T-Cell Development and Selection (Exam III)

Question 1

T cell life cycle

Answer 1

T cell precursors travel from the bone marrow (undifferentiated state) to develop in the thymus (all of selection, and formation of T cell receptor and testing of it).

Mature T cells leave the thymus and travel to secondary lymphoid organs where they can search for the antigen they are specific for

Question 2

Thymic involution

Answer 2

Thymus goes through involution.

0-10 years old, thymus is in its full funciton, but as humans age, the thymus becomes smaller and has less function

Question 3

T cells are called _ while they wait to develop into T cells

Answer 3

thymocytes

Question 4

When stem cells move from the bone marrow to the thymus, they begin their transformation

Answer 4

uncommitted progenitor cell -> double negative thymocyte comitted to the T cell lineage

Question 5

When stem cells enter the thymus

Answer 5

• Express CD34 (stem cell marker) as they enter the thymus, and eventually they downregulate CD34 and begin to upregulate CD2

Early developmental phenotype.

Question 6

CD2 (after CD34)

Answer 6

Adhesion and signaling

CD2 signals that the cell is comitted to the T cell lineage.

Question 7

TCR genes

Answer 7

Antigen receptor

Uncommitted to T cell: germline
Committed to T cell: beginning rearrangement

Question 8

CD4 and CD8 are not expressed, in either

Answer 8

uncommitted stage or the committed stage.

Question 9

T cell selection happens in

Answer 9

the thymus

Question 10

Regions of the thymus

Answer 10

Cortex - very dense

Medulla - less dense

Question 11

region between medulla and cortex

Answer 11

cortico-medullary junction

Question 12

Cortex houses what cells?

Answer 12

• Cortical epithelial cells
• Thymocyte (cells that undergo the selection process)
• Medullary eptithelial cells

Question 13

Thymic epithelial cells perform

Answer 13

positive selection (happens in the cortex)

Question 14

where does positive selection occur

Answer 14

cortex of thymus

Question 15

where does negative selection occur

Answer 15

cortico-meduallar junction region of the thymus

Question 16

cells that mediate negative selection of thymocytes

Answer 16

• Dendritic cells
• Macrophage

Question 17

cortical epithelial cells origin

Answer 17

thymic origin

Question 18

thymocyte origin

Answer 18

bone marrow origin

Question 19

medullary epithelial cell origin

Answer 19

thymic origin

Question 20

dendritic cell origin

Answer 20

bone marrow origin

Question 21

Macrophage origin

Answer 21

bone marrow origin

Question 22

cells that undergo T cell selection

Answer 22

thymoctyes

Question 23

The early development of a;b T cells in the thymus

Answer 23

1. progenitor cells
2. proliferation
3. double (-) T cells commit to T cell lineage
4. Rearrange beta genes
5. CHECKPOINT for pre-TCR
6. proliferating double (-) pre-T cells
7. immature double positive cells rearrange alpha genes
8. CHECKPOINT for TCR
9. mature double positive cells

Question 24

After a productive rearrangement..

Answer 24

First: Positive selection
- Thymic epithelial cells do the selecting (Thymic origin)
- Poor binders eliminated (If the T cell receptor does not bind to MHC, the T cell dies).
- Positive selection is happening when the T cell receptor is able to bind to MHC.
- Region of thymus: Cortex

Opposite in B cells, they first undergo negative selection.

Question 25

Second step after rearrangement

Answer 25

**Negative Seletion** - *Dendritic cells do the selecting* (bone marrow) - Overly strong binders eliminated - Region: **corticomedullary junction**

Question 26

Do gamma/delta cells go through negative or positive selection?

Answer 26

No no regulation of if they bind MHC or too tightly to a cell.

Question 27

What step determines if a a T cell will commit to the CD4 or CD8 phenotype

Answer 27

positive selection

Question 28

If a TCR happens to interact with a MHC class I molecule with reasonable affinity during positive selection

Answer 28

the CD8 molecule will join that interaction and downregulate CD4 and signal the **formation of a CD8 T cell**

Question 29

If a TCR happens to bind MHC class II with reasonable affinity

Answer 29

CD4 joins the interaction and will send a signal to the T cell and upregulating CD4 and downregulate CD8, **becoming a CD4 cell**.

Question 30

during positive selection the T cell goes from being _ to _

Answer 30

double positive to single positive Either CD4/CD8 is upregulated, while the other is downregulated

Question 31

CD4-, CD8- (first step)

Answer 31

Stage in Development: - proliferation and differentation to double positive CD3+ thymocytes Thymocyte location: - double negative CD3- thymocytes in the subcapsular zone

Question 32

CD4+,CD8+ (second step)

Answer 32

Stage in development: **positive selection** Thymocyte location - double positive thymocytes in the thymic cortex

Question 33

CD4+, CD8+ (third step)

Answer 33

Stage in developemnt: - **Negative selection** Thymocyte location and characteristics - Double positive CD3+ thymocytes throughout cortex and especially at the cortico-medullary junction

Question 34

Either CD4+ only or CD8+ only

Answer 34

Stage in development - Entry to circulation Thymocyte location and characteristics - mature self-restricted, self-tolerant, single positive CD4 or CD8 T cells leave the thymus in blood venules