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Tolerance - T-cell tolerance - Central

10 important questions on Tolerance - T-cell tolerance - Central

What are double-negative thymocytes?

This are the earliest cell population in the thymus that does not express any of the CD4, CD8 or T-cell receptor complex molecules.

What is the right order in which the T-cells are moving in the thymus?

1. They first enter the tymus via the venule.
2. Then they go to the subcapsular region
3. Cortex
4. Corticollary junction
5. Medulla

What are the two main regions of the thymus?

The peripheral cortex where most of the T-cell development takes place and the central medulla where only single-positive thymocytes are seen.

How do the precursor thymocytes enter the thymus?

They enter the thymus from the bloodstream via venules near the cortico-medullary junctions.

How does a T-cell go from double negative to double positive for CD4?

When the thymocytes receptor interact with the MHC-II molecule on the cortical epithelial cell it revieves a survial signal but a different maturation signal eventually it stops expression of CD8.

How does a T-cell go from double negative to double positive for CD8?

When the thymocytes receptor interact with the MHC-1 molecule on the cortical epithelial cell it receives both a survival and a maturation signal, eventually its stops expression CD4.

What happens with T-cells that don’t recognize an MHC-I or a MHC-II molecule?

It doesn’t receive survival molecules and will apoptoses.

How does a single positive thymocyte form?

The double-positive thymocytes enlarge and divide but become small resting double-positive cells that express low levels of the TCR. Most of them die within the thymus after becoming small double positive but those cells whose receptors can interact with self peptide;self MHC molecular complexes lose the expression of one of the co-receptors (CD4 or CD8) and increase the level of that TCR. The outcome is then a single-positive thymocyte.

Why is AIRE so important for the self-tolerance?

AIRE promotes the expression of may tissue-specific proteins in the thymic medullary cells. Peptides from these proteins are presented to the developing thymocytes as they undergo negative selection in the thymus, causing deletion of these cells. In the absence of AIRE this deletion does not occur and the autoreactive thymocytes mature and exported to the periphery where they could cause a autoimmune disease.

Where is aire expressed?

This is expressed in a small proportion of the medullary thymic epithelial cells

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Immunology

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Tolerance - T-cell tolerance - Central

10 important questions on Tolerance - T-cell tolerance - Central

What are double-negative thymocytes?

What is the right order in which the T-cells are moving in the thymus?

What are the two main regions of the thymus?

How do the precursor thymocytes enter the thymus?

How does a T-cell go from double negative to double positive for CD4?

How does a T-cell go from double negative to double positive for CD8?

What happens with T-cells that don’t recognize an MHC-I or a MHC-II molecule?

How does a single positive thymocyte form?

Why is AIRE so important for the self-tolerance?

Where is aire expressed?

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