Activation Of T Lymphocytes Flashcards
Activated T cells differentiate into effector cells. What are the two fates of the effector cells?
Remain in the lymphoid organs to help B lymphocytes
Migrate to sites of infection to help activate macrophages.
What cytokine is secreted as Ags are recognized by T cells?
IL-2.
This results in clonal expansion as a result of proliferation and differentiation of the T cells into effector or memory cells.
How do effector CD4 T cells respond to Ags?
They produce cytokines that have several actions, such as the recruitment and activation of leukocytes and activation of B cells.
What is the function of effector CD8 CTLs?
They kill infected and altered host cells.
What three things ocur when Ag recognition and other activating stimuli induce responses in T cells?
Secretion of cytokines
Proliferation (clonal expansion)
Differentiation into effector and memory cells.
What are the functions of effector T cells?
To perform functions that are responsible for the elimination of microbes, and in disease states, for tissue damage.
What occurs to T cell responses after the Ag is eliminated?
T cell responses decline.
What are the three signals needed for the proliferation of T lymphocytes and their differentiation into effector and memory cells?
Ag recognition
Costimulation
Cytokines
What is required for the activation of naive T cells?
Ag presented by DCs.
The effector T cells can recognize Ags presented by tissue macrophages and B cells.
What results from the activation of PLC1?
The production of IP3 and DAG.
What occurs from the production of IP3?
Increases of cytosolic free calcium
What does T cell receptor signaling overall result in?
The activation of Ras and MAPK, which activate transcription factors such as NFAT and NF-KB.
What do superantigens bind to?
To MHC class II molecules and the V region of the beta subunit of the TCR.
What occurs to T cells upon superantigen acitvation?
T cells produce massive amounts of cytokines which may lead to shock.
How do superantigens (SAgs) bind to TCR?
Via the variable region of the beta chain.
When activated APCs are present, what is there increased expression of?
Costimulators, as well as the secretion of cytokine IL-2
What are the three signals required in costimulation in T cell activation?
Ag recognition
Inflammation and activation of costimulators (B7)
Production of cytokiens of IL-12
What results from increased secretion of IL-2 or expression of IL-2R?
Cell proliferation
What is the best characterized costimulatory pathway in T cell activation?
T cell surface receptor CD 28, which binds co stimulatory molecules B7-1 and B7-2 (CD80 and CD86).
These are expressed on activated APCs
What is the function of B7 costimulators?
It ensures that T lymphocyte responses are initiated only wheen needed.
What is the result of CD28 and Ag recognition?
The survival, proliferation and differentiation of specific T cells.
How is T cell activation influenced?
It is influenced by a balance between engagement of activating and inhibitory receptors of the CD28 family.
What is the result of CD28 and B7-1?
Costimulationof naive T cells; generation of regulatory T cells.
What is the function of B7-2 and CTLA-4?
Negative regulation of immune responses; self-tolerance
Where are B7-1 and B7-2 found?
DCs, macrophages and B cells.
Where are CD28, CTLA-4, iCOS and PD-1 found?
On T cells
What is the function of iCOS?
Costimulatio nof effector and regulatory T cells; generation of follicular helper T cells.
What is the function of CD274 and CD273 & PD-1?
Negative regulation of T cells.
When is CTLA4-mediated immune checkpoint induced in naive T cells?
At the time of their initial response to Ag.
True or false: naive memory T cells express high levels of cell surface CD28 but do not express CTLA4 which is stored in intracellular vesicles.
True
After a TCR is triggered by an AG encounter, where is CTLA4 transported to?
The cell surface
The stronger the stimulation through the TCR (and CD28), the ____ the amount of CTLA4 that is deposited on the T cell surface.
Greater.
Therefore, CTLA4 functions as a signal dampener to maintain a consistent level of T cell activation.
What is the major role of the programmed cell death protein 1 (PD1 pathway)?
To regulate inflammatory responses in tissues by effector T cells recognizing Ag in peripheral tissues.
What do activated T cells upregulate?
PD1
What do inflammatory signals in the tissue induce?
The expression of PD1 ligands.
What is the function of PD1L?
It downregulates the activity of T cells and thus limits collateral tissue damage in response to a microorganism infection in that tissue.
What occur when there is excessive induction of PD1 on T cells?
It can induce an exhaused or anergic state in T cells.
What is the primary function of IL-2?
It is a survival signal.
What are functions of IL-2?
Autocrine growth factor for CD4+ and CD8+ T cells
Potentiates cytotoxicity of NK cells and CD8+ T cells.
Costimulates T cells to produce IL-4, IL-5, and IFN-gamma
Promotes the development of regulatory T cells.
Induces an autocrine activation-induced death in T cells.
What cytokine induces the anti-apoptotic protein Bcl-2?
Il-2
True or false: no other cytokine can replace IL-2 for the maintenance of functional Treg cells.
True
What is another term for IL-2R alpha?
CD25
What is the function of CD69?
It binds to and reduces surface expression of 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.
When is a period in which CD6 expression decreases?
After cel division.
What is the result of the expression of S1PR1?
Effector and memory cells can exit lymphoid organs.
What does CD28 bind to on an APC?
A costimulator (B7)
This causes the expression of IL-2R alpha
What does Ag recognition induce?
The expression of CD40 ligand on the activated T cells.
What is the function of CD40L?
It enables activated T cells to help DCs, macrophages and B cells to become better APCs.
What is the function of CTLA-4?
It functions as an inhibitor of T cell activation and thus as a regulator of the response.
Elimination of Ag leads to __ of T cell response.
Contraction
What occurs as levels of costimulation and IL-2 decrease?
The levels of anti-apoptotic proteins in the cells drop.
IL-2 starvation triggers the mitochondrial pathway of apoptosis.
What regulatory mechanisms contribute to the normal contraction of immune responses?
CTLA4 and PD-1
Apoptosis induced by TNFRI and Fas
Treg cells
According to the linear model of memory T cell differentiation:
Most effector cells die
Some survivors develop into the memory cells.
According to the branched differentiation model:
Effector and memory cells are alternative fates of activated T cells.
How long to memory cells specific for Ags last?
Years or even a lifetime.
What cells constitute the most abundant lymphocyte population in the body for the majority of a person’s lifetime?
Memory T cells.
Where do the vast majority of memory T cells reside?
In tissue sites, including lymphoid tissues, intestines, lungs and skin.
What is the role of T-bet?
It drives the differentiation of effector cells in CD4+ T cells.
What does Blimp-1 promote the generation of?
Memory cells
What are three major properties of memory cells?
They can remain dormant without an Ag.
They mount larger enhanced responses to Ag than do naive cells.
The number of memory T cells specific for any Ag is greater than the number of naive cells specific for the same Ag
True or false: memory cells are able to migrate to peripheral tissues and respond to Ag at the sites.
True
Memory cells undergo slow ___ that may contribute to the long life span of the memory pool.
Self-renewing
The maintenance of memory cells is dependent on ____ but does not require Ag presence.
Cytokines
What cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation?
IL-7 and IL-15
What three distinct phases to memory T cells pass through?
Memory generation
Memory homeostasis
Immunosenescence
What are phenotypic markers for memory T cells?
IL-7R
CD45
CD27
What do central memory T cells express, and where do they home to?
They express CCR7 and L-selectin and home mainly to LNs, spleen and circulate in the blood.
Where do effector memory T cells proliferate, and what do they produce?
IFN-gamma dn TNF or become cytotoxic.
What are resident tissue memory T cells?
T cells that reside in epithelial barrier tissues at the interface between the host and the environment.
What do resident tissue memory T cells produce?
IFN-gamma and TNF.
They are specific for pathogens and other Ags that have been encountered previously through that barrier epithelium.
When does activation of naive T cell occur in the lymph nodes?
Activation occurs if they encounter TCR specific Ags.
