Primer: Immunity and Autoimmunity

  1. Massimo Pietropaolo1,
  2. Julie M. Surhigh1,
  3. Patrick W. Nelson2 and
  4. George S. Eisenbarth3
  1. 1Laboratory of Immunogenetics, The Brehm Center for Type 1 Diabetes Research and Analysis, Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
  2. 2Department of Mathematics, University of Michigan, Ann Arbor, Michigan
  3. 3Barbara Davis Center for Childhood Diabetes, Department of Pediatrics, University of Colorado Denver, Aurora, Colorado
  1. Corresponding author: Massimo Pietropaolo, maxtp{at}

For nonimmunologists, a daunting and rapidly evolving immunologic vocabulary, our incomplete understanding of both normal and abnormal immune function, and multiple interrelated complex immune cellular pathways can be a barrier to using basic immunology to understand and improve care for patients with type 1 diabetes. Our task in this review is to introduce current immune concepts specifically relevant to type 1 diabetes. Because our understanding is not complete, as evidenced perhaps by our lack of standard immunotherapy to prevent type 1 diabetes, we can only provide a partial framework. Perhaps the simplest framework (which may be wrong) is to consider the development of type 1 diabetes as the balance between regulatory and effector T lymphocytes. We know that in the absence of a major portion of regulatory T lymphocytes in a rare syndrome caused by mutation of the FOXP3 gene, most infants (even neonates) develop type 1 diabetes. Central to the development of type 1 diabetes are T lymphocytes with specific T-cell receptors that recognize islet molecules. When a T-cell is activated through its receptor, it can orchestrate protection from infection or autoimmunity, depending on the target. Other T-cells can suppress or enhance autoimmunity (either in general or only for T lymphocytes in islets). The activation of a T-cell involves multiple different cell types and genes, as we will discuss.


The modern era of immunology began with the clonal selection theory independently expressed by David W. Talmage and Sir Frank Macfarlane Burnet (1,2). The clonal selection theory postulates that a foreign antigen entering the body binds to one unique antibody selected from an unlimited repertoire of antibodies formed early in the organism's life. This explains how the immune system is able to recognize and respond to a virtually inestimable number of foreign antigens.

The immune system is a …

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