differentiation and effector functions of CD8 T cells Flashcards
naive CD8 T cells recognize ____ Ags presented by DCs in the LNs
peptide
CD8 CTLs enter the circulation and ____ to the site of Ag acquistition by DCs
migrate
activation of CD8 CTLs requires 3 signals
1.
2.
3.
- antigen presentation
- co-stimulation
- cytokines
activation of CTLs (Signal 1 Ag Presentation):
- virally infected cell phagocytosed by ____
- DC migrates to T-cell zone in LN via ____ ____
- through ____ , DC will present the intracellular/viral Ag to CD8 and CD4 T cells
- DC
- afferent lymphatics
- cross-presentation
activation of CTLs (signal 2 co-stimulation):
____ (on T-cell) engages ____ (on DC)
CD28 engages CD80/86 (B7)
activation of CD8 CTLs (signal 3 cytokines):
- peripheral ____ : required for expansion of CD8
- CD8 cells alone ____ produce sufficient amounts of IL-2
- IL-2
- do not
activated CTLs contain numerous granules called lysosomes that contain ____ and ____ used by the cells to kill other cells
perforin and granzymes
activated CTLs secrete cytokines, mostly ____ that potently activate macrophages
IFN-gamma
similar to activation of Th1 cells, the molecular events in CTL differentiation involved trascriptional factor ____
T-bet
the magic of cross-presentation:
- cells infected with intracellular microbes, such as viruses, are ingested by ____
- extracellular Ags are processed and presented within class II MHS, but they are also presented in association with ____
- the mechanism called Ag cross-presentation - some viral Ags are relased from ____ in cytoplasm of DC and then presented with ____
- the same cross-presenting APC also display microbial peptides within ____ for CD4 helper T cells
- DCs
- MHC I
- phagosome MHC I
- MHC II
what happens first, the generation of CD4 T effector cells or the appearance of CD8 T cells
CD4
why do CD4 T effector cells appear before CD8 T cells
because DC needs “education” or “licensing” by CD4 cells
dendritic cell licensing/education:
- to reach full capacity of CD8 proliferation, DC has to first activate ____ (in LN)
- once CD4 T cell is activated it will express ____ → ____ on DC and releases ____ to DC
- ____ is then upregulated on DC which amplifies ____ and co-stimulation to CTLs
- DC release ____
- CD4
- CD40L → CD40 IFN-gamma
- CD80/86 cross-presentation
- IL-12
key cytokines in CD8 differentiation: IL-2 (from T cells)
promotes proliferation and differentiation of ____
CD8
key cytokines in CD8 differentiation: IL-12 (from DC and MØ) and IFN-gamma:
- key cytokines for directing towards ____ T cell differentiation
- these cytokines are necessary for ____/____ functions
- CD8
- surviva/effector
key cytokines in CD8 differentiation: IL-15 (from DC and MØ):
important for ____ of memory CD8 T cells
survival
key cytokines in CD8 differentiation: IL-21 (from activated CD4 , CD8 , and NKT)
- ____ CD8 memory T cell formation
- prevents CD8 T cell ____
- enhances ____
- initaties
- exhaustion
- cytotoxicity
most potent activator of macrophages
IFN-gamma
functions of IFN-gamma:
- increases ____ expression
- favors development of ____ cells
- promotes ____ Ab class switch
- decreases ____ Ab class switch
- MHC
- Th1
- IgG
- IgE
what cells release IFN-gamma
CD8
CD4
Th1
activated NK, gamma-delta T cells, NKT cells
what releases IL-12
DC and macrophages
what release IL-15
DC and macrophages
IL-12
released by:
functions:
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
IL-15:
released by:
functions:
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
what cells produce IL-21
CD4 , NKT , CD8
functions of IL-21 on CD4
proliferation
Th17 differnentiation
inhibits Treg generation
function of IL-21 on NKT
proliferation
enhances cytotoxicity
functions of IL-21 on CD8
proliferation
memory cell formation
enhances cytotoxicity
enhanced antiviral and antitumor activity
functions of IL-21
- conventional DC
- bone marrow-derived DC
- NK
- B cells
- macrophage
- apoptosis
- inhibits function
- enhances cytotoxicity
- proliferation, apoptosis, Ig class-switching, plasma cell differentiation
- enhances phagocytosis, M2 → M1 transition
IL-21 promotes a range of ____ diseases
autoimmune
activated CTLs secrete proinflammatory cytokine ____ and ____ and cytotoxic ____ and ____
IFN-gamma and TNF-b
perforin and granzymes
after viral clearance, the CD8 cells undergo an extensive ____ phase mediated by ____
contraction
apoptosis
in some chronic viral infections, the responses of CD8 cells may be initiated but gradually extinguished, this is called ____
exhaustion
exhausted CD8 cells show reduced proudction of ____ and increased expression of ____
IFN-gamma
PD-1 inhibitory receptor
____ - mediated T cell exhaustion may contribute to teh chronicity of HIV and hepatitis C virus (HCV)
PD-1
anti ____/____ are effective treatments in immunotherapy of tumor
PD-1/CTLA-4
CD8 cells kill via apoptosis:
- ____-mediated apoptosis
- ____-mediated apoptosis
- Fas-FasL
- granzyme
binding of FasL (on CD8) to Fas (on target cell) recruits ____ through the FADD adaptor and converts it into the active enzyme ____
procaspase-8
capsase 8
FasL - Fas:
- in type I cells (thymocytes), caspase 8 → ____ cleaves caspase-3
(mitochondria independent)
- in type II cells (virus-infected hepatocytes), caspase 8→ cleaves ____ → relase of ____ → cytochrome c + ____ + ATP → activates ____ → activates ____ → degrades ____ → activated ____ → degrades ____
(mitochondria dependent)
- in type I cells (thymocytes), caspase 8 → directly cleaves caspase-3
- 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
granzyme-mediated apoptosis:
- TCR recognizes specific Ag with ____ molecules
- 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
- CTLs are not ____ during the killing of targets
- MHC I
- immunological synapse
- injured
immunological synapse formation is crucial to prevent
collateral damage
perforin is a membrane-perturbig molecule that is homologous to the ____ complement protein
C9
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
internalization
perforin and granzymes
granzymes are
serine proteases
what granzyme is required for cytotoxicity
granzyme B
CD4 T cell can activate DCs by interaction of ____ with ____ on the DC
CD40
CD40L
activation of DCs results in upregulation of maturation markers ____
CD80/86
CD4 and CD8 and intracellular bacteria:
- ____ (from CD4) can improve phagolysosomal killing intracellular bacteria
- intracellular bacteria are phagocytized by macrophages and may survive in phagosome and escape into the ____ , in which CD8 can initiate ____
- this ____ up reservoirs of pathogen/bacteria to be cleared by other means
- IFN-gamma
- cytoplasm apoptosis
- frees
