Week 4: T Cell Development Part 1

Question 1

Where do T cells derive from?

Answer 1

Common lymphoid progenitors (CLP) in the thymus

Question 2

What is the function of T cells?

Answer 2

1. Recognizes peptide antigens in context of MHCs
2. Involved in adaptive immunity
3. Mediates cellular immunity

Question 3

How are T cells involved in adaptive immune response?

Answer 3

1. Acquired immunity
2. Highly specific
3. Requires an educational process

Question 4

What are the lineages of T cells?

Answer 4

ab T cells (majority) and gd T cells (5%)

Question 5

Describe the development of the thymus?

Answer 5

1. Fully developed at birth
2. 1 year after birth the thymus degenerates and replaced with fat
3. Decreases steadily with age: involution of the thymus

Question 6

Describe the development of T cells?

Answer 6

1. Early T cell precursor (CLP) development occurs in the bone marrow
2. Precursors leave the BM and and travel through the blood to the thymus where they go through selection and educational processes
3. Mature T cells leave the thymus and travel to secondary lymphoid tissues

Question 7

How do progenitor cells differentiate to T cells?

Answer 7

1. Not committed to T lineage when they enter the thymus
2. Interacts with thymus stroll cells, progenitor lose their stem cell surface proteins/receptors and become thymocytes

Question 8

What are thymocytes?

Answer 8

Immature T cells that lack TCR but begin to rearrange their TCR genes (double negative thymocytes DN)

Question 9

What develops a T cell?

Answer 9

Thymus stromal cells produce growth factors and glands that contribute

Question 10

What factors and ligands are released by the thymus stromal cell?

Answer 10

IL-7

Question 11

What is Notch 1?

Answer 11

Receptor of progenitor cell that binds to signals to commit it to T lineage

Question 12

What is IL-7?

Answer 12

Growth factor that is secreted by thymic stromal cells and binds to the IL-7R on T cell progenitors to induce progenitor into DN thymocyte

Question 13

Does the TCR bind to MHC Class 1 and 2 strongly?

Answer 13

No: death
Yes: survive

Question 14

Does he TCR bind with low or high affinity to self-antigen on MHC?

Answer 14

Low: survive
High: death

Question 15

In what ways are T cells screened to make sure TCR is functional?

Answer 15

Checkpoint 1: is b chain functional
Checkpoint 2: is a chain functional

Question 16

Describe the process of gene arrangement of ab T cells?

Answer 16

1. The first rearrangement is b chain, producing a functioning b chain and a surrogate a chain
2. When a b chain is produced, it forms a complex with CD3
3. TCR complex undergoes a chain rearrangement
4. Once complete TCR is formed, the cell expresses both CD4 and CD8 TCR co-receptors and is considered double positive (DP)

Question 17

Where does positive selection occur?

Answer 17

The cortical region of the thymus

Question 18

What is purpose of positive selection?

Answer 18

Ensures MHC restriction

Question 19

What occurs during positive selection?

Answer 19

1. DP T cells interact with cortical epithelial cells that have both MHC class 1 and 2 molecules
2. If the DP TCR binds to the MHC, then it is positively selected
3. if the DP TCR is unable to bind to MHC, the cell undergoes apoptosis

Question 20

What happens to thymocytes that are positively selected?

Answer 20

Induced to become single positive T cells (SP)

Question 21

Describe the difference between DP cells binding to MHC class 1 and 2?

Answer 21

1: Induction to become CD8+ cytotoxic T cell
2: Induction to become CD4+ helper T cell

Question 22

Where does negative selection occur?

Answer 22

Medular region of the thymus

Question 23

What occurs during negative selection?

Answer 23

1. DP cells progress to SP
2. Eliminates potentially harmful thymocytes that have high affinity TCRs for self peptides

Question 24

What can undergo negative selection?

Answer 24

1. Interaction of positively selected thymocyte with epithelial cells, macrophages, and DCs that present self-antigen
2. Only thymocytes whose TCR have low affinity for MHC molecules on APCs are selected

Question 25

What is a self-antigen?

Answer 25

Antigen that comes from dead cells that are phagocytized from the thymus

Question 26

What happens in TCR binding affinity of the thymocyte is high with MHC?

Answer 26

Cell will die

Question 27

What is the purpose of negative selection?

Answer 27

Eliminates thymocytes that react of self antigen

Question 28

What are naive mature T cells?

Answer 28

Have not been activated by their antigen

Question 29

How can naive T cells encounter their antigen?

Answer 29

Circulates thought the blood to the secondary lymphoid tissues and lymph

Question 30

What are effector T cells?

Answer 30

When naive T cells encounter antigens is will divide and differentiate

Question 31

Where are effector T cells located?

Answer 31

Secondary tissue or migrate to site of infection