Chapter 11 - Functions of CD8 Flashcards
What kind of Ags do CD8 T cells recognize?
viruses or tumors
Where are CD8 T cells activated and by what?
what happens afterwards?
LN by DC
proliferate and then leave LN
Describe CD8 Cross Presentation
DC ingests extracellular pathogen, it is released into the cytoplasm and presented to class I MHC
What are the 3 signals for CTL activation?
1) recognize Ag
2) costimulation of CD28-CD80
3) proliferative, CD4 may provide cytokines
Activated CTLs contain granules called what?
what is used by the cells to kill others?
lysosomes
perforin and granzymes
What TF is involved in CTL differentiation?
T-bet
T-bet regulates genes encoding for what?
perforin, granzyme, IFN-gamma
When are CD4 helper T cells required for CD8 T cell responses?
weak innate immune reactions evoked by latent viral infections, organ transplants, and tumors
Are CD4 helper cells more important for generation of CD8 memory cells or differentiation of naive CD8 T cells into effector CTLs?
memory
What do activated CD4 Th cells express?
CD40L which binds to CD40 on Ag-loaded DC
IL-2 shares what common component with IL-15 and IL-21?
gamma chain
what stimulates the differentiation of naive CD8 T cells into effector CTLs?
how do naive CD8 T cells proliferate?
IL-12 and type I IFNs
in response to TCR and CD28
what produces IL-15?
what is it important for?
DCs and macrophages
survival of memory CD8 T cells
What produces IL-21?
what role does it play?
activated CD4 T Cells
induction of CD8 T cell memory and prevention of CD8 T cell exhaustion
What is IL-2?
what kind of loop does it contain and operate through?
local release of IL-2 can lead to act. of nearby CD8s in what fashion?
T cell growth factor
autocrine loop
paracrine fashion
IL-12 promotes production of what pro-inflammatory cytokines?
what does it also activate?
What does it assist in?
IFN-gamma and TNF-beta
NK cells
prevention of CD8 T cell exhaustion
what does exogenous IL-15 favor?
what does IL-15 act as?
what does IL-15 costimulate?
Th1 cell differentiation in vitro
potent chemoattractant for T cells
innate immune IFN-gamma production
Is IFN-gamma a homo or heterodimer?
What is it released by?
what immunoglobin does it favor?
homodimer, 25 kDa
Th1 cells, CTLs, NK cells
IgG away from IgE
What are the 5 steps of the kinetics of CD8 T cell in acute viral infections?
1) DC present viral Ag to CD8 T cell
2) clonal expansion and differentiation into CTL
3) Activated CTL secretes TNF-beta, IFN-gamma, perforin, granzymes
4) after viral clearance, extensive contraction, mediated by apoptosis
5) memory CD8 T cells persist for years
What is exhaustion?
chronic viral infections, the response of CD8 T cells is gradually extinguished
what do exhausted CD8 t cells show?
reduced production of IFN-gamma
Increased expression of PD-1 inhibitory receptor (may contribute to HIV and hepatitis C)
In the immunological synapse, can perforin and granzyme diffuse to other nearby cells?
what are some interactions?
NO
LFA1 on CTL - ICAM 1 on target cell
What are the 2 main mechanisms of killing of target cells by CTLs?
1) perforin (and granzyme) dependent mechanism that induce apoptosis
2) FasL expressed on activated CTLs engages Fas on target cell, induces apoptosis
What are granzymes A, B, and C?
which one is required for CTL cytotoxicity in vivo?
serine proteases
B
