ABSTRACT
Scarce information exists about the role of lung antigen-presenting cells (APCs) in vivo during pulmonary tuberculosis. As APCs activate cellular immunity, following intratracheal inoculation with virulent Mycobacterium tuberculosis, we assessed in situ lung APC recruitment, distribution, granuloma involvement, morphology and mycobacterial burden by using MHC-CII, CD14, scavenger receptor class A (SRA), the murine dendritic cell (DC)-restricted marker CD11c and Ziehl-Neelsen staining. CD11c(+) DC and CD14(+) cell recruitment into lungs appeared by day 14, continuing until day 60. MHC-CII(+) cells increased since day 7, persisting until day 60. Thus, virulent mycobacteria delays (14-21 days) lung APC recruitment compared to model antigens and nonvirulent bacilli (24-48 h). Regarding granuloma constitution, highly bacillary CD14(+) and SRA(+) cells were centrally located. MHC-CII(+) cells were more peripheral, with less mycobacteria. CD11c(+) cells were heterogeneously distributed within granulomas, with scarce bacilli. When labelling lung suspensions for MHC-CII and classifying cells as macrophages or DC, then staining for Ziehl-Neelsen, a remarkable segregation was found regarding bacillary burden. Most macrophage-like cells contained numerous bacilli, while DC had no or scarce mycobacteria. This implies differential APC contributions in situ during pulmonary tuberculosis regarding mycobacterial uptake, granuloma involvement and perhaps bacillary growth.
Subject(s)
Antigen-Presenting Cells/immunology , Lung/immunology , Tuberculosis, Pulmonary/immunology , Animals , CD11c Antigen/immunology , Dendritic Cells/immunology , Immunohistochemistry/methods , Macrophages, Alveolar/immunology , Male , Mice , Mice, Inbred BALB C , Models, Animal , Time Factors , VirulenceABSTRACT
Despite tuberculosis resurgence and extensive dendritic cell (DC) research, there are no in vivo studies evaluating DC within regional lymphoid tissue during airways infection with virulent Mycobacterium tuberculosis (Mtb) H37Rv. Using DC-specific antibodies, immunocytochemistry, flow cytometry and Ziehl-Neelsen (ZN) for bacilli staining, we searched for Mtb and DC changes within mediastinal lymph nodes, after intratracheal (ITT) inoculation of virulent Mtb. ZN and immunocytochemistry in frozen and paraffin sections of mediastinal lymph nodes identified Mtb until day 14 after ITT inoculation, associated with CD11c(+) and Dec205(+) DC. Analysing CD11c, MHC-CII, and Dec205 combinations by flow cytometry in MLN suspensions revealed that CD11c(+)/MHC-CII(+) and CD11c(+)/Dec205(+) DC did not increase until day 14, peaked on day 21, and sharply declined by day 28. No changes were seen in control, saline-inoculated animals. The costimulatory molecules evaluated in CD11c(+) DCs followed a similar trend; the CD80 increase was negligible, slightly surpassed by CD40. CD86 increased earlier and the three markers peaked at day 21, declining by day 28. While antigen-specific proliferation was not evident for MLN CD4(+) T cells at 2 weeks postinfection, delayed-type hypersensitivity responses upon ITT inoculation revealed that, as early as day 3 and 7, both the priming and peripheral systemic immune responses were clearly established, persisting until days 14-21. While airways infection with virulent Mtb triggers an early, systemic peripheral response maintained for three weeks, this seems dissociated from regional events within mediastinal lymph nodes, such as antigen-specific T-cell reactivity and a delay in the influx and local activation of DC.
Subject(s)
Dendritic Cells/immunology , Lymph Nodes/immunology , Mycobacterium tuberculosis/pathogenicity , Tuberculosis, Pulmonary/immunology , Animals , CD11c Antigen/analysis , Cell Division/immunology , Hypersensitivity, Delayed/immunology , Immunity, Cellular , Immunoenzyme Techniques , Male , Mediastinum , Mice , Mice, Inbred BALB C , T-Lymphocytes/immunology , VirulenceABSTRACT
Recientemente se informó la asociación del virus de Epstein-Barr (VEB) y los tumores de músculo liso, principalmente en niños inmunosuprimidos; pero el papel que juega en la patogenia de estos tumores, no se ha esclarecido. Informamos un caso en que establecimos la presencia de VEB y leiomiosarcoma en un hombre de 28 años con insuficiencia renal crónica terminal que en 1994, recibió un trasplante renal. En 1996 ingresó con lesiones nodulares en ambas bases pulmonares, hígado, bazo, car anterior del muslo izquierdo y ganglios retroperitoneales; un año después falleció. En las biopsias de muslo e hígado se observó leiomiosarcoma. Las reacciones de inmunoperoxidasa fueron positivas para vimentina y para actina de músculo liso. La hibridación in situ fue positiva para antígenos nucleares del VEB (EBNA-2) en células neoplásicas. Este caso corresponde al primer sarcoma observado en pacientes trasplantados en nuestra institución como un caso poco frecuente de leiomiosarcoma asociado a VEB en adulto
Subject(s)
Humans , Male , Adult , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/pathogenicity , In Situ Hybridization , Immunoenzyme Techniques , Leiomyosarcoma/pathology , Leiomyosarcoma/virology , Kidney Transplantation , VimentinABSTRACT
Se estudió mediante microscopía de luz, electrónica e inunohistoquímica un caso de colangiolocarcinoma en un hombre de 68 años de edad. El tumor se encontraba constituido por células neoplásicas formando estructuras parecidas a ductos. El estudio inmunohistoquímico mostró positividad para células ductales (citoqueratina 7) y hepatocitos (fibrinógeno) en las células neoplásicas. El estudio ultraestructural mostró células con características de células epiteliales de conducto y hepatocitos. De estos hallazgos se concluye que los colangiolocarcinomas puede derivar de una célula transicional común, probablemente similar a las células ovales observadas en los modelos de carcinogénesis experimental en hígado de ratas
Subject(s)
Humans , Male , Aged , Carcinoma/pathology , Carcinoma/ultrastructure , Immunohistochemistry , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Liver Neoplasms/ultrastructureABSTRACT
En un estudio previo se sugirió que la dieta suplementada con semilla de nabo evita el desarrollo de cirrosis experimental en la rata. En el presente trabajo se demostró por morfometría que la semilla de nabo produce hipertrofia de los hepatocitos. Este crecimiento, a juzgar por los hallazgos con microscopía electrónica, dependió fundamentalmente de la superficie citoplásmica, y en menor grado, del núcleo del hepatocito. La combinación de semilla de nabo con tetracloruro de carbono (CC14) produjo igualmente hipertrofia; sin embargo, aquélla no modificó el cuadro histológico de cirrosis inducida por CC14. El hecho de que la hipertrofia provocada por la semilla de nabo sea básicamente a expensas de organelos membranosos sustenta la idea de que algún ingrediente de ésta modifica la actividad de síntesis o degradación proteínica del hepatocito.