Autoimmunity-LehighUniversity.pptVIP

Autoimmunity “n. of, relating to, or caused by autoantibodies or lymphocytes that attack molecules, cells, or tissues of the organism producing them.” (from Webster’s Online) The Study of Autoimmunity Molecular Mechanisms of Autoimmunity Animal Models for Autoimmune Dysfunction Treatments for Autoimmune Diseases Gender Differences in Autoimmunity Three Common Autoimmune Diseases Molecular Mechanisms of Autoimmunity Molecular Mechanisms of Autoimmunity Cross-reactivity (Molecular and Viral Mimicry) Viral and nonviral peptides can mimic self-peptides and induce autoimmunity Example: papilloma virus (HPV) and insulin receptor Cross-Reactivity Molecular Mechanisms of Autoimmunity Release of Sequestered Antigen Antibodies in blood can attack Myelin Basic Protein if Blood-Brain barrier is breached. Molecular Mechanisms of Autoimmunity Inappropriate MHC expression Type I Diabetes: Pancreatic β cells express abnormally high levels of MHC I and MHC II (?) MHC II – APC only! This may hypersensitize TH cells to β cell peptides. Inappropriate MHC Expression Normal Pancreas Pancreas with Insulitis Fig. 20-3 Molecular Mechanisms of Autoimmunity Polyclonal B Cell Activation by Viruses and Bacteria If B cells reactive to self-peptides are activated, autoimmunity can occur. Example: Epstein-Barr Virus, which is the cause of infectious mononucleosis. Putting it all together…the big picture Autoimmunity can be caused by immunological, genetic, viral, drug-induced, and hormonal factors. There are 4 immunological mechanisms of autoimmunity. All mechanisms cause abnormal B or T cell activation. Centrality of the Ternary Complex Most instances of autoimmune diseases occur with multiple mechanisms, which makes treatment difficult. Animal Models for Autoimmune Diseases Why have them? Animal models of autoimmune diseases contribute valuable insights into the mechanisms of autoimmunity and to our understanding of autoimmunity in humans and how we ma