Autoimmune Disease: Pathogenesis

Abstract

Autoimmune diseases are a vast array of organ‐specific as well as systemic diseases, whose pathogenesis stems from the activation of B‐ and T‐lymphocytes reacting against antigens of the body's own tissues (defined as ‘self’). Lymphocytes are the main components of the adaptive arm of the immune system, and their major task is to rapidly remove pathogens (e.g. viruses or bacteria) in the absence of relevant tissue damage and self‐recognition. Also, innate immunity participates to this process by sensing pathogens, activating lymphocytes and contributing to pathogen clearance. In physiologic conditions, the cooperative efforts of central and peripheral tolerance mechanisms avoid responsiveness of the immune system to self‐antigens, and the development of autoimmune diseases. Conversely, genetic predisposition and environmental triggers contribute to the alteration of either one of the two mechanisms, thus, favouring the induction of autoimmunity, and either complete and irreversible loss of function of the targeted tissue or its hyperfunction.

Key Concepts

  • Autoimmune diseases are the result of specific immune responses directed against structures of the self.
  • Autoimmune diseases are the consequence of an altered function of the immune system.
  • Autoimmune disease may involve a single tissue or multiple organs.
  • Consequences of an autoimmune reaction may either be the loss of function or the hyperfunction of the target tissue.
  • An autoimmune response may be primarily T‐ or B‐cell mediated, or both.
  • Innate immunity contributes to the pathogenesis of autoimmune diseases by activating lymphocytes and participating to the tissue damage.

Keywords: autoimmunity; autoimmune disease; pathogenesis; tolerance

Figure 1. All types of immune‐mediated tissue damage may cause autoimmune diseases. See text for details. Ig, immunoglobulin; NK, natural killer; CD, cluster of differentiation.
Figure 2. In systemic lupus erythematosus (SLE), immune complexes and complement deposited at the renal glomeruli cause glomerulonephritis. (a) Proliferative SLE nephritis (World Health Organisation class IV) with mesangial expansion in all lobules, segmental double contours and abundant, numerous subendothelial linear deposits (AFOG, acid fuchsin orange G; original magnification ×125). (b) Immunofluorescence microscopy showing C1q capillary linear deposits (original magnification ×40). (c) Diffuse subendothelial linear deposits, counterpart to the wire‐loop lesion, in a double‐contour pattern. Smaller deposits are present in the mesangium. Bar, 2.5 µm (uranyl acetate and lead citrate stain; original magnification ×3000). Courtesy of Dr G Dell'Antonio, H San Raffaele, Milan, Italy.
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References

Altman JD, Moss PA, Goulder PJ, et al. (1996) Phenotypic analysis of antigen‐specific T lymphocytes. Science 274: 94–96.

Bellone M (2000) Apoptosis, cross‐presentation, and the fate of the antigen specific immune response. Apoptosis 5: 307–314.

Bennett CL, Christie J, Ramsdell F, et al. (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genetics 27: 20–21.

Bottazzo GF, Dean BM, McNally JM, et al. (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetes insulitis. New England Journal of Medicine 313 (6): 353–360.

von Bubnoff D, Andrès E, Hentges F, et al. (2010) Natural killer cells in atopic and autoimmune diseases of the skin. Journal of Allergy and Clinical Immunology 125: 60–68.

Burnet FM (1957) A modification of Jerne's theory of antibody production using the concept of clonal selection. Australian Journal of Science 20: 67–72.

Burnet FM and Fenner F (1949) The Production of Antibodies. Melbourne: Macmillan.

Chen Y, Kuchroo VK, J‐i I, Hafler DA and Weiner HL (1994) Regulatory T‐cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265: 1237–1240.

Conti‐Fine BM, Protti MP, Bellone M and Howard JF Jr (1997) Myasthenia Gravis: The Immunobiology of an Autoimmune Disease. Austin, TX: RG Landes.

Coombs RRA and Gell PGH (1975) Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: Gell PGH, Coombs RRA and Lachmann PJ (eds) Clinical Aspects of Immunology, 3rd edn, pp. 761–781. Oxford: Blackwell Scientific.

Davidson A and Diamond B (2010) Autoimmune diseases. New England Journal of Medicine 345: 340–350.

Ehrlich P and Morgenroth J (1901) Ueber Hamolysine, Funfte milleilung. Berliner Klinische Wochenschrift 38: 251.

Fisher GH, Rosenberg FJ, Straus SE, et al. (1995) Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 81: 935–946.

Gammon G and Sercarz E (1989) How some T cells escape tolerance induction. Nature 342: 183–185.

Gaulton GN, Stein ME, Safko B and Stadecker MJ (1989) Direct induction of Ia antigen on murine thyroid‐derived epithelial cells by reovirus. Journal of Immunology 142 (11): 3821–3825.

Gershon RK and Kondo K (1971) Infectious immunological tolerance. Immunology 21 (6): 903–914.

Groux H, O'Garra A, Bigler M, et al. (1997) A CD4+T‐cell subset inhibits antigen‐specific T‐cell responses and prevents colitis. Nature 389: 737–742.

Lehmann PV, Forsthuber T, Miller A and Sercarz EE (1992) Spreading of T‐cell autoimmunity to cryptic determinants of an autoantigen. Nature 358: 155–157.

Mathis D and Benoist C (2009) Aire. Annual Review of Immunology 27: 287–312.

Matzinger P (1994) Tolerance, danger, and the extended family. Annual Review of Immunology 12: 991–1045.

Mauri C and Bosma A (2012) Immune regulatory function of B cells. Annual Review of Immunology 30: 221–241.

Miossec P, Korn T and Kuchroo VK (2009) Interleukin‐17 and type 17 helper T cells. New England Journal of Medicine 361: 888–898.

Novak EJ, Liu AW, Nepom GT and Kwock WW (1999) MHC class‐II tetramers identify peptide‐specific human CD4(+) T‐cells proliferating in response to influenza A antigen. Journal of Clinical Investigation 104: R63–R67.

Olsson B, Andersson P‐O, Jernas M, et al. (2003) T‐cell‐mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nature Medicine 9: 1123–1124.

Perazella MA and Markowitz GS (2010) Drug‐induced acute interstitial nephritis. Nature Reviews Nephrology 8: 461–470.

Pitzalis C, Jones GW, Bombardieri M, et al. (2014) Ectopic lymphoid‐like structures in infection, cancer and autoimmunity. Nature Reviews Immunology 14: 447–462.

Ridge JP, Fuchs EJ and Matzinger P (1996) Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science 271: 1723–1726.

Sakaguchi S, Sakaguchi N, Asano M, Itho M and Toda M (1995) Immunologic self‐tolerance maintained by activated T cells expressing IL‐2 receptor α‐chain. Journal of Immunology 155: 1151–1164.

Skowera A, Ellis RJ, Varela‐Calviño R, et al. (2008) CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose‐regulated preproinsulin epitope. Journal of Clinical Investigation 118: 3390–3402.

Stollerman GH (1997) Rheumatic fever. Lancet 349: 935–942.

Sutton B, Corper A, Bonagura V and Taussig M (2000) The structure and origin of rheumatoid factors. Immunology Today 21: 177–183.

Ueda H, Howson JM, Esposito L, et al. (2003) Association of the T‐cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423: 506–511.

Further Reading

Abbas AK, Lichtman AH and Pillai S (2014) Immunologic tolerance and Autoimmunity. In: Abbas AK, Lichtman AH and Pillai S (eds) Cellular and Molecular Immunology, International edn, pp. 315–338. Amsterdam: Elsevier.

Murphy K (2012) Autoimmunity and transplantation. In: Murphy K (ed) Janway's Immunobiology, 8th edn, pp. 611–665. New York: Garland Science.

Schwartz RS (2013) Autoimmunity and autoimmune diseases. In: Paul WE (ed) Fundamental Immunology, 7th edn, pp. 1069–1112. Alphen aan den Rijn: Wolters Kluwer.

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Bellone, Matteo(Sep 2015) Autoimmune Disease: Pathogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001276.pub4]