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VBSC 211: The Immune System > Exam 5: Chapter 7 > Flashcards

Exam 5: Chapter 7 Flashcards

1
Q

Why are the GD cells produced during embryogenesis lacking in diversity?

A

Each cell within a wave uses the same Vg segment and same D rearrangement

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2
Q

What is positive selection?

A

The selection of TCRs that bind self MHC isoforms

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3
Q

Do T cells with two functional TCRs ever make it into the periphery?

A

No

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4
Q

What region of the body does the second wave of embryonic GD cells colonize?

A

The reproductive tract epithelium

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5
Q

What cells populate the cortex?

A

Cortical epithelial cells

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6
Q

How do thymocytes transition from being Double Positive to being Single Positive?

A

CD8 is initially shut off, and the T cell tests to see if the TCR signal is still present. If it is, the cell is a CD4+ cell. If the signal is not present, CD4 is shut off and IL7 sends a signal to turn CD8 back on. The cell then becomes a CD8+ cell

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7
Q

How does T cell development proceed through the thymus?

A

T cell development starts in the cortex and proceeds into the medulla; naïve T cells that survive selection exit from the medulla

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8
Q

How do B cells and T cells differ in terms of longevity?

A

B cells last a few days or weeks, while T cells last years

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9
Q

What are Regulatory T cells (Treg)?

A

CD4+ cells that are also CD25+ and express transcription factor FoxP3; these cells regulate T cell response to prevent them from destroying self tissues

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10
Q

What is the medulla?

A

The inner portion of the thymus

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11
Q

How are lymphoid progenitor cells marked for T cell lineage?

A

Via notch signaling

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12
Q

What happens to cells that fail to productively rearrange their TCR?

A

They die via apoptosis and are removed by the macrophages in the cortex

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13
Q

What are the four checkpoints in T cell development?

A

Productive Beta chain arrangement, Productive Alpha chain arrangement, Positive Selection, Negative Selection

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14
Q

Which T cells are initially made during embryogenesis?

A

GD cells

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15
Q

What do T cells do if they survive both positive and negative selection?

A

They migrate through the blood stream and to the secondary lymphoid organs, where they collect in the T cell areas and interact with specific antigens

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16
Q

What is negative selection?

A

The deletion of TCRs that bind self peptides

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17
Q

What phenotype is observed in those lacking a thymus?

A

A SCID-like phenotype

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18
Q

What are immature T cell progenitors called?

A

Thymocytes

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19
Q

What cells populate the medulla?

A

Medullary epithelial cells, macrophages, dendritic cells

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20
Q

What percentage of double positive thymocytes are positively selected?

A

2%

21
Q

When does the thymus begin to shrink in size?

A

Around puberty

22
Q

Why are productive rearranged AB cells referred to as Double Positive T cells?

A

Pre-T cell receptor signaling induces the expression of both CD4 and CD8 on the cell surface

23
Q

What is the cortex?

A

The outer portion of the thymus

24
Q

How many tries does the beta chain have to produce a productive rearrangement?

A

4 tries - 2 per locus

25
Q

How does positive selection work?

A

Cortical epithelial cells express both class 1 and class 2 MHC, which present self peptides; double positive cells that are able to interact with the MHC are positively selected for

26
Q

What is the first step of T cell development?

A

Progenitor cells migrate from the bone marrow to the thymus

27
Q

What is required for the suppression of auto-reactive T cells?

A

For both the auto-reactive T cell and the Treg cell to interact with the same antigen-presenting cell

28
Q

What happens if auto-reactive T cells escape negative selection?

A

The T cells enter a state of anergy that “pauses” them for a period of time

29
Q

Where do T cells develop?

A

In the thymus

30
Q

Which cells mediate negative selection?

A

Bone marrow-derived macrophages and dendritic cells

31
Q

What region of the body does the first wave of embryonic GD cells colonize?

A

The skin epithelium

32
Q

Why is there a possibility that two functional T-cell receptors are produced by a single cell?

A

Both alpha chain loci rearrange at the same time, and both can have productive rearrangements

33
Q

What are the two possibilites that occur after Alpha/Gamma/Delta rearrangement?

A
  1. Gamma and Delta genes rearrange productively and produce a GD T cell
  2. Alpha gene rearranges productively and produces an AB T cell
34
Q

What happens if FoxP3 is mutated in Treg cells?

A

No Treg cells are produced and an X-linked autoimmune disease occurs as a result

35
Q

How are all possible peptides able to be expressed by the thymus?

A

The transcription factor AIRE (autoimmune regulator) ensures that nearly every gene is expressed in the thymus, thus allowing most self peptides to be presented

36
Q

Where does negative selection occur?

A

In the medulla of the thymus

37
Q

Which T cell gene(s) rearrange first?

A

Gamma, delta, and beta genes

38
Q

Where does positive selection occur?

A

In the cortex of the thymus

39
Q

Which T cell chain has more chances to rearrange?

A

The alpha chain

40
Q

How does negative selection work?

A

The thymic epithelium presents class 1 and class 2 peptides. T cells that bind moderately (i.e. to MHC but not peptide) survive, while cells that bind tightly (i.e. to both MHC and peptide) die

41
Q

What are the two possibilities that occur after Beta/Gamma/Delta rearrangement?

A
  1. Gamma and Delta genes rearrange productively and produce a GD T cell
  2. Beta gene rearranges productively and pairs with pTalpha to form the pre-T cell receptor
42
Q

What induces progenitors to proliferate into thymocytes?

A

Interaction with cortical epithelial cells

43
Q

What happens if there is a lack of notch signaling?

A

T cell development will be blocked

44
Q

What would happen if a transplant patient received a bone marrow transplant with completely different HLA types than their own?

A

The derived T-cells would be positively selected on the recipient’s HLA allotypes, but the antigen-presenting cells in other bodily tissues would present antigens on donor HLA types; no T cells would thus be able to bind HLA and respond to the infection

45
Q

Where are the precursor cells to T cells “born?”

A

In the bone marrow

46
Q

What happens if AIRE is mutated?

A

Patients end up with autoimmune polyglandular syndrome type 1

47
Q

How does the Pre-TCR produce a signal?

A

By crosslinking to form a superdimer

48
Q

What is the role of the pre-T cell receptor?

A

To turn off recombination of the beta, gamma, and delta genes

49
Q

Why are early thymocytes called Double Negative thymocytes?

A

They express neither CD4 nor CD8

VBSC 211: The Immune System (10 decks)

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