Altered Immune Competence Research Articles

The impact of salinity and dissolved oxygen regimes on transcriptomic immune responses to oil in early life stage Fundulus grandis

Understanding the effects of oil exposure on early life stage fish species is critical to fully assessing the environmental impacts of oil spills. Oil released from the 2010 Deepwater Horizon spill reached habitats where estuarine fish routinely spawn. In addition, estuaries are highly dynamic environments, therefore, fish in these areas are routinely exposed to varying salinity and dissolved oxygen (DO) levels, each of which are known to modulate transcriptional responses. Fish exposed to oil often display altered immune competence, and several studies have shown that Deepwater Horizon oil in particular causes modulation of various immune functions. However, few studies have directly examined how environmental parameters may affect oil-induced immunomodulation, particularly in early life stage fishes when the immune system is still developing. To this end, we examined transcriptional patterns of immune genes and pathways in Fundulus grandis larvae to various oil (0, 15 μg/L), salinity (3, 30 ppt), and DO (2.5, 6 mg/L) regimes in a fully factorial design. Our results suggest that immune pathways are generally activated in all treatment groups with the exception of the Low Salinity/No Oil/Hypoxia treatment where immune pathways are largely suppressed, and the High Salinity/No Oil/Hypoxia treatment where pathways are unchanged. The High Salinity/Oil/Hypoxia treatment had the largest number of enriched immune pathways (44 as defined by IPA and 43 as defined by ConsensusPathDB), indicating that oil under certain environmental conditions has the potential to further modulate immune-related genes, pathways, and responses in fish.

IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients: IL-10 polymorphism and plasma levels in leukemia patients.

Acute Lymphoblastic Leukemia is the leading form of cancer in infancy, and compelling evidences suggest an involvement of altered immune competence on this malignancy pathogenesis. Interleukin 10 (IL-10) is a pleiotropic cytokine designated as an immunosuppressive molecule, but may act as an immunostimulant factor in cancer development and progression. An IL-10 single nucleotide polymorphism (SNP) rs1800896 has been associated with disease progression to ALL, and might influence cytokine expression. This study analyzed the IL-10 rs1800896 polymorphism and performed a case-control study to determine the significant associations with ALL susceptibility and prognosis. IL-10 plasma levels were determined and associated with genotypes and disease phase. The study consisted of 67 childhood ALL patients and 75 age-related healthy controls. The rs1800896 was not associated with ALL susceptibility or risk of relapse. No significant association was observed between different genotypes of the rs1800896 and plasma levels of IL-10. Cytokine plasma levels were significantly higher in the diagnosis group (9.71 pg/mL ± 3.7), comparing to the treatment (3.48 pg/mL ± 1.3; p=0.01) and remission phase (0.12 pg/mL ± 0.1; p=0.0001) groups. This work indicates that the IL-10 plasma expression is altered from ALL disease diagnosis and remission. Moreover, prospective studies will establish the functional role of IL-10 in immune modulation in childhood ALL.

Cardiac responses to elevated seawater temperature in Atlantic salmon

BackgroundAtlantic salmon aquaculture operations in the Northern hemisphere experience large seasonal fluctuations in seawater temperature. With summer temperatures often peaking around 18-20°C there is growing concern about the effects on fish health and performance. Since the heart has a major role in the physiological plasticity and acclimation to different thermal conditions in fish, we wanted to investigate how three and eight weeks exposure of adult Atlantic salmon to 19°C, previously shown to significantly reduce growth performance, affected expression of relevant genes and proteins in cardiac tissues under experimental conditions.ResultsTranscriptional responses in cardiac tissues after three and eight weeks exposure to 19°C (compared to thermal preference, 14°C) were analyzed with cDNA microarrays and validated by expression analysis of selected genes and proteins using real-time qPCR and immunofluorescence microscopy. Up-regulation of heat shock proteins and cell signaling genes may indicate involvement of the unfolded protein response in long-term acclimation to elevated temperature. Increased immunofluorescence staining of inducible nitric oxide synthase in spongy and compact myocardium as well as increased staining of vascular endothelial growth factor in epicardium could reflect induced vascularization and vasodilation, possibly related to increased oxygen demand. Increased staining of collagen I in the compact myocardium of 19°C fish may be indicative of a remodeling of connective tissue with long-term warm acclimation. Finally, higher abundance of transcripts for genes involved in innate cellular immunity and lower abundance of transcripts for humoral immune components implied altered immune competence in response to elevated temperature.ConclusionsLong-term exposure of Atlantic salmon to 19°C resulted in cardiac gene and protein expression changes indicating that the unfolded protein response, vascularization, remodeling of connective tissue and altered innate immune responses were part of the cardiac acclimation or response to elevated temperature.

Management of the ear, nose, and throat manifestations of Wegener granulomatosis: an otorhinolaryngologist's perspective.

A diagnosis of Wegener granulomatosis requires granulomatous manifestations in the respiratory tract. With the increasing use of antineutrophil cytoplasmic autoantibodies as a diagnostic tool, Wegener granulomatosis is diagnosed earlier than in the past, and not infrequently when only ear, nose and throat manifestations are present, placing the otorhinolaryngologist in a central role in diagnosis and management. Diagnostic biopsies should be obtained from active lesions in the nose and paranasal sinuses and concomitant infection should be identified. Because of the apparent relation between infection and activation of disease, the management of infections-especially those due to Staphylococcus aureus-requires special attention. The increasing numbers of early cases identified warrants further investigations of whether less toxic treatment regimens will be of advantage in such cases. Medical and surgical treatment of the acute and chronic manifestations presents specific problems because of altered immune competence, prevalent superinfection, and tissue destruction, and is therefore best taken care of by specially dedicated otorhinolaryngologists.

Assessing the effects of anthropogenic stressors on Puget Sound flatfish populations

Puget Sound is an estuary in the northwestern United States which serves as the habitat for a number of recreationally and commercially important species of flatfish. Over the past 100 years, there has been substantial urban and industrial development within this region, resulting in heavy inputs of chemical contaminants at selected sites, as well as significant loss or alteration of marine habitat. Studies show that feral flatfish in Puget Sound are experiencing a range of biological effects due to chemical contaminant exposure, including reproductive dysfunction, altered immune competence, and development of toxicopathic diseases, and there is some evidence of reduced survival in fish from urban areas of Puget Sound from increased infectious and toxicopathic disease. Puget Sound sole are also subject to other anthropogenic stressors, such as fishing pressure or alteration of nearshore nursery habitats. The cumulative impact of these stressors on flatfish abundance in Puget Sound, however, is poorly understood. In a series of field and laboratory studies, we determined vital rates and other life history parameters in English sole ( Pleuronectes vetulus) subpopulations from urban and non-urban sites in Puget Sound, and are using this information to estimate potential population level impacts of anthropogenic stressors, with age and stage-based Leslie-matrix models. Initial results suggest that declines in the fecundity component of the model, as observed in field studies of fish from contaminated sites, could reduce the size of sub-populations in these areas if the loss of recruits is not offset by density-dependent changes in recruitment, immigration, or other compensating mechanisms. Studies on flatfish species from a variety of sites in Europe and North America suggest that contaminant-related disease and reproductive impairment are widespread in this group of fish, although substantial differences in sensitivity have been observed, even among closely related species. Comparative studies with a variety of Pleuronectid species will enable us to better evaluate the risk posed by anthropogenic stressors to flatfish, and contribute to improved assessment and management of this important fisheries resource.

Approaches for Determining Effects of Pollution on Fish Populations of Puget Sound

Puget Sound is a large marine and estuarine ecosystem in Washington State that serves as the habitat for a number of recreationally and commercially important species of groundfish and Pacific salmon Onchorhynchus spp. Over the past several decades, the human population of the Puget Sound drainage basin has increased substantially, resulting in increased habitat degradation and chemical pollution. There is now a body of evidence showing that groundfish and salmon in Puget Sound are experiencing a range of biological effects from chemical contaminant exposure, including impairment of several stages in the reproductive process, increased susceptibility to pathogens resulting from altered immune competence, and development of toxicopathic diseases. Preliminary studies suggest the potential for reduced survival of fish from urban areas of Puget Sound resulting from increased infectious and idiopathic diseases. The question that now must be addressed is whether contaminant-related reductions in reproductive and survival rates are sufficient to affect fish abundance in Puget Sound. In the current study, the potential impact of contaminant-related mortality and reproductive impairment on the population growth rate of English sole Pleuronectes vetulus was examined by simulation modeling. An initial Leslie matrix population model was constructed for investigation of contaminant effects. The adult mortality rate for English sole in Puget Sound was estimated from recent historical data. Age-specific fecundity was determined from previously collected English sole ovary samples. Existing data on the effects of contaminants on reproduction, including impaired gonadal development, reduced spawning ability, and decreased egg and larval viability, were incorporated into the fecundity component of the model. The influence of density-dependent population regulation on model results was also examined. Results suggest that declines in the fecundity component of the model, like those observed in field studies of fish from contaminated sites such as the Duwamish Waterway and Eagle Harbor, could substantially decrease the population growth rate (r) if density dependence is weak or moderate, Estimated declines in r are comparable in magnitude to those associated with typical levels of commercial fishing pressure, However, a compensation for loss of recruits due to contaminant effects is observed if strong density-dependent population regulation is assumed.

The identification of chemicals with sensitizing or immunosuppressive properties in routine toxicology

In the context of this paper, immunotoxicity is taken to encompass immunosuppression/immunopotentiation and allergy. Over the last 10 to 15 years, well characterized methods for the assessment of altered immune competence have been reported. This has led to proposals for tiered testing schemes. This review examines the suitability of immunotoxicity parameters for inclusion in routine 28-day studies and comments on methods that have been proposed for incorporation within the guidelines issued by the US FDA and US EPA and OECD. It is recommended that the existing OECD Guideline 407 is modified to incorporate total and differential blood cell counts, spleen and thymus weight and histopathology, and draining and distal lymph node histopathology for Tier I level testing. Data so generated will provide a reliable and accurate means of identifying at an early stage potential immunotoxic effects. Tier II testing should be carried out on a case by case basis and only assuming positive results are obtained at Tier I. An increasingly sophisticated understanding of the nature of immune responses to chemical allergens has facilitated the design of novel predictive methods for the identification of sensitizing activity. Opportunities which arise from these new developments in allergy testing such as the local lymph node assay, mouse ear swelling test, and the mouse IgE test should be monitored closely.

Immunosuppression by phenytoin: implication for altered immune competence in brain-tumor patients.

This investigation was conducted to examine the immunosuppressive potential of phenytoin in vivo and to document a correlation between phenytoin therapy and depressed lymphocyte responsiveness to mitogens. It was thought that phenytoin, the most widely used anticonvulsant agent, may play some role in the immunosuppression seen in brain-tumor patients. The effect of phenytoin on mitogen-stimulated lymphocyte function was evaluated by tritiated (3H)-thymidine incorporation and lymphocyte nuclear size distribution. Lymphocytes from either phenytoin-treated or normal rabbits were incubated for 90 hours in culture medium in the presence of three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Significant suppression of mitogen-induced activation of the lymphocytes from treated animals was demonstrated. The present studies suggest a possible connection between phenytoin therapy and altered immune competence in brain-tumor patients.