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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

Human adenovirus can cause persistent infections in man. Implicated in this phenomenon is the early transcription unit 3 (E3) of the virus which encodes proteins that are primarily devoted to counteract the lytic attack by the host immune system: Several E3 proteins (14.7K, 10.4K and 14.5K) protect infected cells from the lytic activity of tumor necrosis factor alpha (TNF) while the most abundant E3 protein, E3/19K, inhibits lysis by cytotoxic T cells. E3/19K interacts with class I histocompatibility (MHC) antigens in the rough endoplasmic reticulum, thereby preventing transport of MHC molecules to the cell surface and, consequently, MHC-restricted T cell recognition. In addition, the 10.4K and 14.5K proteins downregulate cell surface expression of the epidermal growth factor receptor. Interestingly, adenovirus-mediated pneumonia in mice is accompanied by induction of TNF, a cytokine known to enhance MHC expression. We previously showed that TNF is unable to restore MHC class I expression in E3/19K transfected cells but rather leads to a further reduction of MHC antigens. This effect correlated with an increased production of E3/19K mRNA and protein. We now find in addition an upregulation of other E3 proteins in transfected as well as in infected cells. This coordinated upregulation of E3 proteins indicates that TNF stimulates the E3 promoter, probably by activating the transcription factor NF-kappa B. Thus, a novel interaction between the immune system and adenovirus is described in which the virus takes advantage of an immune mediator to promote expression of several immunosubversive proteins supporting its escape from immunosurveillance.
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PMID:Tumor necrosis factor alpha increases expression of adenovirus E3 proteins. 853 Jan 42

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

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

The murine gamma-herpesvirus MHV-68 causes an acute, transient pneumonitis, followed by an infectious mononucleosis (IM)-like illness with splenomegaly, widespread latent infection of B lymphocytes and an expansion of Vbeta4+ CD8+ T cells. CD8+ T cells specific for an H-2Db-restricted epitope were prominent during the acute respiratory infection, but their prevalence declined rapidly during the mononucleosis. In contrast, CD8+ T cells specific for an H-2Kb-restricted epitope, apparently expressed by virus-infected B lymphocytes, were most numerous during the mononucleosis illness and were maintained at relatively high frequencies thereafter. The prevalence of all peptide-specific CD8+ T cells decreased during the expansion of the Vbeta4+ CD8+ population, which did not recognize any peptide epitopes identified and was apparent also in an MHC class I-deficient environment. The CD8+ T cell population recognizing productively infected epithelial cells thus differed substantially from that responding during the IM illness.
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PMID:Changing patterns of dominance in the CD8+ T cell response during acute and persistent murine gamma-herpesvirus infection. 1022 71

In a local immune response, the priming and expansion of the antigen-specific T cell population has been thought to largely take place in the draining lymphoid tissue. This model was primarily based on indirect enumeration of antigen-specific T cells by limiting dilution analyses. Here, tetrameric MHC class I complexes were used to evaluate the contribution of different secondary lymphoid organs in a local immune response by following the CD8+ T cell responses against the immunodominant epitopes of influenza A virus and herpes simplex virus-1. Mice were either intranasally infected with influenza A virus and developed pneumonia or were intradermally injected with herpes simplex virus-1. Remarkably, even though these viruses cause a local infection, the spleen of infected animals contains approximately 50-fold more antigen-specific cytotoxic T cells than the draining lymph nodes. Although antigen-specific T cells in spleen appear not to have experienced any recent encounter with antigen, this population is actively dividing, and over time, the formation of a memory T cell population is observed. These data reveal that there is a remarkably large and distinct population of antigen-specific T cells in spleen in the course of a local antigenic challenge. This T cell compartment may not only form the foundation of a memory T cell pool but could also provide a safeguard against systemic spreading of an infection.
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PMID:Systemic T cell expansion during localized viral infection. 1022 83

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

Much of the CD8(+) T cell response in H2(b) mice with influenza pneumonia is directed at the nucleoprotein(366-374) (NP(366)) and acid polymerase(224-233) (PA(224)) peptides presented by the H2D(b) MHC class I glycoprotein. These D(b)NP(366)- and D(b)PA(224)-specific T cell populations are readily analyzed by staining with tetrameric complexes of MHC(+) peptide (tetramers) or by cytokine production subsequent to in vitro stimulation with the cognate peptides. The D(b)PA(224)-specific CD8(+) effector T cells make more tumor necrosis factor (TNF) alpha than the comparable CD8(+)D(b)NP(366)(+) set, a difference reflected in the greater sensitivity of the CD8(+)D(b)PA(224)(+) population to TNF receptor (TNFR) 2-mediated apoptosis under conditions of in vitro culture. Freshly isolated CD8(+)D(b)NP(366)(+) and CD8(+)D(b)PA(224)(+) T cells from influenza-infected TNFR2(-/-) mice produce higher levels of IFN-gamma and TNF-alpha after in vitro stimulation with peptide, although the avidity of the T cell receptor-epitope interaction does not change. Increased numbers of both CD8(+)D(b)PA(224)(+) and CD8(+)D(b)NP(366)(+) T cells were recovered from the lungs (but not the spleens) of secondarily challenged TNFR2(-/-) mice, a pattern that correlates with the profiles of TNFR expression in the TNFR2(+/+) controls. Thus, it seems that TNFR2-mediated editing of influenza-specific CD8(+) T cells functions to limit the numbers of effectors that have localized to the site of pathology in the lung but does not modify the size of the less activated responder T cell populations in the spleen. Therefore, the massive difference in magnitude for the secondary, although not the primary, response to these D(b)NP(366) and D(b)PA(224) epitopes cannot be considered to reflect differential TNFR2-mediated T cell editing.
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PMID:Differential tumor necrosis factor receptor 2-mediated editing of virus-specific CD8+ effector T cells. 1499 9

Pneumonia virus of mice (PVM) is a natural pathogen of mice and has been proposed as a tractable model for the replication of a pneumovirus in its natural host, which mimics human infection with human respiratory syncytial virus (RSV). PVM infection in mice is highly productive in terms of virus production compared with the situation seen with RSV in mice. Because RSV suppresses CD8 T cell effector function in the lungs of infected mice, we have investigated the nature of PVM-induced CD8 T cell responses to study pneumovirus-induced T cell responses in a natural virus-host setting. PVM infection was associated with a massive influx of activated CD8 T cells into the lungs. After identification of three PVM-specific CD8 T cell epitopes, pulmonary CD8 T cell responses were enumerated. The combined frequency of cytokine-secreting CD8 T cells specific for the three epitopes was much smaller than the total number of activated CD8 T cells. Furthermore, quantitation of the CD8 T cell response against one of these epitopes (residues 261-270 from the phosphoprotein) by MHC class I pentamer staining and by in vitro stimulation followed by intracellular IFN-gamma and TNF-alpha staining indicated that the majority of pulmonary CD8 specific for the P261 epitope were deficient in cytokine production. This deficient phenotype was retained up to 96 days postinfection, similar to the situation in the lungs of human RSV-infected mice. The data suggest that PVM suppresses T cell effector functions in the lungs.
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PMID:Activation and inactivation of antiviral CD8 T cell responses during murine pneumovirus infection. 1627 14

Pneumocystis, a fungal, extracellular pathogen causes a life-threatening pneumonia in patients with severe immunodeficiencies. In the absence of CD4 T cells, Pneumocystis infection results in vigorous CD8 T cell influx into the alveolar and interstitial spaces of the lung. This response results in lung damage characterized by low pO2 and albumin leakage into the bronchoalveolar lavage fluid similar to other CD8 T cell-mediated interstitial lung diseases. How this extracellular pathogen elicits a CD8 T cell response is not clear, and it was the aim of our study to determine the Ag specificity of the recruited CD8 T cells and to determine whether MHC class I (MHC I) expression was necessary to initiate lung damage. Using an adoptive T cell-transfer model with either polyclonal wild-type CD8 T cells or transgenic influenza virus-specific CD8 T cells we found that CD8 T cell recruitment is Ag-specific and requires the continuous presence of the Pneumocystis pathogen. Bone marrow chimera experiments using Rag-1 and beta2-microglobulin-deficient mice as hosts demonstrated a requirement for MHC I expression on nonbone marrow-derived cells of the lung. This suggests either direct processing of Pneumocystis Ags by nonbone marrow-derived cells of the lung or the induction of lung damage triggered by a lung-specific autoantigen. Using perforin-, Fas-, and IFN-gamma-deficient animals, we showed that these molecules are not directly involved in the CD8-mediated lung damage. However, CD8 T cell-mediated lung damage is Ag-specific is induced by a MHC I-expressing nonbone marrow-derived cell in the lung and is dependent on the continued presence of live Pneumocystis.
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PMID:CD8 T cell-mediated lung damage in response to the extracellular pathogen pneumocystis is dependent on MHC class I expression by radiation-resistant lung cells. 1633 67


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