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immunology final > Chapter 7 Part 1 -- Development of T lymphocytes > Flashcards

Chapter 7 Part 1 -- Development of T lymphocytes Flashcards

1
Q

T cells derive from what precursor

A

common lymphoid precursor

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2
Q

true or false

T cells are similar to B cells in their gene rearrangements

A

true

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3
Q

how many distinct lineages do T cells have? name them

A

2:

a:B T cell
gamma:delta T cell

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4
Q

where does T cell development take place?

A

in the thymus

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5
Q

what are “thymus dependent lymphocytes”?

A

T cells

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6
Q

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

A

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

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7
Q

recap: pluripotent hematopoetic stem cells express ___ ONLY

A

CD34

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8
Q

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

A

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

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9
Q

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

A

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

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10
Q

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

A

travel from the BONE MARROW to develop in the THYMUS

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11
Q

Mature T cells leave the thymus and travel to _____

A

secondary lymphoid tissues

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12
Q

explain the anatomy of the thymus

A

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

located above the heart and between the lungs

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13
Q

the thymus is a ____ lymphoid organ

A

PRIMARY

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14
Q

is the thymus involved in lymphocyte recirculation?

A

no

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15
Q

does the thymus receive lymph from other tissues?

A

no – not connected to the lymphatics

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16
Q

what is located in the CORTEX of the thymus?

A

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

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17
Q

what is located in the MEDULLA of the thymus?

A

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

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18
Q

what are hassall’s corpuscles?

A

concentrically arranged epithelial cells

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19
Q

when in life is the thymus FULLY DEVELOPED?

A

at birth

20
Q

when does the thymus begin to degenerate?

A

1 year after birth

21
Q

what does involution mean

A

shrinkage of an organ with age

22
Q

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

A

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

called the INVOLUTION of the thymus

23
Q

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

A

no

24
Q

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

A

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

25
Q

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

A

IL-7 (cytokine)
and Notch Signaling

26
Q

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

A

~1 week

27
Q

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?

A

DN thymocytes (double negative thymocytes)

because they lack both CD4 and CD8 expression

28
Q

what are DN thymocytes doing?

A

beginning to rearrange their gene segments

29
Q

explain the beginnings of the rearrangements of T cells

A

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

30
Q

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

A

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

31
Q

rearrangements halt while the B chain is incorporated into the Pre T cell receptor.

when do rearrangements begin again?

A

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)

32
Q

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?

A

a pre-T cell

33
Q

failure to make any productive rearrangements results in ___________.

A

apoptosis

these dead cells are cleared by macrophages

34
Q

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

A

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

35
Q

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

A

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

36
Q

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

A

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

37
Q

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

A

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

38
Q

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

A

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

39
Q

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

this complex serves as….

A

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

40
Q

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

A

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

41
Q

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

A

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

42
Q

if the superdimer checkpoint fails, what happens?

A

cell death

43
Q

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

A

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

44
Q

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

A

LARGE PRE T CELL
allelic exclusion

45
Q
A

immunology final (12 decks)

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