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Immune Tolerance and Autoimmune Regulator (AIRE) – Autoimmune Diseases

by Peter Delves, PhD
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    At the heart of the development of autoimmune disease is a breakdown in immunological tolerance. In fact, the immunological tolerance mechanisms have evolved to prevent harmful autoimmunity. Whilst T-cells are developing in the thymus and B-cells are developing in the bone marrow, they can undergo central tolerance. Recognition of self antigen in these primary lymphoid organs can lead to apoptotic cell death, with deletion of those particular cells. Or in the case of B-cells, there is also the possibility for the B-cell to change the specificity of its antigen receptor. This is referred to as receptor editing. And regulatory lymphocytes can develop that can suppress unwanted autoimmune responses. Central tolerance is not 100% efficient, so it is backed up with a number of peripheral tolerance mechanisms. These can involve the induction of anergy, non-responsiveness in lymphocytes when antigen is seen in the absence of co-stimulation. Usually during an infection, co-stimulatory molecules such as CD80 and CD86 are up-regulated on dendritic cells. But when autoantigens are being shown to lymphocytes by dendritic cells, there is no co-stimulation and this results in anergy. Apoptosis can also occur as a mechanism of peripheral tolerance. And finally suppressor cells can suppress these responses in the periphery. An important discovery a few years ago was that in the thymus, there is a transcription factor called the autoimmune regulator. The function of AIRE, the autoimmune regulator is to cause expression of what are normally tissue-restricted antigens so that these antigens are also expressed in the thymus to facilitate tolerance. There will be negative selection of the self-reactive T-cells and apoptotic cell death leading to deletion of those autoreactive T-cells. In the absence of AIRE which can occur due to mutations, individuals will fail to delete tissue specific T-cells resulting in autoimmunity and this can lead to...

    About the Lecture

    The lecture Immune Tolerance and Autoimmune Regulator (AIRE) – Autoimmune Diseases by Peter Delves, PhD is from the course Hypersensitivity and Autoimmune Disease. It contains the following chapters:

    • Immunological Tolerance to Self Antigens
    • The Development of Autoimmune Disease

    Included Quiz Questions

    1. B-cells
    2. Helper T-cells
    3. Cytotoxic T-cells
    4. Regulatory T-cells
    5. Plasma cells
    1. The creation of Tissue Restricted Antigens which leads to negative selection and apoptosis of T cells without central tolerance
    2. Creating T cells that show anergy in the presence of antigen
    3. Producing Regulator T cells which recognize T cells with self-antigen and inducing apoptosis
    4. Creating anti-self antibodies which will help target infected cells and tumor cells
    5. Facilitating apoptosis in peripheral T cells
    1. A breakdown in tolerance
    2. Upregulation of genes for AIR
    3. Infection
    4. Peripheral lymphoid tissue destruction
    5. Increase in anergy

    Author of lecture Immune Tolerance and Autoimmune Regulator (AIRE) – Autoimmune Diseases

     Peter Delves, PhD

    Peter Delves, PhD


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