Autoimmunity and type 1 diabetes

Published on January 31, 2021   45 min

Other Talks in the Series: The Immune System - key concepts and questions

Hello, I'm Anne Cooke and I'm Emeritus Professor of Immunobiology in the Pathology Department at the University of Cambridge. Today I'm going to be talking to you about "Autoimmunity and Type 1 Diabetes".
The aim of the lecture is to examine factors governing the development of autoimmune disease and I'm really going to emphasize type 1 diabetes because that's actually what I work on mainly.
Examples of autoimmune disease, which you have probably seen in textbooks. People have actually usually split them into organ-specific leading down to systemic. But in fact, obviously, there are some overlaps between these. A classic organ-specific disease would be Grave's disease, or Hashimoto's disease or thyroid disease, where the autoimmune destruction is targeted to the thyroid gland. At the other end of the spectrum, the systemic lupus erythematosus, sometimes known as SLE, where the immune response is targeted to DNA, proteins associated with DNA, and obviously that's distributed throughout your whole body.
Now one thing which is important to recognize is, although most autoimmune diseases are under polygenic control, that is, under complex genetic control. Some single gene defects can cause autoimmune pathology. Fas/FasL ligand deficient humans will develop autoimmune lymphoproliferative syndrome, sometimes known as ALPS, A-L-P-S, characterized by defective lymphocyte apoptosis. These individuals have splenomegaly, lymphadenopathy, and autoimmunity, which is often where they have autoantibodies to DNA and DNA-associated proteins. Individuals who have caspase 8 or caspase 10 deficiency, have impaired apoptosis of their T-cells, and they have symptoms similar to the ALPS patients, this lymphoproliferative syndrome. Now AIRE, the autoimmune regulator is a gene where mutations cause the recessively inherited disorder, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, otherwise known as APECED, or also known as autoimmune polyendocrinopathy syndrome 1, APS1. Patients with a deficiency in Foxp3 develop IPEX, which is a polyendocrine autoimmune condition. Patients with CD25 deficiency can have an autoimmune enteropathy and type 1 diabetes. Individuals have any defects in TCR signaling molecules such as phosphorylation defects, these can lead to autoimmune disorders characterized by antinuclear antibodies as in SLE and nephritis. People often get nephritis or kidney disease because of immune complex depositions in the kidney. Patients with cytokine deficiencies such as IL-10, IL-10 receptor can develop inflammatory bowel disease or arthritis. You can see these mimicked in animal models as well. The factors that govern the onset of autoimmunity,