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Conceptual Models in Immunity/Tolerance: Application to Transplantation

  • Chapter
Immunobiology of Organ Transplantation

Abstract

The vertebrate immune system has an innate component (various phagocytic cells etc.) that has been “hardwired” through evolution to respond to appropriate stimuli, and an adaptive component (comprised of lymphocytes) that requires the selection and expansion of the appropriate specific clones from a large pool of cells within each individuals’2. A central question for more than 50 years in immunology has been “how does the immune system `know’ what to respond to and what not to respond to (tolerance)?” Much of our understanding of such fundamental questions in immunology has come from experiments involving the transplantation of tissues. This is because transplantation studies provide one of the best ways to dissect the function of the immune system; grafts appear to provide a clear assay for immunity to “foreign” antigens and tolerance to self. Moreover, transplantation studies provide a simple way to generate data that reinforces the primary dogma of immunology, that the immune system discriminates self from nonself. Herein I will explore transplantation within the framework of current conceptual models of the immunity/tolerance decision. The discussion will center on time and context of antigen presentation-based models, including the recent Danger model, perhaps the most radical model since it abandons the idea that the response of the immune system is governed by a self nonself (SNS) discrimination. A well-formulated alternative model based on ignorance of peripheral self-antigens is beyond the scope of the current discussion. Clear descriptions of this viewpoint can be found in ref. [3] and references therein. I will focus on transplantation studies that shed light on more general aspects of T-cell biology, rather than aspects that may be unique to the situation of transplantation. In an effort to understand the mechanism(s) the immune system evolved to determine tolerance vs immunity, I will highlight studies employing minor-H mismatched transplants since the question of peripheral tolerance

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Authors and Affiliations

  1. Departments of Surgery and Medical Microbiology and Immunology, Surgical-Medical Research Institute, 1074 Dentistry/Pharmacy Centre, University of Alberta, Edmonton, T6G 2N8, Canada

    Colin C. Anderson

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  1. Colin C. Anderson
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Editors and Affiliations

  1. Microbiology and Immunobiology, Division of Pulmonary and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, Indiana

    David S. Wilkes M.D. (Calvin H. English Professor of Medicine) (Calvin H. English Professor of Medicine)

  2. Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, Wisconsin

    William J. Burlingham Ph.D. (Associate Professor) (Associate Professor)

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Anderson, C.C. (2004). Conceptual Models in Immunity/Tolerance: Application to Transplantation. In: Wilkes, D.S., Burlingham, W.J. (eds) Immunobiology of Organ Transplantation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8999-4_11

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  • DOI: https://doi.org/10.1007/978-1-4419-8999-4_11

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