Molecular mimicry and autoimmunity Academic Article

abstract

  • El mimetismo molecular es uno de los principales mecanismos por los cuales los agentes infecciosos o químicos pueden inducir la autoinmunidad.Ocurre cuando las similitudes entre los péptidos ajenos y los autopéptidos favorecen una activación de To células B por un antígeno de origen extranjero en un individuo susceptible. Sin embargo, es poco probable que el mimetismo molecular seael único mecanismo subyacente para las respuestas autoinmunes; otros factores como la ruptura de la tolerancia central,la activación inespecífica de los transeúntes, o los estímulos antigénicos persistentes (entre otros) también pueden contribuir a ladesarrollo de enfermedades autoinmunes. La genética del huésped, la exposición a la microbiota y los productos químicos ambientales sonenlaces adicionales a nuestra comprensión de la mímica molecular. Nuestro conocimiento actual de los mecanismos detalladosde la imitación molecular está limitada por los períodos prolongados de latencia antes de la aparición de la enfermedad,la falta de suficiente poder estadístico en los estudios epidemiológicos, las limitaciones del papel potencial de la genética enestudios en humanos, la relevancia de los modelos murinos endogámicos para la diversa población humana y especialmente eltecnología limitada para diseccionar sistemáticamente el repertorio de células T humanas y las respuestas de las células B. Sin embargo,estudios sobre el papel de las células T autoreactivas que se generan de forma secundaria a la mímica molecular, la diversidad de las células TRepertorios de receptores de células T de células T autorreactivas, el papel de la exposición a antígenos crípticos, la generación derespuestas autoinmunes de las células B, la interacción de la microbiota y los adyuvantes químicos con el sistema inmunológico del huéspedproporcionan pistas para avanzar en nuestra comprensión de los mecanismos moleculares que intervienen en la evolución de la enfermedad.de mimetismo molecular y también puede ayudar potencialmente en la prevención y el tratamiento de las enfermedades autoinmunes.
  • Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual. However, molecular mimicry is unlikely to be the only underlying mechanism for autoimmune responses; other factors such as breach in central tolerance, non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to the development of autoimmune diseases. Host genetics, exposure to microbiota and environmental chemicals are additional links to our understanding of molecular mimicry. Our current knowledge of the detailed mechanisms of molecular mimicry is limited by the issues of prolonged periods of latency before the appearance of disease, the lack of enough statistical power in epidemiological studies, the limitations of the potential role of genetics in human studies, the relevance of inbred murine models to the diverse human population and especially the limited technology to systematically dissect the human T-cell repertoire and B-cell responses. Nevertheless, studies on the role of autoreactive T-cells that are generated secondary to molecular mimicry, the diversity of the T-cell receptor repertoires of auto-reactive T-cells, the role of exposure to cryptic antigens, the generation of autoimmune B-cell responses, the interaction of microbiota and chemical adjuvants with the host immune systems all provide clues in advancing our understanding of the molecular mechanisms involved in the evolving concept of molecular mimicry and also may potentially aid in the prevention and treatment of autoimmune diseases.
  • Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity.It occurs when similarities between foreign and self-peptides favor an activation of autoreactive Tor B cells by a foreign-derived antigen in a susceptible individual. However, molecular mimicry is unlikely to bethe only underlying mechanism for autoimmune responses; other factors such as breach in central tolerance,non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to thedevelopment of autoimmune diseases. Host genetics, exposure to microbiota and environmental chemicals areadditional links to our understanding of molecular mimicry. Our current knowledge of the detailed mechanismsof molecular mimicry is limited by the issues of prolonged periods of latency before the appearance of disease,the lack of enough statistical power in epidemiological studies, the limitations of the potential role of genetics inhuman studies, the relevance of inbred murine models to the diverse human population and especially thelimited technology to systematically dissect the human T-cell repertoire and B-cell responses. Nevertheless,studies on the role of autoreactive T-cells that are generated secondary to molecular mimicry, the diversity of theT-cell receptor repertoires of auto-reactive T-cells, the role of exposure to cryptic antigens, the generation ofautoimmune B-cell responses, the interaction of microbiota and chemical adjuvants with the host immunesystems all provide clues in advancing our understanding of the molecular mechanisms involved in the evolvingconcept of molecular mimicry and also may potentially aid in the prevention and treatment of autoimmunediseases.

publication date

  • 2018/10/26

edition

  • 95

keywords

  • autoreactive
  • mimicry
  • molecular
  • responses
  • role

International Standard Serial Number (ISSN)

  • 0896-8411

number of pages

  • 24

start page

  • 1
  • 2068

end page

  • 2074