CSIM 1.25 - T-cells 2 Flashcards
What is Di-George’s syndrome?
Hereditary condition in which there is a missing thymus/parathyroid gland, therefore NO T-cell maturation can occur
When does T-cell receptor VDJ recombination occur?
When the T-cell progenitors are double-negative - VDJ recombination leads to the formation of CD4 and CD8 receptors (double-positive)
Describe positive T-cell selection within the thymus?
Successful T-cell recognition with MHC molecule induces survival signals
Describe negative T-cell selection within the thymus?
T-cell is tested against SELF-Ag in the thymus medulla - T-cells which bind avidly with self-Ag are apoptosed (central tolerance)
Which T-cell binds to MHC class 1?
CD8 T-cytotoxic cells
Which T-cell binds to MHC class 2?
CD4 T-helper cells
Structurally how does Ag recognition by T-cells occur?
Ag bound at MHC-cleft of antigen presenting cell and the CDR.3 region of the T-cell receptor binds to the Ag
Where are viral proteins synthesised in host cells and how are they converted into peptide Ag?
Cytosol
Proteosomes
Once viral protein is degraded where are the peptide Ag transported and how?
Endoplasmic reticulum lumen
TAP 1 and TAP 2 enzymes
Where are MHC class 1 molecules synthesised?
Endoplasmic reticulum lumen
How does the Ag end up inside the MHC class 1 molecule cleft?
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
Name a pathogen which replicates in endosomes and state why this may be problematic?
T.B
Protein is not accessible to proteosomes (cytosol)
What happens as the endosome progresses into the cell interior?
Increases in acidity and protein inside endosome is degraded
Where are MHC class 2 molecules synthesised?
Endoplasmic reticulum lumen
Which molecule blocks the MHC class 2 cleft following its synthesis and what is its significance?
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
Describe polyclonal proliferation and give a clinical example resulting from when this occurs in excess?
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
How are naive T-cells activated?
Specific Ag in conjunction with specific MHC complex
2nd co-stimulatory signal by APC interaction
Describe the co-stimulatory signals required to activate T-cells?
APC - CD80 (B7.1) and CD86 (B7.2)
T-cell - CD28
Signals up-regulated with danger signals
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?
The T-cell becomes anergic - unresponsive to further stimulation by the specific Ag (shot it’s gun)
What is special about memory T-cells?
Do NOT require the 2ndary co-stimulatory signal from the APC to activate
