Changes

===Central Tolerance===

===Central Tolerance===

[[Image:Thymic selection of t cells.jpg|thumb|right|150px|Negative selection of t cells- copyright Brian Catchpole]]

[[Image:Thymic selection of t cells.jpg|thumb|right|200px|Negative selection of t cells- copyright Brian Catchpole]]

*Takes place within the thymus

Tolerance at a central level takes place within the thymus, and induces both '''positive''' and '''negative''' selections:

*Involves the processes '''positive''' and '''negative''' selection

* During positive selection, cells passing through the thymic cortex encounter cortical epithelial cells expressing MHC molecules. Those with a suitable level of binding affinity for the MHC recieve 'survival' signals and apoptosis is prevented (at the same time cells lose either their CD4 or CD8 co-receptor)

** During positive selection, cells passing through the thymic cortex encounter cortical epithelial cells expressing MHC molecules. Those with a suitable level of binding affinity for the MHC recieve 'survival' signals and apoptosis is prevented (at the same time cells lose either their CD4 or CD8 co-receptor)

*During negative selection, cells passing through the corticomedullary junction and thymic medulla once again encounter MHC molecules, on epithelial cells, dendritic cells and macrophages, this time bound to self-peptide. Cells bearing receptors that bind too strongly to this complex are deleted through induced apoptosis.

**During negative selection, cells passing through the corticomedullary junction and thymic medulla once again encounter MHC molecules, on epithelial cells, dendritic cells and macrophages, this time bound to self-peptide. Cells bearing receptors that bind too strongly to this complex are deleted through mechanisms that induce apoptosis.

===Peripheral Tolerance===

===Peripheral Tolerance===