Lecture 13 - Differentiation and Functions Of CD8+ T Cells Flashcards
What signals are involved in CTL activation and what is the response to activation?
L13 S5
Signal 1:
-recognition of protein Ag presented by MHC I
Signal 2:
-costimulation by CD28:CD80
Signal 1 and 2 produce transcription factor T-bet
T-bet stimulates production of perforing, granzymes and IFN-γ
What cytokines are involved in CTL activation?
L13 S11
IL-2:
IL-12/IFN-γ:
IL-15:
IL-21:
What are the main characteristics/functions of IL-2?
L13 S12
- produced by CD4+ cells
- main stimulator of activation and proliferation of CD8+ cells
Autocrine loop:
- Ag-activated CD8+ cells by APCs present IL-2R
- IL-2 is released by activated CD4+ cells and activate CD8+ cells
What are the main characteristics/functions of IFN-γ?
L13 S13
- produced by Th1 cells, CTLs, and NK cells
- main activator of Mφ; increases metabolic, phagocytic, and killing activity
- increases MHC class I expression and slightly increases MHC class II expression
- stimulates IgG production by B cells
What are the main characteristics/functions of IL-12?
L13 S14
- produced by DCs and Mφ
- differentiates naïve CD4+ cells in to Th1 cells
- survival signal for CD8+ T cells and optimizes function
- prevents CD8+ T cell exhaustion
-activates NK cells
What are the main characteristics/functions of IL-15?
L13 S16
- produced by DCs and Mφ
- similar function with IL-2 due to shared signaling components
- stimulates proliferation of CTLs
- stimulates differentiation of naïve CD4+ cells into Th1 cells
- chemoattactant
IL-15 stimulates IFN-γ production and IFN-γ stimulates IL-15 production
What are the main characteristics/functions of IL-21?
L13 S20-21
Pleiotropic:
- B cell differentiation into plasma cell
- T(fH) differentiation
- survival of CD8+ T cells and enhances function
- development of Th17 cells
Treatment of solid tumors
Autoimmune disease
What is the process of CTL activation and viral clearance?
L13 S23
- DCs present viral Ag to CD8+ cells which undergo clonal expansion and differentiate into CTL
- CTL release pro-inflammatory TNF-β and IFN-γ in addition to cytotoxic perforin and granzymes
- CTL population contraction and memory cell development
What is exhaustion?
L13 S24
In chronic infections, CTLs decrease production of IFN-γ and increase expression of PD-1 (inhibitory receptor) thus blocking activation of CTLs. What
What are the effector mechanisms of CTLs?
L13 S27
Fas-FasL-mediated apoptosis
Granzyme-mediated apoptosis
What are the different mechanisms of Fas-FasL-mediated apoptosis?
L13 S28
-Fas-FasL recruits procaspase-8 through FADD converting it into caspase-8
Type-I cells:
- caspase-8 activates caspase-3
- no mitochondrial involvement
Type II-cells:
- caspase-8 activates Bid
- Bid stimulates release of cytochrome c from mitochondria
- cytochrome c and Apaf-1 activate caspase-9
- caspase-9 activates caspase-3
Caspase-3:
- caspase-3 degrades ICAD (inhibitor of CAD) activating CAD (caspase-activated DNase)
- CAD degrades DNA
What is the mechanisms of granzyme-mediated apoptosis?
L13 S29
Initiated by Ag presentation to CTL by MHC class I. Forms immunologic synapse.
CTL releases perforins and granzymes
-perforins are similar to C9 and form a pore-like complex
- granzyme B activates caspase-3
- caspase-3 degrades ICAD (inhibitor of CAD) activating CAD (caspase-activated DNase)
- CAD degrades DNA
