasL - Fas:

  1. in type I cells (thymocytes), caspase 8 → ____ cleaves caspase-3

(mitochondria independent)

  1. in type II cells (virus-infected hepatocytes), caspase 8→ cleaves ____ → relase of ____ → cytochrome c + ____ + ATP → activates ____ → activates ____ → degrades ____ → activated ____ → degrades ____

(mitochondria dependent)

A
  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
40
Q

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
A
  1. MHC I
  2. immunological synapse
  3. injured
41
Q

immunological synapse formation is crucial to prevent

A

collateral damage

42
Q

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

A

C9

43
Q

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

A

internalization

perforin and granzymes

44
Q

granzymes are

A

serine proteases

45
Q

what granzyme is required for cytotoxicity

A

granzyme B

46
Q

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

A

CD40

CD40L

47
Q

activation of DCs results in upregulation of maturation markers ____

A

CD80/86

48
Q

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

Immunology (23 decks)

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