UMLS:C0032285 - FACTA Search

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

Because of an increasing number of patients suffering from Leishmania infections and because of the serious consequences of these infections more thorough knowledge of the host factors responsible for resistance and susceptibility to the diseases is needed. In murine models of Leishmania infections the cytokine production by CD4+ T cells has been identified as a major factor in determining the outcome of the infection. In these models Th1 cells producing IFN-gamma provide protection against the infection whereas Th2 cells producing IL-4 and IL-10 aggravate the disease. The fatal outcome of Leishmania infections in humans with defects in T-cell functions illustrates that these cells are fundamental in the defence against Leishmania in humans also. However, as for many other infectious diseases (meningococcal disease and other septicaemic conditions, pneumonia, viral hepatitis, schistosomiasis) the immune reactions to Leishmania parasites in humans can be associated with both protection and pathogenesis. Many individuals without previous exposure to Leishmania parasites have T cells which can respond to Leishmania antigens. These cells have the potential to generate either Th1 or Th2 like responses. During infection with Leishmania parasites humans develop specific T-cell recognition of well-characterized parasite antigens. T cells producing disease-exacerbating factors such as IL-4 in response to Leishmania antigen stimulation have been identified in humans as well as in mice. Both Th1 like and Th2 like cells recognizing Leishmania antigens can be expanded during infection. At the polyclonal level Th1 like responses to Leishmania antigens are found in individuals who have had self-healing or asymptomatic infections. Factors secreted by such Leishmania specific Th1 like cells can induce killing of intracellular parasites in infected macrophages. In individuals who have been cured from uncontrollable disseminating disease both Th1 and Th2 like responses can be detected. A restriction in the antigen recognition to particular protein fractions could not be demonstrated in the Th1 or Th2 like responses. These findings suggest an association between the pattern of cytokines produced by parasite specific T cells and the clinical course of the infection similar to the one seen in mice. In the murine model the cytokine pattern present in the animal at the time of infection can determine whether a Th1- or a Th2 response will develop. In vitro studies on human and murine cells have confirmed that certain cytokines (e.g. IFN-gamma, IL-12) will favour maturation of Th1 responses whereas others (e.g. IL-4, IL-10) support Th2 development. If similar immunoregulatory mechanisms operate in mouse and man, design of vaccines against human leishmaniasis should aim at introducing powerful Th1 like responses. Importantly, once generation of either Th1 or Th2 has started, the immune response seems to be locked in this pattern, even when it is harmful to the host. Therefore new vaccines against leishmaniasis should be designed in a way that they generate controlled Th1 like primary responses.
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PMID:Regulator and effector functions of T-cell subsets in human Leishmania infections. 906 93

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

Whether there is a pathogenic or protective outcome to chlamydial infection may be defined by the host response. We infected C57BL/6 (C57) and C3H/HeN (C3H) mice with the human biovar of Chlamydia trachomatis, serovar E, and, in select experiments, with the mouse pneumonitis agent of C. trachomatis (MoPn). We compared the courses of infection, histopathology, and host responses that resulted from these infections. The duration of infection with either chlamydial biovar was significantly increased in the C3H strain of mice. The intensity of infection was examined in mice infected with serovar E, and it was significantly increased in the C3H strain. Histopathology revealed the incidence of severe hydrosalpinx to be significantly greater in C3H mice than in C57 mice. In contrast, severe distention of the uterine horns was observed in all infected C57 mice compared to none of the C3H mice infected with serovar E and only 25% of those infected with MoPn. Acute inflammation was significantly increased in the uterine horns of C57 mice compared to that of C3H mice. Examination of antigen-specific responses revealed qualitatively similar responses in the two strains. Determination of gamma interferon- versus interleukin 4- producing cells revealed the predominance of a Th1 response in both strains. Serum enzyme-linked immunosorbent assays for immunoglobulin G1 (IgG1) and IgG2a revealed a predominance of IgG2a antibody in both strains, although the levels of antibody were significantly greater in C3H mice. Lymphocyte proliferation studies revealed increased proliferation in the iliac nodes of both strains at 1 to 3 weeks after infection. Because of the early eradication of infection observed in the C57 strain, we explored the relative production of tumor necrosis factor alpha (TNF-alpha) in the two strains. TNF-alpha levels were significantly increased in the genital tract secretions of C57 mice compared to that of C3H mice during the first week of infection. Increased TNF-alpha may be beneficial to the host by leading to earlier eradication of infection, thereby preventing infection of the oviduct and thus the major disease sequelae associated with chlamydial infection of the genital tract.
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PMID:Mouse strain-dependent variation in the course and outcome of chlamydial genital tract infection is associated with differences in host response. 923 55

Mycobacteria are ubiquitous in the environment, but they are not part of the normal human microbial flora. It has been suggested that variable contact with mycobacteria can influence susceptibility to mycobacterial pathogens and the efficacy of subsequent Mycobacterium bovis BCG vaccination. To test this, mice were immunized with high or low doses of an environmental saprophyte, M. vaccae, that is intensely immunogenic as an autoclaved preparation. Two months later, they received an intratracheal challenge with M. tuberculosis H37Rv. Recipients of a low Th1-inducing dose (10(7) organisms) were partially protected and maintained a high ratio of interleukin 2 (IL-2)-positive to IL-4-positive cells in the perivascular, peribronchial, and granulomatous areas of the lung, whereas in unimmunized controls the IL-4-positive cells increased markedly between days 21 and 28. In contrast, recipients of the high dose (10(9) organisms), which primes Th2 as well as Th1 cytokine production, died more rapidly than unimmunized controls and showed massive pneumonia from day 7. The ratio of IL-2-positive to IL-4-positive cells in all compartments of the lung rapidly fell to 1 by day 14 for these animals. These events correlated with cytokine mRNA profiles and with increases in the local toxicity of tumor necrosis factor alpha (TNF-alpha), demonstrable only when a major Th2 component was present. These data indicate that cross-reactive epitopes present in an environmental saprophyte can evoke either protective responses or responses that increase susceptibility to M. tuberculosis. The latter are associated with the presence of a Th2 component and increased sensitivity to TNF-alpha.
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PMID:Pathogenesis of tuberculosis in mice exposed to low and high doses of an environmental mycobacterial saprophyte before infection. 923 93

To determine whether different antibody isotypes associated with T helper 1 (Th1) or Th2 responses are protective against Pneumocystis carinii, mice with disrupted interleukin 4 genes (IL-4(-/-) mice) or gamma interferon genes (IFN-gamma(-/-) mice) along with wild-type C57BL/6 mice were immunized intratracheally against P. carinii, depleted of T cells in vivo by use of monoclonal antibodies, and rechallenged intratracheally with 10(7) viable P. carinii organisms. Nearly all immunized mice resolved their lung P. carinii infections (limit of detection, log10 4.06) within 21 days of challenge even though they were depleted of T cells. Unimmunized mice depleted of T cells had significant lung infections (>log10 5.5) at day 21 post-P. carinii challenge. IFN-gamma(-/-) and wild-type mice developed P. carinii-specific immunoglobulin primarily of the immunoglobulin G1 (IgG1) subclass with relatively little P. carinii-specific IgG2a, IgG2b, or IgG3 in their sera, characteristic of a Th2-type response. In contrast, IL-4(-/-) mice had primarily an IgG2b P. carinii-specific antibody response in their sera with very little IgG1. Although IgG2b was the predominant isotype in IL-4(-/-) mice, optical density values of IgG2a and IgG3 were significantly higher in these mice (two and three times, respectively) than in IFN-gamma(-/-) mice, characteristic of a Th1-type response. Together, these data indicate that resolution of P. carinii infection can be mediated by specific antibody responses and that the antibody response can be either a predominantly Th1 or Th2 type. Furthermore, although wild-type mice mounted a Th2-like antibody response, IL-4(-/-) mice could resolve P. carinii pneumonia, indicating that resistance to P. carinii can occur in the absence of IL-4.
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PMID:Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses. 939 95

Immunity to Mycobacterium tuberculosis requires a T helper 1 (Th1) cytokine balance accompanied by tumour necrosis factor-alpha (TNF-alpha), and activated macrophages. These facets of the immune response are sensitive to suppression by glucocorticoids (GC), which can reactivate and exacerbate tuberculosis in man and animals. Dehydroepiandrosterone (DHEA) and its derivative, 3beta,17beta androstenediol (AED), are reported to have antiglucocorticoid properties in vivo. We therefore investigated the effects of predetermined optimal doses of these compounds, on the course of pulmonary tuberculosis in an established model in BALB/c mice in which an early phase of Th1-mediated response accompanied by adrenal hyperplasia, is followed by a switch to Th2, progressive loss of TNF-alpha expression and disease progression. Both compounds were protective, particularly AED which caused a fall in bacterial counts and prolonged survival. These effects correlated with the appearance within 3 days of cellular infiltrates rich in cells expressing interleukin-2 (IL-2), IL-1alpha and TNF-alpha, and with partial suppression of the switch to IL-4 producing cells that occurred in controls. AED also caused enhanced development of granulomas at 14 days, and persistence of granuloma formation to 120 days, with a corresponding suppression of areas affected by pneumonia. Much of the therapeutic effect of AED and DHEA was obtained by treating for only the first 3 weeks, which is the phase of adrenal hyperplasia. These results suggest that the ratio of GC to anti-GC steroids may play a role in the pathogenesis of tuberculosis, and further investigation could lead to novel treatment strategies.
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PMID:The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice. 982 81

A 38-year-old man was hospitalized in our university hospital because of pulmonary opacities with bilateral hilar and mediastinal lymphadenopathy seen on chest radiograph. Eosinophilia was observed in the circulation and bronchoalveolar lavage (BAL) fluid. Histological examination revealed noncaseating epithelioid granulomas and eosinophilic infiltration in the lung. Based on these findings, a diagnosis of sarcoidosis combined with chronic eosinophilic pneumonia was made. The infiltrates on chest radiograph and BAL eosinophilia were promptly reduced with corticosteroid therapy, but only mild reduction was observed in diffuse nodular shadows and hilar and mediastinal lymphadenopathy, and high amounts of lymphocytes in BAL fluid remained. Increased IFN-gamma, IL-4 and IL-5 were detected in the BAL fluid, and corticosteroid therapy reduced IL-4 and IL-5 (Th-2 cytokines) but not IFN-gamma (Th-1 cytokine). These cytokine levels in BAL fluid were intimately correlated with the clinical course of sarcoidosis and chronic eosinophilic pneumonia.
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PMID:A case of sarcoidosis associated with chronic eosinophilic pneumonia. 986 74

Resistance to Pneumocystis carinii is achieved through cell-mediated and humoral immunity, but the interplay between these two systems in the immunocompetent host is not fully understood. TCRbetaxdelta-/- double-mutant mice deficient of all T cell populations naturally acquired P. carinii pneumonia with lethal consequences. Moribund mutants displayed numbers of pulmonary pathogens comparable to RAG-1-/- mice lacking all functional T and B lymphocytes. Pulmonary lavage cells of diseased TCRbetaxdelta-/- mutants secreted proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-12, and interferon-gamma, but not IL-4, -5, or -10. Serum immunoglobulin levels of both healthy and diseased mice were significantly reduced compared with immunocompetent animals. Secreted antibodies were mainly IgM, which also bound P. carinii. Mutants completely lacked IgG1, emphasizing strict T cell dependence of immunoglobulin switching to this isotype. Other IgG subclasses were strongly reduced and did not bind P. carinii. These results suggest that T cells are crucial for generation of antibodies against P. carinii relevant to resistance.
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PMID:Pneumocystis carinii pneumonia in mutant mice deficient in both TCRalphabeta and TCRgammadelta cells: cytokine and antibody responses. 987 31

We studied cytokine proteins and mRNAs in mice with two forms of Toxoplasma gondii pneumonia resulting from reactivation of infection. In the first form, mice were infected with T. gondii, developed and recovered from systemic disease, and then developed pneumonia 3 weeks later. As pulmonary inflammation developed, levels of cytokine mRNAs for gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 increased in bronchoalveolar lavage (BAL) cells or lung tissue, and the level of IFN-gamma protein increased in BAL fluid. The second form of pneumonia occurred as a complication of primary cytomegalovirus (CMV) disease in mice with dormant T. gondii infection. During CMV disease, IL-2 mRNA levels decreased in lung tissue, IL-10 protein levels increased in lung tissue, and IL-10 protein levels increased in BAL fluid. As the mice recovered from CMV disease, T. gondii infection was reactivated in the lungs and was manifested as T. gondii pneumonia. During CMV-induced T. gondii pneumonia, IFN-gamma, IL-2, IL-4, and IL-10 mRNA levels increased in BAL cells or lung tissue, and both IFN-gamma and IL-2 protein levels increased in BAL fluid. We concluded that both forms of T. gondii pneumonia are accompanied by increases in both type 1 T-helper and type 2 T-helper cytokine levels in lungs. The mechanism of CMV-induced reactivation of T. gondii infection in lungs may involve local decreases in IL-2 levels and/or increases in IL-10 levels.
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PMID:Changes in cytokine levels during reactivation of Toxoplasma gondii infection in lungs. 1022 58

Delayed-type hypersensitivity (DTH) has been demonstrated to be a Th1 type immune response which is important in the host defense against infection with intracellular bacteria, including Chlamydia. In the present study, we surprisingly observed that C. trachomatis mouse pneumonitis MoPn-infected IFN-gamma gene knockout (KO) mice mounted strong DTH responses following foopad challenge with inactivated organisms. The DTH responses in IFN-gamma KO mice were associated with Th2 cytokine production and partially blocked by anti-IL-4 monoclonal antibodies. In addition, the inflammatory cells in IFN-gamma KO mice failed to target the cellular sites of chlamydial inclusions in infected tissues and failed to clear the infection. The data, in conjunction with previous studies, suggest that different types (Th1 and Th2 associated) of DTH responses may function differently in host defense against chlamydial infection and that the functional differences in DTH responses may account for the dual role that DTH is speculated to play in chlamydial protective immunity and immunopathology. Moreover, the data suggest that the IFN-gamma KO mouse is a useful model system for studying chlamydial pathogenesis.
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PMID:IFN-gamma knockout mice show Th2-associated delayed-type hypersensitivity and the inflammatory cells fail to localize and control chlamydial infection. 1055 35

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