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**Host and Defense > T cell Development > Flashcards

T cell Development Flashcards

1
Q

What are the steps in the life of a T cell?

A
  1. T cell progenitors develop in the bone marrow and migrate to the thymus
  2. Positive and negative selection in the thymus
  3. Mature T cells migrate to the peripheral lymphoid organs
  4. Active T cells migrate to sites of infection
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2
Q

What are Thymocytes?

A

Developing T cells within the thymus

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3
Q

Which type of T cells maintain Tissue Integrity?

A

gamma:delta T cells

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4
Q

Which type of T cell does not express CD8 or CD4 co-receptors?

A

Gamma:delta T cells

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5
Q

Which type of T cells interact with non-classical receptors?

A

gamma:delta T cells

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6
Q

Which type of T cells are considered Helper T cells?

A

CD4

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7
Q

What are the subtypes of a CD4 cell?

A
  • Th1
  • Th2
  • Th17
  • Tfh
  • Treg
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8
Q

Which type of T cells regulate adaptive and innate immune function?

A

CD4 T cells

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9
Q

Which T cells are cytotoxic?

A

CD8 T cells

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10
Q

Which T cells have a direct effector function?

A

CD8 cells

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11
Q

What is the site of all T cell development?

A

Thymus

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12
Q

Selection of T cells happens as thymocytes move from ______ to ______ in the thymus.

A
  1. Cortex

2. Medulla

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13
Q

TCR development happens where?

A

Cortex of Thymus

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14
Q

What happens to the T cell production of the thymus with age?

A

It is reduced

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15
Q

T/F T cells have long half lives

A

True

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16
Q

What is the half life of a CD4 T cell?

A

4.2 years

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17
Q

What is the half life of a CD8 T cell?

A

6.5 years

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18
Q

T/F with the reduction of T cell production, T-cell mediated immunity is also greatly diminished

A

False, T cell-mediated immunity is not grossly affected

*probably because of the long half life

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19
Q

What is Notch1?

A

T cell transcription factor complex

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20
Q

What is Pax-5?

A

B cell transcription factor

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21
Q

T cell progenitors don’t commit until they reach what?

A

The thymus

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22
Q

When is the first checkpoint in T cell development?

A

Pre-T cell

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23
Q

When is the second checkpoint in T cell development?

A

Positive and Negative selection

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24
Q

Thymic location influences ________

A

T cell development

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25
Q

What dictates T cell lineage?

A

Gene rearrangement

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26
Q

What genes rearrange first?

A

Beta, Gamma, and Delta

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27
Q

T/F Gamma or Delta rearrangement enhances Beta and Alpha

A

False, is suppresses Beta and Alpha

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28
Q

Which T cells leave the thymus with little selection?

A

Gamma:Delta T cells

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29
Q

Beta chain production drives _________

A

CD4 and CD8 expression

*Double Positive

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30
Q

What would initiate an alpha:beta lineage?

A

B chain formation

31
Q

Between Alpha and Beta, which chain is rearranged first?

32
Q

How many attempts can be made to achieve a productive rearrangement of the Beta chain?

A

4 attempts

- Two attempts per locus
- Two genes
33
Q

What is the order of rearrangement on the Beta chain?

A

1st: Vb-Db-Jb -> Vb-DJb
2nd: Vb-DJb -> VDJb

34
Q

T/F Beta chain locus is organized similar to immunoglobulin chains

A

False, it is organized differently

35
Q

Alpha chain rearrangement occurs in _________

A

Pre-T cells

36
Q

Alpha chain rearrangement follows what?

A

Proliferation and CD4/8 expression

37
Q

Just before alpha chain rearrangement, what is still a possible fate for this cell?

A

May still develop into gamma:delta T cells

38
Q

Once you have had Alpha chain rearrangement what is no longer possible?

A

gamma:delta T cells

39
Q

What purpose does Positive selection serve?

A

Selects for a functional T cell receptor

40
Q

What purpose does Negative Selection serve?

A

Ensures no self-antigen binding

41
Q

Within T cell development, what are the stages in development for a mature double-positive cell?

A
  1. Poliferation and differentiation to double-positive CD3+ thymocytes
  2. Positive Selection
  3. Negative selectdion
  4. Entry to the circulation
42
Q

What are the thymocyte location and characteristics at the time of proliferation and differentiation to double positive CD3+ thymocytes?

A

Double-negative CD3- thymocytes in the subcapsular zone

43
Q

Describe thymocyte location and characteristics at the time of positive selection

A

Double-positive CD3+ thymocytes in the thymic cortex

44
Q

Describe Thymocyte location and characteristics during negative selection

A

Double-positive CD3+ thymocytes throughout cortex and especially at the cortico-medullary junction

45
Q

Describe thymocyte location and characteristics as they enter the circulation

A

Mature self-restricted, self-tolerant, single-positive CD4 or CD8 T cells leave the thymus in blood venules

46
Q

Positive selection ensures _____ is bound

47
Q

Positive Selection of alpha:beta T cells is done by _______ in the ________-

A
  1. Corical epithelial cells

2. Thymus

48
Q

How do epithelial cells conduct positive selection?

A
  • Epithelial cells present MHC I/II self-peptide complexes
  • If the TCR binds moderately or strong it lives
  • If the TCR has weak or no binding, it dies
49
Q

In positive selection, TCR must bind MHC within ________

A

3 to 4 days

50
Q

What effect does binding of TCR to MHC have on the RAG 1/2 complex?

A

It turns it off

51
Q

T/F in the 3 to 4 days that TCR has to bind MHC, alpha chain rearrangement can occur

A

True,

I think this would be to modify it to bind with more affinity to MHC

52
Q

T/F Positive selection is the second checkpoint in T cell development

53
Q

What determines CD4 vs CD8 expression?

A

Positive Selection

54
Q

How Does Positive selection determine CD4 or CD8 expression?

A

Basically, the T cell is presented with MHC 1 and 2 and whichever one it interacts with the best determines whether it is CD8 or CD4 lineage

55
Q

During Positive Selection what would a Double positive thymocyte become if it interacted with MHC1?

A

A CD8 T cell

56
Q

During Positive selection, what would a double positive thymocyte become if it interacted with a MHC II?

A

A CD4 T cell

57
Q

What is required in positive selection to determin CD4 vs. CD8 expression?

A

Co-signaling

58
Q

T/F There are different models of selection for CD4 or CD8 expression

59
Q

What cells perform negative selection of alpha:beta T cells?

A
  • Dendritic cells
  • Macrophages
  • Other cells in the thymus
60
Q

How is negative selection performed?

A
  1. Dendritic cells and macrophages present self-peptides
  2. Excessively binding induces apoptosis
  3. Moderate binding allows the cell to live
61
Q

T/F Central Tolerance is a result of Negative selection

62
Q

What other type of tolerance may also occur other than central?

A

Peripheral

63
Q

T/F Following Selection, Naive Mature T cells are done differentiating

A

False, They can still undergo differentiation

64
Q

Naive T cells can enter a draining lymph node by two routes. What are they?

A
  1. In the blood

2. In the afferent lymph coming from an upstream lymph node

65
Q

In the life of a T cell, what happens as T cell progenitors develop in the bone marrow and migrate to the thymus?

A

T-cell precursor rearranges its T-cell receptor genes in the thymus

66
Q

In the life of a T cell, what happens during positive and negative selection? (in a general sense)

A

Immature T cells that recognize self MHC receive signals for survival. Those that interact strongly with self-antigen are removed from the repertoire

67
Q

In the life of a T cell, what happens as Mature T cells migrate to the peripheral lymphoid organs?

A

Mature T cells encounter foreign antigens in the peripheral lymphoid organs and are activated

68
Q

In the life of a T cells what happens as Activated T cells migrate to the sites of infection?

A

Activated T cells Proliferate and eliminate infection

69
Q

Beta chain rearrangement forms ___________

A

Pre-T cell Receptors

70
Q

During the first Checkpoint of T cell development, the beta chain binds a ________

A

Surrogate alpha-chain analogue (pTa)

71
Q

T/F a CD3 complex is assembled during the first checkpoint in T cell development

72
Q

What happens if signaling occurs during the first checkpoint of T cell development?

A
  • Signaling drives further development
    • RAG function halts
    • Proliferation
73
Q

T/F Pre-T cell receptor formation and the first checkpoint involves the formation of a superdimer

**Host and Defense (31 decks)

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