Chapter 7 Part 1 -- Development of T lymphocytes

Question 1

T cells derive from what precursor

Answer 1

common lymphoid precursor

Question 2

true or false

T cells are similar to B cells in their gene rearrangements

Answer 2

true

Question 3

how many distinct lineages do T cells have? name them

Answer 3

2:

a:B T cell
gamma:delta T cell

Question 4

where does T cell development take place?

Answer 4

in the thymus

Question 5

what are “thymus dependent lymphocytes”?

Answer 5

T cells

Question 6

future T cells leave the bone marrow as ___ and travel through circulation to the _____

Answer 6

future T cells leave the bone marrow as UNCOMITTED STEM CELLS (cd34+ precursors)and travel through circulation to the THYMUS

Question 7

recap: pluripotent hematopoetic stem cells express ___ ONLY

Answer 7

CD34

Question 8

CD34+ precursors (hematopoetic stem cell precursors) enter the thymus where?

Answer 8

enter the thymus at the border of the cortex and medulla through the HEV (high endothelial venule)

Question 9

CD34+ precursors that have entered the thymus go where in the thymus?

Answer 9

they become embedded in stromal cells in the epithelium of the thymus

Question 10

T cell precursors travel from the ____ to develop in the _____

Answer 10

travel from the BONE MARROW to develop in the THYMUS

Question 11

Mature T cells leave the thymus and travel to _____

Answer 11

secondary lymphoid tissues

Question 12

explain the anatomy of the thymus

Answer 12

has a right lobe and a left lobe, septa, and a lobule.

located above the heart and between the lungs

Question 13

the thymus is a ____ lymphoid organ

Answer 13

PRIMARY

Question 14

is the thymus involved in lymphocyte recirculation?

Answer 14

no

Question 15

does the thymus receive lymph from other tissues?

Answer 15

no – not connected to the lymphatics

Question 16

what is located in the CORTEX of the thymus?

Answer 16

-immature T cells (called thymocytes)
-cortical epithelial cells
-macrophages

Question 17

what is located in the MEDULLA of the thymus?

Answer 17

-mature thymocytes
-medullary epithelial cells
-dendritic cells
-macrophages
-Hassall’s corpuscles

Question 18

what are hassall’s corpuscles?

Answer 18

concentrically arranged epithelial cells

Question 19

when in life is the thymus FULLY DEVELOPED?

Answer 19

at birth

Question 20

when does the thymus begin to degenerate?

Answer 20

1 year after birth

Question 21

what does involution mean

Answer 21

shrinkage of an organ with age

Question 22

The thymus begins to degenerate 1 year after birth.
explain how this happens

Answer 22

the thymocyte area (immature T cells in the cortex) is replaced by fat

called the INVOLUTION of the thymus

Question 23

does the reduction of functional thymus making T cells, or loss of the thymus in adults (thymectomy) affect T-cell mediated immunity?

Answer 23

no

Question 24

upon entering the thymus, what happens to T cell precursors?

Answer 24

T cell precursors contact stromal epithelial cells within the thymus.
this provides signals for proliferation and differentiation

Question 25

the commitment of T cell precursors to T cell lineage is driven by......

Answer 25

IL-7 (cytokine) and Notch Signaling

Question 26

after how long in the thymus do T cell precursors have a commitment to T cell lineage?

Answer 26

~1 week

Question 27

what is the term for those T cell precursors that have spent ~1 week in the thymus and are now committed to T cell lineage?

Answer 27

DN thymocytes (double negative thymocytes) because they lack both CD4 and CD8 expression

Question 28

what are DN thymocytes doing?

Answer 28

beginning to rearrange their gene segments

Question 29

explain the beginnings of the rearrangements of T cells

Answer 29

Begin CONCURRENTLY at gamma, delta, and beta loci. NO RESTRICTION to a particular locus

Question 30

how is it determined if gamma:delta is made or alpha:beta is made?

Answer 30

a RACE to make productive rearrangements. if gamma and delta chains are made first, the T cell is committed to gamma:delta T cell if B chain is produced first, STILL NOT COMMITTED. the Beta chain is incorporated into the Pre T cell receptor. rearrangements halt and proliferation begins. CD4 and CD8 are expressed. Called DP THYMOCYTES (double positive) bc both CD4 and CD8 are expressed

Question 31

rearrangements halt while the B chain is incorporated into the Pre T cell receptor. when do rearrangements begin again?

Answer 31

at the DP thymocyte stage. rearrangement of alpha chain genes is now allowed, and rearrangement at gamma and delta chain genes also continues. if a:B TCR is produced first, the cell commits to a:B lineage as a committed a:B T cell (PRE T CELL)

Question 32

IF a:B TCR is produced first, the cell commits to a:B lineage as a committed a:B T cell. what is the term for this cell?

Answer 32

a pre-T cell

Question 33

failure to make any productive rearrangements results in ___________.

Answer 33

apoptosis these dead cells are cleared by macrophages

Question 34

is there a lot to "clean up" due to the apoptosis of cells with unproductive rearrangements? explain

Answer 34

YES there is a lot for the macrophages to clean up. this is so bc only around 2% of thymocytes ultimately survive

Question 35

explain the differences in the paths of double negative T cells.

Answer 35

double negative T cell undergoes a RACE to make productive rearrangements. if gamma: delta chain genes rearrange, a gamma:delta receptor assembles. this receptor signals to STOP FURTHER REARRANGEMENTS and is COMMITTED to gamma:delta lineage. the gamma:delta T cell then matures, leaves the thymus, and migrates to the peripheral tissues if the Beta chain gene rearranges first, it is not yet fully committed to alpha:beta lineage. A pre T cell receptor assembles, which signals to STOP REARRANGEMENT and induce the proliferation and expression of CD4 and CD8 (double positive thymocyte) the Pre-T cell then resumes rearrangement of ALPHA, gamma, and delta genes. Race to see which it will be

Question 36

in double negative thymocyte rearrangement, either ___ or ____ will be produced

Answer 36

pre gamma:delta T cell receptor or pre-T cell receptor (if beta rearranges first)

Question 37

explain what happens if the Double Negative thymocyte rearranges gamma and delta first

Answer 37

the gamma and delta chains are produced and assemble with CD3/Zeta chain signaling complex that gets moved to the cell surface and signals to STOP BETA CHAIN REARRANGEMENT. fully committed to gamma:delta T cell lineage. the fully mature gamma:delta T cell exits the thymus and enters circulation

Question 38

Explain what happens if the double negative thymocyte rearranges the beta chain first

Answer 38

the Beta chain is produced and moved to the ER. there, it is tested for its ability to bind SURROGATE ALPHA CHAIN (called PTa(lpha) -- it's an invariant peptide. if the binding is successful, the complex will assemble with CD3/zeta chain signaling complex to form a PRE-T CELL RECEPTOR Pre-T cell receptor consists of: -2 beta chains and 2 pta molecules. called a SUPERDIMER

Question 39

the pre-T cell receptor consists of 2 beta chains and 2 pta molecules. It is called a superdimer. this complex serves as....

Answer 39

a stringent TEST of beta chain conformation and its capacity to form a T-cell receptor.

Question 40

the super dimer (2 beta chains and 2 pta molecules) bonding sends signals to do what?

Answer 40

the binding of the superdimer sends signals to halt gene segment rearrangements

Question 41

the formation of the superdimer is a CHECKPOINT. if the checkpoint is successfully passed, what happens?

Answer 41

a pre-T cell receptor forms. (2 beta chains + 2 pta molecules + CD3/Zeta chain signaling complex)

Question 42

if the superdimer checkpoint fails, what happens?

Answer 42

cell death

Question 43

productive rearrangements favor which chain fate? why? give the approximate success rate

Answer 43

beta chain -there are TWO constant regions in the Beta locus. enables successive rearrangements -2 loci on homologous chromosomes 4 total chances to rearrange Beta chin ~80% success rate

Question 44

the successful assembly of a pre-T cell receptor produces a.... this process is governed by...

Answer 44

LARGE PRE T CELL allelic exclusion