Autoimmune Disease: Pathogenesis


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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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.

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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. [doi: 10.1002/9780470015902.a0001276.pub4]