Lecture 9: Activation of T Lymphocytes Flashcards
The proliferation of T lympohcytes and their differentiation into effector and memory cells reuires what three signals
- Ag recognition (signal 1)
- Costimulation (signal 2)
- Cytokines (signal 3)
Activation of naive T cells requires recognition of Ag presented by ____ meanwhile effector T cells can recognize Ags presented by ____ and _____
Naive T cells require DCs
Effector T cells can recognize Ags presented by Tissue macrophages and B cells
Superantigens (Sags) bind simultaneously
- MHC class II molecules (not in the peptide-binding groove) and the V region of the beta subunit of the TCR
- this leads to T cells produce massive amounts of cytokines (such as TNF-alpha, IL-1beta, and IL-2) which may lead to shock
The best characterized costimulatory pathway in T cell acitvation
- T cell surface receptor CD28
- binds costimulatory molecules B7-1 (CD80) and B7-2 (CD86) expressed on activated APCs
- B7 costimulators are regulated and ensure that T lympocyte responses are initiated only when needed.
CTLA-4-mediated immune checkpoint is induced in naive T cells at the time
of their intial response to Ag
The stronger the stimulation through the TCR and CD28 the greater the amount of ___ that is deposited on the T cell surface from the inracellular vesicles
CTLA4
Inflammatory signals in the tissues have what effect on expression of PD1 ligands
- induce expression of PD1
- this is a way to downregulate the activity of T cells and thus limit collateral tissue damage in response to a microorganism infection in that tissue.
No other cytokine can replace ____ for the mainenance of functional Treg cells
IL-2
CD69 binds to and reduces surface expression fo the ________ receptor _____
- Sphingosine-1-phosphate receptor S1PR1
- as a result, activated T cells are retained in the LNs long enough to receive the signals that initiate their proliferation and differentiation into effector and memory cells
IL-2Ralpha is also known as CD___
CD25
What are the inhibitory receptors on T cells
- CTLA4
- PD-1
various regulatory mechanisms contribute to the normal contraction of T cells, such as:
- The inhibitory receptors CTLA4 and PD-1
- Apoptosis induced by death receptors TNFRI and Fas
- Treg cells
- (not that IL-2 secretion decreases as well)
The vast majority of memory T cells reside in
tissue sites, including lymphoid tissues, intestines, lungs and skin
What transcription factor promotes the generation of T memory cells
Blimp-1
The number of memory T cells specific for any Ag is ____ than the number of naive cells specific for the same Ag
greater (typically 10-100 fold more than the pool of naive cells)
What cytokines induce the expression of anti-apototic proteins and stimulate low-level proliferation of memory cells
IL-7 and IL-15
memory T cells pass through what three distinct phases
- Memory generation
- memory homeostasis
- immunosenescence
What are the phenotypic markers for memory T cells
- IL-7R
- CD45
- CD27
The central memory T cells (Tcmcells) express the chemokine receptor ____ and _____ and home mainly to
- The central memory T cells (Tcmcells) express the chemokine receptor CCR7 and L-selectin and home mainly to LNs, spleen, and circulate in the blood
- Proliferate (high production of IL-2) and generate many effector cells on Ag challenge
Effector memory T cells (TEMcells) circulate in the blood. They do not proliferate but produce
- IFN-gamma and TNF or become cytotoxic
