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PubMed2002

[Analysis of gene expression patterns of periphery lymphocytes in patients with nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: The periphery T and B lymphocytes are most important immune cells in a body. Analysis for the gene expression profiles of the immune cells will contribute to the understanding of the biological essence of immune suppression. The advanced technique of DNA microarray make it possible to monitor the expression of thousands of genes simultaneously in one hybridization experiment until recently. In this paper, the authors investigated the genes differentially expression in periphery lymphocytes between the patients with Nasopharyngeal Carcinoma(NPC) and health donors to explore the features of gene expression in immune cells of NPC patients. METHODS: The BioDoor10s/D chips containing 2000 spots of cDNAs were used to investigate the difference of the expression. Both the mRNAs from periphery lymphocytes of NPC patients (2 x 10(8)) and health donors(2 x 10(8)) were reversely transcribed to cDNA with the incorporation of fluorescent(cy5 and cy3) labeled dUTP to prepare the hybridization probes. After hybridization, BioDoor10s/D chips were scanned for the fluorescent intensity. The differentially expressed genes were screened. RESULTS: The total of 62 genes has differentially expression in NPC periphery lymphocytes. The number of over- and lower-expressed genes were 5 and 57, respectively. There were 3 genes coding for signal transductive proteins in 5 over-expressed genes. Five genes coding for signal transductive proteins were involved in 9 genes with lowest-expression (cy5/cy3 > or = 0.3). CONCLUSION: There was the consistent tendency toward lower-expressed gene in periphery lymphocytes from the patients with NPC. The disorder in signal transductive function of lymphocytes may be a factor distinguishing NPC immunity from the health one. Improvement of gene expressing profil may also be a way to enhance immune function in tumor patients.

Adult↗
PubMed2006

Immune responses to trichloroethylene and skin gene expression profiles in Sprague Dawley rats.

OBJECTIVE: To characterize the immune reaction in SD rats exposed to trichloroethylene (TCE) and to identify the gene expression profiles involved in skin after TCE exposure. METHODS: Fifteen percent of TCE was injected intradermally into the rat back (100 microL/120 g) at intervals of 7 days. Whole blood was collected 24 h after the fifth or seventh intradermic administration of TCE. The percentages of CD4+ and CD8+ of T lymphocytes were measured by a flow cytometer. The concentrations of IFN-gamma and IL-4 in the serum were semi-quantified by ELISA. Total RNAs of skin samples at 3 h or 24 h after the seventh dose of TCE in SD rats were extracted, and gene expression profiles of these tissues were analyszed by rat toxicology U34 array of Affymetrix. RESULTS: Obvious decline of CD4+ in T lymphocytes was observed in the TCE-administer group. No significant concentration differences in IFN-gamma and IL-4 were found between TCE-treated and control rats. Gadd45a and Mel were significantly up regulated in skin tissue 24 h after TCE exposure. The expression regulation of immune response factors was as active as proteins associated with lipid metabolism and synthesis process in these skin samples of SD rats exposed to TCE. CONCLUSION: T-helper type 1 cells mediate immune response can not be elicited in TCE-treated SD rats, but certain immune disorder can be induced.

Animals↗
PubMed1994

Inadequate immunization among 2-year-old children: a profile of children at risk.

A community survey was conducted to assess the immunization status of 2-year-old children and barriers to immunization. The 299 respondents were more affluent and well-educated than the general population. Eighty-three percent of the respondents received immunizations from private physicians. Only 31.1% of the children were age-appropriately immunized with deficiencies primarily in receiving the 18-month dosages of diphtheria-tetanus-pertussis (DTP) and polio. Parents reported multiple barriers and beliefs about immunization amenable to change by health providers. A profile of risk factors differentiating nonimmunized from immunized children was developed.

Adult↗
PubMed2005

Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals.

Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. HUG95A Affymetrix DNA chips that contained oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student t-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signalling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases, including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T cells. Some of the up-regulated genes, such as TGM1, IVL, FABP5, CSTA and SPRR, are well-known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the up-regulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic interferon- and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.

Adult↗
PubMed2002

Salivary gland extract from Ixodes ricinus tick modulates the host immune response towards the Th2 cytokine profile.

In our previous work, the salivary gland extract (SGE) from Ixodes ricinus ticks impaired T-lymphocyte proliferation and clearly modulated the immune response towards the Th2 pattern in human peripheral blood mononuclear cell culture. In the present work, the results obtained on mouse splenocytes are compared with those on human leukocytes. ELISA (protein level) and RNAse protection assay (mRNA level) showed that SGE enhanced interleukin (IL)-1alpha, IL-1beta, IL-1Ra, IL-6, and IL-12p40 cytokines, whereas production of IL-2, IL-5, IL-10, and IL-13 was decreased. The minute levels of IL-9, IL-15 and IL-12p70 were not changed after the addition of tick saliva. IL-4 was upregulated, whereas the production of gamma interferon and migratory inhibition factor was downregulated after the addition of SGE. Tick saliva decreased concanavalin A-stimulated spleen cell proliferation and the percentage of activated T-cells. We conclude that the Th2 polarization did not involve all of the cytokines tested. However, the Th2 subset-augmenting effect of tick saliva was confirmed.

Animals↗
PubMed1983

Acquired immune dysfunction in homosexual men: immunologic profiles.

Homosexual men with Kaposi sarcoma, lymphadenopathy syndrome, opportunistic infection, and nonhomosexual traditional Kaposi sarcoma were evaluated for B cell, T cell, and complement immunity and compared to normal controls and homosexual controls. No significant immunologic abnormalities were found in the traditional Kaposi group. All homosexual groups, including the homosexual controls, had a significant decrease in the helper/suppressor cell ratio. Functional abnormalities of T-cell immunity were observed in the homosexual Kaposi sarcoma, lymphadenopathy syndrome, and opportunistic infection groups. Significant elevations of IgG, IgM, IgA, and IgE were found in the lymphadenopathy group, while only IgG and IgA were elevated in the Kaposi sarcoma group. C3, C4, and immune complexes were normal, while total hemolytic complement activity was increased in the Kaposi sarcoma and lymphadenopathy syndrome groups.

Acquired Immunodeficiency Syndrome↗
PubMed2003

High-resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein D.

Lung surfactant protein D (SP-D) can directly interact with carbohydrate residues on pulmonary pathogens and allergens, stimulate immune cells, and manipulate cytokine and chemokine profiles during the immune response in the lungs. Therapeutic administration of rfhSP-D, a recombinant homotrimeric fragment of human SP-D comprising the alpha-helical coiled-coil neck plus three CRDs, protects mice against lung allergy and infection caused by the fungal pathogen Aspergillus fumigatus. The high resolution crystal structures of maltose-bound rfhSP-D to 1.4A, and of rfhSP-D to 1.6A, define the fine detail of the mode and nature of carbohydrate recognition and provide insights into how a small fragment of human SP-D can bind to allergens/antigens or whole pathogens, and at the same time recruit and engage effector cells and molecules of humoral immunity. A previously unreported calcium ion, located on the trimeric axis in a pore at the bottom of the funnel formed by the three CRDs and close to the neck-CRD interface, is coordinated by a triad of glutamate residues which are, to some extent, neutralised by their interactions with a triad of exposed lysine residues in the funnel. The spatial relationship between the neck and the CRDs is maintained internally by these lysine residues, and externally by a glutamine, which forms a pair of hydrogen-bonds within an external cleft at each neck-CRD interface. Structural links between the central pore and the cleft suggest a possible effector mechanism for immune cell surface receptor binding in the presence of bound, extended natural lipopolysaccharide and phospholipid ligands. The structural requirements for such an effector mechanism, involving both the trimeric framework for multivalent ligand binding and recognition sites formed from more than one subunit, are present in both native hSP-D and rfhSP-D, providing a possible explanation for the significant biological activity of rfhSP-D.

Amino Acid Sequence↗
PubMed1986

Differential regulation of effector responses of cell mediated immunity in experimental salmonellosis.

Delayed type hypersensitivity (DTH) and protective cell mediated immunity showed different profiles with respect to time following intraperitoneal immunization with live Salmonella enteritidis. Whereas the DTH response decreased with time the Protection Index increased. The decline in DTH response was found to be associated with suppressor cells generated by intraperitoneal immunization and could be prevented by cyclophosphamide treatment prior to immunization. It was concluded that the two effector responses of cell mediated immunity were under differential regulation.

Animals↗
PubMed2005

The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes.

n-3 Polyunsaturated fatty acids (PUFAs) are recognized as having an anti-inflammatory effect, which is initiated and propagated via a number of mechanisms involving the cells of the immune system. These include: eicosanoid profiles, membrane fluidity and lipid rafts, signal transduction, gene expression and antigen presentation. The wide-range of mechanisms of action of n-3 PUFAs offer a number of potential therapeutic tools with which to treat inflammatory diseases. In this review we discuss the molecular, animal model and clinical evidence for manipulation of the immune profile by n-3 PUFAs with respect to inflammatory bowel disease. In addition to providing a potential therapy for inflammatory bowel disease there is also recent evidence that abnormalities in fatty acid profiles, both in the plasma phospholipid membrane and in perinodal adipose tissue, may be a key component in the multi-factorial aetiology of inflammatory bowel disease. Such abnormalities are likely to be the result of a genetic susceptibility to the changing ratios of n-3 : n-6 fatty acids in the western diet. Evidence that the fatty acid components of perinodal adipose are fuelling the pro- or anti-inflammatory bias of the immune response is also reviewed.

Dietary Fats, Unsaturated↗
PubMed2003

Parasitic infection and the polarized Th2 immune response can alter a vaccine-induced immune response.

The AIDS epidemic in the Developing World represents a major global crisis. It is imperative that we develop an effective vaccine. Vaccines are economically the most efficient means of controlling viral infections. However, the development of a vaccine against HIV-1 has been a formidable task, and in developing countries chronic parasitic infection adds another level of complexity to AIDS vaccine development. Helminthic and protozoan infections, common in developing countries, can result in a constant state of immune activation that is characterized by a dominant Th2 type of cytokine profile, high IgE levels, and eosinophilia. Such an immune profile may have an adverse impact on the efficacy of vaccines, in particular, an HIV-1 vaccine. Indeed, the CD8 cellular immune response and the corresponding Th1 type cytokines that enhance the CD8 cellular immune response are important for clearing many viral infections. It is believed that an antigen specific CD8 cellular immune response will be an important component of an HIV-1 vaccine.

AIDS Vaccines↗
PubMed2005

Differential protease, innate immunity, and NF-kappaB induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice.

Cigarette smoke exposure is a major determinant of adverse lung health, but the molecular processes underlying its effects on inflammation and immunity remain poorly understood. Therefore, we sought to understand whether inflammatory and host defense determinants are affected during subchronic cigarette smoke exposure. Dose-response and time course studies of lungs from Balb/c mice exposed to smoke generated from 3, 6, and 9 cigarettes/day for 4 days showed macrophage- and S100A8-positive neutrophil-rich inflammation in lung tissue and bronchoalveolar lavage (BAL) fluid, matrix metalloproteinase (MMP) and serine protease induction, sustained NF-kappaB translocation and binding, and mucus cell induction but very small numbers of CD3+CD4+ and CD3+CD8+ lymphocytes. Cigarette smoke had no effect on phospho-Akt but caused a small upregulation of phospho-Erk1/2. Activator protein-1 and phospho-p38 MAPK could not be detected. Quantitative real-time PCR showed upregulation of chemokines (macrophage inflammatory protein-2, monocyte chemoattractant protein-1), inflammatory mediators (TNF-alpha, IL-1beta), leukocyte growth and survival factors [granulocyte-macrophage colony-stimulating factor, colony-stimulating factor (CSF)-1, CSF-1 receptor], transforming growth factor-beta, matrix-degrading MMP-9 and MMP-12, and Toll-like receptor (TLR)2, broadly mirroring NF-kappaB activation. No upregulation was observed for MMP-2, urokinase-type plasminogen activator, tissue-type plasminogen activator, and TLRs 3, 4, and 9. In mouse strain comparisons the rank order of susceptibility was Balb/c > C3H/HeJ > 129SvJ > C57BL6. Partition of responses into BAL macrophages vs. lavaged lung strongly implicated macrophages in the inflammatory responses. Strikingly, except for IL-10 and MMP-12, macrophage and lung gene profiles in Balb/c and C57BL/6 mice were very similar. The response pattern we observed suggests that subchronic cigarette smoke exposure may be useful to understand pathogenic mechanisms triggered by cigarette smoke in the lungs including inflammation and alteration of host defense.

Animals↗
PubMed2004

Development and maturation of the immune system in zebrafish, Danio rerio: a gene expression profiling, in situ hybridization and immunological study.

The development and maturation of the immune system in zebrafish was investigated using immune-related gene expression profiling by quantitative real-time polymerase chain reaction, in situ hybridization (ISH), immunoglobulin (Ig) detection by immuno-affinity purification and Western blotting as well as immersion immunization experiments. Ikaros expression was first detected at 1 day post-fertilization (dpf) and thereafter increased gradually to more than two-fold between 28 and 42dpf before decreasing to less than the initial 1dpf expression level in adult fish (aged 105dpf). Recombination activating gene-1 (Rag-1) expression levels increased rapidly (by 10-fold) between 3 and 17dpf, reaching a maximum between 21 and 28dpf before decreasing gradually. However, in adult fish aged 105dpf, the expression level of Rag-1 had dropped markedly, and was equivalent to the expression level at 3dpf. T-cell receptor alpha constant region and immunoglobulin light chain constant region (IgLC) isotype-1, 2 and 3 mRNAs were detected at low levels by 3dpf and their expression levels increased steadily to the adult range between 4 and 6 weeks post-fertilization (wpf). Using tissue-section ISH, Rag-1 expression was detected in head kidney by 2wpf while IgLC-1, 2 and 3 were detected in the head kidney and the thymus by 3wpf onwards. Secreted Ig was only detectable using immuno-affinity purification and Western blotting by 4wpf. Humoral response to T-independent antigen (formalin-killed Aeromonas hydrophila) and T-dependent antigen (human gamma globulin) was observed in zebrafish immunized at 4 and 6wpf, respectively, indicating that immunocompetence was achieved. The findings reveal that the zebrafish immune system is morphologically and functionally mature by 4-6wpf.

Animals↗
PubMedDate not supplied

[A computer system for analysis and presentation of the results of studies of the immune status of patients with a profile of resuscitation].

Logical principles for the use of computer technology in the assessment of medical information in intensive care units are outlined. A computer system for the assessment of the results of immune status studies has been presented. The potentials are demonstrated to form the data bank with realization of precedent search function, presentation of information with the help of computer graphics and calculation of highly informative secondary indexes on the basis of primary ones.

Computer Systems↗
PubMed2026

Transcriptomic Profiling Reveals NF-κB-Associated Immune Regulatory Signatures Underlying the Regenerative Effects of Hypoxia-Preconditioned Tendon Stem Cell-Derived Extracellular Vesicles.

Remodeling of the immune microenvironment is a critical determinant of tissue regeneration, yet the molecular programs associated with the enhanced therapeutic activity of hypoxia-preconditioned extracellular vesicles remain incompletely defined. In this study, we investigated the regenerative and immunomodulatory effects of hypoxia-preconditioned tendon stem cell-derived extracellular vesicles (Hypo-EVs) and employed transcriptomic profiling to identify molecular signatures associated with their biological activity. The therapeutic effects of Hypo-EVs were evaluated using a rat patellar tendon defect model and lipopolysaccharide-stimulated RAW 264.7 macrophages. Histological analysis, immunostaining, biomechanical testing, and reverse transcription-quantitative polymerase chain reaction were performed to assess tendon healing and macrophage polarization, while RNA sequencing was conducted in macrophages treated with Hypo-EVs or normoxia-derived EVs, followed by Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes pathway analyses. Hypo-EVs significantly alleviated local inflammatory responses, improved collagen organization and biomechanical properties of repaired tendons, and promoted macrophage polarization toward a reparative M2 phenotype both in vivo and in vitro. Consistent with these biological effects, transcriptomic profiling revealed extensive remodeling of inflammation-related gene expression programs, including significant suppression of NF-κB, TNF, IL-17, and cytokine-cytokine receptor interaction pathways. Integrative bioinformatic analyses identified an NF-κB-associated immune-regulatory signature that distinguished Hypo-EV-treated macrophages from those receiving normoxic EVs. Mechanistically, Hypo-EVs attenuated NF-κB activation, as evidenced by reduced phosphorylation of p65 and IκBα, whereas TNF-α-mediated NF-κB activation partially diminished their macrophage-repolarizing effects. Collectively, these findings demonstrate that hypoxic preconditioning enhances the immunomodulatory and regenerative functions of tendon stem cell-derived EVs. Transcriptomic analyses identified an NF-κB-associated immune-regulatory signature linked to the biological activity of Hypo-EVs, providing a molecular framework for understanding EV-mediated immune modulation and supporting the development of transcriptome-guided molecular signatures for regenerative therapies targeting tendon immune homeostasis.

Animals↗
PubMed1998

Anti-120-kDa alpha-fodrin immune response with Th1-cytokine profile in the NOD mouse model of Sjögren's syndrome.

Our recent study suggested that the 120-kDa alpha-fodrin molecule may be an important autoantigen in the pathogenesis of Sjögren's syndrome, and anti-120-kDa alpha-fodrin antibodies have been detected in patients with Sjögren's syndrome. Here we have analyzed anti-120-kDa alpha-fodrin immune responses during development of spontaneous autoimmune sialadenitis in NOD mice as a model of Sjögren's syndrome. We found specific autoantibody production against 120-kDa alpha-fodrin, and its production correlated closely with autoimmune sialadenitis. A specific T cell response of splenocytes against the 120-kDa alpha-fodrin autoantigen was observed in NOD mice from the early onset of autoimmune sialadenitis. In addition, production in vitro by splenic T cells of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), but not IL-4, was detected by enzyme-linked immunosorbent assays. We found up-regulation of local cytokine genes, including those of Th1 type (IL-1beta, TNF-alpha, IL-2, IFN-gamma, IL-6), as well as IL-10 and IL-12(p40), in the tissue-infiltrating cells during the course of autoimmune sialadenitis. These findings suggest that in spontaneous autoimmune sialadenitis in NOD mice, there may be a specific anti-120-kDa alpha-fodrin immune response in the development of autoimmune lesions resembling human Sjögren's syndrome, and that the autoreactive Th1 cells possess an up-regulated cytokine profile besides IL-10 and IL-12.

Amino Acid Sequence↗
PubMed2003

Protective effects of a recombinant fragment of human surfactant protein D in a murine model of pulmonary hypersensitivity induced by dust mite allergens.

Lung surfactant protein D (SP-D) is a carbohydrate pattern recognition immune molecule. It can interact with a range of pathogens, stimulate immune cells and manipulate cytokine profiles during host's immune response. SP-D has also been shown to interact, via its carbohydrate recognition domains, with glycoprotein allergens of house dust mite (Dermatophagoides pteronyssinus, Derp), inhibiting specific IgE isolated from mite-sensitive asthmatic patients from binding these allergens, and blocking subsequent histamine release from sensitized basophils. In the present study, we have examined the protection offered by various doses of intranasal administration of a recombinant fragment of human SP-D (rhSP-D) in a murine model of pulmonary hypersensitivity to Derp allergens which showed characteristic high levels of specific IgE antibodies, peripheral blood eosinophilia, pulmonary infiltrates and a Th2 cytokine response. Treatment of Derp mice with rhSP-D led to significant reduction in Derp-specific IgE levels, blood eosinophilia and pulmonary cellular infiltration. The levels of IL-4 and IL-5 were decreased, while those of IL-12 and IFN-gamma were raised in the supernatant of the cultured splenocytes, indicating a Th2 to Th1 polarization. These results suggest that SP-D has a protective role in the modulation of allergic sensitization and in the development of allergic reactions to Derp allergens and highlight potential of the rhSP-D as a therapeutic for pulmonary hypersensitivity.

Administration, Intranasal↗
PubMed1995

Protective immunity against malaria: cellular changes in the liver vary according to the method of immunization.

Characterization of cells present in the extravascular compartment of murine liver was performed after different immunization procedures against the malaria parasite Plasmodium yoelii. Mice were immunized with live or irradiated sporozoites or with parasitized erythrocytes. Whatever the immunization protocol used, the mice were protected against a sporozoite challenge but each immunization procedure induced a specific profile of cell types. Immunization with irradiated sporozoite induce a significant increase in CD8+ lymphocytes, parasitized erythrocytes stimulates production of monocytes/macrophages and CD8+ lymphocytes while, after live sporozoites immunization, polymorphonuclear cells, macrophages/monocytes, B cells and a range of T cell subsets were increased in number.

Animals↗