Thymus

Question 1

Where is the thymus located?

Answer 1

In the anterior mediastinum (between the lungs and below the thyroid)

Question 2

What is the general structure of the thymus?

Answer 2

multiple lobules, each with a cortex and medulla that are surrounded by a capsule

Question 3

What 5 cell types make up the thymus?

Answer 3

1. thymocytes (immature T cells)
2. Cortical epithelial cells
3. Dendritic cells
4. Macrophages
5. Epithelio-reticular cells

Question 4

Which two factors mediate the homing of immature T cell precursors to the thymus from the bone marrow

Answer 4

1. alpha 4 integrin

2. CD44

Question 5

Which occurs first? positive or negative selection? what does this involve?

Answer 5

Positive selection (weak recognition of self MHC and peptide) by interacting with cortical epithelial cells

Question 6

What is the order of rearrangement of the TCR chains?

Answer 6

the TCRß chain is rearranged first and then, only if this is successful, the TCR alpha chain can be rearranged

Question 7

What happens at the pre-TCR expression stage?

Answer 7

• Stops TCRb chain locus rearrangement (alleleic exclusion)

* Activates TCRa chain rearrangement •Stimulates proliferation

Question 8

What is the order of gene rearrangement in the TCR alpha and beta chains?

Answer 8

D–>J, then V –> DJ for the ß chain

just V –> J for the alpha chain
- doesn’t have a D region

Question 9

What two things are stimulated with the a/ß TCR is expressed?

Answer 9

1. proliferation

2. CD4 and CD8 expression

Question 10

What do immature thymocytes become after successful rearrangement of their TCR genes? where?

Answer 10

double positive thymocytes

in the cortex

Question 11

What do CD4+/CD8+ thymocytes undergo?

Answer 11

Positive selection

Question 12

What are the two possible outcomes of positive selection?

Answer 12

• Weak binding to self MHC/peptide complex on cortical epithelial cells leads to survival.
• No binding leads to apoptosis.

Question 13

What happens to CD4+/CD8+ thymocytes that survive positive selection?

Answer 13

downregulate expression of either CD4 or CD8 (depending on TCR specificity) and become single positive thymocytes

Question 14

What is being tested for during negative selection?

Answer 14

Strong binding to self MHC/peptide complex on Dendritic cells.

Question 15

What are the two possible outcomes from negative selection?

Answer 15

• Strong binding to self MHC/peptide complex on DC leads to apoptosis.
• Weak or no binding leads to survival and T cell maturation

Question 16

What is the role of cortical epithelial cells in thymocyte maturation? where are they?

Answer 16

Interact with double positive thymocytes in the cortex to mediate positive selection.

Question 17

What is the role of dendritic cells in thymocyte maturation?

Answer 17

• Dendritic cells are located in the thymic medulla.

* They interact with single positive thymocytes and mediate negative selection

Question 18

What is the role of macrophages in thymocyte maturation?

Answer 18

• Phagocytosis of apoptotic thymocytes

Question 19

What is the role of epithelio-reticular cells in thymocyte development? what do they form? what does this prevent?

Answer 19

• Form a continuous cellular layer that lines the capsule and around the blood vessels.
• This is called the blood-thymus barrier.
• This barrier prevents exposure of the immature Thymocytes to blood borne antigens.

Question 20

What are Hassall’s corpuscles?

Answer 20

Epithelial cells that have degenerated and formed concentric eosinophilic whorls of material in the medulla of the thymus

Question 21

Is thymic differentiation based on pos/neg selection model sufficient to explain self tolerant state?

Answer 21

not really no

Question 22

what explains the self tolerant state (in addition to positive and negative selection?

Answer 22

the presence of Treg cells

Question 23

How are Treg cells generated? what is their avidity like?

Answer 23

on the autoreactive side but are still positively selected and induced to become Treg cells

Question 24

What is thymic involution?

Answer 24

a normal process by which the functional parenchyma of the organ is replaced with fat and connective tissue, and the organ as a whole diminishes in size