Lymphocyte Development

Question 1

What do TCRs bind to?

Answer 1

1. Antigen-derived peptide
2. peptide bound to MHC class

Question 2

Describe the structure of the TCR.
- regions
- disulfide bonds
- transmembrane domain
- recombination chains

Answer 2

α chain = VJ
β = VDJ

Question 3

How do T-cells express unique antigen receptors?

Answer 3

VDJ/VJ recombination

Question 4

Cells entering the thymus are (_____) to becoming a lymphocyte and express antigen-specific receptors.
A. not committed
B. naive/mature
C. B cells

Answer 4

A. not committed

Question 5

T/F. Cells leaving the thymus are naive/mature T-cells and express specific antigen TCRs.

Answer 5

True

Question 6

T-cells development occurs in the:

Answer 6

thymus

Question 7

Describe the migration of T-cell development.

Answer 7

1. precursor T-cells develop in the bone marrow
2. Immature T-cells migrate from bone marrow through the blood into the thymus
3. Immature T-cells travel through the thymus at the cortex
4. T-cells that undergo selection migrate to the medulla

Question 8

List the stages the T-cells undergo in the thymus.

Answer 8

1. Double negative (DN): do not express CD4 or CD8
2. Double positive (DP): express both CD4 and CD8
3. Single positive: expresses either CD4 or CD8

Question 9

In which stage does the recombination of the TCR gene segments (VDJ/VJ) occur?

Answer 9

DN stages

Question 10

What are the two stages T-cell development occurs?

Answer 10

1. Early thymocyte development
   - commit to T-cell lineage
   - Initiate V(D)J recombiation
   - expand cells
2. T cell maturation
   - positive selection
   - negative selection
   - lineage commitment

Question 11

When thymocytes arrive at the thymus, what early cells do they have the possibility of becoming?

Answer 11

• NK cells
• dendritic cells
• B cells

Question 12

T/F. When cells arrive at the thymus they are T-cells.

Answer 12

False. When cells arrive at the thymus they aren’t technically T-cells.

Question 13

T cell lineage commitment occurs due to signals received by the progenitor cell from thymic epithelial cells. Name that signaling receptor.

Answer 13

Notch

Question 14

If the cell has Notch+ or Notch- which cell lineage are they committed to?

Answer 14

Notch+: T cells
Notch-: B cells

Question 15

When thymocytes progress to the DN stages what essentially occurs?

Answer 15

• gets TCR α and β
• cells will test β chain via β selection = proliferation
• initiates α chain rearrangement and selection
• VDJ rearrangement is stopped once selection occurs
• enters DP stage

Question 16

After β selection, what stage do the thymocytes enter?

Answer 16

DP

Question 17

What occurs in the DP stage?

Answer 17

• functional TCR
• cell expresses both CD4 AND CD8 (CD4+, CD8+)
• undergoes positive and negative selection

Question 18

Describe positive and negative selection of thymic cells.

Answer 18

1. positive selection: selects thymocytes receptors capable of binding self-MHC molecules with low affinity
   - MHC restriction
2. negative selection: selects against thymocytes receptors with high affinity for self-MHC/peptide complexes
   - self tolerance

Question 19

MHCI is present on …

Answer 19

all nucleated cells
- T cells
- B cells
- macrophages
- dendritic cells
- epithelial cells of the thymus

Question 20

MHCII is present in …..

Answer 20

APCs
- B cells
- macrophages
- dendritic cells
- epithelial cells of the thymus

Question 21

The function of cortical thymic epithelial cells (cTEC)?

Answer 21

express high levels of MHC class I and II
- mediate positive selection

Question 22

Double positive thymocytes learn (____) in the thymus.

Answer 22

MHC restriction

Question 23

What are the 3 possible outcomes when T cells encounter self-peptide/MHC?

Answer 23

1. TCRs can’t bind = death by neglect
2. TCRs bind too strongly (high affinity) = apoptosis
3. TCRs bind just right (low affinity) = positive selection
   - recognizes and interacts with self peptide
   - ensures MHC restriction
   - becomes CD4 or CD8, single positive

Question 24

Negative selection ensures….

Answer 24

self tolerance (central tolerance)

Question 25

If a thymocyte has a high affinity for binding antiself what occurs?

Answer 25

Clonal deletion via apoptosis

Question 26

What are AIRE proteins? Are they in relation to positive or negative selection?

Answer 26

Negative selection - induces expression of mTECs - binds epigenetic marks to recruit transcription factors - mediate negative selection

Question 27

What cells help regulate self tolerance and what do they express?

Answer 27

Treg cells (CD4+) Express: FoxP3 transcription factor

Question 28

How do Treg cells negatively regulate?

Answer 28

- deplete stimulating cytokines - produce inhibitory cytokines (IL-10) - inhibit APC activity - directly kill T cells (cytotoxic T cells)

Question 29

What peripheral mechanisms protect against autoreactive thymocytes?

Answer 29

- some self-anitgens are hidden - some self-antigens are presented by non-APCs

Question 30

On the BCR complex, what is involved in signal transduction?

Answer 30

- Igα and Igβ transduce signals via ITAMs

Question 31

Where do B-cells develop?

Answer 31

begins in the bone marrow and completed in the periphery

Question 32

Describe positive and negative selection in B-cells.

Answer 32

Positive: signaling through BCR Negative: eliminated auto-reactive B-cells

Question 33

Immature B-cells express which ligand on their membrane? A. IgM B. B220 C. CD25 D. CD19 E. All of the above

Answer 33

E. All of the above

Question 34

What are the two possible outcomes of BCRs being tested against self-anitgens?

Answer 34

1. Clonal deletion: autoreactive cells eliminated by apoptosis 2. Receptor editing: reactivation of light-chain recombination

Question 35

Once in the spleen for maturation, what do B-cells do?

Answer 35

- express IgM and IgD - recirculate between blood and lymphoid organs - respond to antigens with T-helper cells by producing antibodies