CHP 5 - T Cell development Flashcards
What are the major roles of the thymus in T cell developement?
1) signal T cells to develop and mature, and go through positive and negative selection
Positive selection: T cell ability to recognize MHC peptide complexes
Negative selection: T cell self tolerance ability
Which cells are essential to the selection events requires to ensure tolerance and prevent T cell autoreactivity?
Thymic Cells
A thymocyte is
immature T cell
In which region of the thymus do thymocytes undergo developmental steps to ensure proper TCR expression?
Cortex
In which region of the thymus do thymocytes undergo negative selection and finish their development into naive T-cells?
Medulla
What does a double negative (DN) thymocyte mean?
Do not express T cell receptors (CD8 or CD4)
What does double positive (DP) thymocyte mean?
Express both T cell receptors CD8 and CD4
DN thymocytes interact with ___________________ to begin their development into T cells.
cortical thymic epithelial cells (cTECs)
In which region of the thymus are thymocytes tested for self-reactivity by medullary thymic epithelial cells (mTECs)?
Medulla
Which cells are responsible for the development of thymocytes into naive T cells?
1) Thymic epithelial cells
2) Macrophages
3) Dendritic cells
4) Medulla
Which cell in the thymus plays a major role in activating genes required for development in their maturation. As well as several key developmental checkpoints of thymocyte differentiation?
Thymic epithelial cells
What is the role of macrophages in the thymus?
Removal thymocytes that did not develop properly and undergoing apoptosis
What signals do lymphoid progenitors must receive to commit to the T cell lineage?
Notch signaling and IL7 secreted by thymic epithelial cells
Once Notch 1 is released what happens next?
Notch1 intracellular domain translocate to the nucleus to initiate transcription of genes necessary for development into T cells – Change in gene expression
In which region of the thymus are DN thymocytes typically found?
Cortex
Rearrangement of T cell receptor loci begins at the ________________ genes.
Beta, gamma, and delta
Why are gamma delta T cells important?
1) protects fetus during development
2) in adults it plays a role in protecting mucosal surfaces
How many productive B chain rearrangements possibilities are there?
Four
Recombination of the alpha chain locus occurs once which checkpoint is passed?
B chain checkpoint
T/F: cTECs can express both MHC class I and MHC class II molecules
True
Selection process that is based on the affinity of the T cell receptor for the MHC peptide complexes
Positive selection
T/F: epigenetics and transcriptional controls play a role in T cell lineage commitment
True
What are the two current models that explain how T cell lineage commitment occurs?
1) Instructive Model
2) Kinetic Signaling
The instructive model for T cell lineage commitment states?
The MHC molecule type with an antigen, TCR engages with is the type of T cell lineage it will commit too
1) TCR engages with MHC 1 with peptide = promotes CD8 interaction = shut down of CD4
2) TCR engages with MHC 2 with peptide = CD4 engagement = prevention of CD8 expression
In the instructive model, when TCR engages with MHC II presenting a peptide. What occurs?
CD4 coreceptor will engage = prevention of CD8 expression
In the instructive model, when TCR engages with MHC I presenting a peptide. What occurs?
Interaction promotes CD8 = shut down of CD4 expression
What does the kinetic signaling model of T cell lineage commitment state?
Strong continuous signaling events drive CD4 expression, weaker/interrupted signaling events can drive CD8 expression
Kinetic signaling model states that cytokine IL-7 drives T cells to which lineage?
CD8
Regarding the kinetic signaling model, positively selected thymocytes will become CD8+ if the signal is ______________.
Weak/interrupted
Regarding the kinetic signaling model, positively selected thymocytes will become CD4+ if the T cell receptor signal is _____________.
Continuous
Where does negative selection occur?
Thymic medulla
Where is central tolerance driven?
Thymic medulla
Negative selection occurs in primary lymphoid tissues and is responsible for the removal of?
Self-reactive lymphocytes
What transcriptional activator allows for mTECS to express genes not normally expressed by epithelial cells of the thymus?
AIRE
Why is AIRE important?
is an autoimmune regulator that allows mTECS to express and expose thymocytes to different self molecules, further intensifying the negative selection process
Which cells are able to present tissue specific antigens via MHC class II?
Medullary thymic dendritic cells
Which cells active a subset of thymocytes to develop into T cells?
Dendritic cells in the thymic medulla
In order for thymocytes to develop into regulatory T cells they must express transcription factor?
FOXP3
The development of natural regulatory T cells (nTregs) derive from with T cell lineage and must express transcription factor?
CD4+ T cell that expresses FOXP3
Which cells are responsible for peripheral tolerance?
natural regulatory T cells (nTregs)
What is the purpose of nTregs?
Promotor peripheral tolenrance
Which protein expressed by mTECs triggers thymic dendritic cells to activate a subset of thymocytes into nTregs?
Thymic Stromal lymphopoietin protein (TSLP)
Which cells express TSLP?
Medullary thymic epithelial cells
