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Breaking Ignorance: The Case of the Brain

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Book cover Current Concepts in Autoimmunity and Chronic Inflammation

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 305))

Abstract

Immunological self-tolerance is maintained through diverse mechanisms, including deletion of autoreactive immune cells following confrontation with autoantigen in the thymus or in the periphery and active suppression by regulatory cells. A third way to prevent autoimmunity is by hiding self tissues behind a tissue barrier impermeable for circulating immune cells. The latter mechanism has been held responsible for self-tolerance within the nervous tissue. Indeed, the nervous tissues enjoy a conditionally privileged immune status: they are normally unreachable for self-reactive T and B cells, they lack lymphatic drainage, and they are deficient in local antigen-presenting cells. Yet the immune system is by no means fully ignorant of the nervous structures. An ever-growing number of brain specific autoantigens is expressed within the thymus, which ensures an early confrontation with the unfolding T cell repertoire, and there is evidence that B cells also contact CNS-like structures outside of the brain. Then pathological processes such as neurodegeneration commonly lift the brain’s immune privilege, shifting the local milieus from immune-hostile to immune-friendly. Finally, brain-reactive T cells, which abound in the healthy immune repertoire, but remain innocuous throughout life, can be activated and gain access to their target tissues. On their way, they take an ordered migration through peripheral lymphoid tissues and blood circulation, and undergo a profound reprogramming of their gene expression profile, which renders them fit to enter the nervous system and to interact with local cellule elements.

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  1. MPI Neuroimmunology, Martinsried, Germany

    H. Wekerle

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  1. H. Wekerle
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  1. Deutsches Rheumaforschungszentrum Berlin (DRFZ), Schumannstr.21/22, 10117, Berlin, Germany

    Andreas Radbruch Ph.D.

  2. National Institute of Arthritis and Musculoskeletal and Skin Diseases, 9000 Rockville Pike, Bethesda, MD, 20892-1560, USA

    Peter E. Lipsky MD

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Wekerle, H. (2006). Breaking Ignorance: The Case of the Brain. In: Radbruch, A., Lipsky, P.E. (eds) Current Concepts in Autoimmunity and Chronic Inflammation. Current Topics in Microbiology and Immunology, vol 305. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29714-6_2

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