Immunologic Tolerance

Abstract: There is accumulating evidence that T-cell-mediated dominant control of self-reactive T-cells contributes to the maintenance of immunologic self-tolerance and its alteration can cause autoimmune disease. Efforts to delineate such a regulatory T-cell population have revealed that CD25+ cells in the CD4+ population in normal naive animals bear the ability to prevent autoimmune disease in vivo and, upon antigenic stimulation, suppress the activation/proliferation of other T cells in vitro. The CD25+ CD4+ regulatory T cells, which are naturally anergic and suppressive, appear to be produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling tumor immunity and transplantation tolerance.

Abstract: Chapter 1: Introduction to the Immune System The Nomenclature, General Properties, and Components of the Immune System Chapter 2: Innate Immunity The Early Defense Against Infections Chapter 3: Antigen Capture and Presentation to Lymphocytes What Lymphocytes See Chapter 4: Antigen Recognition in the Adaptive Immune System Structure of Lymphocyte Antigen Receptors and the Development of Immune Repertoires Chapter 5: Cell-Mediated Immune Responses Activation of T Lymphocytes by Cell-Associated Microbes Chapter 6: Effector Mechanisms of Cell-Mediated Immunity Eradication of Intracellular Microbes Chapter 7: Humoral Immune Responses Activation of B Lymphocytes and Production of Antibodies Chapter 8: Effector Mechanisms of Humoral Immunity The Elimination of Extracellular Microbes and Toxins Chapter 9: Immunologic Tolerance and Autoimmunity Self-Nonself Discrimination in the Immune System and Its Failure Chapter 10: Immune Responses Against Tumors and Transplants Immunity to Noninfectious Transformed and Foreign Cells Chapter 11: Hypersensitivity Diseases Disorders Caused by Immune Responses Chapter 12: Congenital and Acquired Immunodeficiencies Diseases Caused by Defective Immune Responses Suggested Readings Appendix I: Principal Features of CD Molecules Appendix II: Glossary Appendix III: Clinical Cases Index

Abstract: Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in 'industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this 'microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a 'balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.