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Genetic Susceptibility to Autoimmune Diseases and Mechanisms – Autoimmune Diseases

by Peter Delves, PhD
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    So there’s a genetic susceptibility, in the vast majority of cases. This is many different genes acting together resulting in a failure of self tolerance and the development of self reactive lymphocytes. Coupled with these multiple genetic factors, are environmental stimuli such as tissue injury, inflammation, infection and so on. This can lead to the activation of tissue antigen presenting cells. And these antigen presenting cells can activate self reactive lymphocytes, which then become self reactive effector lymphocytes that are actually going to carry out the damage that is occurring. There’ll be tissue injury, and the result will be autoimmune disease. So let's have a look at some of the genes that have been implicated. In animal studies, it’s quite clear that maybe in a given autoimmune disease, perhaps as many as 20 or 30 different genes can contribute. And the genes that have been identified both in animal studies and in human patients include the following - The MHC is nearly always implicated. And the MHC of course is involved in antigen presentation to T-cells. And this is a gene that virtually all polygenic autoimmune diseases, which is 99% of autoimmune diseases, have a MHC influence on their development. CTLA4 which is a molecule that you find on the surface of T-cells, and actually acts as a kind of negative regulator of T-cells, and stops excessive T-cell responses. This gene or polymorphisms of this gene have been implicated in thyroid autoimmune diseases, in type I diabetes and in rheumatoid arthritis. A molecule called PTPN22, which is involved in antigen receptor signaling has also been implicated in those particular diseases. In other words, thyroid autoimmune disease, type I diabetes and rheumatoid arthritis. Polymorphisms of complement components, particularly C1q, C2 and C4 are involved in the development of systemic lupus erythematosus....

    About the Lecture

    The lecture Genetic Susceptibility to Autoimmune Diseases and Mechanisms – Autoimmune Diseases by Peter Delves, PhD is from the course Hypersensitivity and Autoimmune Disease. It contains the following chapters:

    • Mechanisms of Autoimmune Disease
    • MHC Associations in Autoimmune Disease
    • Role of Infection in the Development of Autoimmune Disease

    Included Quiz Questions

    1. HLA-B27
    2. HLA-B2
    3. HLA-B7
    4. HLA-B8
    5. HLA-B72
    1. Tissue injury which causes self presenting APCs and self-reactive effector lymphocytes
    2. Accumulation of APCs around tissue effected by stimuli
    3. Lymphocytes that are reactive to environmental elements which mutate and become autoreactive
    4. Changes in morphology of MHC leading to self presenting APCs and self-reactive effector lymphocytes
    5. Changes in genetic expression of tumor suppressor genes
    1. IL-10
    2. CTLA4
    3. IL-2
    4. BLK
    5. MHC
    1. Type I Diabetes
    2. Hasimoto's Disease
    3. Myasthenia Gravis
    4. Ankylosing spondylitis
    5. Rheumatoid arthritis
    1. A sharing of structures or sequences between self antigens and microbial antigens, leading to autoimmunity
    2. A B cell mediated reaction which results in production of identical autoantibodies
    3. Destruction of healthy tissue cells because they resemble damaged tissue cells
    4. Autoimmune complexes that mimic antigens and deposit in lymphocytes
    5. Inability to clear antigens which are deposited in damaged tissues, leading to tissue destruction

    Author of lecture Genetic Susceptibility to Autoimmune Diseases and Mechanisms – Autoimmune Diseases

     Peter Delves, PhD

    Peter Delves, PhD


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