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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of radiation pneumonitis is not completely understood. The long latent period and involvement of unirradiated lung tissue may indicate an immune reaction in the injurious process of irradiated lung. To investigate the role of pulmonary macrophages in radiation pneumonitis, morphology and membrane antigen expression of pulmonary macrophages were studied in irradiated rat lung tissue following 4000 R hemithoracic irradiation. Lungs were explanted at 2, 4, 6, 8, 16, and 28 weeks after irradiation. Cryosections of irradiated lung tissue were immunohistochemically studied, and alveolar macrophages in bronchoalveolar lavage fluid were also analyzed using monoclonal antibodies to rat major histocompatibility complex (MHC) antigens and macrophages with flow cytometry. Macrophage subpopulations were analyzed using a panel of monoclonal antibodies to MHC class I (HAM2), MHC class II (OX6) and macrophage differentiation antigens (ED1, ED2, ED3). Alveolar macrophages in bronchoalveolar lavage were morphologically studied by smear and flow cytometry of forward light scatter and 90 degrees light scatter. At 2 weeks after irradiation, when histological changes did not appear, small lymphocyte-like macrophages and large foamy macrophages were observed in both the smear and histograms by flow cytometry. At 4, 6, and 8 weeks after irradiation, these new populations had markedly increased. However, at 16 and 28 weeks after irradiation, the size and shape of alveolar macrophages had returned to normal. In the expression of macrophage membrane antigens, an increase in the frequency of MHC class II+ cells in lavaged cells appeared at 2 weeks after irradiation, and became significant at 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pulmonary macrophages in rats after hemithoracic irradiation: analysis of morphology and expression of surface antigen]. 823 Aug 92

Pulmonary disease was studied in four patients with ataxia-telangiectasia. Immunodeficiency was characterized by lymphopaenia, hypo-gammaglobulinaemia and decreased T-cell response to phytohaemagglutinin stimulation in mixed lymphocyte cultures. All four patients died from respiratory failure. Autopsy revealed that all four patients suffered from bronchiolitis obliterans in all lobes. Immunohistochemical examination demonstrated expression of MHC class II antigens on bronchiolar epithelium. Pulmonary infections in ataxia-telangiectasia patients included a case of mycoplasma pneumonia, one of cytomegalovirus pneumonia and one of Pseudomonas aeruginosa infection. The aetiology and immunological background of bronchiolitis obliterans are discussed. Bronchiolitis obliterans is a characteristic finding in ataxia-telangiectasia and may be due to the underlying immune deficit.
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PMID:Bronchiolitis obliterans in ataxia-telangiectasia. 908 16

A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4+ T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8+ T-cell function (beta2-microglobulin deficient, MHC class I deficient [Beta2m-/-]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh-/-]), and gamma interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg-/-]) or interleukin-4 (C57BL/6J(tm1Cgn29) [IL4-/-]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development. Resistance to reinfection with MoPn was heavily dependent on CD4+ T cells. CD4 T-cell-deficient MHC class II-/- mice were very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance. These mice lacked antibody production but did produce IFN-gamma, apparently by mechanisms involving NK and CD8+ T cells. Neutralization of IFN-gamma in these mice led to a borderline increase in susceptibility, showing a possible role (albeit small) of this cytokine in this setting. Tumor necrosis factor alpha (TNF-alpha) was also present at increased levels in these mice. Igh-/- B-cell-deficient mice which produce no antibody to MoPn were only modestly more susceptible to reinfection than immunized B-cell-intact controls, showing that antibody, including lung immunoglobulin A, is not an absolute requirement for relatively successful host defense in this setting. Levels of lung IFN-gamma and TNF-alpha were elevated in Igh-/- mice compared to those in controls. IL-4-/- mice (deficient in Th2 function) could develop normal resistance to reinfection with MoPn. Conversely, normal mice rendered partially IFN-gamma deficient by antibody depletion were somewhat impaired in their ability to develop acquired immunity to MoPn, again indicating a role for this cytokine in host defense against rechallenge. Of most importance, however, congenitally IFN-gamma-deficient Ifg-/- mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating factor) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma is not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s). In vivo depletion of TNF-alpha significantly increased MoPn levels in the lungs in these mice. Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4+ T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody. Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study.
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PMID:Humoral and cellular immunity in secondary infection due to murine Chlamydia trachomatis. 919 62

The aim of the study was the morphological and the phenotypic characterization of the porcine non-lymphocytic bronchoalveolar lavage (BAL) cell population of unaffected- and intrabronchial with Pasteurella multocida- (P.m.) infected swine using flow cytometry. Three non-lymphocytic cell populations of the porcine bronchoalveolar lavage could be differentiated: (1) large, high autofluorescent cells, (LHC); (2) small, high autofluorescent cells, (SHC); (3) small, low autofluorescent cells, (SLC). In comparison with the control animals, the percentage of the LHC and SHC within the whole non-lymphocytic cell population was decreased, whereas the SLC was significantly enhanced after infection. In order to investigate the phenotype of these cell populations, monoclonal antibodies against porcine antigens (SWC1, SWC3a, MHC class II, 2G6 (against macrophages)) were used. The results showed that the cells of the SLC seem to belong to the granulocytes, whereas the LHC and the SHC are lung macrophages. After the infection of the animals the percentage of the SWC1 positive cells of LHC and SHC were significantly increased, indicating an entrance of more immature macrophages. The percentage of the MHC class II antibody binding cells of all three non-lymphocytic populations was-decreased after infection, indicating a restricted MHC class II dependent antigen recognition in P.m. pneumonia.
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PMID:Heterogeneity of porcine alveolar macrophages in experimental pneumonia. 926 65

As the most common cause of sexually transmitted disease in women, chlamydial infections can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To better understand the role played by sex hormones in modulating the immune response of the genital tract to microbial infections, we have developed a rat model to study Chlamydia trachomatis infection. Inbred female Lewis rats were primed with progesterone and inoculated by intrauterine instillation of C. trachomatis (mouse pneumonitis strain MoPn) into each uterine horn. When infected animals were examined for the presence of chlamydial antigens 14 days postinfection, both the uterus and vagina were found to be positive compared to those of saline-treated animals, which did not show specific staining. The involvement of local and systemic immune systems following chlamydial infection was determined by analyzing major histocompatibility complex (MHC) class II expression in the reproductive tract and lymphocyte proliferation in response to mitogenic and chlamydia-specific stimulation of cells from the spleen and lymph nodes (LN) draining the reproductive tract. Enhanced proliferation was observed in LN following mitogenic but not antigenic (MOMP [major outer membrane protein]) stimulation. In contrast, spleen cell proliferation was lower in chlamydia-infected rats than in saline-treated controls. MHC class II expression, an indicator of inflammatory responses, was upregulated in the uterus, on glandular epithelial cells, and adjacent to glands in response to chlamydial infection. In other experiments, when rats were infected at estrus and diestrus without prior progesterone priming, chlamydial inclusions were not detected in either the uterus or vagina. However, enhanced lymphocyte proliferation was observed in response to mitogenic and MOMP stimulation in the reproductive tract-draining LN from estrous and diestrous animals. These findings indicate that under appropriate endocrine conditions, the rat uterus is susceptible to C. trachomatis infection and that immune responses to this pathogen can be detected locally and systemically. Further, they suggest that clearance of the infection from the reproductive tract involves immune cells from the LN draining the reproductive tract.
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PMID:Chlamydia trachomatis infection in the female reproductive tract of the rat: influence of progesterone on infectivity and immune response. 948 72

Chlamydia species are the causative agents of trachoma, various forms of pneumonia, and the most common sexually transmitted diseases. Although the infection cycle has been extensively characterized in epithelial cells, where the Chlamydia entry-vacuoles avoid fusion with host-cell lysosomes, the cellular immune response has received less attention. Moreover, despite the abundant presence of dendritic cells (DC) in the sites of infection, the interaction between Chlamydia and DC has never been studied. We observe that DC kill Chlamydia trachomatis and Chlamydia psittaci. The chlamydiae are internalized by the DC in a nonspecific manner through macropinocytosis, and the macropinosomes fuse subsequently with DC lysosomes expressing MHC class II molecules. The interaction induces maturation of the DC, since presentation of an exogenous Ag is severely inhibited after a 1-day incubation, although chlamydial Ags are still presented and recognized by Chlamydia-specific CD4+ T cells. Thus, DC most likely play a role in initiating the T cell response in vivo and could potentially be used in adoptive transfer therapies to vaccinate against Chlamydia.
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PMID:Internalization of Chlamydia by dendritic cells and stimulation of Chlamydia-specific T cells. 957 May 47

Human parainfluenza virus type 3 (HPIV3) infection causes severe damage to the lung epithelium, leading to bronchiolitis, pneumonia, and croup in newborns and infants. Cellular immunity that plays a vital role in normal antiviral action appears to be involved, possibly because of inappropriate activation, in the infection-related damage to the lung epithelium. In this study, we investigated the expression of major histocompatibility complex (MHC) class I and II molecules on human lung epithelial (A549) and epithelium-like (HT1080) cells following HPIV3 infection. MHC class I was induced by HPIV3 in these cells at levels similar to those observed with natural inducers such as beta and gamma interferon (IFN-beta and -gamma). MHC class II was also efficiently induced by HPIV3 in these cells. UV-irradiated culture supernatants from infected cells were able to induce MHC class I but not MHC class II, suggesting involvement of released factors for the induction of MHC class I. Quantitation of IFN types I and II in the culture supernatant showed the presence of IFN-beta as the major cytokine, while IFN-gamma was undetectable. Anti-IFN-beta, however, blocked the HPIV3-mediated induction of MHC class I only partially, indicating that viral antigens, besides IFN-beta, are directly involved in the induction process. The induction of MHC class I and class II directed by the viral antigens was confirmed by using cells lacking STAT1, an essential intermediate of the IFN signaling pathways. HPIV3 induced both MHC class I and class II molecules in STAT1-null cells. Furthermore, MHC class II was also induced by HPIV3 in cells defective in class II transactivator, an important intermediate of the IFN-gamma-mediated MHC class II induction pathway. Together, these data indicate that the HPIV3 gene product(s) is directly involved in the induction of MHC class I and II molecules. The induction of MHC class I and II expression by HPIV3 suggests that it plays a role in the infection-related immunity and pathogenesis.
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PMID:Human parainfluenza virus type 3 up-regulates major histocompatibility complex class I and II expression on respiratory epithelial cells: involvement of a STAT1- and CIITA-independent pathway. 988 46

Resistance to the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis has been mapped to MHC class II-restricted, IL-12-dependent CD4+ T cells that secrete a type 1 profile of proinflammatory cytokines, which includes IFN-gamma and TNF-alpha. The relative contribution of IFN-gamma is controversial, however, due to variation in results presented by different laboratories. To determine whether C. trachomatis strain differences contributed to this apparent conflict, the relative resistance of IFN-gamma-deficient mice to murine and human strains of C. trachomatis was compared. All human serovars were much more sensitive to the direct inhibitory actions of IFN-gamma than the MoPn strain. Furthermore, genital clearance of human serovar D in the C57BL/6 mouse was mediated by class II-independent mechanisms that probably involved local production of IFN-gamma by cells of the innate immune system. TNF-alpha also contributed indirectly to host resistance against all strains tested. The differential susceptibility of distinct C. trachomatis strains to effector cytokines such as IFN-gamma could not have been predicted by interstrain biologic variation or by the profile of cytokines stimulated during infection. These findings indicate that strain variation should be considered in situations where related isolates of a given parasite produce conflicting data in models of infection and immunity. They also suggest that stimulation of mucosal IFN-gamma activity is a relevant goal for a human chlamydial vaccine.
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PMID:Differential sensitivity of distinct Chlamydia trachomatis isolates to IFN-gamma-mediated inhibition. 1009 12

Tumour necrosis factor-alpha (TNF) plays a central role in the recruitment and activation of mononuclear cells in mycobacterial infection. In the absence of type 1 TNF receptor, Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection of mice is not contained, leading to fatal disease. Because type 1 TNF receptor binds both TNF and lymphotoxin-a, we used TNF-deficient mice to determine the specific role of TNF in the host resistance to BCG infection. The bacterial burden of the lungs of TNF-deficient mice was substantially increased and the mice succumbed to pneumonia between 8 and 12 weeks with a defective granuloma response. Atypical granulomas developed by 4 weeks expressing low levels of MHC class II, intracellular adhesion molecule (ICAM-1), CD11b and CD11c. Macrophages showed little signs of activation and had low levels of acid phosphatase activity and inducible nitric oxide synthase (INOS) expression. Despite the defective cellular recruitment, the chemokines, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1alpha), were increased in broncho-alveolar lavage fluid of TNF-deficient mice. The defective host response was corrected by the transplantation of normal bone marrow cells into irradiated TNF-deficient mice. These results demonstrate that TNF derived from hemopoietic cells rather than from mesenchymal origin are essential for a normal host response to BCG infection. Furthermore, TNF dependent expression of adhesion molecules may be essential for the recruitment of mononuclear cells for the formation of bactericidal BCG granulomas.
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PMID:Correction of defective host response to Mycobacterium bovis BCG infection in TNF-deficient mice by bone marrow transplantation. 1087 41

Human parainfluenza virus type 3 (HPIV3) is one of the major causes of bronchiolitis, pneumonia, and croup in newborns and infants. Cellular immunity involving major histocompatibility complex (MHC) class I and class II molecules plays an important role in controlling virus infection. Several viruses have been shown to down-regulate gamma interferon (IFN-gamma)-mediated MHC class II expression. In this communication, we show that HPIV3 strongly inhibits the IFN-gamma-induced MHC class II expression in HT1080 human fibrosarcoma cells. The culture supernatant of HPIV3-infected cells also inhibited IFN-gamma-induced MHC class II expression, a phenomenon that was found to be due, in large part, to alpha/beta interferon (IFN-alpha/beta). Expression of MHC class I and intercellular adhesion molecule 1 occurred efficiently in cells simultaneously infected with HPIV3 and treated with IFN-gamma, indicating that the inhibitory effect of HPIV3 was specific to MHC class II. STAT1 activation was not affected by HPIV3 at early postinfection times but was partially inhibited at later times. These data suggested that the potent inhibition of MHC class II expression was, in major part, due to a defect downstream of STAT1 activation in the IFN-gamma-induced MHC class II expression pathway. Class II transactivator (CIITA) is the unique mediator of IFN-gamma-induced transcription from the MHC class II promoter. By RNase protection analysis, CIITA expression was found to be strongly inhibited in HPIV3-infected cells. The culture supernatant containing IFN-alpha/beta, on the other hand, inhibited MHC class II expression without affecting STAT1 and CIITA expression. These data indicate that HPIV3 inhibits IFN-gamma-induced MHC class II expression primarily by the viral gene products targeting CIITA and additionally by inducing IFN-alpha/beta to target one or more steps further downstream.
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PMID:Human parainfluenza virus type 3 inhibits gamma interferon-induced major histocompatibility complex class II expression directly and by inducing alpha/beta interferon. 1115 85


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