Inflammatory bowel disease consists of two disorders, Crohn's disease and ulcerative colitis, in which T cellmediated inflammation causes intestinal injury. Crohn's disease is characterized by chronic inflammation and destruction of the intestinal wall, with frequent formation of fistulas. In ulcerative colitis, the lesions are largely confined to the mucosa and consist of ulcers with underlying foci of inflammation. The pathogenesis of inflammatory bowel disease was described in Chapter 13. New therapies for these diseases include antibodies against TNF, IL-17, and the p40 chain of IL-12 and IL-23.
responses of lymphocytes specific for self antigens and to induce tolerance in these cells.
* Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes illustrate many of the effector mechanisms that cause tissue injury in hypersensitivity reactions and the roles of susceptibility genes and environmental factors in the development of autoimmunity.
selected readings General Principles
Davidson A, and B Diamond. Autoimmune diseases. New
England Journal of Medicine 345:340-350, 2001. Goodnow CC. Multistep pathogenesis of autoimmune disease.
Cell 130:25-35, 2007. Nagata S, R Hanayama, and K Kawane. Autoimmunity and the clearance of dead cells. Cell 140:619-630, 2010.
Antibody and Immune Complex-Mediated
Banchereau J, and V Pascual. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25:383-392, 2006.
D'Cruz DP, MA Khamashta, and GR Hughes. Systemic lupus erythematosus. Lancet 369:587-596, 2007.
Fairhurst AM, AE Wandstrat, and EK Wakeland. Systemic lupus erythematosus: multiple immunological phenotypes in a complex genetic disease. Advances in Immunology 92:1-69, 2006.
Jancar S, and M Sanchez Crespo. Immune complex-mediated tissue injury: a multistep paradigm. Trends in Immunology 26:48-55, 2005.
Munoz LE, K Lauber, M Schiller, AA Manfredi, and M Herrmann. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nature Reviews Rheumatology 6:280-289, 2010.
Plotz PH. The autoantibody repertoire: searching for order. Nature Reviews Immunology 3:73-78, 2003.
T Cell-Mediated Disorders
Frohman EM, MK Racke, and CS Raine. Multiple sclerosis—the plague and its pathogenesis. New England Journal of Medicine 354:942-955, 2006.
Gutcher I, and B Becher. APC-derived cytokines and T cell polarization in autoimmune inflammation. Journal of Clinical Investigation 117:1119-1127, 2007.
Imboden JB. The immunopathogenesis of rheumatoid arthritis. Annual Review of Pathology 4:417-434, 2009.
Palmer MT, and CT Weaver. Autoimmunity: increasing suspects in the CD4+ T cell lineage. Nature Immunology 11:36-40, 2010.
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