CHP 5 - T Cell development Flashcards

1
Q

What are the major roles of the thymus in T cell developement?

A

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

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2
Q

Which cells are essential to the selection events requires to ensure tolerance and prevent T cell autoreactivity?

A

Thymic Cells

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3
Q

A thymocyte is

A

immature T cell

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4
Q

In which region of the thymus do thymocytes undergo developmental steps to ensure proper TCR expression?

A

Cortex

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5
Q

In which region of the thymus do thymocytes undergo negative selection and finish their development into naive T-cells?

A

Medulla

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6
Q

What does a double negative (DN) thymocyte mean?

A

Do not express T cell receptors (CD8 or CD4)

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7
Q

What does double positive (DP) thymocyte mean?

A

Express both T cell receptors CD8 and CD4

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8
Q

DN thymocytes interact with ___________________ to begin their development into T cells.

A

cortical thymic epithelial cells (cTECs)

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9
Q

In which region of the thymus are thymocytes tested for self-reactivity by medullary thymic epithelial cells (mTECs)?

A

Medulla

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10
Q

Which cells are responsible for the development of thymocytes into naive T cells?

A

1) Thymic epithelial cells
2) Macrophages
3) Dendritic cells
4) Medulla

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11
Q

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?

A

Thymic epithelial cells

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12
Q

What is the role of macrophages in the thymus?

A

Removal thymocytes that did not develop properly and undergoing apoptosis

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13
Q

What signals do lymphoid progenitors must receive to commit to the T cell lineage?

A

Notch signaling and IL7 secreted by thymic epithelial cells

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14
Q

Once Notch 1 is released what happens next?

A

Notch1 intracellular domain translocate to the nucleus to initiate transcription of genes necessary for development into T cells – Change in gene expression

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15
Q

In which region of the thymus are DN thymocytes typically found?

A

Cortex

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16
Q

Rearrangement of T cell receptor loci begins at the ________________ genes.

A

Beta, gamma, and delta

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17
Q

Why are gamma delta T cells important?

A

1) protects fetus during development
2) in adults it plays a role in protecting mucosal surfaces

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18
Q

How many productive B chain rearrangements possibilities are there?

19
Q

Recombination of the alpha chain locus occurs once which checkpoint is passed?

A

B chain checkpoint

20
Q

T/F: cTECs can express both MHC class I and MHC class II molecules

21
Q

Selection process that is based on the affinity of the T cell receptor for the MHC peptide complexes

A

Positive selection

22
Q

T/F: epigenetics and transcriptional controls play a role in T cell lineage commitment

23
Q

What are the two current models that explain how T cell lineage commitment occurs?

A

1) Instructive Model
2) Kinetic Signaling

24
Q

The instructive model for T cell lineage commitment states?

A

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

25
In the instructive model, when TCR engages with MHC II presenting a peptide. What occurs?
CD4 coreceptor will engage = prevention of CD8 expression
26
In the instructive model, when TCR engages with MHC I presenting a peptide. What occurs?
Interaction promotes CD8 = shut down of CD4 expression
27
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
28
Kinetic signaling model states that cytokine IL-7 drives T cells to which lineage?
CD8
29
Regarding the kinetic signaling model, positively selected thymocytes will become CD8+ if the signal is ______________.
Weak/interrupted
30
Regarding the kinetic signaling model, positively selected thymocytes will become CD4+ if the T cell receptor signal is _____________.
Continuous
31
Where does negative selection occur?
Thymic medulla
32
Where is central tolerance driven?
Thymic medulla
33
Negative selection occurs in primary lymphoid tissues and is responsible for the removal of?
Self-reactive lymphocytes
34
What transcriptional activator allows for mTECS to express genes not normally expressed by epithelial cells of the thymus?
AIRE
35
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
36
Which cells are able to present tissue specific antigens via MHC class II?
Medullary thymic dendritic cells
37
Which cells active a subset of thymocytes to develop into T cells?
Dendritic cells in the thymic medulla
38
In order for thymocytes to develop into regulatory T cells they must express transcription factor?
FOXP3
39
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
40
Which cells are responsible for peripheral tolerance?
natural regulatory T cells (nTregs)
41
What is the purpose of nTregs?
Promotor peripheral tolenrance
42
Which protein expressed by mTECs triggers thymic dendritic cells to activate a subset of thymocytes into nTregs?
Thymic Stromal lymphopoietin protein (TSLP)
43
Which cells express TSLP?
Medullary thymic epithelial cells