Exam 2 - German - T Cell Development

Question 1

Tell me the overall life cycle of a T cell.

Answer 1

T-cell progenitors develop in the bone marrow and migrate to the thymus

Positive and negative selection happens in the thymus - Immature T cells that interact strongly with self antigen are removed from the repertoire

Mature T cells migrate to the peripheral lymphoid organs - Foreign antigens in periphery are detected and T cells are activated

Activated T cells migrate to sites of infection - Activated T cells proliferate and eliminate infection

Question 2

What are thymocytes?

Answer 2

Developing T cells w/in the thymus

Question 3

Gamma-delta T cells do what? 3 things.

Answer 3

Maintain tissue integrity

Do not express CD4 or CD4 co-receptors

Interact with NON-CLASSICAL receptors

Question 4

CD4 T cells do what?

Answer 4

Helper T cells

Several subtypes: TH1, TH2, TH17, TFH, Treg

Regulate adaptive and innate immune function

INTERACT WITH MHC CLASS II

Question 5

What do CD8 T cells do?

Answer 5

Cytotoxic T cells

Direct effector fx

INTERACT WITH MHC CLASS I

Question 6

In what organ does a lot of T cell development occur?

Answer 6

THYMUS

Question 7

W/in the thymus, T cells go where first?

Answer 7

Cortical epi cells (Cortex)

Question 8

Where do developing thymocytes move after the cortex?

Answer 8

To the medulla (Medullary epi cells)

*Selections take place here

**Once it leaves the thymus, it is now a mature, naive T cell

Question 9

T/F - Thymus involuted with age.

Answer 9

TRUE

Reduced T cell production

Question 10

The thymus involutes, yet T cell-mediated immunity is not grossly affected. Why?

Answer 10

T CELLS HAVE LONG HALF LIVES

CD4 - 4.2 years
CD8 - 6.5 years

*Keep in mind that those are half-lives. Meaning that half of all the CD4 dies w/in 4.2 years. The other half persists even still

Question 11

T cell progenitors don’t commit until they reach the _________.

Answer 11

Thymus

Question 12

What two molecules are important leaders for T cell development?

Answer 12

IL-7 receptor - CD127

Notch1 - T cell transcription factor complex

Question 13

What is the first TCR chain that is rearranged?

Answer 13

BETA chain

Question 14

T/F - The gamma and the delta chains can rearrange at the same time that the beta chain rearranges.

Answer 14

TRUE

Question 15

If the gamma and delta chains rearrange successfully, then what occurs?

Answer 15

The T cell will become a gamma-delta T cell

Question 16

If the alpha chain rearranges successfully, what happens?

Answer 16

The T cell becomes an alpha-beta T cell

Question 17

The ______ chain is similar to the ________ chain in B cell development.

Answer 17

Beta

Heavy

Question 18

What is the first checkpoint in T cell development?

Answer 18

The beta chain interacting with a “surrogate alpha” chain

Question 19

When do CD4 and CD8 begin their expression?

Answer 19

When the gene rearrangement occurs after the first checkpoint has been passed.

Question 20

Up until right after the first checkpoint and pre-T cells are proliferating, what is that section called?

Answer 20

Double-negative

Question 21

The double-positive region includes what?

Answer 21

Alpha, delta, and gamma rearrangement and the second checkpoint

Positive and Negative selection happen here as well

Question 22

Tell me the route that T cell progenitor cells take in the thymus.

Answer 22

Proliferates in the medulla

Double-negative T cells commit to T lineage in cortex

Rearrange beta genes in the cortex

Hit first checkpoint in the medulla and proliferating double-negative pre-T cells

Immature double-positive cells and rearrangement of alpha genes and hit second checkpoint in the cortex

Question 23

T/F - Gene rearrangement dictates T cell lineage.

Answer 23

TRUE

Question 24

T/F - There is a greater likelihood that 1 chain will rearrange instead of 2 chains.

Answer 24

TRUE

Question 25

Tell me the rough idea about rearrangement.

Answer 25

Beta, gamma, delta genes re-arrange first

Gamma or delta rearrangement suppresses beta and alpha

Gamma-delta T cells leave the thymus with little selection

Beta chain production drives CD4 and CD8 expression
-Double-positive

Question 26

What initiates the alpha-beta lineage?

Answer 26

Beta-chain formation

Question 27

1st - V-D-J —> ??

2nd - V-DJ —> ??

Answer 27

V-DJ

VDJ

Question 28

When the beta-chain binds a surrogate alpha chain what assembles to help stabilize the complex?

Answer 28

CD3 complex

*Signaling drives further development
—RAG fx halts
—Proliferation happens

Question 29

Alpha-chain rearrangement excludes what?

Answer 29

Gamma-delta T cells

Question 30

T/F - Double negative thymocytes, no CD4 or CD8, but double positive thymocytes, both CD4 and CD8.

Answer 30

TRUE

Question 31

______ and ________ _________ matures thymocytes.

Answer 31

Positive

Negative

Selection

Question 32

Positive selection = ?

Answer 32

Functional TCR

Question 33

Negative selection = ?

Answer 33

No self-antigen binding

Question 34

What is the process of positive selection?

Answer 34

A cortical epithelial cell in the thymus presents self-peptide to alpha:beta cells.

If the T cell does NOT bind MHC, it will NOT get a survival signal, and it dies.

If the T cell DOES bind MHC, it does get a survival signal and it lives

—Cells have about 3 days to bind MHC or else they will die. Cells can also go back and rearrange the alpha chain and try to re-bind
—Binding turns off RAG 1/2 complex

Question 35

Positive selection determines what?

Answer 35

CD4 or CD8 expression

This occurs 1st in T cell development, but 2nd in B cell development

Question 36

Explain negative selection.

Answer 36

Dendritic cells and macrophages present self peptides

If tight binding, cell dies

If moderate binding, cell lives

This is central tolerance

*Following this, naive mature T cells can still undergo differentiation (e.g. CD4 subtypes)

Question 37

How do naive T cells enter a draining lymph node? 2 ways

Answer 37

In the blood

In the afferent lymph from an upstream lymph node