How does the immune system distinguish self from non-self?

Lymphocyte education in the thymus and bone marrow deletes most self-reactive cells, but the rules governing tolerance versus autoimmunity are not fully understood. Why some individuals develop multiple sclerosis or type 1 diabetes while most do not remains an open question.

Open sub-questions include the role of regulatory T cells, the microbiome, and the breakdown of tolerance triggered by infections.