RESUMO
Secretory IgA (S-IgA) mediates local immunity to influenza virus in the murine upper respiratory tract and may play an important role in local immunity to various microorganisms in the female reproductive tract as well. Although the presence of IgA in cervicovaginal or uterine secretions has been correlated with immunity to a number of pathogens, there has been no direct demonstration of the mediation of uterine antiviral immunity by S-IgA. Influenza virus, although not a normal pathogen of the reproductive tract, was used to develop a model for the investigation of mucosal immunity in the uterus. PR8 (H1N1) influenza virus injected into the ovarian bursa of BALB/c mice grew well, with peak titers between days 3 and 5. Intravenous injection of polymeric IgA anti-influenza virus monoclonal antibody before or 30 min after viral challenge protected mice against viral infection. We believe this work to be the first direct demonstration of S-IgA-mediated antiviral uterine immunity. It provides a model for further investigation of immunity in the female reproductive tract.
Assuntos
Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Imunidade nas Mucosas , Imunoglobulina A Secretora/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Antivirais/administração & dosagem , Feminino , Imunização Passiva , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Ovário/imunologia , Ovário/virologia , Replicação Viral/imunologiaRESUMO
The roles of IgG and secretory IgA in the protection of the respiratory tract (RT) against influenza infection remain unclear. Passive immunization with Ab doses resulting in serum IgG anti-influenza virus Ab titers far in excess of those observed in immune mice has compounded the problem. We compared the effects of i.v. anti-influenza virus IgG and i.v. anti-influenza virus polymeric IgA (pIgA) mAb administered in amounts designed to replicate murine convalescent serum or nasal Ab titers, respectively. A serum anti-influenza virus IgG titer 2.5 times the normal convalescent serum anti-influenza virus IgG titer was required for detectible Ab transudation into nasal secretions, and a serum IgG titer 7 times normal was needed to lower nasal viral shedding by 98%. Anti-influenza virus pIgA at a nasal Ab titer comparable to that seen in convalescent mice eliminated nasal viral shedding. The RT of influenza-infected pIgA- or IgG-protected mice were studied by scanning electron microscopy. Only pIgA was found to prevent virally induced pathology in the upper RT, suggesting that IgG did not prevent viral infection of the nose, but neutralized newly replicated virus after infection had been initiated. In contrast, IgG, but not pIgA, was found to prevent viral pathology in the murine lung. Our results help to resolve the controversy of IgA- vs IgG-mediated protection of the RT; both Abs are important, with plasma IgG Ab serving as the back-up for secretory IgA-mediated protection in the nasal compartment, and IgG being the dominant Ab in protection of the lung.
Assuntos
Anticorpos Antivirais/imunologia , Imunoglobulina A Secretora/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/análise , Anticorpos Antivirais/uso terapêutico , Brônquios/imunologia , Brônquios/ultraestrutura , Brônquios/virologia , Convalescença , Feminino , Imunização Passiva , Imunoglobulina A Secretora/análise , Imunoglobulina G/análise , Imunoglobulina G/uso terapêutico , Vírus da Influenza A/fisiologia , Pulmão/imunologia , Pulmão/ultraestrutura , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Muco/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/ultraestrutura , Mucosa Nasal/virologia , Testes de Neutralização , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/prevenção & controle , Traqueia/imunologia , Traqueia/ultraestrutura , Traqueia/virologiaRESUMO
OBJECTIVE: To assess whether lack of enteral feeding significantly impairs generation of specific immune responses to an acute viral infection. SUMMARY BACKGROUND DATA: Parenteral feeding provides adequate nutrients to meet metabolic needs, but lack of enteral stimulation creates a defect in mucosal immunity characterized by loss of IgA-mediated defenses in the respiratory tract. METHODS: The enzyme-linked Immunospot (ELISPOT) assay was used to determine accumulation of immunologic cells in the nasal passages after diet manipulation. Viral shedding and nasal IgA levels were measured in additional groups of mice. RESULTS: After determining the time course of antibody-forming cells (AFCs) via ELISPOT to an active infection with the A/PR8 influenza virus, a significant reduction was found in total AFCs, IgA-producing AFCs, and IgG-producing AFCs over the course of a 13-day experiment with significant depression in viral-specific respiratory IgA levels. Eight days following an active infection, seven of nine total parenteral nutrition-fed animals continued to have viral shedding in the nasal passages compared to one of nine chow-fed mice and one of six animals fed a complex enteral diet. CONCLUSIONS: Lack of enteral stimulation significantly impairs the generation of IgA-mediated mucosal immunity.