Lymphocyte Selection and Tolerance Chander Raman 2004. Lecture Focus: Lymphocyte Selection: Central Tolerance T-cell selection B-cell selection Peripheral Tolerance Peripheral control of autoreactivity. Breakdown of tolerance Autoimmune diseases Restoration of tolerance
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Tolerance: Inability to respond to antigen stimulation OR Immunological unresponsiveness.
Clonal deletion occurs by induction of programmed cell death or apoptosis
(Positive selection for ability to recognize antigen)
Death by Neglect
(Positive selection based on MHC reactivity)
Autoantibodies to different organs shown in GREEN in AIRE-deficient mice
AIRE allows for the expression of antigens to which T-cells are negatively selected.
Sensitive to Negative Selection – Central Tolerance
Binding to self molecules in the bone marrow can lead to the deletion or inactivation of immature B cells.
Control of autoreactive T cells in the periphery is termedPeripheral Tolerance
Maloy and Powrie, Nature Immunol. 2:816
Feinberg & Silvestri, Nature Immunol, 3:215
Lutz and Schuler, Trends Immunol: 23:9
Focus on Autoimmunity
Nature Immunology, Sept 2001 (Vol 2)
Contribution of Susceptibility Gene Alleles to Development of Autoimmunity
Ware, Nature. 404:949