Información del artículo
Abstract
Three years after the pandemic, major advances have been made in our understanding of the innate and adaptive immune responses to the influenza A(H1N1)pdm09 virus and those responses’ contribution to the immunopathology associated with this infection. Severe disease is characterized by early secretion of proinflammatory and immunomodulatory cytokines. This cytokine secretion persisted in patients with severe viral pneumonia and was directly associated with the degree of viral replication in the respiratory tract. Cytokines play important roles in the antiviral defense, but persistent hypercytokinemia may cause inflammatory tissue damage and participate in the genesis of the respiratory failure observed in these patients. An absence of pre-existing protective antibodies was the rule for both mild and severe cases. A role for pathogenic immunocomplexes has been proposed for this disease. Defective T cell responses characterize severe cases of infection caused by the influenza A(H1N1)pdm09 virus. Immune alterations associated with accompanying conditions such as obesity, pregnancy or chronic obstructive pulmonary disease may interfere with the normal development of the specific response to the virus. The role of host immunogenetic factors associated with disease severity is also discussed in this review. In conclusion, currently available information suggests a complex immunological dysfunction/alteration that characterizes the severe cases of 2009 pandemic influenza. The potential benefits of prophylactic/therapeutic interventions aimed at preventing/correcting such dysfunction warrant investigation.
Keywords:
Influenza
H1N1pdm
Innate
Adaptative
Hypercytokinemia
Cross-immunity
T cell
Antibody
Immune dysfunction
Viral escape
Resumen
El posterior estudio de la gripe pándemica de 2009 hasta la actualidad ha dado como fruto un mayor conocimiento de las respuestas inmunológicas innatas y adaptativas al virus de la gripe A(H1N1)pdm09 y de la contribución de las respuestas a la inmunopatología asociada con esta infección. Se ha comprobado que la enfermedad grave se caracteriza por la secreción de citocinas proinflamatorias e inmunomoduladoras desde el principio de la enfermedad. En los pacientes con neumonía viral grave la secreción de citocinas se mantuvo y estaba relacionada directamente con el grado de replicación viral en el tracto respiratorio. Si bien las citocinas tienen un papel importante en la defensa antiviral, sin embargo la persistencia de hipercitoquinemia puede dañar el tejido inflamatorio y ser uno de los motivos que provocan el fracaso respiratorio observado en estos pacientes. En casi todos los casos leves y graves de enfermedad se observó ausencia de anticuerpos protectores preexistentes. Se ha propuesto que los inmunocomplejos patogénicos tienen un papel en esta enfermedad. Los casos graves de infección causados por el virus de la gripe A(H1N1)pdm09 se caracterizan por una respuesta defectuosa de las células T. En el desarrollo normal de la respuesta específica al virus pueden interferir trastornos inmunológicos asociados con situaciones concomitantes como obesidad, embarazo o enfermedad pulmonar obstructiva crónica. Los autores de esta revisión plantean también el papel que tienen los factores inmunogenéticos del huésped en la gravedad de la enfermedad. La gripe pandémica de 2009, de acuerdo con la información disponible 3 años más tarde, se caracteriza por una disfunción/alteración inmunológica compleja, por lo que los potenciales beneficios de las intervenciones terapéuticas deben ir dirigidos a corregir dicha disfunción y siempre garantizados mediante la investigación.
Palabras clave:
Gripe
H1N1pdm
Innato
Adaptativa
Hipercitoquinemia
Inmunidad cruzada
Células T
Anticuerpo
Disfunción inmunológica
Escape viral
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