CSIM 1.25 - T-cells 2

Question 1

What is Di-George’s syndrome?

Answer 1

Hereditary condition in which there is a missing thymus/parathyroid gland, therefore NO T-cell maturation can occur

Question 2

When does T-cell receptor VDJ recombination occur?

Answer 2

When the T-cell progenitors are double-negative - VDJ recombination leads to the formation of CD4 and CD8 receptors (double-positive)

Question 3

Describe positive T-cell selection within the thymus?

Answer 3

Successful T-cell recognition with MHC molecule induces survival signals

Question 4

Describe negative T-cell selection within the thymus?

Answer 4

T-cell is tested against SELF-Ag in the thymus medulla - T-cells which bind avidly with self-Ag are apoptosed (central tolerance)

Question 5

Which T-cell binds to MHC class 1?

Answer 5

CD8 T-cytotoxic cells

Question 6

Which T-cell binds to MHC class 2?

Answer 6

CD4 T-helper cells

Question 7

Structurally how does Ag recognition by T-cells occur?

Answer 7

Ag bound at MHC-cleft of antigen presenting cell and the CDR.3 region of the T-cell receptor binds to the Ag

Question 8

Where are viral proteins synthesised in host cells and how are they converted into peptide Ag?

Answer 8

Cytosol

Proteosomes

Question 9

Once viral protein is degraded where are the peptide Ag transported and how?

Answer 9

Endoplasmic reticulum lumen

TAP 1 and TAP 2 enzymes

Question 10

Where are MHC class 1 molecules synthesised?

Answer 10

Endoplasmic reticulum lumen

Question 11

How does the Ag end up inside the MHC class 1 molecule cleft?

Answer 11

MHC class 1 molecule (synthesised in the ER lumen) binds to TAP enzyme (transporting Ag) and Ag moves into MHC class 1 cleft. This is then transported to the cell surface

Question 12

Name a pathogen which replicates in endosomes and state why this may be problematic?

Answer 12

T.B

Protein is not accessible to proteosomes (cytosol)

Question 13

What happens as the endosome progresses into the cell interior?

Answer 13

Increases in acidity and protein inside endosome is degraded

Question 14

Where are MHC class 2 molecules synthesised?

Answer 14

Endoplasmic reticulum lumen

Question 15

Which molecule blocks the MHC class 2 cleft following its synthesis and what is its significance?

Answer 15

Li - MHC(II)/Li complex transported and fused to the acidified endosome where the Li is degraded and Ag binds to MHC class 2 cleft. This is then transported to the cell surface

Question 16

Describe polyclonal proliferation and give a clinical example resulting from when this occurs in excess?

Answer 16

As APC potentially carry multiple Ag, multiple naive and specific T-cells may be activated
Toxic shock syndrome (acute septicaemia) occurs with activation of >50% of the body’s T-cells

Question 17

How are naive T-cells activated?

Answer 17

Specific Ag in conjunction with specific MHC complex

2nd co-stimulatory signal by APC interaction

Question 18

Describe the co-stimulatory signals required to activate T-cells?

Answer 18

APC - CD80 (B7.1) and CD86 (B7.2)
T-cell - CD28
Signals up-regulated with danger signals

Question 19

What happens when a naive T-cell recognises its specific Ag and MHC complex and DOES NOT receive a co-stimulatory signal by the APC?

Answer 19

The T-cell becomes anergic - unresponsive to further stimulation by the specific Ag (shot it’s gun)

Question 20

What is special about memory T-cells?

Answer 20

Do NOT require the 2ndary co-stimulatory signal from the APC to activate