Autorreactividad y autoinmunidad

  1. Díaz Martín, D.
  2. Barcenilla Rodríguez, H.
  3. Úbeda Cantera, M.
  4. Muñoz Zamarrón, L.
Medicine: Programa de Formación Médica Continuada Acreditado

ISSN: 0304-5412

Year of publication: 2017

Series: 12

Issue: 24

Pages: 1418-1427

Type: Article


More publications in: Medicine: Programa de Formación Médica Continuada Acreditado

Sustainable development goals


Abstract Definition of Autoimmunity and autoimmune diseases Autoimmunity is an immune response against one or several self-antigens. Autoimmune diseases are the result of damage or loss of physiological function in organs and tissues due to an autoimmune response. This specific recognition is mediated by cells of the adaptive immune system, i.e., T and B lymphocytes, while in the mechanisms of damage also participate cells and molecules of the innate immune system. Features of the autoimmune diseases Autoimmune diseases are chronic and often progressive. The persistence of the antigen, antigen-specific memory T and B cells and the powerful inflammatory mechanisms of amplification are pathogenetic mechanisms that perpetuate the disease. Immune tolerance The mechanisms of tolerance are essential for the control of the autoreactivity, mainly in the periphery by T lymphocytes. These mechanisms are typically divided into central tolerance, peripheral tolerance and tolerance mediated by regulatory T cells (Tregs). Etiology of the autoimmune diseases The etiology of the autoimmune diseases is not evident, although it seems clear that it is multifactorial. The genetic propensity is an important factor and certain sets of alleles of genes can predispose to the disease. In addition, environmental factors as the infection and the tissue injury seem fundamental in its development.

Bibliographic References

  • Root-Bernstein R, Fairweather D. Complexities in the relationship between infection and autoimmunity. Curr Allergy Asthma Rep. 2014;14(1): 407.
  • Rosenblum MD, Remedios KA, Abbas AK. Mechanisms of human autoimmunity. J Clin Invest. 2015;125(6):2228-33.
  • McCombe PA, Greer JM, Mackay IR Sexual dimorphism in autoimmune disease. Curr Mol Med. 2009;9(9):1058-79.
  • Bluestone JA, Bour-Jordan H, Cheng M, Anderson M. T cells in the control of organ specific autoimmunity. J Clin Invest. 2015; 125(6):2250-60.
  • Bluestone JA. Mechanisms of tolerance. Immunol Rev. 2011; 241(1):5-19.
  • Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298(5597):1395-401.
  • Mills KH1. TLR dependent T cell activation in autoimmunity. Nat Rev Immunol. 2011;11(12):807-22.
  • Strasser A, Bouillet P. The control of apoptosis in lymphocyte selection. Immunol Rev. 2003;193:82-92.
  • Zhang J, Xu X, Liu Y. Activation induced cell death in T cells and autoimmunity. Cell Mol Immunol. 2004;1(3):186-92.
  • Alessandri C, Barbati C, Vacirca D, Piscopo P, Confaloni A, Saánchez M. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J. 2012;26(11):4722-32.
  • Xu K, Xu P, Yao JF, Zhang YG, Hou WK, Lu SM. Reduced apoptosis correlates with enhanced autophagy in synovial tissues of rheumatoid ar-thritis. Inflamm Res. 2013;62(2):229-37.
  • Caspi RR. Immunotherapy of autoimmunity and cancer: the penalty for success. Nat Rev Immunol. 2008;8(12):970-6.
  • Singh RP, Waldron RT, Hahn BH. Genes, tolerance and systemic autoimmunity. Autoimmun Rev. 2012;11(9):664-9.
  • Kim JI, Rothstein DM, Markmann JF. Role of B cells in tolerance induction. Curr Opin Organ Transplant. 2015;20(4):369-75.
  • Blair PA, Noreña LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR. CD19(+) CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity. 2010;32:129.
  • Flores-Borja F, Bosma A, Ng D. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentia-tion. Sci Transl Med. 2013;5:173ra23.
  • Gray M, Miles K, Salter D, Gray D, Savill J. Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc Natl Acad Sci U S A. 2007;104(35):14080-5.
  • Lee KM, Stott RT, Zhao G, SooHoo J, Xiong W, Lian MM. TGF-beta producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol. 2014;44(6):1728-36.
  • Matsushita T, Horikawa M, Iwata Y, Tedder TF. Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling expe-rimental autoimmune encephalomyelitis initiation and late-phase immu-nopathogenesis. J Immunol. 2010;185(4):2240-52.
  • Baecher-Allan C, Viglietta V, Hafler DA. Human CD4+CD25+ regulatory T cells. Semin Immunol. 2004;16(2):89-98.
  • Long SA, Buckner JH. CD4+FOXP3+ T regulatory cells in human au-toimmunity: more than a numbers game. J Immunol. 2011;187(5): 2061-6.
  • Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015;7(315):315ra189.
  • Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4):330-6.
  • Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, Victora GD. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antago-nizing RORgammat function. Nature. 2008;453(7192):236-40.
  • Wang J, Ioan-Facsinay A, van der Voort EI, Huizinga TW, Toes RE. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol. 2007;37(1):129-38.
  • Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8(7):523-32.
  • Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, Ye X. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008;28(4):546-58.
  • Grossman WJ, Verbsky JW, Tollefsen BL, Kemper C, Atkinson JP, Ley TJ. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood. 2004;104(9):2840-8.
  • Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322(5899):271-5.
  • Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A. Adenosine generation catalyzed by CD39 and CD73 expressed on regu-latory T cells mediates immune suppression. J Exp Med. 2007;204(6):1257-65.
  • Chinen T, Kannan AK, Levine AG, Fan X, Klein U, Zheng Y. An essential role for the IL-2 receptor in Treg cell function. Nat Immunol. En prensa. 2016.
  • Rosenzwajg M, Churlaud G, Mallone R, Six A, Dérian N, Chaara W, et al. Low dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun. 2015;58:48-58.
  • Von Spee-Mayer C, Siegert E, Abdirama D, Rose A, Klaus A, Alexander T. Low dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016; 75(7):1407-15.
  • Rioux JD, Abbas AK. Paths to understanding the genetic basis of autoimmune disease. Nature. 2005;435(7042):584-9.
  • Abramson J, Husebye ES. Autoimmune regulator and self tolerance molecular and clinical aspects. Immunol Rev. 2016;271(1):127-40.
  • Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annu Rev Immunol. 2009;27:363-91.
  • Lauro ML, Burch JM, Grimes CL. The effect of NOD2 on the microbiota in Crohn’s disease. Curr Opin Biotechnol. 2016;40:97-102.
  • Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity friends or foes? Trends Immunol. 2009;30(8): 409-14.
  • Doria A, Sarzi-Puttini P, Shoenfeld Y. Infections, rheumatism and autoimmunity: the conflicting relationship between humans and their envi-ronment. Autoimmun Rev. 2008;8(1):1-4.
  • Romani L. Parasites and autoimmunity: the case of fungi. Autoimmun Rev. 2008;8(2):129-33.
  • Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature. 2016;535(7610):75-84.
  • Lleo A, Battezzati PM, Selmi C, Gershwin ME, Podda M. Is autoimmunity a matter of sex? Autoimmun Rev. 2008;7(8):626-30.