RESUMO
Hepatitis B is an important cause of morbidity and mortality around the world. One-third of the world's population has been estimated to be infected with hepatitis B virus (HBV). A significant amount of evidence suggests that both humoral and cellular immune responses are important to eliminate the virus and that, cellular immunity is involved in the pathogenesis of the disease. Vaccination with HBsAg is considered as the main strategy for effective control of the infection and viral transmission. However, approximately 5-10% of immunized individuals fail to elicit detectable specific antibodies and remain at risk for hepatitis B infection. In this work we have reviewed the current status in the pathogenesis of the disease and the mechanisms described to explain nonresponsiveness to the vaccine as well. Since nonresponders to the vaccine are at risk for the infection, a common mechanism to explain the absence or inappropriate immune response to virus components is proposed. Within the suggested model an impaired activation of T lymphocytes against viral antigens, both in nonresponders to vaccination and chronically infected patients, is described. These observations could be consistent with potential differences in the MHC/Ag presentation; therefore contributing to our understanding of the altered T helper response as an underlying mechanism for the lack of protective immunity against VHB.
Assuntos
Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Ativação Linfocitária , Linfócitos T/imunologia , Hepatite B/prevenção & controle , Hepatite B/virologia , Vacinas contra Hepatite B , Humanos , Linfócitos T Citotóxicos/imunologiaRESUMO
La hepatitis B es una causa importante de morbilidad y mortalidad en el mundo. Un cúmulo importante de evidencias sugiere que tanto la respuesta humoral como la celular son importantes para la eliminación del virus y que la respuesta celular se ha involucrado en la patogénesis de la enfermedad. La vacunación con el antígeno de superficie (HBsAg) es considerada como la estrategia principal para el control de la infección. Sin embargo, aproximadamente 5 a 10 por ciento de los individuos fallan en producir anticuerpos específicos. En este trabajo se han revisado aspectos fundamentales en la inmunopatogenia de la Hepatitis B, así como también fenómenos que explican la ausencia de respuesta a la vacuna. Partiendo de la premisa que los individuos no respondedores a la vacuna contra la Hepatitis B, están en riesgo de infección, se propone un mecanismo común para explicar la ausencia de respuesta frente al virus. En el contexto del modelo planteado se describe una alteración en la activación de los linfocitos T, tanto en no respondedores como en infectados crónicos. Estas observaciones son consistentes con diferencias potenciales en el eje de presentación MHC/Ag, contribuyendo al entendimiento sobre la alteración de la respuesta T cooperadora como un mecanismo de base para la ausencia de inmunidad protectora contra el virus de la hepatitis B (VHB)
Assuntos
Humanos , Citocinas , Vírus da Hepatite B , Imunoterapia Ativa , Linfócitos T , Vacinas , Ativação Viral , Medicina , VenezuelaRESUMO
Nonresponsiveness against hepatitis B vaccination has been described in 4-10% of immunized subjects. We have explored the specific cell response to hepatitis B surface antigen by analyzing: PBMC proliferation, cytokine production (Th1, Th2 profiles, and TGF-beta), and activation molecules on Th cells. A poor proliferative response was demonstrated in nonresponders (P < 0.05). T cells from responders produced all tested cytokines (P < 0.01), in contrast with nonresponders subjects (P < 0.05). Expression of CD69 and CD25 was diminished in T cells from nonresponders (P < 0.01). A reduced expression of CD40L was also detected in T cells from nonresponders (P < 0.01). An elevated correlation coefficient was observed between CD40L on CD4+ cells and antibody production. These results suggest an overall inability of T cells to be activated which could be consistent with potential differences in antigen presentation. In conclusion, our results suggest that an altered Th response may be a consequence of inappropriate early activation events.