Loss of self tolerance can lead to autoimmunity.
Early Observations
Ray Owen, 1945
Dizygotic cattle twins that shared the same placenta were blood cell chimaeras, ie contained blood cells of two different haplotypes in adults and, - these two haplotypes co-existed in the adults without mutual rejection.
➢ Immune system becomes tolerant to these Ags.
➢ In 1953, Billingham, Brent and Medawar demonstrated that immunological tolerance could be acquired by introduction of donor cells during fetal development – tolerance permanent and Ag specific.
Immunosuppression: A condition where the activation or efficacy of the immune system is reduced (induced by an immunosuppressant ).
Natural Tolerance (self tolerance):
Central tolerance
Paradox: It is critical to delete thymocytes expressing TCRs that would react with self peptides presented by MHC molecules on BM-derived APCs in the periphery. Some peptides are derived from circulating blood cells or serum components. Deletion of T cells in the thymus also requires local expression of the tissue specific antigens (e.g. insulin, MBP). What cell in the thymus is expressing self-proteins? What makes this particular cell to express all these tissue-specific genes?
