Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Measles, accounting for nearly 1 million deaths each year, presents intense involvement of lymphoid organs and the lungs. The immune response in situ in the lungs was determined in blocks recovered from 42 necropsies of children who died from measles determined by immune cell phenotype (CD4, CD8, CD20, CD45RO, CD68, natural killer [NK], and antigen S-100 B [S100]) and cytokine production (interferon, tumor necrosis factor, interleukin [IL]-1, IL-2, IL-4, IL-10, and IL-12). Compared with the lungs of age-paired controls, patients with measles presented severe depletion of CD4+, CD20+, CD68+, NK+, and S100+ cells in alveolus- and bronchus-associated lymphoid tissue without depletion of CD8+ cells. Most of these features were similar in both forms of measles lung involvement, Hecht giant cell, or interstitial pneumonia, but S100+ cells were depleted in bronchus-associated lymphoid tissue from patients with Hecht pneumonia, which also occurs more frequently in malnourished children. IL-10- and IL-12-producing cells were depleted in patients with measles, whereas IL-1-, interferon-, and IL-4-producing cells were more frequently seen in the alveolus of patients with measles compared with controls. Quantitative in situ immune cell phenotype and function in the lung in measles demonstrated severe immune dysfunction, with loss of key cells, such as dendritic, CD4+, and NK+ cells, and deficient cytokine production, which allows for a better comprehension of local reactions in this process.
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PMID:Lung involvement in childhood measles: severe immune dysfunction revealed by quantitative immunohistochemistry. 1749 39

Interaction of ICOS with its ligand is essential for germinal center formation, T cell immune responses, and development of autoimmune diseases. Human ICOS deficiency has been identified worldwide in nine patients with identical ICOS mutations. In vitro studies of the patients to date have shown only mild T cell defect. In this study, we report an in-depth analysis of T cell function in two siblings with novel ICOS deficiency. The brother displayed mild skin infections and impaired Ig class switching, whereas the sister had more severe symptoms, including immunodeficiency, rheumatoid arthritis, inflammatory bowel disease, interstitial pneumonitis, and psoriasis. Despite normal CD3/CD28-induced proliferation and IL-2 production in vitro, peripheral blood T cells in both patients showed a decreased percentage of CD4 central and effector memory T cells and impaired production of Th1, Th2, and Th17 cytokines upon CD3/CD28 costimulation or PMA/ionophore stimulation. The defective polarization into effector cells was associated with impaired induction of T-bet, GATA3, MAF, and retinoic acid-related orphan nuclear hormone receptor (RORC). Reduced CTLA-4(+)CD45RO(+)FoxP3(+) regulatory T cells and diminished induction of inhibitory cell surface molecules, including CTLA-4, were also observed in the patients. T cell defect was not restricted to CD4 T cells because reduced memory T cells and impaired IFN-gamma production were also noted in CD8 T cells. Further analysis of the patients demonstrated increased induction of receptor activator of NF-kappaB ligand (RANKL), lack of IFN-gamma response, and loss of Itch expression upon activation in the female patient, who had autoimmunity. Our study suggests that extensive T cell dysfunction, decreased memory T cell compartment, and imbalance between effector and regulatory cells in ICOS-deficient patients may underlie their immunodeficiency and/or autoimmunity.
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PMID:Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. 1938 Aug

We characterized the cellular immune response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in 12- to 14-month-old BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs, with peak titers on day 2 postinfection. Enhanced production of cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-6 [IL-6]) and chemokines (CXCL10, CCL2, CCL3, and CCL5) correlated with migration of NK cells, macrophages, and plasmacytoid dendritic cells (pDC) into the lungs. By day 7, histopathologic evidence of pneumonitis was seen in the lungs when viral clearance occurred. At this time, a second wave of enhanced production of cytokines (TNF-alpha, IL-6, gamma interferon [IFN-gamma], IL-2, and IL-5), chemokines (CXCL9, CXCL10, CCL2, CCL3, and CCL5), and receptors (CXCR3, CCR2, and CCR5), was detected in the lungs, associated with an influx of T lymphocytes. Depletion of CD8(+) T cells at the time of infection did not affect viral replication or clearance. However, depletion of CD4(+) T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed clearance of SARS-CoV from the lungs, which was associated with reduced neutralizing antibody and cytokine production and reduced pulmonary recruitment of lymphocytes. Innate defense mechanisms are able to control SARS-CoV infection in the absence of CD4(+) and CD8(+) T cells and antibodies. Our findings provide new insights into the pathogenesis of SARS, demonstrating the important role of CD4(+) but not CD8(+) T cells in primary SARS-CoV infection in this model.
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PMID:Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. 1990 20


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