Lecture 14 - Differentiation and Functions of CD8+ T cells Flashcards
All T lymphocytes have what marker?
CD3 (TCR)
All T cells are derived from what?
Thymus
Helper T cells have what marker?
CD4
CTLs have what marker?
CD8
What is the typical percentage of Th and CTLs in blood?
Th - 66%
CTLs - 33%
T cells make up what percentage of all lymphocytes in the blood?
70%
B cells comprise the remaining 30%
CD8+ T cells are activated where and by what cells?
In the LN and by dendritic cells loaded with Ags exactly as CD4+ T cells are.
What do CTLs recognize?
Class I MHC-associated peptides
Once CTLs are activated, what follows?
They proliferate and leave the LN
CD8+ T cells are activated by mechanisms that involves what?
Cross-presentation of antigens to CD8+ T cells
Cells infected with intracellular microbes, such as viruses, are ingested by what?
DCs
CD8+ T cells are class ___ MHC- restricted
I
Naive CD8+ T cells recognize what?
Peptide Ags presented by DCs in the lymph nodes
CD*+ T cells are stimulated to do what?
Proliferate and differentiate into CTLs (and memory cells)
Once CTLs are activated the enter what?
The circulation and migrate to the site of Ag
CD8+ CTLs recognize the Ag at the site of Ag in the tissues and respond how?
By killing the target cells where the Ag is produced
The naive CD8+ T cells, like all naive T cells, are activated by what?
Ags presented by DCs
Ags recognized by CD8+ T cells may be from what?
Viruses or tumors derived from a variety of cell types
The process of cross-presentation is critically important for what?
Ag presentation by professional APCs within class I MHC
Exogenous Ags derived from ingested infected cells, tumor cells, or their proteins are transferred into the cytosol for processing, loading and presentation on what?
Class I MHC molecules
What is the first signal for the activation of naive CD8+ cell?
Recognition of Ags
What is the second signal for the proliferation and differentiation of CD8+ cells into effector CTLs?
CD28-CD80 costimulation
Activated CTLs contain numerous amounts of what?
Granules called lysosomes
What do granules contain?
Perforin and granzymes used by the cells to kill other cells
What do activated CTLs secrete?
Cytokines, mostly IFN-γ, that potently activate macrophages
Similar to the activation of Th1 cells, the molecular events in CTL differentiation involve what TF?
T-bet
What does T-bet regulate?
Transcription of genes encoding perforin, granzymes, and IFN-γ
What provides signal 3 in the form of cytokines which enhance activation of CTLs?
CD4+ helper T cells
Of particular importance, CD4+ helper T cells are required for CD8+ T cells responses when?
Relatively weak innate immune reactions are evoked by laten viral infections, organ transplants, and tumors
Evidence suggests that CD4+ helper T cells are more important for the generation of what ?
CD8+ memory T cells than for the differentiation of naive CD8+ T cells into effector CTLs
Licensing of the APC occurs when?
The CD4+ T cell recognizes Ag presented by an MHC class II+ APC
Licensing of APC delivers activating signals through what?
CD80/CD86 and CD40
Activated CD4+ Th cells express what?
CD40L
What does CD40L bind to?
To CD40 on Ag-loaded DCs
What does the CD40-CD40L interaction upregulates?
Expression of CD80/CD86 on professional APCs which makes them more efficient at sitmulating the differentiation of CD8+ T cells
True or False?
IT is required for CD4+ and CD8+ T cells should come in contact with APC at the same time?
FALSE
What role does IL-2 play in the activation of CD8+ T cells into CTLs and memory cells?
It promotes the proliferation and differentiation
What may CD8+ T cells express at high levels after activation?
α subunit of IL-2R
The IL-2 shares a common receptor component (the γ chain) with what?
IL-15 and IL-21
IL-12 and Type I IFNs stimulate what?
The differentiation of naive CD8+ T cells into effector CTLs
Naive CD8 T cells proliferate in response to what? What is needed for survival and development for optinal effector functions?
TCR and CD28 signals, but require IL-12 or type I IFN for survival and development of optinal effector functions
IL-15 may be produced by what cells?
DCs and tissue Mo