Mysteries and Surprises of Autoimmunity

About 100 years ago Paul Erlich used the term Horror Autoxicus to describe the idea that the immune system could attack, via antibodies, foreign materials, but not the content of its host. Although there was evidence that the idea was incorrect, the notion of autoimmunity didn’t reach full strength until about the 1950s, with experiments showing that animals, including humans, could produce antibodies against their own tissues. The internet tells us that about 150 such diseases have so far been named. Many genetic variants have been linked to these diseases, most powerfully, alleles of major histocompatibility complex (MHC) proteins. Because we now understand that MHC proteins are involved in T cell biology, notions about autoimmunity include both T and B cell activity. Also, it is now known that the immune system has several ways of preventing autoimmunity, via death of autoreactive T cells in the thymus, modification of autoreactive B cells in the bone marrow, inhibition of activity of autoreactive lymphocytes, and, as recognized by one of this year’s Nobel Prizes, the activity of regulatory T cells. Lots of questions remain unanswered. Why is it that only some people become autoimmune? What precisely do autoimmune lymphocytes recognize in their host? Can antigen specific treatments be used to lower the symptoms of or completely prevent autoimmunity? Why are women more likely to become autoimmune than men? Some of these questions will be discussed.