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Sample records for suboptimal immune function

  1. Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

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    Francesca S. M. Tang

    2015-01-01

    Full Text Available Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood and suboptimal (ASubopt asthma symptom control. Methods. Peripheral blood neutrophils from AGood (ACQ 0.75, n=7, and healthy controls (HC (n=9 were stimulated with bacterial (LPS (1 μg/mL, fMLF (100 nM, and viral (imiquimod (3 μg/mL, R848 (1.5 μg/mL, and poly I:C (10 μg/mL surrogates or live rhinovirus (RV 16 (MOI1. Cell-free supernatant was collected after 1 h for neutrophil elastase (NE and matrix metalloproteinase- (MMP- 9 measurements or after 24 h for CXCL8 release. Results. Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.

  2. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort

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    Colebunders Robert

    2011-02-01

    Full Text Available Abstract Background Antiretroviral therapy (ART partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods T-cell activation (CD38+HLA-DR+ and immune exhaustion (PD-1+ were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199 cells/μl], N = 34 ], optimal [282 (200-415 cells/μl, N = 64] and super-optimal [528 (416-878 cells/μl, N = 30]. Results Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+ was higher among suboptimal relative to optimal (P P = 0.022]. Conclusion T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.

  3. Suboptimal treatment adherence in bipolar disorder: impact on clinical outcomes and functioning

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    Montes JM

    2013-01-01

    Full Text Available Jose Manuel Montes1, Jorge Maurino2, Consuelo de Dios3, Esteban Medina21Department of Psychiatry, Hospital Universitario del Sureste, 2AstraZeneca Medical Department, 3Department of Psychiatry, Hospital Universitario La Paz, Madrid, SpainBackground: The primary aim of this study was to assess drug treatment adherence in patients with bipolar disorder and to identify factors associated with adherence. The secondary aim was to analyze the impact of suboptimal adherence on clinical and functional outcomes.Methods: A cross-sectional study was conducted in a sample of outpatients receiving an oral antipsychotic drug. Medication adherence was assessed combining the 10-item Drug Attitude Inventory, the Morisky Green Adherence Questionnaire, and the Compliance Rating Scale. Logistic regression was used to determine significant variables associated with suboptimal adherence to medication.Results: Three hundred and three patients were enrolled into the study. The mean age was 45.9 ± 12.8 years, and 59.7% were females. Sixty-nine percent of patients showed suboptimal adherence. Disease severity and functioning were significantly worse in the suboptimal group than in the adherent group. Multivariate analysis showed depressive polarity of the last acute episode, presence of subsyndromal symptoms, and substance abuse/dependence to be significantly associated with suboptimal treatment adherence (odds ratios 3.41, 2.13, and 1.95, respectively.Conclusion: A high prevalence of nonadherence was found in an outpatient sample with bipolar disorder. Identification of factors related to treatment adherence would give clinicians the opportunity to select more adequately patients who are eligible for potential adherence-focused interventions.Keywords: bipolar disorder, treatment adherence, functioning, polarity, subsyndromal symptoms

  4. Immune function in arctic mammals

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    Desforges, Jean-Pierre; Jasperse, Lindsay; Jensen, Trine Hammer

    2018-01-01

    Natural killer (NK) cells are a vital part of the rapid and non-specific immune defense against invading pathogens and tumor cells. This study evaluated NK cell-like activity by flow cytometry for the first time in three ecologically and culturally important Arctic mammal species: polar bear (Ursus...... the effector:target cell ratio increased. Comparing NK activity between fresh and cryopreserved mouse lymphocytes revealed little to no difference in function, highlighting the applicability of cryopreserving cells in field studies. The evaluation of this important innate immune function in Arctic mammals can...... contribute to future population health assessments, especially as pollution-induced suppression of immune function may increase infectious disease susceptibility....

  5. Monounsaturated fats and immune function

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    P. Yaqoob

    1998-04-01

    Full Text Available Animal studies suggest that olive oil is capable of modulating functions of cells of the immune system in a manner similar to, albeit weaker than, fish oils. There is some evidence that the effects of olive oil on immune function in animal studies are due to oleic acid rather than to trace elements or antioxidants. Importantly, several studies have demonstrated effects of oleic acid-containing diets on in vivo immune responses. In contrast, consumption of a monounsaturated fatty acid (MUFA-rich diet by humans does not appear to bring about a general suppression of immune cell functions. The effects of this diet in humans are limited to decreasing aspects of adhesion of peripheral blood mononuclear cells, although there are trends towards decreases in natural killer cell activity and proliferation. The lack of a clear effect of MUFA in humans may be attributable to the higher level of monounsaturated fat used in the animal studies, although it is ultimately of importance to examine the effects of intakes which are in no way extreme. The effects of MUFA on adhesion molecules are potentially important, since these molecules appear to have a role in the pathology of a number of diseases involving the immune system. This area clearly deserves further exploration

  6. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

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    Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

    2015-03-01

    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

  7. Vitamin C and Immune Function

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    Anitra C. Carr

    2017-11-01

    Full Text Available Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100–200 mg/day, which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

  8. Season of birth shapes neonatal immune function

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    Thysen, Anna Hammerich; Rasmussen, Morten Arendt; Kreiner-Møller, Eskil

    2016-01-01

    Birth season has been reported to be a risk factor for several immune-mediated diseases. We hypothesized that this association is mediated by differential changes in neonatal immune phenotype and function with birth season. We sought to investigate the influence of season of birth on cord blood...... immune cell subsets and inflammatory mediators in neonatal airways. Cord blood was phenotyped for 26 different immune cell subsets, and at 1 month of age, 20 cytokines and chemokines were quantified in airway mucosal lining fluid. Multivariate partial least squares discriminant analyses were applied...... to determine whether certain immune profiles dominate by birth season, and correlations between individual cord blood immune cells and early airway immune mediators were defined. We found a birth season-related fluctuation in neonatal immune cell subsets and in early-life airway mucosal immune function...

  9. Suboptimal Muscle Synergy Activation Patterns Generalize their Motor Function across Postures.

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    Sohn, M Hongchul; Ting, Lena H

    2016-01-01

    We used a musculoskeletal model to investigate the possible biomechanical and neural bases of using consistent muscle synergy patterns to produce functional motor outputs across different biomechanical conditions, which we define as generalizability. Experimental studies in cats demonstrate that the same muscle synergies are used during reactive postural responses at widely varying configurations, producing similarly-oriented endpoint force vectors with respect to the limb axis. However, whether generalizability across postures arises due to similar biomechanical properties or to neural selection of a particular muscle activation pattern has not been explicitly tested. Here, we used a detailed cat hindlimb model to explore the set of feasible muscle activation patterns that produce experimental synergy force vectors at a target posture, and tested their generalizability by applying them to different test postures. We used three methods to select candidate muscle activation patterns: (1) randomly-selected feasible muscle activation patterns, (2) optimal muscle activation patterns minimizing muscle effort at a given posture, and (3) generalizable muscle activation patterns that explicitly minimized deviations from experimentally-identified synergy force vectors across all postures. Generalizability was measured by the deviation between the simulated force direction of the candidate muscle activation pattern and the experimental synergy force vectors at the test postures. Force angle deviations were the greatest for the randomly selected feasible muscle activation patterns (e.g., >100°), intermediate for effort-wise optimal muscle activation patterns (e.g., ~20°), and smallest for generalizable muscle activation patterns (e.g., synergy force vector was reduced by ~45% when generalizability requirements were imposed. Muscles recruited in the generalizable muscle activation patterns had less sensitive torque-producing characteristics to changes in postures. We

  10. The effect of plant-based diet and suboptimal environmental conditions on digestive function and diet-induced enteropathy in rainbow trout (Oncorhynchus mykiss)

    NARCIS (Netherlands)

    Mosberian-Tanha, P.; Schrama, J.W.; Landsverk, T.; Mydland, L.T.; Øverland, M.

    2018-01-01

    This experiment investigated intestinal enteropathy and digestive function of rainbow trout challenged with soybean meal-based diet (SBM) at optimal or suboptimal environments created by normal or reduced water flow, respectively. Oxygen level remained above 7 mg L-1 for optimal environment and

  11. Molecular and Functional Neuroscience in Immunity.

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    Pavlov, Valentin A; Chavan, Sangeeta S; Tracey, Kevin J

    2018-04-26

    The nervous system regulates immunity and inflammation. The molecular detection of pathogen fragments, cytokines, and other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. The functional organization of this neural control is based on principles of reflex regulation. Reflexes involving the vagus nerve and other nerves have been therapeutically explored in models of inflammatory and autoimmune conditions, and recently in clinical settings. The brain integrates neuro-immune communication, and brain function is altered in diseases characterized by peripheral immune dysregulation and inflammation. Here we review the anatomical and molecular basis of the neural interface with immunity, focusing on peripheral neural control of immune functions and the role of the brain in the model of the immunological homunculus. Clinical advances stemming from this knowledge within the framework of bioelectronic medicine are also briefly outlined.

  12. Stressor Controllability and Immune Function

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    1986-10-17

    susceptibility to infectious disease . In E. Kurstak, P. V. Morozov, & Z. P. Lipowski (Eds.), Viruses , immunity, and mental health. Plenum Press, in press. w...following inmunization . a. ELISA Procedure. We-Tsof a flat bottomed microtiter plate (NUNC, certified Immunopla.e I) were coated with KLH (0.2 mi/well, 0.5 mg...because the, rats were being infected with viruses and other agents tnat could alter proliferation. We thus began to purchase pathogen-free animals and

  13. Modulation of Immune Functions by Foods

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    Shuichi Kaminogawa

    2004-01-01

    Full Text Available Evidence is rapidly accumulating as to the beneficial effects of foods. However, it is not always clear whether the information is based on data evaluated impartially in a scientific fashion. Human research into whether foods modulate immune functions in either intervention studies or randomized controlled trials can be classified into three categories according to the physical state of subjects enrolled for investigation: (i studies examining the effect of foods in healthy individuals; (ii studies analyzing the effect of foods on patients with hypersensitivity; and (iii studies checking the effect of foods on immunocompromized subjects, including patients who had undergone surgical resection of cancer and newborns. The systematization of reported studies has made it reasonable to conclude that foods are able to modulate immune functions manifesting as either innate immunity (phagocytic activity, NK cell activity or acquired immunity (T cell response, antibody production. Moreover, improvement of immune functions by foods can normalize the physical state of allergic patients or cancer patients, and may reduce the risk of diseases in healthy individuals. Therefore, it is valuable to assess the immune-modulating abilities of foods by measuring at least one parameter of either innate or acquired immunity.

  14. Problematic Internet Usage and Immune Function.

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    Reed, Phil; Vile, Rebecca; Osborne, Lisa A; Romano, Michela; Truzoli, Roberto

    2015-01-01

    Problematic internet use has been associated with a variety of psychological comorbidities, but it relationship with physical illness has not received the same degree of investigation. The current study surveyed 505 participants online, and asked about their levels of problematic internet usage (Internet Addiction Test), depression and anxiety (Hospital Anxiety and Depression Scales), social isolation (UCLA Loneliness Questionnaire), sleep problems (Pittsburgh Sleep Quality Index), and their current health - General Health Questionnaire (GHQ-28), and the Immune Function Questionnaire. The results demonstrated that around 30% of the sample displayed mild or worse levels of internet addiction, as measured by the IAT. Although there were differences in the purposes for which males and females used the internet, there were no differences in terms of levels of problematic usage between genders. The internet problems were strongly related to all of the other psychological variables such as depression, anxiety, social-isolation, and sleep problems. Internet addiction was also associated with reduced self-reported immune function, but not with the measure of general health (GHQ-28). This relationship between problematic internet use and reduced immune function was found to be independent of the impact of the co-morbidities. It is suggested that the negative relationship between level of problematic internet use and immune function may be mediated by levels of stress produced by such internet use, and subsequent sympathetic nervous activity, which related to immune-supressants, such as cortisol.

  15. Problematic Internet Usage and Immune Function.

    Directory of Open Access Journals (Sweden)

    Phil Reed

    Full Text Available Problematic internet use has been associated with a variety of psychological comorbidities, but it relationship with physical illness has not received the same degree of investigation. The current study surveyed 505 participants online, and asked about their levels of problematic internet usage (Internet Addiction Test, depression and anxiety (Hospital Anxiety and Depression Scales, social isolation (UCLA Loneliness Questionnaire, sleep problems (Pittsburgh Sleep Quality Index, and their current health - General Health Questionnaire (GHQ-28, and the Immune Function Questionnaire. The results demonstrated that around 30% of the sample displayed mild or worse levels of internet addiction, as measured by the IAT. Although there were differences in the purposes for which males and females used the internet, there were no differences in terms of levels of problematic usage between genders. The internet problems were strongly related to all of the other psychological variables such as depression, anxiety, social-isolation, and sleep problems. Internet addiction was also associated with reduced self-reported immune function, but not with the measure of general health (GHQ-28. This relationship between problematic internet use and reduced immune function was found to be independent of the impact of the co-morbidities. It is suggested that the negative relationship between level of problematic internet use and immune function may be mediated by levels of stress produced by such internet use, and subsequent sympathetic nervous activity, which related to immune-supressants, such as cortisol.

  16. Problematic Internet Usage and Immune Function

    Science.gov (United States)

    Reed, Phil; Vile, Rebecca; Osborne, Lisa A.; Romano, Michela; Truzoli, Roberto

    2015-01-01

    Problematic internet use has been associated with a variety of psychological comorbidities, but it relationship with physical illness has not received the same degree of investigation. The current study surveyed 505 participants online, and asked about their levels of problematic internet usage (Internet Addiction Test), depression and anxiety (Hospital Anxiety and Depression Scales), social isolation (UCLA Loneliness Questionnaire), sleep problems (Pittsburgh Sleep Quality Index), and their current health – General Health Questionnaire (GHQ-28), and the Immune Function Questionnaire. The results demonstrated that around 30% of the sample displayed mild or worse levels of internet addiction, as measured by the IAT. Although there were differences in the purposes for which males and females used the internet, there were no differences in terms of levels of problematic usage between genders. The internet problems were strongly related to all of the other psychological variables such as depression, anxiety, social-isolation, and sleep problems. Internet addiction was also associated with reduced self-reported immune function, but not with the measure of general health (GHQ-28). This relationship between problematic internet use and reduced immune function was found to be independent of the impact of the co-morbidities. It is suggested that the negative relationship between level of problematic internet use and immune function may be mediated by levels of stress produced by such internet use, and subsequent sympathetic nervous activity, which related to immune-supressants, such as cortisol. PMID:26244339

  17. Mental resilience, perceived immune functioning, and health

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    Van Schrojenstein Lantman M

    2017-03-01

    Full Text Available Marith Van Schrojenstein Lantman,1 Marlou Mackus,1 Leila S Otten,1 Deborah de Kruijff,1 Aurora JAE van de Loo,1,2 Aletta D Kraneveld,1,2 Johan Garssen,1,3 Joris C Verster1,2,4 1Division of Pharmacology, Utrecht University, Utrecht, the Netherlands; 2Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands; 3Nutricia Research, Utrecht, the Netherlands; 4Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia Background: Mental resilience can be seen as a trait that enables an individual to recover from stress and to face the next stressor with optimism. People with resilient traits are considered to have a better mental and physical health. However, there are limited data available assessing the relationship between resilient individuals and their perspective of their health and immune status. Therefore, this study was conducted to examine the relationship between mental resilience, perceived health, and perceived immune status. Methods: A total of 779 participants recruited at Utrecht University completed a questionnaire consisting of demographic characteristics, the brief resilience scale for the assessment of mental resilience, the immune function questionnaire (IFQ, and questions regarding their perceived health and immune status. Results: When correcting for gender, age, height, weight, smoker status, amount of cigarettes smoked per week, alcohol consumption status, amount of drinks consumed per week, drug use, and frequency of past year drug use, mental resilience was significantly correlated with perceived health (r=0.233, p=0.0001, perceived immune functioning (r=0.124, p=0.002, and IFQ score (r=−0.185, p=0.0001. Conclusion: A significant, albeit modest, relationship was found between mental resilience and perceived immune functioning and health. Keywords: mental resilience, immune functioning, health, vitality, quality of life

  18. Exercise and the Regulation of Immune Functions.

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    Simpson, Richard J; Kunz, Hawley; Agha, Nadia; Graff, Rachel

    2015-01-01

    Exercise has a profound effect on the normal functioning of the immune system. It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular moderate intensity exercise is beneficial. Single bouts of exercise evoke a striking leukocytosis and a redistribution of effector cells between the blood compartment and the lymphoid and peripheral tissues, a response that is mediated by increased hemodynamics and the release of catecholamines and glucocorticoids following the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Single bouts of prolonged exercise may impair T-cell, NK-cell, and neutrophil function, alter the Type I and Type II cytokine balance, and blunt immune responses to primary and recall antigens in vivo. Elite athletes frequently report symptoms associated with upper respiratory tract infections (URTI) during periods of heavy training and competition that may be due to alterations in mucosal immunity, particularly reductions in secretory immunoglobulin A. In contrast, single bouts of moderate intensity exercise are "immuno-enhancing" and have been used to effectively increase vaccine responses in "at-risk" patients. Improvements in immunity due to regular exercise of moderate intensity may be due to reductions in inflammation, maintenance of thymic mass, alterations in the composition of "older" and "younger" immune cells, enhanced immunosurveillance, and/or the amelioration of psychological stress. Indeed, exercise is a powerful behavioral intervention that has the potential to improve immune and health outcomes in the elderly, the obese, and patients living with cancer and chronic viral infections such as HIV. © 2015 Elsevier Inc. All rights reserved.

  19. Role of Polyamines in Immune Cell Functions

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    Rebecca S. Hesterberg

    2018-03-01

    Full Text Available The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for l-arginine and l-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine. Polyamines have several purported roles and high levels of polyamines are manifest in tumor cells as well in autoreactive B- and T-cells in autoimmune diseases. In the tumor microenvironment, l-arginine catabolism by both tumor cells and suppressive myeloid cells is known to dampen cytotoxic T-cell functions suggesting there might be links between polyamines and T-cell suppression. Here, we review studies suggesting roles of polyamines in normal immune cell function and highlight their connections to autoimmunity and anti-tumor immune cell function.

  20. Vitamin D and neonatal immune function.

    LENUS (Irish Health Repository)

    Clancy, N

    2013-05-01

    Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

  1. Zinc as a Gatekeeper of Immune Function

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    Inga Wessels

    2017-11-01

    Full Text Available After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14, zinc “exporters” (ZnT 1–10, and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.

  2. Immune functions of the garment workers.

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    Sultana, R; Ferdous, K J; Hossain, M; Zahid, M S H; Islam, L N

    2012-10-01

    Occupational exposure to cotton dust, fibers, metal fumes and different chemicals used in the aparrel manufacturing industries cause a wide range of physical and psychological health problems in the garment workers that may also affect their immune function. To assess the immune system function in garment workers. A total of 45 workers of a garment factory, and 41 control subjects, not exposed to the garment working environment were enrolled in this study. In the study subjects, the complement system function was assessed as bactericidal activity on Escherichia coli DH5α cells using the standard plate count method. Serum complement components C3 and C4 were measured by immunoprecipitation, and IgG was measured by immunonephelometry. The bactericidal activity of serum complement in the garment workers (range: 93.5%-99.9%) was significantly (pgarment workers, the mean levels of complement C3, and C4 were 1.75 and 0.26 g/L, respectively that were close to those of the controls. The mean IgG level in the garment workers was 13.5 g/L that was significantly (pgarment factory may affect the immune system.

  3. Low Dose Ionizing Radiation Modulates Immune Function

    International Nuclear Information System (INIS)

    Nelson, Gregory A.

    2016-01-01

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a 'Th2 polarized' immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in

  4. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  5. Suboptimal choice, reward-predictive signals, and temporal information.

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    Cunningham, Paul J; Shahan, Timothy A

    2018-01-01

    Suboptimal choice refers to preference for an alternative offering a low probability of food (suboptimal alternative) over an alternative offering a higher probability of food (optimal alternative). Numerous studies have found that stimuli signaling probabilistic food play a critical role in the development and maintenance of suboptimal choice. However, there is still much debate about how to characterize how these stimuli influence suboptimal choice. There is substantial evidence that the temporal information conveyed by a food-predictive signal governs its function as both a Pavlovian conditioned stimulus and as an instrumental conditioned reinforcer. Thus, we explore the possibility that food-predictive signals influence suboptimal choice via the temporal information they convey. Application of this temporal information-theoretic approach to suboptimal choice provides a formal, quantitative framework that describes how food-predictive signals influence suboptimal choice in a manner consistent with related phenomena in Pavlovian conditioning and conditioned reinforcement. Our reanalysis of previous data on suboptimal choice suggests that, generally speaking, preference in the suboptimal choice procedure tracks relative temporal information conveyed by food-predictive signals for the suboptimal and optimal alternatives. The model suggests that suboptimal choice develops when the food-predictive signal for the suboptimal alternative conveys more temporal information than that for the optimal alternative. Finally, incorporating a role for competition between temporal information provided by food-predictive signals and relative primary reinforcement rate provides a reasonable account of existing data on suboptimal choice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

    Science.gov (United States)

    Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

    2016-10-01

    The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

  7. Nutrition, immune function and health of dairy cattle

    DEFF Research Database (Denmark)

    Ingvartsen, Klaus Lønne; Moyes, Kasey

    2013-01-01

    not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our......) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where...... the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response...

  8. Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function

    Directory of Open Access Journals (Sweden)

    Phillips R

    2006-04-01

    Full Text Available Abstract Background Dendritic cells (DCs are central to the initiation and regulation of the adaptive immune response during infection. Modulation of DC function may therefore allow evasion of the immune system by pathogens. Significant depression of the host's systemic immune response to both concurrent infections and heterologous vaccines has been observed during malaria infection, but the mechanisms underlying this immune hyporesponsiveness are controversial. Results Here, we demonstrate that the blood stages of malaria infection induce a failure of DC function in vitro and in vivo, causing suboptimal activation of T cells involved in heterologous immune responses. This effect on T-cell activation can be transferred to uninfected recipients by DCs isolated from infected mice. Significantly, T cells activated by these DCs subsequently lack effector function, as demonstrated by a failure to migrate to lymphoid-organ follicles, resulting in an absence of B-cell responses to heterologous antigens. Fractionation studies show that hemozoin, rather than infected erythrocyte (red blood cell membranes, reproduces the effect of intact infected red blood cells on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas of the spleen in vivo. Conclusion Plasmodium infection inhibits the induction of adaptive immunity to heterologous antigens by modulating DC function, providing a potential explanation for epidemiological studies linking endemic malaria with secondary infections and reduced vaccine efficacy.

  9. Immune functions in crustaceans: lessons from flies

    NARCIS (Netherlands)

    Stet, R.J.M.; Arts, J.A.J.

    2005-01-01

    In recent years insects, notably Drosophila, have emerged as a popular model for studying immune responses to bacterial and fungal pathogens. Due to the availability of the complete genome sequence, genome-wide scans of immune responses have been performed using microarray analyses. These analyses

  10. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

  11. Does Exercise Alter Immune Function and Respiratory Infections?

    Science.gov (United States)

    Nieman, David C.

    2001-01-01

    This paper examines whether physical activity influences immune function as a consequence risk of infection from the common cold and other upper respiratory tract infections (URTI) and whether the immune system responds differently to moderate versus intense physical exertion. Research indicates that people who participate in regular moderate…

  12. Biliary Innate Immunity: Function and Modulation

    Directory of Open Access Journals (Sweden)

    Kenichi Harada

    2010-01-01

    Full Text Available Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with primary biliary cirrhosis (PBC and biliary atresia. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR family and recognize pathogen-associated molecular patterns (PAMPs. Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA is not found. In PBC, CD4-positive Th17 cells characterized by the secretion of IL-17 are implicated in the chronic inflammation of bile ducts and the presence of Th17 cells around bile ducts is causally associated with the biliary innate immune responses to PAMPs. Moreover, a negative regulator of intracellular TLR signaling, peroxisome proliferator-activated receptor-γ (PPARγ, is involved in the pathogenesis of cholangitis. Immunosuppression using PPARγ ligands may help to attenuate the bile duct damage in PBC patients. In biliary atresia characterized by a progressive, inflammatory, and sclerosing cholangiopathy, dsRNA viruses are speculated to be an etiological agent and to directly induce enhanced biliary apoptosis via the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL. Moreover, the epithelial-mesenchymal transition (EMT of biliary epithelial cells is also evoked by the biliary innate immune response to dsRNA.

  13. In-Situ Monitoring of Immune Function, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Monitoring the health and wellness of mission pilots is a critically important function. Space flight has an adverse effect on the human immune response. During...

  14. Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women

    International Nuclear Information System (INIS)

    Spector, June T.; De Roos, Anneclaire J.; Ulrich, Cornelia M.; Sheppard, Lianne; Sjoedin, Andreas; Wener, Mark H.; Wood, Brent

    2014-01-01

    Background: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. Objectives: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. Methods: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. Results: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. Conclusions: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. - Highlights: • Plasma PCBs and immune function were measured in 109 women at baseline and one year. • Immune measures included T lymphocyte proliferation

  15. Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Spector, June T., E-mail: spectj@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105 (United States); Department of Medicine, School of Medicine, University of Washington, Seattle, WA (United States); De Roos, Anneclaire J., E-mail: ajd335@drexel.edu [Epidemiology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, Seattle, WA 98109 (United States); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Ulrich, Cornelia M., E-mail: neli.ulrich@nct-heidelberg.de [Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (United States); Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, Seattle, WA 98109 (United States); National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Sheppard, Lianne, E-mail: sheppard@uw.edu [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105 (United States); Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA (United States); Sjoedin, Andreas, E-mail: asjodin@cdc.gov [National Center for Environmental Health, CDC, 4770 Buford Highway NE, Atlanta, GA 30341 (United States); Wener, Mark H., E-mail: wener@u.washington.edu [Department of Medicine, School of Medicine, University of Washington, Seattle, WA (United States); Wood, Brent, E-mail: woodbl@u.washington.edu [Department of Medicine, School of Medicine, University of Washington, Seattle, WA (United States); and others

    2014-05-01

    Background: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. Objectives: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. Methods: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. Results: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5 µg/mL PHA-TLP/50.0 pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. Conclusions: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. - Highlights: • Plasma PCBs and immune function were measured in 109 women at baseline and one year. • Immune measures included T lymphocyte proliferation

  16. Maternal immunization increases nestling energy expenditure, immune function, and fledging success in a passerine bird

    Directory of Open Access Journals (Sweden)

    Gary Burness

    2018-04-01

    Full Text Available Female birds transfer maternally derived antibodies (matAb to their nestlings, via the egg yolk. These antibodies are thought to provide passive protection, and allow nestlings to avoid the costs associated with mounting an innate immune response. To test whether there is an energetic benefit to nestlings from receiving matAb, we challenged adult female tree swallows (Tachycineta bicolor prior to clutch initiation with either lipopolysaccharide (LPS or saline (Control. Following hatching, one half of each female's nestlings were immunized on day 8 post-hatch with LPS or saline, and the 4-h post-immunization nestling metabolic rate (MR was measured. There was no difference in either LPS-reactive antibodies or total Ig levels between offspring of immunized and non-immunized mothers on day 6 or 14 post-hatch, possibly reflecting a relatively short half-life of matAbs in altricial birds. Additionally, we found no evidence that nestlings from LPS-immunized mothers could avoid the growth suppression that may result from activation of an inflammatory response. Unexpectedly, we found that control nestlings from LPS mothers had higher resting MR than control nestlings of control mothers. We attribute the increased MR to the costs associated with a general non-specific enhancement of immune function in nestlings from LPS-immunized mothers. Consistent with enhanced immune function, nestlings of immunized mothers had a more robust inflammatory response to phytohaemagglutinin and higher fledging success. Our results suggest that maternal antigen exposure pre-laying can result in increased fitness for both mothers and offspring, depending on food availability.

  17. Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

    Science.gov (United States)

    Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

    2017-01-01

    Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

  18. Innate immune functions of microglia isolated from human glioma patients

    Directory of Open Access Journals (Sweden)

    Grimm Elizabeth

    2006-03-01

    Full Text Available Abstract Background Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human glioma-infiltrating microglia (GIM. Methods GIM were isolated by sequential Percoll purification from patient tumors immediately after surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays were used to analyze the phenotype and function of these cells. Results GIM expressed significant levels of Toll-like receptors (TLRs, however they do not secrete any of the cytokines (IL-1β, IL-6, TNF-α critical in developing effective innate immune responses. Similar to innate macrophage functions, GIM can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were statistically less able to mediate tumor cytotoxicity compared to microglia isolated from normal brain. In addition, the expression of Fas ligand (FasL was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosuppression by microglia. Conclusion We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.

  19. Sleep and immune function: glial contributions and consequences of aging.

    Science.gov (United States)

    Ingiosi, Ashley M; Opp, Mark R; Krueger, James M

    2013-10-01

    The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5'-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging. Copyright © 2013. Published by Elsevier Ltd.

  20. Design considerations for a suboptimal Kalman filter

    Science.gov (United States)

    Difilippo, D. J.

    1995-06-01

    In designing a suboptimal Kalman filter, the designer must decide how to simplify the system error model without causing the filter estimation errors to increase to unacceptable levels. Deletion of certain error states and decoupling of error state dynamics are the two principal model simplifications that are commonly used in suboptimal filter design. For the most part, the decisions as to which error states can be deleted or decoupled are based on the designer's understanding of the physics of the particular system. Consequently, the details of a suboptimal design are usually unique to the specific application. In this paper, the process of designing a suboptimal Kalman filter is illustrated for the case of an airborne transfer-of-alignment (TOA) system used for synthetic aperture radar (SAR) motion compensation. In this application, the filter must continuously transfer the alignment of an onboard Doppler-damped master inertial navigation system (INS) to a strapdown navigator that processes information from a less accurate inertial measurement unit (IMU) mounted on the radar antenna. The IMU is used to measure spurious antenna motion during the SAR imaging interval, so that compensating phase corrections can be computed and applied to the radar returns, thereby presenting image degradation that would otherwise result from such motions. The principles of SAR are described in many references, for instance. The primary function of the TOA Kalman filter in a SAR motion compensation system is to control strapdown navigator attitude errors, and to a less degree, velocity and heading errors. Unlike a classical navigation application, absolute positional accuracy is not important. The motion compensation requirements for SAR imaging are discussed in some detail. This TOA application is particularly appropriate as a vehicle for discussing suboptimal filter design, because the system contains features that can be exploited to allow both deletion and decoupling of error

  1. Functional comparison of innate immune signaling pathways in primates.

    Directory of Open Access Journals (Sweden)

    Luis B Barreiro

    2010-12-01

    Full Text Available Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

  2. Diverse novel functions of neutrophils in immunity, inflammation, and beyond

    OpenAIRE

    Mocsai, A.

    2013-01-01

    Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10–20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellu...

  3. [Impact of thymic function in age-related immune deterioration].

    Science.gov (United States)

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  4. Immune activation is associated with decreased thymic function in ...

    African Journals Online (AJOL)

    Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

  5. Position statement. Part one: Immune function and exercise

    DEFF Research Database (Denmark)

    Walsh, Neil P; Gleeson, Michael; Shephard, Roy J

    2011-01-01

    responses and falls in stimulated B cell Ig synthesis. The cause of this apparent depression in acquired immunity appears to be related to elevated circulating stress hormones, and alterations in the pro/anti-inflammatory cytokine balance in response to exercise. The clinical significance of these changes...... and immediately after exercise, proportional to exercise intensity and duration, with numbers of cells (T cells and to a lesser extent B cells) falling below pre-exercise levels during the early stages of recovery, before returning to resting values normally within 24 h. Mobilization of T and B cell subsets...... risk of URTI during heavy training. An important question for exercise immunologists remains: how does one measure immune function in a meaningful way? One approach to assessing immune function that extends beyond blood or salivary measures involves challenging study participants with antigenic stimuli...

  6. The multitasking organ: recent insights into skin immune function.

    Science.gov (United States)

    Di Meglio, Paola; Perera, Gayathri K; Nestle, Frank O

    2011-12-23

    The skin provides the first line defense of the human body against injury and infection. By integrating recent findings in cutaneous immunology with fundamental concepts of skin biology, we portray the skin as a multitasking organ ensuring body homeostasis. Crosstalk between the skin and its microbial environment is also highlighted as influencing the response to injury, infection, and autoimmunity. The importance of the skin immune network is emphasized by the identification of several skin-resident cell subsets, each with its unique functions. Lessons learned from targeted therapy in inflammatory skin conditions, such as psoriasis, provide further insights into skin immune function. Finally, we look at the skin as an interacting network of immune signaling pathways exemplified by the development of a disease interactome for psoriasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Nutrition, immune function and health of dairy cattle.

    Science.gov (United States)

    Ingvartsen, K L; Moyes, K

    2013-03-01

    The large increase in milk yield and the structural changes in the dairy industry have caused major changes in the housing, feeding and management of the dairy cow. However, while large improvements have occurred in production and efficiency, the disease incidence, based on veterinary records, does not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our understanding of disease risk and our effort to develop health and welfare improving strategies, including proactive management for preventing diseases and reducing the severity of diseases. To build onto this the main purpose of this review will therefore be on the effect of physiological imbalance (PI) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response and the effect of nutrition may be directly through nutrients or indirectly by metabolites, for example, in situations with PI. This review discusses the complex relationships between metabolic status and immune function and how these complex interactions increase the risk of disease during early lactation. A special focus will be placed on the major energetic fuels currently known to be used by immune cells (i.e. glucose, non-esterified fatty acids, beta

  8. Functional demonstration of adaptive immunity in zebrafish using DNA vaccination

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja

    Due to the well characterized genome, overall highly synteny with the human genome and its suitability for functional genomics studies, the zebrafish is considered to be an ideal animal model for basic studies of mechanisms of diseases and immunity in vertebrates including humans. While several s...

  9. Chromatin versus pathogens: the function of epigenetics in plant immunity

    Science.gov (United States)

    Ding, Bo; Wang, Guo-Liang

    2015-01-01

    To defend against pathogens, plants have developed a sophisticated innate immunity that includes effector recognition, signal transduction, and rapid defense responses. Recent evidence has demonstrated that plants utilize the epigenetic control of gene expression to fine-tune their defense when challenged by pathogens. In this review, we highlight the current understanding of the molecular mechanisms of histone modifications (i.e., methylation, acetylation, and ubiquitination) and chromatin remodeling that contribute to plant immunity against pathogens. Functions of key histone-modifying and chromatin remodeling enzymes are discussed. PMID:26388882

  10. Diverse novel functions of neutrophils in immunity, inflammation, and beyond.

    Science.gov (United States)

    Mócsai, Attila

    2013-07-01

    Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10-20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellular pathogens such as viruses and mycobacteria. They have been shown to intimately shape the adaptive immune response at various levels, including marginal zone B cells, plasmacytoid dendritic cells and T cell populations, and even to control NK cell homeostasis. Neutrophils have been shown to mediate an alternative pathway of systemic anaphylaxis and to participate in allergic skin reactions. Finally, neutrophils were found to be involved in physiological and pathological processes beyond the immune system, such as diabetes, atherosclerosis, and thrombus formation. Many of those functions appear to be related to their unique ability to release neutrophil extracellular traps even in the absence of pathogens. This review summarizes those novel findings on versatile functions of neutrophils and how they change our view of neutrophil biology in health and disease.

  11. Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

    Science.gov (United States)

    Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

    2008-01-01

    During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

  12. The function of the Mediator complex in plant immunity.

    Science.gov (United States)

    An, Chuanfu; Mou, Zhonglin

    2013-03-01

    Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

  13. Ultimate explanations and suboptimal choice.

    Science.gov (United States)

    Vasconcelos, Marco; Machado, Armando; Pandeirada, Josefa N S

    2018-07-01

    Researchers have unraveled multiple cases in which behavior deviates from rationality principles. We propose that such deviations are valuable tools to understand the adaptive significance of the underpinning mechanisms. To illustrate, we discuss in detail an experimental protocol in which animals systematically incur substantial foraging losses by preferring a lean but informative option over a rich but non-informative one. To understand how adaptive mechanisms may fail to maximize food intake, we review a model inspired by optimal foraging principles that reconciles sub-optimal choice with the view that current behavioral mechanisms were pruned by the optimizing action of natural selection. To move beyond retrospective speculation, we then review critical tests of the model, regarding both its assumptions and its (sometimes counterintuitive) predictions, all of which have been upheld. The overall contention is that (a) known mechanisms can be used to develop better ultimate accounts and that (b) to understand why mechanisms that generate suboptimal behavior evolved, we need to consider their adaptive value in the animal's characteristic ecology. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

    Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

  15. Impaired immune function in children and adults with Fanconi anemia.

    Science.gov (United States)

    Myers, Kasiani C; Sauter, Sharon; Zhang, Xue; Bleesing, Jacob J; Davies, Stella M; Wells, Susanne I; Mehta, Parinda A; Kumar, Ashish; Marmer, Daniel; Marsh, Rebecca; Brown, Darron; Butsch Kovacic, Melinda

    2017-11-01

    Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls. Compared to non-FA persons of similar ages, FA individuals showed lower absolute total B cells (P candida (P = 0.019), were diminished in FA. Phytohemagglutinin responses and plasma cytokines were normal. Within FA subjects, adults and older children (≥10 years) exhibited higher CD8 + T cells than younger children (P = 0.004). Documented atypical infections were infrequent, although oral human papilloma virus (HPV) prevalence was higher (31% positive) in FA. Overall, these results demonstrate a high rate of significant humoral and cellular immune dysfunction. Continued longitudinal study of immune function is critical to understand evolution with age, bone marrow failure, and cancer development. © 2017 Wiley Periodicals, Inc.

  16. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

    Science.gov (United States)

    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  17. Strategies to enhance immune function for marathon runners : what can be done?

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Pedersen, Bente K

    2007-01-01

    immune cells. During this period of immune suppression, by some referred to as an 'open window' in immune function, it has been hypothesised that viruses and bacteria might gain a foothold, which would increase the risk of infections. In light of this, nutritional interventions that can enhance immune...

  18. Olive oil and immune system functions: potential involvement in immunonutrition

    Directory of Open Access Journals (Sweden)

    Álvarez de Cienfuegos, Gerardo

    2004-03-01

    Full Text Available Olive oil plays a crucial role as a main component of the Mediterranean diet, which has shown important benefits for the human health. According to the current knowledge, the administration of diets containing olive oil exerts some beneficial effects on the immune system functions due likely to the action of oleic acid rather than other substances contained in this fat. In the last few years, epidemiological, clinical and experimental studies have evidenced the potential of certain dietary lipids (containing polyunsaturated or monounsaturated fatty acids as modulators of immune system functions due to their ability to suppress several functions of immune system in both humans and animals. As a result, these fats have been applied in the reduction of symptoms from diseases characterized by an overactivation of the immune system (autoimmune diseases or in the reduction of cancer risk. Here, we review several relevant experimental and clinical data associated with the beneficial effects of olive oil upon the health, the mechanisms of action and the immune function susceptible of being be altered by the administration of dietary lipids and particularly of olive oil. In addition, we will also discuss the detrimental effects on the immune system functions caused by the administration of certain dietary lipids attributed mainly to a reduction of host natural resistance against infectious microorganisms as well as the involvement of olive oil diets in the regulation of immune resistance.El aceite de oliva tiene un papel crucial como componente de la dieta Mediterránea, con importantes beneficios sobre la salud humana. Dietas conteniendo aceite de oliva actúan de manera favorable en las funciones del sistema inmune por la acción sobretodo del ácido oleico. Los estudios epidemiológicos, clínicos y experimentales publicados en los últimos años demuestran que ciertos lípidos de la dieta [ácidos grasos monoinsaturados (MUFA y poliinsaturados (PUFA

  19. Health-related quality of life after mild, moderate and severe traumatic brain injury: patterns and predictors of suboptimal functioning during the first year after injury.

    Science.gov (United States)

    Scholten, A C; Haagsma, J A; Andriessen, T M J C; Vos, P E; Steyerberg, E W; van Beeck, E F; Polinder, S

    2015-04-01

    The Glasgow Outcome Scale Extended (GOSE) is the established functional outcome scale to assess disability following traumatic brain injury (TBI), however does not capture the patient's subjective perspective. Health-related quality of life (HRQL) does capture the individual's perception of disability after TBI, and has therefore been recognized as an important outcome in TBI. In contrast to GOSE, HRQL enables comparison of health outcome across various disease states and with healthy individuals. We aimed to assess functional outcome, HRQL, recovery, and predictors of 6 and 12-month outcome in a comprehensive sample of patients with mild, moderate or severe TBI, and to examine the relationship between functional impairment (GOSE) and HRQL. A prospective cohort study was conducted among a sample of 2066 adult TBI patients who attended the emergency department (ED). GOSE was determined through questionnaires or structured interviews. Questionnaires 6 and 12 months after ED treatment included socio-demographic information and HRQL measured with Short-Form Health Survey (SF-36; reflecting physical, mental and social functioning) and Perceived Quality of Life Scale (PQoL; measuring degree of satisfaction with functioning). 996 TBI survivors with mild, moderate or severe TBI completed the 6-month questionnaire. Functional outcome and HRQL after moderate or severe TBI was significantly lower than after mild TBI. Patients with moderate TBI showed greatest improvement. After one year, the mild TBI group reached outcomes comparable to population norms. TBI of all severities highly affected SF-36 domains physical and social functioning, and physical and emotional role functioning. GOSE scores were highly related to all SF-36 domains and PQoL scores. Female gender, older age, co-morbidity and high ISS were strongest independent predictors of decreased HRQL at 6 and 12 months after TBI. HRQL and recovery patterns differ for mild, moderate and severe TBI. This study indicates

  20. Interactions between Temperament, Stress, and Immune Function in Cattle

    Directory of Open Access Journals (Sweden)

    N. C. Burdick

    2011-01-01

    Full Text Available The detrimental effects caused by stressors encountered by animals during routine handling can pose economic problems for the livestock industry due to increased costs ultimately borne by the producer and the consumer. Stress adversely affects key physiological processes of the reproductive and immune systems. In recent years stress responsiveness has been associated with cattle behavior, specifically temperament. Cattle with more excitable temperaments, as measured by chute score, pen score, and exit velocity (flight speed, exhibit greater basal concentrations of glucocorticoids and catecholamines. Similar to stressed cattle, more temperamental cattle (i.e., cattle exhibiting greater exit velocity or pen and chute scores have poorer growth performance, carcass characteristics, and immune responses. Thus, understanding the interrelationship of stress and temperament can help in the development of selection and management practices that reduce the negative influence of temperament on growth and productivity of cattle. This paper discusses the relationship between stress and temperament and the developing evidence of an effect of temperament on immune function of cattle that have been handled or restrained. Specifically, the paper discusses different methodologies used to measure temperament, including chute score, pen score, and exit velocity, and discusses the reaction of cattle to different stressors including handling and restraint.

  1. Validation of Procedures for Monitoring Crewmember Immune Function

    Science.gov (United States)

    Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

    2009-01-01

    There is ample evidence to suggest that space flight leads to immune system dysregulation, however the nature of the phenomenon as it equilibrates over longer flights has not been determined. This dysregulation may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk (if any) for exploration-class space flight is unknown, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles (RNA, intracellular, secreted), viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. This study is currently ongoing. To date, 10 short duration and 5 long-duration crewmembers have completed the study. Technically, the study is progressing well. In-flight blood samples are being collected, and returned for analysis, including functional assays that require live cells. For all in-flight samples to date, sample viability has been acceptable. Preliminary data (n = 4/7; long/short duration, respectively) indicate that distribution of most peripheral leukocyte subsets is largely unaltered during flight. Exceptions include elevated T cells, reduced B/NK cells, increased memory T cells and increased central memory CD8+ T cells. General T cell function, early blastogenesis response to mitogenic stimulation, is markedly

  2. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  3. Functional disorders of T-cell immunity at persons engaged in the Chernobyl emergency operations in a 10 years after the accident

    International Nuclear Information System (INIS)

    Potapnev, M.P.; Kuz'menok, O.I.; Potapova, S.M.; Smol'nikova, V.V.; Myslitskj, V.F.; Rzheutskij, V.A.; Vaslevskaya, T.A.; Vasyukhina, L.V.

    1998-01-01

    Functional disorders of T-cell immunity in persons engaged in Chernobyl emergency operations - 10 years after the accident. The results evaluating T-cell immunity of 148 liquidators of Chernobyl accident are presented. It was estimated that 10 years after the accident immuno phenotyping of peripheral blood lymphocytes did not reveal marked disturbance in lymphocyte subpopulation content in exposed group as compared with healthy control. Determination of cell proliferation in vitro indicated the decrease in DNA synthesis of T-lymphocytes stimulated with optimal and particularly suboptimal concentrations of polyclonal T-cell activators. Based on individual deviation of the results of T-lymphocyte proliferation the groups with high and low level of response were sorted out for future examination

  4. Differential Gender Effects in the Relationship between Perceived Immune Functioning and Autistic Traits.

    Science.gov (United States)

    Mackus, Marlou; Kruijff, Deborah de; Otten, Leila S; Kraneveld, Aletta D; Garssen, Johan; Verster, Joris C

    2017-04-12

    Altered immune functioning has been demonstrated in individuals with autism spectrum disorder (ASD). The current study explores the relationship between perceived immune functioning and experiencing ASD traits in healthy young adults. N = 410 students from Utrecht University completed a survey on immune functioning and autistic traits. In addition to a 1-item perceived immune functioning rating, the Immune Function Questionnaire (IFQ) was completed to assess perceived immune functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) was completed to examine variation in autistic traits, including the domains "social insights and behavior", "difficulties with change", "communication", "phantasy and imagination", and "detail orientation". The 1-item perceived immune functioning score did not significantly correlate with the total AQ score. However, a significant negative correlation was found between perceived immune functioning and the AQ subscale "difficulties with change" (r = -0.119, p = 0.019). In women, 1-item perceived immune functioning correlated significantly with the AQ subscales "difficulties with change" (r = -0.149, p = 0.029) and "communication" (r = -0.145, p = 0.032). In men, none of the AQ subscales significantly correlated with 1-item perceived immune functioning. In conclusion, a modest relationship between perceived immune functioning and several autistic traits was found.

  5. Trade-off between growth and immune function : a meta-analysis of selection experiments

    NARCIS (Netherlands)

    van der Most, Peter; de Jong, Berber; Parmentier, Henk K.; Verhulst, Simon

    P>1. Evidence suggests that developing and maintaining an effective immune system may be costly and that an organism has to make a trade-off between immune function and other fitness-enhancing traits. To test for a trade-off between growth and immune function we carried out a meta-analysis of data

  6. Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

    Science.gov (United States)

    Kuper, C Frieke; van Bilsen, Jolanda; Cnossen, Hilde; Houben, Geert; Garthoff, Jossie; Wolterbeek, Andre

    2016-09-01

    A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effect of radiotherapy on immunity function of cancer patients receiving radiotherapy

    International Nuclear Information System (INIS)

    Li Xinli; Zhu Shentao; Xu Jiuhong

    2003-01-01

    Objective: In order to observe the effect of radiotherapy on immunity function of cancer patients receiving radiotherapy. Methods: Cellular immunity is determined by APAAP; Humoral immunity is determined by transmission method. Results: The items of cellular immunity is lower than the control after radiotherapy. These items decrease continually. The difference between before and after radiotherapy has statistic significance. Of all Humoral immunity items, IgA, IgM decreased after radiotherapy and the difference has statistic significance. Conclusions: Radiotherapy can damage patients' immunity function

  8. Natural material adsorbed onto a polymer to enhance immune function

    Directory of Open Access Journals (Sweden)

    Reinaque AP

    2012-08-01

    Full Text Available Ana Paula Barcelos Reinaque,1 Eduardo Luzía França,2 Edson Fredulin Scherer,3 Mayra Aparecida Côrtes,1 Francisco José Dutra Souto,4 Adenilda Cristina Honorio-França51Post Graduate Program in Material Science, 2Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças, 3Post Graduate Program in Material Science, Institute of Biological and Health Science, Federal University of Mato Grosso, Pontal do Araguaia, 4Faculty of Medical Sciences, Federal University of Mato Grosso, Cuiabá, 5Institute of Biological and Health Science, Federal University of Mato Grosso, Pontal do Araguaia, MT, BrazilBackground: In this study, we produced poly(ethylene glycol (PEG microspheres of different sizes and adsorbing a medicinal plant mixture, and verified their effect in vitro on the viability, superoxide production, and bactericidal activity of phagocytes in the blood.Methods: The medicinal plant mixture was adsorbed onto PEG microspheres and its effects were evaluated by flow cytometry and fluorescence microscopy.Results: Adsorption of the herbal mixture onto the PEG microspheres was achieved and the particles were internalized by phagocytes. PEG microspheres bearing the adsorbed herbal mixture stimulated superoxide release, and activated scavenging and microbicidal activity in phagocytes. No differences in functional activity were observed when the phagocytes were not incubated with PEG microspheres bearing the adsorbed herbal mixture.Conclusion: This system may be useful for the delivery of a variety of medicinal plants and can confer additional protection against infection. The data reported here suggest that a polymer adsorbed with a natural product is a treatment alternative for enhancing immune function.Keywords: natural product, polymer, adsorption, immune function, phagocytes

  9. Functional aspects of the adaptive immune system in arthritis

    NARCIS (Netherlands)

    Jansen, D.T.S.L.

    2017-01-01

    The adaptive immune system is the part of the immune system that is highly specific and generates memory resulting in a fast and specific immune response upon a second infection with the same pathogen. However, when this response is specific for a part of the body itself instead of a pathogen,

  10. Cesarean section and disease associated with immune function

    DEFF Research Database (Denmark)

    Kristensen, Kim; Henriksen, Lonny

    2016-01-01

    colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma. CONCLUSION: Children delivered by CS are at increased......BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought...... to further explore these associations using discrimination between the effects of acute versus elective CS. METHODS: We performed a population- and national register-based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated...

  11. Effects of intensified training and taper on immune function

    Directory of Open Access Journals (Sweden)

    Elena Papacosta

    2013-03-01

    Full Text Available Although resting immune function is not very different in athletes compared with non-athletes periods of intensified training (overreaching in already well trained athletes can result in a depression of immunity in the resting state. Illness-prone athletes appear to have an altered cytokine response to antigen stimulation and exercise. Having low levels of salivary IgA secretion also makes athletes more susceptible to upper respiratory tract infections. Overtraining is associated with recurrent infections and immunodepression is common, but immune functions do not seem to be reliable markers of impending overtraining. There are several possible causes of the diminution of immune function associated with periods of heavy training. One mechanism may simply be the cumulative effects of repeated bouts of intense exercise (with or without tissue damage with the consequent elevation of stress hormones, particularly glucocorticoids such as cortisol, causing temporary inhibition of TH-1 cytokines with a relative dampening of the cell-mediated response. When exercise is repeated frequently there may not be sufficient time for the immune system to recover fully. Tapering has been described as a gradual reduction in the training load which allows the recovery of physiological capacities that were impaired by previous intensive training and permits further training-induced adaptations to occur accompanied by competition performance enhancements. The majority of the studies that have examined the recovery of immunoendocrine responses during 1-3 week tapers in trained athletes have mainly reported enhanced performance, often accompanied by increased anabolic activity, reduced physiological stress and restoration of mucosal immunity and immune function.Quando se compara a função imune, em repouso, de atletas e não atletas, não se verificam grandes diferenças. Porém, períodos de treinamento intensificado ("overreaching" em atletas bem treinados podem

  12. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  13. Action-Dependent Photobiomodulation on Health, Suboptimal Health, and Disease

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2014-01-01

    Full Text Available The global photobiomodulation (PBM on an organism was studied in terms of function-specific homeostasis (FSH and scale-free functional network in this paper. A function can be classified into a normal function in its FSH and a dysfunctional function far from its FSH. An FSH-specific stress (FSS disrupting an FSH can also be classified into a successful stress in its FSS-specific homeostasis (FSSH and a chronic stress far from its FSSH. The internal functions of an organism can be divided into essential, special nonessential, and general nonessential functions. Health may be defined as a state of an organism in which all the essential and special nonessential functions are normal or their stresses are successful. Suboptimal health may be defined as a state of a disease-free organism in which only some special nonessential functions are dysfunctional in comparison with its healthy state. Disease may be defined as a state of an organism which is not in both health and suboptimal health. The global PBM of health, suboptimal health, or disease suggested that the PBM may depend on the organism action.

  14. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging

    OpenAIRE

    Palmer, Clovis S.; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M.

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impa...

  15. Resolving the paradox of suboptimal choice.

    Science.gov (United States)

    Zentall, Thomas R

    2016-01-01

    When humans engage in commercial (totally probabilistic) gambling they are making suboptimal choices because the return is generally less than the investment. This review (a) examines the literature on pigeon suboptimal choice, (b) describes the conditions under which it occurs, (c) identifies the mechanisms that appear to be responsible for the effect, and (d) suggests that similar processes may be able to account for analogous suboptimal choice when humans engage in commercial gambling. Pigeons show suboptimal choice when they choose between 1 alternative that 20% of the time provides them with a signal that they will always get fed or 80% of the time with a signal that they will not get fed (overall 20% reinforcement) and a second alternative that 100% of the time provides them with a signal that they will get fed 50% of the time (overall 50% reinforcement). The pigeons' strong preference for the suboptimal choice was investigated in a series of experiments that found the preference for the suboptimal alternative was determined by the value of the signal that predicted reinforcement, rather its frequency and that the frequency of the signal that predicted nonreinforcement had little effect on the suboptimal choice. Paradoxically, this account makes the prediction that pigeons will be indifferent between an alternative that 50% of the time provides a fully predictive stimulus for reinforcement and an alternative that 100% of the time provides a fully predictive stimulus for reinforcement. The similarities and differences of this suboptimal choice task to human gambling are discussed. (c) 2016 APA, all rights reserved).

  16. Regulatory immune cells and functions in autoimmunity and transplantation immunology.

    Science.gov (United States)

    Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

    2017-05-01

    In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Trade-offs between sexual advertisement and immune function in the pied flycatcher (Ficedula hypoleuca).

    OpenAIRE

    Kilpimaa, Janne; Alatalo, Rauno V.; Siitari, Heli

    2004-01-01

    Good genes models of sexual selection assume that sexual advertisement is costly and thus the level of advertisement honestly reveals heritable viability. Recently it has been suggested that an important cost of sexual advertisement might be impairment of the functioning of the immune system. In this field experiment we investigated the possible trade-offs between immune function and sexual advertisement by manipulating both mating effort and activity of immune defence in male pied flycatcher...

  18. Lysozyme's lectin-like characteristics facilitates its immune defense function

    KAUST Repository

    Zhang, Ruiyan

    2017-06-06

    Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.

  19. Functional Bowel Disorders Are Associated with a Central Immune Activation

    Directory of Open Access Journals (Sweden)

    Per G. Farup

    2017-01-01

    Full Text Available Background. Subjects with depression and unexplained neurological symptoms have a high prevalence of gastrointestinal comorbidity probably related to the brain-gut communication. This study explored associations between functional gastrointestinal disorders (FGID and inflammatory markers in subjects with these disorders. Methods. The FGID, including irritable bowel syndrome (IBS, were classified according to the Rome III criteria, and degree of symptoms was assessed with IBS symptom severity score (IBS-SSS. A range of interleukins (IL, chemokines and growth factors, tryptophan, and kynurenine were analysed in serum and the cerebrospinal fluid (CSF, and short-chain fatty acids (SCFA were analysed in the faeces. The results are reported as partial correlation (pc and p values. Results. Sixty-six subjects were included. IBS was associated with high levels of tryptophan (p=0.048 and kynurenine (p=0.019 and low level of IL-10 (p=0.047 in the CSF. IBS-SSS was associated with high tumor necrosis factor and low IL-10 in the CSF; pc=0.341 and p=0.009 and pc=−0.299 and p=0.023, respectively. Propionic minus butyric acid in faeces was negatively associated with IL-10 in the CSF (pc=−0.416, p=0.005. Conclusions. FGID were associated with a proinflammatory immune activation in the central nervous system and a disturbed tryptophan metabolism that could have been mediated by the faecal microbiota.

  20. Lysozyme's lectin-like characteristics facilitates its immune defense function

    KAUST Repository

    Zhang, Ruiyan; Wu, Lisha; Eckert, Thomas; Burg-Roderfeld, Monika; Rojas-Macias, Miguel A.; Lü tteke, Thomas; Krylov, Vadim B.; Argunov, Dmitry A.; Datta, Aritreyee; Markart, Philipp; Guenther, Andreas; Norden, Bengt; Schauer, Roland; Bhunia, Anirban; Enani, Mushira Abdelaziz; Billeter, Martin; Scheidig, Axel J.; Nifantiev, Nikolay E.; Siebert, Hans-Christian

    2017-01-01

    Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.

  1. Segmentation precedes face categorization under suboptimal conditions

    Directory of Open Access Journals (Sweden)

    Carlijn eVan Den Boomen

    2015-05-01

    Full Text Available Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG. Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

  2. Segmentation precedes face categorization under suboptimal conditions.

    Science.gov (United States)

    Van Den Boomen, Carlijn; Fahrenfort, Johannes J; Snijders, Tineke M; Kemner, Chantal

    2015-01-01

    Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

  3. Functional analysis of PGRP-LA in Drosophila immunity.

    Directory of Open Access Journals (Sweden)

    Mathilde Gendrin

    Full Text Available PeptidoGlycan Recognition Proteins (PGRPs are key regulators of the insect innate antibacterial response. Even if they have been intensively studied, some of them have yet unknown functions. Here, we present a functional analysis of PGRP-LA, an as yet uncharacterized Drosophila PGRP. The PGRP-LA gene is located in cluster with PGRP-LC and PGRP-LF, which encode a receptor and a negative regulator of the Imd pathway, respectively. Structure predictions indicate that PGRP-LA would not bind to peptidoglycan, pointing to a regulatory role of this PGRP. PGRP-LA expression was enriched in barrier epithelia, but low in the fat body. Use of a newly generated PGRP-LA deficient mutant indicates that PGRP-LA is not required for the production of antimicrobial peptides by the fat body in response to a systemic infection. Focusing on the respiratory tract, where PGRP-LA is strongly expressed, we conducted a genome-wide microarray analysis of the tracheal immune response of wild-type, Relish, and PGRP-LA mutant larvae. Comparing our data to previous microarray studies, we report that a majority of genes regulated in the trachea upon infection differ from those induced in the gut or the fat body. Importantly, antimicrobial peptide gene expression was reduced in the tracheae of larvae and in the adult gut of PGRP-LA-deficient Drosophila upon oral bacterial infection. Together, our results suggest that PGRP-LA positively regulates the Imd pathway in barrier epithelia.

  4. Investigation of Immune Function in Naval Marine Mammals

    National Research Council Canada - National Science Library

    Romano, Tracy

    2000-01-01

    ... (dolphins, whales, and porpoises). This is due in part to obtaining access to animals and tissue samples as well as the lack of cetacean-specific reagents to carry out investigations of the immune system...

  5. Gut microbiome can control antitumor immune function in liver

    Science.gov (United States)

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  6. Functional characterization of Foxp3-specific spontaneous immune responses

    DEFF Research Database (Denmark)

    Larsen, Susanne Købke; Munir, S; Andersen, Anders Woetmann

    2013-01-01

    Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. The transcription factor forkhead box P3 (Foxp3) is generally expressed in Tregs. Here, we identify and characterize spontaneous cytotoxic immune responses to Foxp3-expressing cel....... Consequently, induction of Foxp3-specific cytotoxic T-cell responses appears as an attractive tool to boost spontaneous or therapeutically provoked immune responses, for example, for the therapy of cancer....

  7. Effect of immune nutritional support on immune function and inflammatory factor in postoperative patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Hua-Jia Dai

    2016-05-01

    Full Text Available Objective: To investigate the effect of immune nutritional support on immune function and inflammatory factor in postoperative patients with gastric cancer. Methods: A total of 100 patients with gastric cancer were selected and randomly divided into the observation group and the control group with 50 cases in each group. The control group received routine perioperative enteral and parenteral nutrition, on the basis of conventional nutritional support, and the observation group was given enteral nutrition emulsion immune support. Then, the immune function and the inflammatory factor of postoperative day 1 and day 7 were compared between the two groups. Results: (1 With the preoperative data as the basis, the levels of serum IgG, IgA, C3 and C4 decreased at the postoperative day 1 and then increased at the postoperative day 7, while the level of IgM showed an increasing trend and then a decreasing trend in the two groups, and the corresponding figures for the postoperative day 1 and day 7 were statistically different between the two groups. In the observation group, the levels of IgG, IgA, C3 and C4 were higher, while the level of IgM was lower at the postoperative day 1 and day 7 than that in the control group, and the differences were statistically significant; (2 With the preoperative data as the basis, the levels of serum TNF-α, IL-6 and CRP significantly increased at the postoperative day 1 and then decreased at the postoperative day 7 in the two groups, and the corresponding figures for the postoperative day 1 and day 7 in the observation group were lower than those in the control group, and the differences were statistically significant. Conclusion: Immune nutritional support can help to reduce the damage of immune function and the inflammatory response induced by surgery in patients with gastric cancer, which is worthy of clinical application.

  8. How suboptimal are linear sharing rules?

    DEFF Research Database (Denmark)

    Jensen, Bjarne Astrup; Nielsen, Jørgen Aase

    2016-01-01

    that significant losses can arise when investors are diverse in their risk attitude. We also show that an investor with a low degree of risk aversion, like the logarithmic or the square root investor, often applied in portfolio choice models, can either inflict or be subject to severe losses when being forced...... two sources of suboptimal investment decisions as seen from each of the two investors individually. One is the suboptimal choice of portfolio, the other is the forced linear sharing rule. We measure the combined consequence for each investor by their respective loss in wealth equivalent. We show...

  9. Maintenance of systemic immune functions prevents accelerated presbycusis.

    Science.gov (United States)

    Iwai, Hiroshi; Baba, Susumu; Omae, Mariko; Lee, Shinryu; Yamashita, Toshio; Ikehara, Susumu

    2008-05-07

    There is no effective therapy for progressive hearing loss such as presbycusis, the causes of which remain poorly understood because of the difficulty of separating genetic and environmental contributions. In the present study, we show that the age-related dysfunctions of the systemic immune system in an animal model of accelerated presbycusis (SAMP1, senescence-accelerated mouse P1) can be corrected by allogeneic bone marrow transplantation (BMT). We also demonstrate that this presbycusis can be prevented; BMT protects the recipients from age-related hearing impairment and the degeneration of spiral ganglion cells (SGCs) as well as the dysfunctions of T lymphocytes, which have a close relation to immune senescence. No donor cells are infiltrated to the spiral ganglia, confirming that this experimental system using BMT is connected to the systemic immune system and does not contribute to transdifferentiation or fusion by donor hematopoietic stem cells (HSCs), or to the direct maintenance of ganglion cells by locally infiltrated donor immunocompetent cells. Therefore, another procedure which attempts to prevent the age-related dysfunctions of the recipient immune system is the inoculation of syngeneic splenocytes from young donors. These mice show no development of hearing loss, compared with the recipient mice with inoculation of saline or splenocytes from old donors. Our studies on the relationship between age-related systemic immune dysfunctions and neurodegeneration mechanisms open up new avenues of treatment for presbycusis, for which there is no effective therapy.

  10. Early enteral immune nutrition support after radical operation for gastric cancer on promoting the recovery of gastrointestinal function and immune function

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Li

    2016-05-01

    Full Text Available Objective: To analyze the effect of early enteral immune nutrition support after radical operation for gastric cancer on the recovery of gastrointestinal function and immune function. Methods: A total of 106 cases of patients received radical operation for gastric cancer in our hospital were selected as research subjects, and according to different ways of postoperative nutrition intervention, all patients were divided into observation group (n=50 and control group (n=56. Control group received conventional enteral nutrition intervention, observation group received postoperative early enteral immune nutrition support, and then differences in postoperative intestinal mucosa barrier function, gastrointestinal hormone levels, immune function levels and nutrition-related indicator values were compared between two groups. Results: After observation group received enteral immune nutrition intervention, serum DAO, PS and D-lactate levels as well as urine L/M ratio were lower than those of control group; serum GAS, CCK, MTL and SP values of observation group after intervention were higher than those of control group, and GLU, VIP, GIP and SS values were lower than those of control group; CD4, IgG, NK cell, C3, C4, CH50 and S-IgA levels of observation group after intervention were higher than those of control group; serum ALB, PRE, TRF and RBP levels of observation group after intervention were higher than those of control group. Conclusion: Early enteral immune nutrition support after radical operation for gastric cancer is conducive to the recovery of gastrointestinal function and the promotion of immune state, eventually promotes patients’ postoperative overall recovery and has active clinical significance.

  11. Plasmodium falciparum erythrocyte invasion: combining function with immune evasion.

    Directory of Open Access Journals (Sweden)

    Gavin J Wright

    2014-03-01

    Full Text Available All the symptoms and pathology of malaria are caused by the intraerythrocytic stages of the Plasmodium parasite life cycle. Because Plasmodium parasites cannot replicate outside a host cell, their ability to recognize and invade erythrocytes is an essential step for both parasite survival and malaria pathogenesis. This makes invasion a conceptually attractive vaccine target, especially because it is one of the few stages when the parasite is directly exposed to the host humoral immune system. This apparent vulnerability, however, has been countered by the parasite, which has evolved sophisticated molecular mechanisms to evade the host immune response so that parasites asymptomatically replicate within immune individuals. These mechanisms include the expansion of parasite invasion ligands, resulting in multiple and apparently redundant invasion "pathways", highly polymorphic parasite surface proteins that are immunologically distinct, and parasite proteins which are poorly immunogenic. These formidable defences have so far thwarted attempts to develop an effective blood-stage vaccine, leading many to question whether there really is an exploitable chink in the parasite's immune evasion defences. Here, we review recent advances in the molecular understanding of the P. falciparum erythrocyte invasion field, discuss some of the challenges that have so far prevented the development of blood-stage vaccines, and conclude that the parasite invasion ligand RH5 represents an essential pinch point that might be vulnerable to vaccination.

  12. Control of Immune Cell Homeostasis and Function by lncRNAs.

    Science.gov (United States)

    Mowel, Walter K; Kotzin, Jonathan J; McCright, Sam J; Neal, Vanessa D; Henao-Mejia, Jorge

    2018-01-01

    The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues. We review here how lncRNAs control the function and homeostasis of cell populations during immune responses, emphasizing the diverse molecular mechanisms by which lncRNAs tune highly contextualized transcriptional programs. In addition, we discuss the new challenges faced in interrogating lncRNA mechanisms and function in the immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  14. Prenatal cadmium exposure alters postnatal immune cell development and function

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Miranda L.; Holásková, Ida; Elliott, Meenal; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B., E-mail: jbarnett@hsc.wvu.edu

    2012-06-01

    Cadmium (Cd) is generally found in low concentrations in the environment due to its widespread and continual use, however, its concentration in some foods and cigarette smoke is high. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports of immunomodulatory effects of prenatal exposure to Cd. This study was designed to investigate the effects of prenatal exposure to Cd on the immune system of the offspring. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at two time points following birth (2 and 7 weeks of age). Thymocyte and splenocyte phenotypes were analyzed by flow cytometry. Prenatal Cd exposure did not affect thymocyte populations at 2 and 7 weeks of age. In the spleen, the only significant effect on phenotype was a decrease in the number of macrophages in male offspring at both time points. Analysis of cytokine production by stimulated splenocytes demonstrated that prenatal Cd exposure decreased IL-2 and IL-4 production by cells from female offspring at 2 weeks of age. At 7 weeks of age, splenocyte IL-2 production was decreased in Cd-exposed males while IFN-γ production was decreased from both male and female Cd-exposed offspring. The ability of the Cd-exposed offspring to respond to immunization with a S. pneumoniae vaccine expressing T-dependent and T-independent streptococcal antigens showed marked increases in the levels of both T-dependent and T-independent serum antibody levels compared to control animals. CD4{sup +}FoxP3{sup +}CD25{sup +} (nTreg) cell percentages were increased in the spleen and thymus in all Cd-exposed offspring except in the female spleen where a decrease was seen. CD8{sup +}CD223{sup +} T cells were markedly decreased in the spleens in all offspring at 7 weeks of age. These findings suggest that even very low levels of Cd exposure during gestation can

  15. Effect of long-term fluticasone treatment on immune function in horses with heaves.

    Science.gov (United States)

    Dauvillier, J; Felippe, M J B; Lunn, D P; Lavoie-Lamoureux, A; Leclère, M; Beauchamp, G; Lavoie, J-P

    2011-01-01

    Corticosteroids currently are the most effective pharmacological treatment available to control heaves in horses. Systemically administered corticosteroids have been shown to alter immune response in horses, humans, and other species. Aerosolized administration theoretically minimizes systemic adverse effects, but the effect of inhaled corticosteroids on immune function has not been evaluated in horses. To evaluate the effects of prolonged administration of inhaled fluticasone on the immune system of heaves-affected horses. Heaves-affected horses were treated with inhaled fluticasone (n = 5) for 11 months or received environmental modifications only (n = 5). Prospective analysis. Clinical parameters and CBC, lymphocyte subpopulations and function, and circulating neutrophil gene expression were sequentially measured. Primary and anamnestic immune responses also were evaluated by measuring antigen-specific antibodies in response to vaccination with bovine viral antigen and tetanus toxoid, respectively. No clinical adverse effects were observed and no differences in immune function were detected between treated and untreated horses. The treatment of heaves-affected horses with inhaled fluticasone at therapeutic dosages for 11 months has no significant detectable effect on innate and adaptive (both humoral and cell-mediated) immune parameters studied. These results suggest that prolonged administration of fluticasone would not compromise the systemic immune response to pathogens nor vaccination in adult horses. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  16. Studying the Impact of Spaceflight Environment on Immune Functions Using New Molecular Diagnostics System

    Science.gov (United States)

    Cohen, Luchino

    Immune functions are altered during space flights. Latent virus reactivation, reduction in the number of immune cells, decreased cell activation and increased sensitivity of astronauts to infections following their return on Earth demonstrate that the immune system is less efficient during space flight. The causes of this immune deficiency are not fully understood and this dysfunction during long-term missions could result in the appearance of opportunistic infections or a decrease in the immuno-surveillance mechanisms that eradicate cancer cells. Therefore, the immune functions of astronauts will have to be monitored continuously during long-term missions in space, using miniature and semi-automated diagnostic systems. The objectives of this project are to study the causes of space-related immunodeficiency, to develop countermeasures to maintain an optimal immune function and to improve our capacity to detect infectious diseases during space missions through the monitoring of astronauts' immune system. In order to achieve these objectives, an Immune Function Diagnostic System (IFDS) will be designed to perform a set of immunological assays on board spacecrafts or on planet-bound bases. Through flow cytometric assays and molecular biology analyses, this diagnostic system could improve medical surveillance of astronauts and could be used to test countermeasures aimed at preventing immune deficiency during space missions. The capacity of the instrument to assess cellular fluorescence and to quantify the presence of soluble molecules in biological samples would support advanced molecular studies in space life sciences. Finally, such diagnostic system could also be used on Earth in remote areas or in mobile hospitals following natural disasters to fight against infectious diseases and other pathologies.

  17. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti

  18. Tradeoffs between immune function and childhood growth among Amazonian forager-horticulturalists.

    Science.gov (United States)

    Urlacher, Samuel S; Ellison, Peter T; Sugiyama, Lawrence S; Pontzer, Herman; Eick, Geeta; Liebert, Melissa A; Cepon-Robins, Tara J; Gildner, Theresa E; Snodgrass, J Josh

    2018-04-24

    Immune function is an energetically costly physiological activity that potentially diverts calories away from less immediately essential life tasks. Among developing organisms, the allocation of energy toward immune function may lead to tradeoffs with physical growth, particularly in high-pathogen, low-resource environments. The present study tests this hypothesis across diverse timeframes, branches of immunity, and conditions of energy availability among humans. Using a prospective mixed-longitudinal design, we collected anthropometric and blood immune biomarker data from 261 Amazonian forager-horticulturalist Shuar children (age 4-11 y old). This strategy provided baseline measures of participant stature, s.c. body fat, and humoral and cell-mediated immune activity as well as subsample longitudinal measures of linear growth (1 wk, 3 mo, 20 mo) and acute inflammation. Multilevel analyses demonstrate consistent negative effects of immune function on growth, with children experiencing up to 49% growth reduction during periods of mildly elevated immune activity. The direct energetic nature of these relationships is indicated by ( i ) the manifestation of biomarker-specific negative immune effects only when examining growth over timeframes capturing active competition for energetic resources, ( ii ) the exaggerated impact of particularly costly inflammation on growth, and ( iii ) the ability of children with greater levels of body fat (i.e., energy reserves) to completely avoid the growth-inhibiting effects of acute inflammation. These findings provide evidence for immunologically and temporally diverse body fat-dependent tradeoffs between immune function and growth during childhood. We discuss the implications of this work for understanding human developmental energetics and the biological mechanisms regulating variation in human ontogeny, life history, and health.

  19. Stress, Immune Function and Collegiate Holiday Drinking: A Pilot Study.

    Science.gov (United States)

    Ceballos, Natalie A; Sharma, Shobhit; Patterson, Thomas L; Graham, Reiko; Howard, Krista

    2015-01-01

    Social aspects of collegiate holiday drinking have been studied frequently, but physiological consequences are often overlooked. This study examined self-reported stress, endocrine and immune indicators in students at an American university before and after their week-long spring break (SB) holiday. Participants (n = 27; 9 males) provided saliva samples and completed surveys pre- and post-SB. Based on their cortisol reaction to SB, participants were grouped as cortisol nonresponders (CNR; n = 14) or increasers (CI; n = 13). Groups were matched on demographics, baseline alcohol use, family history of alcoholism, and SB plans. Differences over time and between groups were examined for α-amylase, quantity/frequency of alcohol use (quantity/frequency index, QFI) and the immunoglobulin A (IgA) to albumin ratio (IgA:albumin). α-Amylase decreased over time. A time × group interaction was noted for QFI, in which CNRs increased drinking over SB, but CIs did not. Time and time × group effects occurred for IgA:albumin. CIs decreased IgA:albumin over SB, whereas CNRs did not. Pre-SB QFI and pre-/post-SB QFI changes were correlated with changes in IgA:albumin. These findings support previously published relationships between blunted cortisol responses and risk for problem drinking, as well as elevated cortisol and decreased immune response. These data also highlight the importance of physiological measures in the study of collegiate holiday drinking. © 2015 S. Karger AG, Basel.

  20. Incubation period and immune function: A comparative field study among coexisting birds

    Science.gov (United States)

    Palacios, M.G.; Martin, T.E.

    2006-01-01

    Developmental periods are integral components of life history strategies that can have important fitness consequences and vary enormously among organisms. However, the selection pressures and mechanisms causing variation in length of developmental periods are poorly understood. Particularly puzzling are prolonged developmental periods, because their selective advantage is unclear. Here we tested the hypotheses that immune function is stronger in species that are attacked at a higher rate by parasites and that prolonged embryonic development allows the development of this stronger immune system. Through a comparative field study among 12 coexisting passerine bird species, we show that species with higher blood parasite prevalence mounted stronger cellular immune responses than species with lower prevalence. These results provide support for the hypothesis that species facing greater selection pressure from parasites invest more in immune function. However, species with longer incubation periods mounted weaker cellular immune responses than species with shorter periods. Therefore, cellular immune responses do not support the hypothesis that longer development time enhances immunocompentence. Future studies should assess other components of the immune system and test alternative causes of variation in incubation periods among bird species. ?? Springer-Verlag 2005.

  1. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

  2. A novel algorithm of artificial immune system for high-dimensional function numerical optimization

    Institute of Scientific and Technical Information of China (English)

    DU Haifeng; GONG Maoguo; JIAO Licheng; LIU Ruochen

    2005-01-01

    Based on the clonal selection theory and immune memory theory, a novel artificial immune system algorithm, immune memory clonal programming algorithm (IMCPA), is put forward. Using the theorem of Markov chain, it is proved that IMCPA is convergent. Compared with some other evolutionary programming algorithms (like Breeder genetic algorithm), IMCPA is shown to be an evolutionary strategy capable of solving complex machine learning tasks, like high-dimensional function optimization, which maintains the diversity of the population and avoids prematurity to some extent, and has a higher convergence speed.

  3. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    Science.gov (United States)

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  4. Obligate brood parasites show more functionally effective innate immune responses: an eco-immunological hypothesis

    Science.gov (United States)

    Hahn, D. Caldwell; Summers, Scott G.; Genovese, Kenneth J.; He, Haiqi; Kogut, Michael H.

    2013-01-01

    Immune adaptations of obligate brood parasites attracted interest when three New World cowbird species (Passeriformes, Icteridae, genus Molothrus) proved unusually resistant to West Nile virus. We have used cowbirds as models to investigate the eco-immunological hypothesis that species in parasite-rich environments characteristically have enhanced immunity as a life history adaptation. As part of an ongoing program to understand the cowbird immune system, in this study we measured degranulation and oxidative burst, two fundamental responses of the innate immune system. Innate immunity provides non-specific, fast-acting defenses against a variety of invading pathogens, and we hypothesized that innate immunity experiences particularly strong selection in cowbirds, because their life history strategy exposes them to diverse novel and unpredictable parasites. We compared the relative effectiveness of degranulation and oxidative burst responses in two cowbird species and one related, non-parasitic species. Both innate immune defenses were significantly more functionally efficient in the two parasitic cowbird species than in the non-parasitic red-winged blackbird (Icteridae, Agelaius phoeniceus). Additionally, both immune defenses were more functionally efficient in the brown-headed cowbird (M. ater), an extreme host-generalist brood parasite, than in the bronzed cowbird (M. aeneus), a moderate host-specialist with lower exposure to other species and their parasites. Thus the relative effectiveness of these two innate immune responses corresponds to the diversity of parasites in the niche of each species and to their relative resistance to WNV. This study is the first use of these two specialized assays in a comparative immunology study of wild avian species.

  5. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging.

    Science.gov (United States)

    Palmer, Clovis S; Palchaudhuri, Riya; Albargy, Hassan; Abdel-Mohsen, Mohamed; Crowe, Suzanne M

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of "inflammaging", a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV + individuals.

  6. Podoplanin: emerging functions in development, the immune system, and cancer

    Directory of Open Access Journals (Sweden)

    Jillian Leigh Astarita

    2012-09-01

    Full Text Available Podoplanin (PDPN is a well-conserved, mucin-type transmembrane protein expressed in multiple tissues during ontogeny and in adult animals, including the brain, heart, kidney, lungs, osteoblasts, and lymphoid organs. Studies of PDPN-deficient mice have demonstrated that this molecule plays a critical role in development of the heart, lungs, and lymphatic system. PDPN is widely used as a marker for lymphatic endothelial cells and fibroblastic reticular cells of lymphoid organs and for lymphatics in the skin and tumor microenvironment. Much of the mechanistic insight into PDPN biology has been gleaned from studies of tumor cells; tumor cells often upregulate PDPN as they undergo epithelial-mesenchymal transition and this upregulation is correlated with increased motility and metastasis. The physiological role of PDPN that has been most studied is its ability to aggregate and activate CLEC-2-expressing platelets, as PDPN is the only known endogenous ligand for CLEC-2. However, more recent studies have revealed that PDPN also plays crucial roles in the biology of immune cells, including T cells and dendritic cells. This review will provide a comprehensive overview of the diverse roles of PDPN in development, immunology, and cancer.

  7. Fish oil supplementation modulates immune function in healthy infants

    DEFF Research Database (Denmark)

    Damsgaard, C.T.; Lauritzen, L.; Kjaer, T.M.R.

    2007-01-01

    Danish infants, who received cow's milk or infant formula alone or with fish oil (FO) (3.4 +/- 1.1 mL/d) from 9 to 12 mo of age. Before and after the intervention, fatty acid composition of erythrocyte membranes, plasma IgE, C-reactive protein, and soluble IL-2 receptor concentrations were measured. TNF......-alpha, INF-gamma, and IL-10 concentrations in whole-blood cultures, stimulated for 22 h with LPS+phytohema-glutinin (PHA) or Lactobacillus paracasei, were also determined. IgA was measured in feces when infants were 10 mo of age. FO supplementation effectively raised erythrocyte (n-3) PUFA (P ....02). Feeding milk rather than formula did not affect cytokine production, but plasma soluble IL-2 receptor concentration was greater in the formula group than in the cow's milk group (P = 0.03). Since the capacity to produce INF-gamma has been proposed as a maturation marker for the immune system in early life...

  8. Constant illumination reduces circulating melatonin and impairs immune function in the cricket Teleogryllus commodus

    Directory of Open Access Journals (Sweden)

    Joanna Durrant

    2015-07-01

    Full Text Available Exposure to constant light has a range of negative effects on behaviour and physiology, including reduced immune function in both vertebrates and invertebrates. It is proposed that the associated suppression of melatonin (a ubiquitous hormone and powerful antioxidant in response to the presence of light at night could be an underlying mechanistic link driving the changes to immune function. Here, we investigated the relationship between constant illumination, melatonin and immune function, using a model invertebrate species, the Australian black field cricket, Teleogryllus commodus. Crickets were reared under either a 12 h light: 12 h dark regimen or a constant 24 h light regimen. Circulating melatonin concentration and immune function (haemocyte concentration, lytic activity and phenoloxidase (PO activity were assessed in individual adult crickets through the analysis of haemolymph. Constant illumination reduced melatonin and had a negative impact on haemocyte concentrations and lytic activity, but its effect on PO activity was less apparent. Our data provide the first evidence, to our knowledge, of a link between exposure to constant illumination and variation in haemocyte concentration in an invertebrate model, while also highlighting the potential complexity of the immune response following exposure to constant illumination. This study provides insight into the possible negative effect of artificial night-time lighting on the physiology of invertebrates, but whether lower and potentially more ecologically relevant levels of light at night produce comparable results, as has been reported in several vertebrate taxa, remains to be tested.

  9. Immune Monitoring in Cancer Vaccine Clinical Trials: Critical Issues of Functional Flow Cytometry-Based Assays

    Directory of Open Access Journals (Sweden)

    Iole Macchia

    2013-01-01

    Full Text Available The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs and tumor-associated antigens (TAAs and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometry- (FCM- based assays combining different phenotypic and functional markers have been developed in the past decade for informative and longitudinal analysis of polyfunctional T-cells. These technologies were designed to address the complexity and functional heterogeneity of cancer biology and cellular immunity and to define biomarkers predicting clinical response to anticancer treatment. So far, there is still a lack of standardization of some of these immunological tests. The aim of this review is to overview the latest technologies for immune monitoring and to highlight critical steps involved in some of the FCM-based cellular immune assays. In particular, our laboratory is focused on melanoma vaccine research and thus our main goal was the validation of a functional multiparameter test (FMT combining different functional and lineage markers to be applied in clinical trials involving patients with melanoma.

  10. Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

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    Joanna Bandoła

    2017-08-01

    Full Text Available Plasmacytoid dendritic cells (pDCs regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR by the antigen-presenting pDCs, mediated by toll-like receptor (TLR 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

  11. Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

    Science.gov (United States)

    Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

    2017-01-01

    Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

  12. Food supplementation and testosterone interact to influence reproductive behavior and immune function in Sceloporus graciosus.

    Science.gov (United States)

    Ruiz, Mayté; French, Susannah S; Demas, Gregory E; Martins, Emília P

    2010-02-01

    The energetic resources in an organism's environment are essential for executing a wide range of life-history functions, including immunity and reproduction. Most energetic budgets, however, are limited, which can lead to trade-offs among competing functions. Increasing reproductive effort tends to decrease immunity in many cases, and increasing total energy via supplemental feedings can eliminate this effect. Testosterone (T), an important regulator of reproduction, and food availability are thus both potential factors regulating life-history processes, yet they are often tested in isolation of each other. In this study, we considered the effect of both food availability and elevated T on immune function and reproductive behavior in sagebrush lizards, Sceloporus graciosus, to assess how T and energy availability affect these trade-offs. We experimentally manipulated diet (via supplemental feedings) and T (via dermal patches) in males from a natural population. We determined innate immune response by calculating the bacterial killing capability of collected plasma exposed to Escherichia coli ex vivo. We measured reproductive behavior by counting the number of courtship displays produced in a 20-min sampling period. We observed an interactive effect of food availability and T-patch on immune function, with food supplementation increasing immunity in T-patch lizards. Additionally, T increased courtship displays in control food lizards. Lizards with supplemental food had higher circulating T than controls. Collectively, this study shows that the energetic state of the animal plays a critical role in modulating the interactions among T, behavior and immunity in sagebrush lizards and likely other species. Copyright 2009 Elsevier Inc. All rights reserved.

  13. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging [version 1; referees: 4 approved

    OpenAIRE

    Clovis S. Palmer; Riya Palchaudhuri; Hassan Albargy; Mohamed Abdel-Mohsen; Suzanne M. Crowe

    2018-01-01

    An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impa...

  14. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis.

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    Dequina Nicholas

    Full Text Available Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96 analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.

  15. Effects of water extract of Curcuma longa (L.) roots on immunity and telomerase function.

    Science.gov (United States)

    Pan, Min-Hsiung; Wu, Jia-Ching; Ho, Chi-Tang; Badmaev, Vladimir

    2017-05-12

    Background Immunity and Longevity Methods A water extract of Curcuma longa (L.) [vern. Turmeric] roots (TurmericImmune™) standardized for a minimum 20 % of turmeric polysaccharides ukonan A, B, C and D was evaluated for its biological properties in in vitro tissue culture studies. Results The water extract of turmeric (TurP) exhibited induced-nitric oxide (NO) production in RAW264.7 macrophages. These results suggested the immunomodulatory effects of TurP. In addition, the polysaccharides up-regulated function of telomerase reverse transcriptase (TERT) equally to the phenolic compound from turmeric, curcumin. Conclusions The ukonan family of polysaccharides may assist in promoting cellular immune responses, tissue repair and lifespan by enhancing immune response and telomere function.

  16. Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function

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    Kathryn M. Lenz

    2018-04-01

    Full Text Available Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer’s disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

  17. Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

    Science.gov (United States)

    Lenz, Kathryn M; Nelson, Lars H

    2018-01-01

    Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

  18. The role of dehydroepiandrosterone on functional innate immune responses to acute stress.

    Science.gov (United States)

    Prall, Sean P; Larson, Emilee E; Muehlenbein, Michael P

    2017-12-01

    The androgen dehydroepiandrosterone (DHEA) responds to stress activation, exhibits anti-glucocorticoid properties, and modulates immunity in diverse ways, yet little is known of its role in acute stress responses. In this study, the effects of DHEA and its sulfate ester DHEA-S on human male immune function during exposure to an acute stressor is explored. Variation in DHEA, DHEA-S, testosterone, and cortisol, along with bacterial killing assays, was measured in response to a modified Trier Social Stress test in 27 young adult males. Cortisol was positively related to salivary innate immunity but only for participants who also exhibited high DHEA responses. Additionally, DHEA positively and DHEA-S negatively predicted salivary immunity, but the opposite was observed for serum-based innate immunity. The DHEA response to acute stress appears to be an important factor in stress-mediated immunological responses, with differential effects on immunity dependent upon the presence of other hormones, primarily cortisol and DHEA-S. These results suggest that DHEA plays an important role, alongside other hormones, in modulating immunological shifts during acute stress. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Effects of γ-rays on Th1 and Th2 immune function of mice

    International Nuclear Information System (INIS)

    Jin Wei; Cui Yufang; An Xiaoxia; Xu Han; Dong Bo; Liu Xiaolan; Luo Qingliang

    2007-01-01

    Objective: To observe the effects of 6 Gy whole body γ-irradiation on immune function of Th1 and Th2 in mouse, and to investigate the cellular and molecular mechanism of immune system injury induced by irradiation. Methods: Surface marker and intracellular cytokines of lymphocytes were stained with fluorescence-labeled monoclonal antibodies, then the changes of lymphocyte subpopulations, especially the Th1 and Th2 in mouse peripheral blood and spleen were analyzed by flow cytometry. Results: (1) 1 d after 6 Gy y- irradiation, lymphocytic subsets of CD 19 + and CD 8 + in spleen decreased apparently and the percentages of them were only 30% and 41% of control groups respectively (P 19 + and 14 d for CD 8 + respectively, however, up to 21 d post-irradiation they still did not return to control level. (2) Th1 subpopulations in mouse peripheral blood and spleen were significantly reduced at 1 d after irradiation and were only 2.6% and 7.6% of control groups (P 4 + / CD 8 + were significantly increased at 1 d post-irradiation in mouse spleen because of swift reduction of CD 8 + cells. Interestingly, either in peripheral blood or in spleen in irradiated mice, the ratio of Th1/Th2 were evidently raised because of the decrement of Th1 cells, exhibited obviously a phenomenon of predominant immune response of Th2 cells. Conclusions: It is suggested that the depression of mouse immune function induced by 6 Gy γ-irradiation might be caused by changes of CD 4 + /CD 8 + ratio, especially the imbalance of Th1/Th2 function subpopulations. It is shown that the imbalance of Th1/Th2 function subpopulations plays an important role in radiation-induced immune injury, thus providing a better insight into the molecular mechanism and new strategies for prevent and treatment measures of immune injury by irradiation. (authors)

  20. Loss of renal function causes premature aging of the immune system.

    Science.gov (United States)

    Betjes, Michiel G H; Meijers, Ruud W J; Litjens, Nicolle H R

    2013-01-01

    Uremia-associated immune deficiency is a well-known complication of loss of renal function and contributes significantly to the overall mortality and morbidity of patients with end-stage renal disease. Chronic inflammation and increased oxidative stress are underlying the uremia-associated immune deficiency. In this review, the differential impact of uremia on the cellular immune system is summarized. Virtually all immune cells studied show a combination of an activated status and loss of function. However, uremia preferentially decreases the number and function of lymphoid cells while myeloid cells show normal and/or elevated cell numbers with increased production of inflammatory cytokines and reactive oxygen species. These particular changes are compatible with immunological aging, which is characterized by loss of thymic function, attrition of telomeres and an expanded memory T cell population. Similar to aging in healthy individuals, the proinflammatory and potential cardiotoxic subsets of CD28(null) T cells and CD16(+) monocytes are increased. Epigenetically changed hematopoietic stem cells may be involved in immunological aging as specific DNA regions become hypermethylated. Proinflammatory T cells and monocytes persist after kidney transplantation, which constitutes a persistent cardiovascular risk factor. Possible therapeutic options to reverse or halt uremia-associated immunological aging are discussed. Premature aging of the immune system is a dominant feature in patients with end-stage renal failure, which corresponds to immunological aging in elderly healthy individuals, which is characterized by preferential loss of cells belonging to the lymphoid cell lineage, inflammation and expansion of proinflammatory immune cells. © 2013 S. Karger AG, Basel.

  1. Function of endoplasmic reticulum calcium ATPase in innate immunity-mediated programmed cell death

    Science.gov (United States)

    Zhu, Xiaohong; Caplan, Jeffrey; Mamillapalli, Padmavathi; Czymmek, Kirk; Dinesh-Kumar, Savithramma P

    2010-01-01

    Programmed cell death (PCD) initiated at the pathogen-infected sites during the plant innate immune response is thought to prevent the development of disease. Here, we describe the identification and characterization of an ER-localized type IIB Ca2+-ATPase (NbCA1) that function as a regulator of PCD. Silencing of NbCA1 accelerates viral immune receptor N- and fungal-immune receptor Cf9-mediated PCD, as well as non-host pathogen Pseudomonas syringae pv. tomato DC3000 and the general elicitor cryptogein-induced cell death. The accelerated PCD rescues loss-of-resistance phenotype of Rar1, HSP90-silenced plants, but not SGT1-silenced plants. Using a genetically encoded calcium sensor, we show that downregulation of NbCA1 results in the modulation of intracellular calcium signalling in response to cryptogein elicitor. We further show that NbCAM1 and NbrbohB function as downstream calcium decoders in N-immune receptor-mediated PCD. Our results indicate that ER-Ca2+-ATPase is a component of the calcium efflux pathway that controls PCD during an innate immune response. PMID:20075858

  2. Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

    Directory of Open Access Journals (Sweden)

    Chun-Jung Huang

    2013-01-01

    Full Text Available Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation.

  3. Immune responses at brain barriers and implications for brain development and neurological function in later life

    Directory of Open Access Journals (Sweden)

    Helen B. Stolp

    2013-08-01

    Full Text Available For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognised that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signalling, or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signalling at the brain barriers that may be an important part of the body’s response to damage or infection. This signalling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation–induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

  4. Comparison of the Functional microRNA Expression in Immune Cell Subsets of Neonates and Adults

    Science.gov (United States)

    Yu, Hong-Ren; Hsu, Te-Yao; Huang, Hsin-Chun; Kuo, Ho-Chang; Li, Sung-Chou; Yang, Kuender D.; Hsieh, Kai-Sheng

    2016-01-01

    Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs) are reported to involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte subpopulations is important for understanding immune system regulation. In order to explore the unique miRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells, and myeloid dendritic cells) from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced interleukin (IL)-6 and TNF-α production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-α production. With this functional approach, we provide intact differential miRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies. PMID:28066425

  5. Comparison of the functional microRNA expression in immune cell subsets of neonates and adults

    Directory of Open Access Journals (Sweden)

    Hong-Ren Yu

    2016-12-01

    Full Text Available Diversity of biological molecules in newborn and adult immune cells contributes to differences in cell function and atopic properties. Micro RNAs (miRNAs are reported involve in the regulation of immune system. Therefore, determining the miRNA expression profile of leukocyte sub-populations is important for understanding immune system regulation. In order to explore the unique microRNA profiling that contribute to altered immune in neonates, we comprehensively analyzed the functional miRNA signatures of eight leukocyte subsets (polymorphonuclear cells, monocytes, CD4+ T cells, CD8+ T cells, natural killer cells, B cells, plasmacytoid dendritic cells (pDCs, and myeloid dendritic cells (mDCs from both neonatal and adult umbilical cord and peripheral blood samples, respectively. We observed distinct miRNA profiles between adult and neonatal blood leukocyte subsets, including unique miRNA signatures for each cell lineage. Leukocyte miRNA signatures were altered after stimulation. Adult peripheral leukocytes had higher let-7b-5p expression levels compared to neonatal cord leukocytes across multiple subsets, irrespective of stimulation. Transfecting neonatal monocytes with a let-7b-5p mimic resulted in a reduction of LPS-induced IL-6 and TNF-alpha production, while transfection of a let-7b-5p inhibitor into adult monocytes enhanced IL-6 and TNF-alpha production. With this functional approach, we provide intact differential microRNA expression profiling of specific immune cell subsets between neonates and adults. These studies serve as a basis to further understand the altered immune response observed in neonates and advance the development of therapeutic strategies.

  6. Hygiene and other early childhood influences on the subsequent function of the immune system.

    Science.gov (United States)

    Rook, Graham A W; Lowry, Christopher A; Raison, Charles L

    2015-08-18

    The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights

  7. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function......). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially...... and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents...

  8. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils

    DEFF Research Database (Denmark)

    Galli, Stephen J; Borregaard, Niels; Wynn, Thomas A

    2011-01-01

    ). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially......Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function...... and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents...

  9. Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations

    Science.gov (United States)

    Verboon, Jeffrey M.; Rahe, Travis K.; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

    2015-01-01

    Drosophila immune cells, the hemocytes, undergo four stereotypical developmental migrations to populate the embryo, where they provide immune reconnoitering, as well as a number of non–immune-related functions necessary for proper embryogenesis. Here, we describe a role for Rho1 in one of these developmental migrations in which posteriorly located hemocytes migrate toward the head. This migration requires the interaction of Rho1 with its downstream effector Wash, a Wiskott–Aldrich syndrome family protein. Both Wash knockdown and a Rho1 transgene harboring a mutation that prevents Wash binding exhibit the same developmental migratory defect as Rho1 knockdown. Wash activates the Arp2/3 complex, whose activity is needed for this migration, whereas members of the WASH regulatory complex (SWIP, Strumpellin, and CCDC53) are not. Our results suggest a WASH complex–independent signaling pathway to regulate the cytoskeleton during a subset of hemocyte developmental migrations. PMID:25739458

  10. A cascade reaction network mimicking the basic functional steps of acquired immune response

    Science.gov (United States)

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-01-01

    Biological systems use complex ‘information processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS which we call Adaptive Immune Response Simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system which responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner which is superficially similar to the most basic responses of the vertebrate acquired immune system, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices. PMID:26391084

  11. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Science.gov (United States)

    Kato, Kazuki; Ishii, Ryohei; Goto, Eiji; Ishitani, Ryuichiro; Tokunaga, Fuminori; Nureki, Osamu

    2013-01-01

    The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  12. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Directory of Open Access Journals (Sweden)

    Kazuki Kato

    Full Text Available The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING, resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  13. PCSK9 at the crossroad of cholesterol metabolism and immune function during infections.

    Science.gov (United States)

    Paciullo, Francesco; Fallarino, Francesca; Bianconi, Vanessa; Mannarino, Massimo R; Sahebkar, Amirhossein; Pirro, Matteo

    2017-09-01

    Sepsis, a complex and dynamic syndrome resulting from microbial invasion and immune system dysregulation, is associated with an increased mortality, reaching up to 35% worldwide. Cholesterol metabolism is often disturbed during sepsis, with low plasma cholesterol levels being associated with poor prognosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of the low-density lipoprotein receptor (LDLR), thus regulating intracellular and plasma cholesterol levels. PCSK9 is often upregulated during sepsis and might have a detrimental effect on immune host response and survival. Accordingly, PCSK9 reduces lipopolysaccharide uptake and clearance by human hepatocytes. Moreover, PCSK9 upregulation exacerbates organ dysfunction and tissue inflammation during sepsis, whereas a protective effect of PCSK9 deficiency has been documented in septic patients. Although a possible detrimental impact of PCSK9 on survival has been described, some beneficial effects of PCSK9 on immune response may be hypothesized. First, PCSK9 is associated with increased plasma cholesterol levels, which might be protective during sepsis. Second, PCSK9, by stimulating LDLR degradation and inhibiting reverse cholesterol transport (RCT), might promote preferential cholesterol accumulation in macrophages and other immune cells; these events might improve lipid raft composition and augment toll-like receptor function thus supporting inflammatory response. Hence, a more clear definition of the role of PCSK9 in septic states might provide additional insight in the understanding of the sepsis-associated immune dysregulation and enhance therapeutic outcomes. © 2017 Wiley Periodicals, Inc.

  14. Shingles Immunity and Health Functioning in the Elderly: Tai Chi Chih as a Behavioral Treatment

    Directory of Open Access Journals (Sweden)

    Michael Irwin

    2004-01-01

    Full Text Available Both the incidence and severity of herpes zoster (HZ or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in older adults is associated with declines in VZV-responder cell frequency (VZV-RCF, an immunological marker of shingles risk. In this review, we discuss recent findings that administration of a relaxation response-based intervention, tai chi chih (TCC, results in improvements in health functioning and immunity to VZV in older adults as compared with a control group. TCC is a slow moving meditation consisting of 20 separate standardized movements which can be readily used in elderly and medically compromised individuals. TCC offers standardized training and practice schedules, lending an important advantage over prior relaxation response-based therapies. Focus on older adults at increased risk for HZ and assay of VZV-specific immunity have implications for understanding the impact of behavioral factors and a behavioral intervention on a clinically relevant end-point and on the response of the immune system to infectious pathogens.

  15. MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

    Science.gov (United States)

    Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

    2016-01-01

    Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

  16. Dim light at night increases immune function in Nile grass rats, a diurnal rodent.

    Science.gov (United States)

    Fonken, Laura K; Haim, Achikam; Nelson, Randy J

    2012-02-01

    With the widespread adoption of electrical lighting during the 20th century, human and nonhuman animals became exposed to high levels of light at night for the first time in evolutionary history. This divergence from the natural environment may have significant implications for certain ecological niches because of the important influence light exerts on the circadian system. For example, circadian disruption and nighttime light exposure are linked to changes in immune function. The majority of studies investigating the effects of light exposure and circadian disruption on the immune system use nocturnal rodents. In diurnal species, many hormones and immune parameters vary with secretion patterns 180° out of phase to those of nocturnal rodents. Thus, the authors investigated the effects of nighttime light exposure on immunocompetence in diurnal Nile grass rats (Arvicanthis niloticus). Rats were housed in either standard 14-h light (L):10-h dark (D) cycles with L ∼150 lux and D 0 lux or dim light at night (dLAN) cycles of LD 14:10 with L ∼150 lux and D 5 lux for 3 wks, then tested for plasma bactericidal capacity, as well as humoral and cell-mediated immune responses. Rats exposed to dLAN showed increased delayed-type hypersensitivity pinna swelling, which is consistent with enhanced cell-mediated immune function. dLAN rats similarly showed increased antibody production following inoculation with keyhole lymphocyte hemocyanin (KLH) and increased bactericidal capacity. Daytime corticosterone concentrations were elevated in grass rats exposed to nighttime dim light, which may have influenced immunological measures. Overall, these results indicate nighttime light affects immune parameters in a diurnal rodent.

  17. Seasonal Redistribution of Immune Function in a Migrant Shorebird : Annual-Cycle Effects Override Adjustments to Thermal Regime

    NARCIS (Netherlands)

    Buehler, Deborah M.; Piersma, Theunis; Matson, Kevin D.; Tieleman, B. Irene; Demas, Greg (associate); Geber, Monica A.

    2008-01-01

    Throughout the annual cycle, demands on competing physiological systems change, and animals must allocate resources to maximize fitness. Immune function is one such system and is important for survival. Yet detailed empirical data tracking immune function over the entire annual cycle are lacking for

  18. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Harmit S. Ranhotra

    2016-07-01

    Full Text Available The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

  19. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  20. Heat and immunity: an experimental heat wave alters immune functions in three-spined sticklebacks (Gasterosteus aculeatus).

    Science.gov (United States)

    Dittmar, Janine; Janssen, Hannah; Kuske, Andra; Kurtz, Joachim; Scharsack, Jörn P

    2014-07-01

    Global climate change is predicted to lead to increased temperatures and more extreme climatic events. This may influence host-parasite interactions, immunity and therefore the impact of infectious diseases on ecosystems. However, little is known about the effects of rising temperatures on immune defence, in particular in ectothermic animals, where the immune system is directly exposed to external temperature change. Fish are ideal models for studying the effect of temperature on immunity, because they are poikilothermic, but possess a complete vertebrate immune system with both innate and adaptive immunity. We used three-spined sticklebacks ( Gasterosteus aculeatus) originating from a stream and a pond, whereby the latter supposedly were adapted to higher temperature variation. We studied the effect of increasing and decreasing temperatures and a simulated heat wave with subsequent recovery on body condition and immune parameters. We hypothesized that the immune system might be less active at low temperatures, but will be even more suppressed at temperatures towards the upper tolerable temperature range. Contrary to our expectation, we found innate and adaptive immune activity to be highest at a temperature as low as 13 °C. Exposure to a simulated heat wave induced long-lasting immune disorders, in particular in a stickleback population that might be less adapted to temperature variation in its natural environment. The results show that the activity of the immune system of an ectothermic animal species is temperature dependent and suggest that heat waves associated with global warming may immunocompromise host species, thereby potentially facilitating the spread of infectious diseases. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  1. The effect of elevated reproductive effort onhumoral immune function in collared flycatcher females

    Science.gov (United States)

    Cichoń, Mariusz; Dubiec, Anna; Chadzińska, Magdalena

    2001-02-01

    In order to test whether high reproductive investments impair immune function in naturally breeding collared flycatchers, we performed a brood manipulation experiment and simultaneously induced an immune response by challenging birds with a non-pathogenic antigen - sheep red blood cells (SRBC). Females rearing experimentally enlarged number of nestlings showed significantly lower level of specific anti-SRBC antibodies than control females attending unaltered broods, but only in one of the two study years. The haemoconcentration of leukocytes did not differ between the two groups in both study years. The significant difference in immunological responsiveness between control and enlarged group coincided with differences in survival probability to the next breeding season: females attending enlarged broods showed lower probability of survival than control females, but there was no relationship between the level of immune response and survival probability. Our results indicate that reproduction may indeed trade for resources with immune functions at least in terms of specific antibody production. However, as in the other studies on reproductive costs, these costs seem not always to be pronounced.

  2. Modulation of immune cell functions by the E3 ligase CBL-b

    Directory of Open Access Journals (Sweden)

    Christina eLutz-Nicoladoni

    2015-03-01

    Full Text Available Maintenance of immunological tolerance is a critical hallmark of the immune system. Several signaling checkpoints necessary to balance activating and inhibitory input to immune cells have been described so far, among which the E3 ligase Cbl-b appears to be a central player. Cbl-b is expressed in all leukocyte subsets and regulates several signaling pathways in T cells, NK cells, B cells and different types of myeloid cells. In most cases Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and co-stimulatory molecules. In line with this function, cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity. Interestingly, genetic association studies link cblb-polymorphisms with autoimmunity also in humans. Vice versa, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections. Accordingly, several reports have shown that cblb knockout mice reject tumors, which mainly depends on cytotoxic T and NK cells. Thus targeting Cbl-b may be an interesting strategy to enhance anti-cancer immunity. In this review we summarize the findings on the molecular function of Cbl-b in different cell types and illustrate the potential of Cbl-b as target for immunomodulatory therapies.

  3. Gap junctions in cells of the immune system: structure, regulation and possible functional roles

    Directory of Open Access Journals (Sweden)

    J.C. Sáez

    2000-04-01

    Full Text Available Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

  4. The effects of stress hormones on immune function may be vital for the adaptive reconfiguration of the immune system during fight-or-flight behavior.

    Science.gov (United States)

    Adamo, Shelley A

    2014-09-01

    Intense, short-term stress (i.e., robust activation of the fight-or-flight response) typically produces a transient decline in resistance to disease in animals across phyla. Chemical mediators of the stress response (e.g., stress hormones) help induce this decline, suggesting that this transient immunosuppression is an evolved response. However, determining the function of stress hormones on immune function is difficult because of their complexity. Nevertheless, evidence suggests that stress hormones help maintain maximal resistance to disease during the physiological changes needed to optimize the body for intense physical activity. Work on insects demonstrates that stress hormones both shunt resources away from the immune system during fight-or-flight responses as well as reconfigure the immune system. Reconfiguring the immune system minimizes the impact of the loss of these resources and reduces the increased costs of some immune functions due to the physiological changes demanded by the fight-or-flight response. For example, during the stress response of the cricket Gryllus texensis, some molecular resources are shunted away from the immune system and toward lipid transport, resulting in a reduction in resistance to disease. However, insects' immune cells (hemocytes) have receptors for octopamine (the insect stress neurohormone). Octopamine increases many hemocyte functions, such as phagocytosis, and these changes would tend to mitigate the decline in immunity due to the loss of molecular resources. Moreover, because the stress response generates oxidative stress, some immune responses are probably more costly when activated during a stress response (e.g., those that produce reactive molecules). Some of these immune responses are depressed during stress in crickets, while others, whose costs are probably not increased during a stress response, are enhanced. Some effects of stress hormones on immune systems may be better understood as examples of reconfiguration

  5. Clinical evaluation of immune-promoting functions of the developed product (HemoHIM)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyoung Soo; Lee, Ill Kyoo; Kwon, Soon Gil [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-07-15

    We performed a clinical study to evaluate the immune promotion and antioxidant effects of the developed product (HemoHIM) in healthy or subhealthy people. Volunteers with white blood cell numbers between 5000 and 10000/ul were recruited and the subjects were selected by appropriate inclusion and exclusion rules. The subjects were randomly assigned to 3 groups (HemoHIM 6g/day, HemoHIM 12g/day, Placebo). HemoHIM or placebo were adminstered for 2 months and the blood were collected and analyzed at 1 month and 2 month after the intake. The collected blood was analyzed for blood cell number, serum biochemical values (liver and kidney function), immunological activity of blood cells, antioxidant activity of blood plasma, and stress hormone level in the saliva. Finally the data of 88 subjects were analyzed for the immune promoting and antioxidant effects of HemoHIM. In results, no significant changes in blood cell numbers (white blood cell, lymphocyte, red blood cell) were observed in HemoHIM intake groups. However, NK cell activity were increased in HemoHIM intake groups and also IFN-gamma and IL-12, the biomarkers of immune cell functions, were increased in proportion to the dose and intake periode of HemoHIM. The antioxidant biomarker (TAS) was not significantly changed by HemoHIM intake. Besides, the serum biochemical analysis for liver and kidney functions, and the general medical examination showed the HemoHIM showed no side-effects, thus reconfirming its safety in humans. In conclusion, this study showed HemoHIM has a significant effects on the promotion of immune functions, while it has neither side-effects nor toxicity in humans. The results of this study may be utilized for the scientific data to acquire the Health Functional Food Certification of HemoHIM from Korea FDA

  6. Streptavidin-functionalized capillary immune microreactor for highly efficient chemiluminescent immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Yang Zhanjun [State Key Laboratory of Analytical Chemistry for Life Science, Department of Chemistry, Nanjing University, Nanjing 210093 (China); College of Chemistry and Engineering, Yangzhou University, 88 South University Avenue, Yangzhou 225002 (China); Zong Chen [State Key Laboratory of Analytical Chemistry for Life Science, Department of Chemistry, Nanjing University, Nanjing 210093 (China); Ju Huangxian, E-mail: hxju@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, Department of Chemistry, Nanjing University, Nanjing 210093 (China); Yan Feng, E-mail: yanfeng2007@sohu.com [Jiangsu Institute of Cancer Prevention and Cure, Nanjing 210009 (China)

    2011-11-07

    Highlights: {yields} A novel capillary immune microreactor was proposed for highly efficient flow-through chemiluminescent immunoassay. {yields} The microreactor was prepared by functionalizing capillary inner wall with streptavidin for capture of biotinylated antibody. {yields} The proposed immunoassay method showed wide dynamic range, good reproducibility, stability and practicality. {yields} The microreactor was low-cost and disposable, and possessed several advantages over the conventional immunoreactors. - Abstract: A streptavidin functionalized capillary immune microreactor was designed for highly efficient flow-through chemiluminescent (CL) immunoassay. The functionalized capillary could be used as both a support for highly efficient immobilization of antibody and a flow cell for flow-through immunoassay. The functionalized inner wall and the capture process were characterized using scanning electron microscopy. Compared to conventional packed tube or thin-layer cell immunoreactor, the proposed microreactor showed remarkable properties such as lower cost, simpler fabrication, better practicality and wider dynamic range for fast CL immunoassay with good reproducibility and stability. Using {alpha}-fetoprotein as model analyte, the highly efficient CL flow-through immunoassay system showed a linear range of 3 orders of magnitude from 0.5 to 200 ng mL{sup -1} and a low detection limit of 0.1 ng mL{sup -1}. The capillary immune microreactor could make up the shortcoming of conventional CL immunoreactors and provided a promising alternative for highly efficient flow-injection immunoassay.

  7. Effects of stress on immune function: the good, the bad, and the beautiful.

    Science.gov (United States)

    Dhabhar, Firdaus S

    2014-05-01

    Although the concept of stress has earned a bad reputation, it is important to recognize that the adaptive purpose of a physiological stress response is to promote survival during fight or flight. While long-term stress is generally harmful, short-term stress can be protective as it prepares the organism to deal with challenges. This review discusses the immune effects of biological stress responses that can be induced by psychological, physiological, or physical (including exercise) stressors. We have proposed that short-term stress is one of the nature's fundamental but under-appreciated survival mechanisms that could be clinically harnessed to enhance immunoprotection. Short-term (i.e., lasting for minutes to hours) stress experienced during immune activation enhances innate/primary and adaptive/secondary immune responses. Mechanisms of immuno-enhancement include changes in dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function as well as local and systemic production of cytokines. In contrast, long-term stress suppresses or dysregulates innate and adaptive immune responses by altering the Type 1-Type 2 cytokine balance, inducing low-grade chronic inflammation, and suppressing numbers, trafficking, and function of immunoprotective cells. Chronic stress may also increase susceptibility to some types of cancer by suppressing Type 1 cytokines and protective T cells and increasing regulatory/suppressor T cell function. Here, we classify immune responses as being protective, pathological, or regulatory, and discuss "good" versus "bad" effects of stress on health. Thus, short-term stress can enhance the acquisition and/or expression of immunoprotective (wound healing, vaccination, anti-infectious agent, anti-tumor) or immuno-pathological (pro-inflammatory, autoimmune) responses. In contrast, chronic stress can suppress protective immune responses and/or exacerbate pathological immune responses. Studies such as the ones discussed

  8. Associations between immune function and air pollution among postmenopausal women living in the Puget Sound airshed

    Science.gov (United States)

    Williams, Lori A.

    Air pollution is associated with adverse health outcomes, and changes in the immune system may be intermediate steps between exposure and a clinically relevant adverse health outcome. We analyzed the associations between three different types of measures of air pollution exposure and five biomarkers of immune function among 115 overweight and obese postmenopausal women whose immunity was assessed as part of a year-long moderate exercise intervention trial. For air pollution metrics, we assessed: (1) residential proximity to major roads (freeways, major arterials and truck routes), (2) fine particulate matter(PM2.5) at the nearest monitor to the residence averaged over three time windows (3-days, 30-days and 60-days), and (3) nitrogen dioxide (NO2) modeled based on land use characteristics. Our immune biomarkers included three measures of inflammation---C-reactive protein, serum amyloid A and interleukin-6---and two measures of cellular immunity---natural killer cell cytotoxicity and T lymphocyte proliferation. We hypothesized that living near a major road, increased exposure to PM2.5 and increased exposure to NO2 would each be independently associated with increased inflammation and decreased immune function. We observed a 21% lower average natural killer cell cytotoxicity among women living within 150 meters of a major arterial road compared to other women. For PM2.5 , we observed changes in 3 of 4 indicators of lymphocyte proliferation stimulated by anti-CD3---an antibody to the T cell receptor associated with increases in 3-day averaged PM2.5. For 30-day averaged PM 2.5 and 60-day averaged PM2.5 we did not observe any statistically significant associations. We observed an increase in lymphocyte proliferation index stimulated by the plant protein phytohemagglutinin (PHA) at 1 of 2 PHA concentrations in association with modeled NO2. For the three inflammatory markers, we observed no notable associations with any of our measures of air pollution. If confirmed, our

  9. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  10. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  11. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.

    Science.gov (United States)

    Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

    2005-12-07

    To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. After one course of treatment with liniment levamisole, the levels of CD3(+), CD4(+), and the ratio of CD4(+)/CD8(+) increased as compared to those before the treatment but the level of CD8(+) decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

  12. Changes in proHB-EGF expression after functional activation of the immune system cells

    Directory of Open Access Journals (Sweden)

    T. O. Chudina

    2017-12-01

    Full Text Available The level of proHB-EGF expression on J774, Raji, KG-1 cells derived from different types of human and mouse immune system cells under the standard in vitro culture conditions and during functional activation of these cells was investigated. Changes in the proHB-EGF expression on the cell surface were found to depend on the density of cell population, the content of fetal bovine serum in the culture medium, the effect of mitogenic factors – bacterial lipopolysaccharide, an inactive full-size form of diphtheria toxin (CRM197 and recombinant soluble HB-EGF – rsHB-EGF. The results obtained are important for the understanding of the functional role of proHB-EGF receptor on the surface of macrophage-like cells and B lymphocytes and indicate the involvement of this receptor in immune response regulation in an organism.

  13. The effects of low dose radiation (LDR) on mice of immune function

    International Nuclear Information System (INIS)

    Feng Li; Deng Daping

    2007-01-01

    Objective: To find out the Effects of Low Dose Radiation(LDR) on mice of immune function. Methods: Through flow cytometry to observe and analyse the effects of the leukomonocyte. Through immunohistochemistry to study IL-2, TNF-α. Results: At dose of 100mGy the stimulative effect on CD 4 + cells, CD 8 + cells and NK activity was higher than that at other doses. At dose of 500mGy leukomonocyte activity was lower. At dose of 100mGy, the colorations about IL-2, TNF-α deepen. Conclusion: LDR could stimulate immune function, especially at dose of 100mGy. while at dose of 500mGy, radiation could restrain the leukomonocyte activity. (authors)

  14. Exercise Improves Immune Function, Antidepressive Response, and Sleep Quality in Patients with Chronic Primary Insomnia

    OpenAIRE

    Passos, Giselle Soares; Poyares, Dalva; Santana, Marcos Gonçalves; Teixeira, Alexandre Abílio de Souza; Lira, Fábio Santos; Youngstedt, Shawn D.; dos Santos, Ronaldo Vagner Thomatieli; Tufik, Sergio; de Mello, Marco Túlio

    2014-01-01

    The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 +/- 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symp...

  15. Guidance on the scientific requirements for health claims related to gut and immune function

    DEFF Research Database (Denmark)

    Tetens, Inge

    2011-01-01

    The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products Nutrition and Allergies (NDA) to draft guidance on scientific requirements for health claims related to gut and immune function. This guidance has been drawn from scientific opinions of the NDA Panel on such health......, was subjected to public consultation (28 September 2010 to 22 October 2010), and was also discussed at a technical meeting with experts in the field on 2 December 2010 in Amsterdam....

  16. The Influence of histamine H1-receptor on liver functions in immunized rabbits.

    Science.gov (United States)

    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Khan, Rahat Ali; Siddiqui, Mashiatullah; Mahdi, Abbas Ali

    2011-10-01

    This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

  17. Functional evaluation of HMGB1 as immune therapeutic effector molecule for cell-based vaccination strategies

    OpenAIRE

    Willenbrock, Saskia

    2013-01-01

    Cancer is a leading cause of death worldwide although extensive research in human cancer medicine is carried out. To develop and improve molecular anticancer therapies, the characterisation of the structure and function of cancer-related genes and proteins is essential. The dog is one of the companion animals being considered as an invaluable model system. The spontaneous development of tumours in the context of an intact immune system in dogs and the striking similarities to human neoplasias...

  18. Effects of psycho-behavioral interventions on immune functioning in cancer patients: a systematic review.

    Science.gov (United States)

    Tong, Guixian; Geng, Qingqing; Cheng, Jing; Chai, Jing; Xia, Yi; Feng, Rui; Zhang, Lu; Wang, Debin

    2014-01-01

    This study aimed at summarizing evidence about effects of psycho-behavioral interventions (PBIs) on immune responses among cancer patients and analyzing quality of published studies so as to inform future researches. Literature retrieval utilized both highly inclusive algorithms searching randomized controlled studies published in English and Chinese and manual searching of eligible studies from references of relevant review papers. Two researchers examined the articles selected separately and extracted the information using a pre-designed form for soliciting data about the trials (e.g., sample size, disease status, intervention, immune responses) and quality ratings of the studies. Both narrative descriptions and meta-analysis (via Review manager 5) were used synthesizing the effects of PBIs on immune responses among cancer patients and state of art of the researches in this area. Seventy-six RCTs met inclusion criteria. PBIs implemented were divided into three major categories including psychological state adjustment, physical activity and dietary modification. Immune indicators measured included CD4+ cells, CD8+ cells, CD4/CDC8+ ratio, CD3+ cells, NK cell activity, etc. Effects of PBIs on immune responses documented in individual papers were mixed and pooled analysis of CD4+ cells, CD4+/CD8+ ratio, CD3+ cells, NKCA, IgG, IgM and IL-2 showed modest effects. However, there were huge discrepancies in intervention effects between studies published in English and Chinese and the results should be interpreted with caution. Besides, most studies suffer from some quality flaws concerning blinding, randomization procedures, compliance, attrition and intention-to-treat analyses, etc. Although there are considerable evidences of PBI effects on some immune indicators, the effect sizes are modest and it is still premature to conclude whether PBIs have effects on immune functions among cancer patients. There is a clear need for much more rigorous efforts in this area

  19. Effects of microbial aerosol in poultry house on meat ducks’ immune function

    Directory of Open Access Journals (Sweden)

    Guanliu YU

    2016-08-01

    Full Text Available The aim of this study was to evaluate effects of microbial aerosols on immune function of ducks and shed light on the establishment of microbial aerosol concentration standards for poultry. A total of 1800 1-d-old Cherry Valley ducks were randomly divided into 5 groups (A, B, C, D and E with 360 ducks in each. To obtain objective data, each group had three replications. Concentrations of airborne bacteria, fungi, endotoxin in different groups were created by controlling ventilation and bedding cleaning frequency. Group A was the control group and hygienic conditions deteriorated progressively from group B to E. A 6-stage Andersen impactor was used to detect the aerosol concentration of aerobes, gram-negative bacteria, fungi and AGI-30 microbial air sampler detect the endotoxin, and Composite Gas Detector detect the noxious gas. In order to assess the immune function of meat ducks, immune indicators including H5 AIV antibody titer, IgG, IL-2, T-lymphocyte transformation rate, lysozyme and immune organ indexes were evaluated. Correlation coefficients were also calculated to evaluate the relationships among airborne bacteria, fungi, endotoxin and immune indicators. The results showed that the concentration of airborne aerobe, gram-negative bacteria, fungi, endotoxin have a strong correlation to H5 AIV antibody titer, IgG, IL-2, T-lymphocyte transformation rate, lysozyme and immune organ indexes, respectively. In addition, when the concentration of microbial aerosol reach the level of group D, serum IgG (6 - 8 weeks, lysozyme (4 week were significantly higher than in group A (P < 0.05; serum IL-2 (7 and 8 weeks , T-lymphocyte transformation rate, lysozyme (7 and 8 weeks, spleen index (6 and 8 weeks and bursa index (8 week were significantly lower than in group A(P < 0.05 or P < 0.01. The results indicated that a high level of microbial aerosol adversely affected the immune level of meat ducks. The microbial aerosol values in group D provide a basis

  20. Effects of rearing temperature on immune functions in sockeye salmon (Oncorhynchus nerka)

    Science.gov (United States)

    Alcorn, S.W.; Murray, A.L.; Pascho, R.J.

    2002-01-01

    To determine if the defences of sockeye salmon (Oncorhynchus nerka) raised in captivity are affected by the rearing temperature or their life-cycle stage, various indices of the humoral and cellular immune functions were measured in fish reared at either 8 or 12??C for their entire life-cycle. Measures of humoral immunity included the commonly used haematological parameters, as well as measurements of complement, and lysozyme activity. Cellular assays quantified the ability of macrophages from the anterior kidney to phagocytise Staphylococcus aureus cells, or the activities of certain bactericidal systems of those cells. The T-dependent antibody response to a recombinant 57 kDa protein of Renibacterium salmoninarum was used to quantify the specific immune response. Fish were sampled during the spring and fall of their second, third and fourth years, corresponding to a period that began just before smolting and ended at sexual maturation. Fish reared at 8??C tended to have a greater percentage of phagocytic kidney macrophages during the first 2 years of sampling than the fish reared at 12??C. During the last half of the study the complement activity of the fish reared at 8??C was greater than that of the 12??C fish. Conversely, a greater proportion of the blood leucocytes were lymphocytes in fish reared at 12??C compared to the fish reared at 8??C. Fish reared at 12??C also produced a greater antibody response than those reared at 8??C. Results suggested that the immune apparatus of sockeye salmon reared at 8??C relied more heavily on the non-specific immune response, while the specific immune response was used to a greater extent when the fish were reared at 12??C. Although a seasonal effect was not detected in any of the indices measured, varying effects were observed in some measurements during sexual maturation of fish in both temperature groups. At that time there were dramatic decreases in complement activity and lymphocyte numbers. This study was unique in

  1. [Effects of electromagnetic radiation on health and immune function of operators].

    Science.gov (United States)

    Li, Yan-zhong; Chen, Shao-hua; Zhao, Ke-fu; Gui, Yun; Fang, Si-xin; Xu, Ying; Ma, Zi-jian

    2013-08-01

    To investigate the effects of electromagnetic radiation on the physiological indices and immune function of operators. The general conditions and electromagnetic radiation awareness rate of 205 operators under electromagnetic radiation were evaluated using a self-designed questionnaire. Physical examination, electrocardiography, and routine urine test were performed in these operators. Peripheral blood was collected from the operators under electromagnetic radiation for blood cell counting and biochemical testing, and their peripheral blood lymphocytes were cultured for determination of chromosomal aberrant frequency and micronucleus frequency. The data from these operators (exposure group) were compared with those of 95 ordinary individuals (control group). The chief complaint of giddiness, tiredness, dizziness, and amnesia showed significant differences between the exposure group and control group (P electromagnetic radiation damage was significantly higher in the exposure group than in the control group. The difference in bradycardia was significant between the two groups (P Electromagnetic radiation may lead to the changes in physiological indices, genetic effects, and immune function and affect the health and immune function in operators. The adverse effects are increased as the working years increase. So it is important to strengthen occupational protection of operators under electromagnetic radiation.

  2. Comprehensive proteome analysis of lysosomes reveals the diverse function of macrophages in immune responses.

    Science.gov (United States)

    Gao, Yanpan; Chen, Yanyu; Zhan, Shaohua; Zhang, Wenhao; Xiong, Feng; Ge, Wei

    2017-01-31

    Phagocytosis and autophagy in macrophages have been shown to be essential to both innate and adaptive immunity. Lysosomes are the main catabolic subcellular organelles responsible for degradation and recycling of both extracellular and intracellular material, which are the final steps in phagocytosis and autophagy. However, the molecular mechanisms underlying lysosomal functions after infection remain obscure. In this study, we conducted a quantitative proteomics analysis of the changes in constitution and glycosylation of proteins in lysosomes derived from murine RAW 264.7 macrophage cells treated with different types of pathogens comprising examples of bacteria (Listeria monocytogenes, L. m), DNA viruses (herpes simplex virus type-1, HSV-1) and RNA viruses (vesicular stomatitis virus, VSV). In total, 3,704 lysosome-related proteins and 300 potential glycosylation sites on 193 proteins were identified. Comparative analysis showed that the aforementioned pathogens induced distinct alterations in the proteome of the lysosome, which is closely associated with the immune functions of macrophages, such as toll-like receptor activation, inflammation and antigen-presentation. The most significant changes in proteins and fluctuations in glycosylation were also determined. Furthermore, Western blot analysis showed that the changes in expression of these proteins were undetectable at the whole cell level. Thus, our study provides unique insights into the function of lysosomes in macrophage activation and immune responses.

  3. Complex multicellular functions at a unicellular eukaryote level: Learning, memory, and immunity.

    Science.gov (United States)

    Csaba, György

    2017-06-01

    According to experimental data, eukaryote unicellulars are able to learn, have immunity and memory. Learning is carried out in a very primitive form, and the memory is not neural but an epigenetic one. However, this epigenetic memory, which is well justified by the presence and manifestation of hormonal imprinting, is strong and permanent in the life of cell and also in its progenies. This memory is epigenetically executed by the alteration and fixation of methylation pattern of genes without changes in base sequences. The immunity of unicellulars is based on self/non-self discrimination, which leads to the destruction of non-self invaders and utilization of them as nourishment (by phagocytosis). The tools of learning, memory, and immunity of unicellulars are uniformly found in plasma membrane receptors, which formed under the effect of dynamic receptor pattern generation, suggested by Koch et al., and this is the basis of hormonal imprinting, by which the encounter between a chemical substance and the cell is specifically memorized. The receptors and imprinting are also used in the later steps of evolution up to mammals (including man) in each mentioned functions. This means that learning, memory, and immunity can be deduced to a unicellular eukaryote level.

  4. The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy.

    Science.gov (United States)

    Paolino, Magdalena; Penninger, Josef M

    2016-10-21

    The TAM receptor protein tyrosine kinases-Tyro3, Axl, and Mer-are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

  5. Understanding how commensal obligate anaerobic bacteria regulate immune functions in the large intestine.

    Science.gov (United States)

    Maier, Eva; Anderson, Rachel C; Roy, Nicole C

    2014-12-24

    The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases.

  6. Understanding How Commensal Obligate Anaerobic Bacteria Regulate Immune Functions in the Large Intestine

    Science.gov (United States)

    Maier, Eva; Anderson, Rachel C.; Roy, Nicole C.

    2014-01-01

    The human gastrointestinal tract is colonised by trillions of commensal bacteria, most of which are obligate anaerobes residing in the large intestine. Appropriate bacterial colonisation is generally known to be critical for human health. In particular, the development and function of the immune system depends on microbial colonisation, and a regulated cross-talk between commensal bacteria, intestinal epithelial cells and immune cells is required to maintain mucosal immune homeostasis. This homeostasis is disturbed in various inflammatory disorders, such as inflammatory bowel diseases. Several in vitro and in vivo studies indicate a role for Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Akkermansia muciniphila and segmented filamentous bacteria in maintaining intestinal immune homeostasis. These obligate anaerobes are abundant in the healthy intestine but reduced in several inflammatory diseases, suggesting an association with protective effects on human health. However, knowledge of the mechanisms underlying the effects of obligate anaerobic intestinal bacteria remains limited, in part due to the difficulty of co-culturing obligate anaerobes together with oxygen-requiring human epithelial cells. By using novel dual-environment co-culture models, it will be possible to investigate the effects of the unstudied majority of intestinal microorganisms on the human epithelia. This knowledge will provide opportunities for improving human health and reducing the risk of inflammatory diseases. PMID:25545102

  7. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

    Science.gov (United States)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-06-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

  8. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

    International Nuclear Information System (INIS)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-01-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

  9. Arabidopsis MKS1 is involved in basal immunity and requires an intact N-terminal domain for proper function

    DEFF Research Database (Denmark)

    Petersen, Klaus; Qiu, Jin-Long; Lütje, Juri

    2010-01-01

    Innate immune signaling pathways in animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. MAP kinase 4 (MPK4) functions downstream of innate immune receptors via a nuclear substrate MKS1 to regulate the activity of the WRKY33 transcription factor, which in turn...

  10. Indices of immune function used by ecologists are mostly unaffected by repeated freeze-thaw cycles and methodological deviations

    NARCIS (Netherlands)

    Hegemann, Arne; Pardal, Sara; Matson, Kevin D.

    2017-01-01

    Background
    Over the past couple of decades, measuring immunological parameters has become widespread in studies of ecology and evolution. A combination of different immunological indices is useful for quantifying different parts of the immune system and comprehensively assessing immune function.

  11. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Science.gov (United States)

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  12. Retinoic Acid-Related Orphan Receptors (RORs: Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Directory of Open Access Journals (Sweden)

    Donald N. Cook

    2015-12-01

    Full Text Available In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs. We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated.

  13. Effects of prenatal yoga on women's stress and immune function across pregnancy: A randomized controlled trial.

    Science.gov (United States)

    Chen, Pao-Ju; Yang, Luke; Chou, Cheng-Chen; Li, Chia-Chi; Chang, Yu-Cune; Liaw, Jen-Jiuan

    2017-04-01

    The effects of prenatal yoga on biological indicators have not been widely studied. Thus, we compared changes in stress and immunity salivary biomarkers from 16 to 36 weeks' gestation between women receiving prenatal yoga and those receiving routine prenatal care. For this longitudinal, prospective, randomized controlled trial, we recruited 94 healthy pregnant women at 16 weeks' gestation through convenience sampling from a prenatal clinic in Taipei. Participants were randomly assigned to intervention (n=48) or control (n=46) groups using Clinstat block randomization. The 20-week intervention comprised two weekly 70-min yoga sessions led by a midwife certified as a yoga instructor; the control group received only routine prenatal care. In both groups, participants' salivary cortisol and immunoglobulin A levels were collected before and after yoga every 4 weeks from 16 to 36 weeks' gestation. The intervention group had lower salivary cortisol (pcontrol group. Specifically, the intervention group had significantly higher long-term salivary immunoglobulin A levels than the control group (p=0.018), and infants born to women in the intervention group weighed more than those born to the control group (pPrenatal yoga significantly reduced pregnant women's stress and enhanced their immune function. Clinicians should learn the mechanisms of yoga and its effects on pregnant women. Our findings can guide clinicians to help pregnant women alleviate their stress and enhance their immune function. Copyright © 2017. Published by Elsevier Ltd.

  14. A non-canonical function of Ezh2 preserves immune homeostasis.

    Science.gov (United States)

    Vasanthakumar, Ajithkumar; Xu, Dakang; Lun, Aaron Tl; Kueh, Andrew J; van Gisbergen, Klaas Pjm; Iannarella, Nadia; Li, Xiaofang; Yu, Liang; Wang, Die; Williams, Bryan Rg; Lee, Stanley Cw; Majewski, Ian J; Godfrey, Dale I; Smyth, Gordon K; Alexander, Warren S; Herold, Marco J; Kallies, Axel; Nutt, Stephen L; Allan, Rhys S

    2017-04-01

    Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2-deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin-independent function of Ezh2 that impacts on the development of the immune system. © 2017 The Authors.

  15. Use of the local lymph node assay in assessment of immune function

    International Nuclear Information System (INIS)

    Berg, Femke A. van den; Baken, Kirsten A.; Vermeulen, Jolanda P.; Gremmer, Eric R.; Steeg, Harry van; Loveren, Henk van

    2005-01-01

    The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene (B[a]P). Subsequently, cell proliferation and interferon-γ (IFN-γ) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse

  16. Use of the local lymph node assay in assessment of immune function.

    Science.gov (United States)

    van den Berg, Femke A; Baken, Kirsten A; Vermeulen, Jolanda P; Gremmer, Eric R; van Steeg, Harry; van Loveren, Henk

    2005-07-01

    The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene, (B[a]P). Subsequently, cell proliferation and interferon-gamma (IFN-gamma) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse.

  17. Antiviral immunity in fish – functional analysis using DNA vaccination as a tool

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja

    2013-01-01

    fingerlings. Vaccination of fish at an early stage appears advantageous, since larger fish require higher doses of vaccine to be protected. Even in fish with an average size of 0.5 g at the time of vaccination, good protection can be obtained. Interestingly, immunity is established already a few days after...... and cellular components both play a role in the long lasting protection. The similarity of the functional immune response profile to that induced by a natural virus infection is striking and is most likely one of the major reasons for the efficacy of the rhabdovirus DNA vaccines. Although other elements like...... protein gene suggest that the structural requirements for antigenicity are different from the requirements for immunogenicity....

  18. Exercise protects from cancer through regulation of immune function and inflammation

    DEFF Research Database (Denmark)

    Hojman, Pernille

    2017-01-01

    Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection are...... regulation of immune and inflammatory functions, and exercise may be pursued as anticancer treatment through incorporation into standard oncological therapy to the benefit of the cancer patients.......Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection...... are just starting to be elucidated. To this end, evasion of immune surveillance and tumor-associated inflammation are established as hallmarks of cancer, and exercise may target cancer incidence and progression through regulation of these mechanisms. Here, I review the role of exercise in protection from...

  19. A cascade reaction network mimicking the basic functional steps of adaptive immune response.

    Science.gov (United States)

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-10-01

    Biological systems use complex 'information-processing cores' composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

  20. Cow's Milk and Immune Function in the Respiratory Tract: Potential Mechanisms.

    Science.gov (United States)

    Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F J; Brugman, Sylvia; van Neerven, R J Joost

    2018-01-01

    During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow's milk. Indeed, recent studies show inverse associations between raw cow's milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow's milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow's milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow's milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow's milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow's milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw

  1. Cow’s Milk and Immune Function in the Respiratory Tract: Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Olaf Perdijk

    2018-02-01

    Full Text Available During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present

  2. The sweet side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation

    Directory of Open Access Journals (Sweden)

    Antonio eInforzato

    2013-01-01

    Full Text Available Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs that recognise pathogen associated molecular patterns (PAMPs and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation.Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.

  3. A novel hybrid stress-function finite element method immune to severe mesh distortion

    International Nuclear Information System (INIS)

    Cen Song; Zhou Mingjue; Fu Xiangrong

    2010-01-01

    This paper introduces a hybrid stress-function finite element method proposed recently for developing 2D finite element models immune to element shapes. Deferent from the first version of the hybrid-stress element constructed by Pian, the stress function φ of 2D elastic or fracture problem is regarded as the functional variable of the complementary energy functional. Then, the basic analytical solutions of φ are taken as the trial functions for finite element models, and meanwhile, the corresponding unknown stress-function constants are introduced. By using the principle of minimum complementary energy, these unknown stress-function constants can be expressed in terms of the displacements along element edges. Finally, the complementary energy functional can be rewritten in terms of element nodal displacement vector, and thus, the element stiffness matrix of such hybrid-function element can be obtained. As examples, two (8- and 12-node) quadrilateral plane elements and an arbitrary polygonal crack element are constructed by employing different basic analytical solutions of different stress functions. Numerical results show that, the 8- and 12-node plane models can produce the exact solutions for pure bending and linear bending problems, respectively, even the element shape degenerates into triangle and concave quadrangle; and the crack element can also predict accurate results with very low computational cost in analysis of stress-singularity problems.

  4. Changes of some immune functions in combined radiation-burn injury in rats

    International Nuclear Information System (INIS)

    Yan Yongtang; Ran Xinze; Wei Shuqing

    1991-01-01

    The characteristics of some immune functions in radiation injury (6 Gy), burn injury (15%, III deg) and combined radiation-burn injury (CRBI) were studied in rats. The results showed that the functions of splenocytes and thymocytes in radiation injury group (RIG) were depressed more markedly 24-72 h after injury. The degree of thymocyte depression in burn injury group (BIG) was significantly lower than that in RIG and recovered more easily. The characteristics of the CRBI effects were as follows: (1) The combined depression effect on thymocytes in CRBI as compared with that in RIG was deeper and the recovery was slower. (2) The depression course of splenocytes was similar to that in RIG, but the depression degree in the early stage was significantly more heavy than that in RIG. (3) In the later stage of CRBI the level of recovery of T H cells was significantly lower than that in RIG. (4) Eschar-excision plus skin grafting at 24 h after combined injury was helpful for the recovery of thymocyte and splenocytes function. The results showed that the depression and recovery of immune functions in combined injury were closely related to the wound of burn

  5. Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function

    Directory of Open Access Journals (Sweden)

    Dorota Kamińska

    2016-01-01

    Full Text Available Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan. Results. Immediate posttransplant graft function (14-day GFR was influenced negatively by TGFB1 (P=0.039 and positively by IL-2 gene expression (P=0.040. Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18 and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P=0.027, FAS: P=0.021, and IFNG: P=0.029 and long-term graft function (24-month GFR CASP3: P=0.003, FAS: P=0.033, IL-18: P=0.044, and IFNG: P=0.04. Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes’ expression in the recipients’ peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function.

  6. Coelomocytes: Biology and Possible Immune Functions in Invertebrates with Special Remarks on Nematodes

    Directory of Open Access Journals (Sweden)

    Qudsia Tahseen

    2009-01-01

    Full Text Available All metazoans are exposed to a wide range of microbes and have evolved complex immune defenses used to repel infectious agents. Coelomocytes play a key role in the defense reactions of most invertebrates. They are involved in important immune functions, such as phagocytosis, encapsulation, graft rejection, and inflammation, as well as the synthesis and secretion of several humoral factors especially in annelids and echinoderms. Coelomocytes in nematodes are variable in shapes from round, ovoid, cuboidal, and spindle-shaped to stellate or branched cells that are found usually at fixed positions in the pseudocoelom. Their number usually varies from 2 to 6. The model nematode, C. elegans lacks an adaptive immune system and the coelomocytes are capable of endocytosis, but their involvement in phagocytosis of bacteria seems unlikely. The aim of this review is to evaluate current knowledge on coelomocytes of invertebrates with special reference to nematodes. The morphology and structure of these coelomocytes are discussed along with their origin. Their relative positions and diversity in different nematode groups have also been discussed and illustrated.

  7. Development of immune functionality in larval and juvenile crimson snapper Lutjanus erythropterus (Bloch 1790

    Directory of Open Access Journals (Sweden)

    Ke Cui

    2018-05-01

    Full Text Available Ontogenetic development of the immune system in crimson snapper (Lutjanus erythropterus Bloch 1790 larvae was histologically and enzymatically studied from hatch to 36 days post-hatch (DPH. Primitive hepatopancreas appeared on 2 DPH and renal tubules started hematopoiesis on 4 DPH. The spleen anlage appeared on 6 DPH and the thymus formed on 14 DPH. Total activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPX and sodium-potassium adenosine triphosphatase (Na+ K+-ATPase gradually increased after hatch, and showed a sharp increase after 29 DPH during the transitional feeding period from Artemia to inert feed. The specific activities of SOD, CAT, and GPX showed a trend of sharp increase and reached the maximum level on 4 DPH when exogenous feeding started, except for Na+ K+-ATPase where the peak occurred on10 DPH. The specific activities of these five enzymes reached the peak during the food transition from rotifers to Artemia, but the total activity of enzymes showed an increasing trend as fish grew. The present study provides new knowledge of the development of functional enzymes relevant to fish larvae immunity, sheds light on the understanding of the change of larval health, and improves hatchery management of crimson snapper. Keywords: Immune system, Enzyme activity, Ontogenetic development, Crimson snapper Lutjanus erythropterus

  8. Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

    Directory of Open Access Journals (Sweden)

    Barbara Ensoli

    2010-11-01

    Full Text Available Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002. Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002, served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+ and CD8(+ cellular activation (CD38 and HLA-DR together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+ T cells and B cells with reduction of CD8(+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+ and CD8(+ T cells were accompanied by increases of CD4(+ and CD8(+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite

  9. Studies on the protection effects of functional foods for skin immune system from radiation damage

    International Nuclear Information System (INIS)

    Yee, Sung Tae; Shin, Seong Hae; Kim, Do Sun; Heo, Ji Yun; Kang, Hye In

    2007-07-01

    We evaluated the protective effects of pilot products (HemoHIM and HemoTonic) on the UV-induced skin immune damages as the following. · Protective effects of HemoHIM and HemoTonic against UV using contact hypersensitivity model - Protection against depression of contact hypersensitivity by administration and skin application of HemoHIM and HemoTonic - Induction of dendritic cell differentiation and maturation by HemoHIM and HemoTonic treatment - Improvement of antigen-presenting activity of dedritic cells by HemoHIM and HemoTonic treatment · Protective effects of HemoHIM and HemoTonic on skin immune system against UV-irradiation - Protection of antigen-presenting activity of dendritic cells under UV-irradiation - In vivo protection of antigen-presenting activity of Langerhans cells in UV-irradiated mice · Protective effects of HemoHIM on UV-induced apoptosis of dendritic cells - Inhibition of cell membrane change, mitochondrial potential change, SubG1 cell population, nuclear condensation, and DNA fragmentation in UV-irradiated dendritic cells · Anti-allergic effects of HemoHIM and HemoTonic in human adipocyte HMC-1 cells - Inhibition of allergic histamine release from adipocytes - Inhibition of secretion of inflammatory cytokines (IL-6, IL-8, TNF-α, GM-CSF) - Inhibition of c-kit, tryptase, FcεRI mRNA expression From these results, the developed functional food products (HemoHIM, HemoTonic) showed the protection and recovery of the immune functions in the UV-irradiated skin. It is suggested that these products may be used as a new functional food or cosmetic material for the protection of skin damage and the promotion of recovery

  10. Studies on the protection effects of functional foods for skin immune system from radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Yee, Sung Tae; Shin, Seong Hae; Kim, Do Sun; Heo, Ji Yun; Kang, Hye In [Sunchon National University, Sunchon (Korea, Republic of)

    2007-07-15

    We evaluated the protective effects of pilot products (HemoHIM and HemoTonic) on the UV-induced skin immune damages as the following. centre dot Protective effects of HemoHIM and HemoTonic against UV using contact hypersensitivity model - Protection against depression of contact hypersensitivity by administration and skin application of HemoHIM and HemoTonic - Induction of dendritic cell differentiation and maturation by HemoHIM and HemoTonic treatment - Improvement of antigen-presenting activity of dedritic cells by HemoHIM and HemoTonic treatment centre dot Protective effects of HemoHIM and HemoTonic on skin immune system against UV-irradiation - Protection of antigen-presenting activity of dendritic cells under UV-irradiation - In vivo protection of antigen-presenting activity of Langerhans cells in UV-irradiated mice centre dot Protective effects of HemoHIM on UV-induced apoptosis of dendritic cells - Inhibition of cell membrane change, mitochondrial potential change, SubG1 cell population, nuclear condensation, and DNA fragmentation in UV-irradiated dendritic cells centre dot Anti-allergic effects of HemoHIM and HemoTonic in human adipocyte HMC-1 cells - Inhibition of allergic histamine release from adipocytes - Inhibition of secretion of inflammatory cytokines (IL-6, IL-8, TNF-alpha, GM-CSF) - Inhibition of c-kit, tryptase, FcepsilonRI mRNA expression From these results, the developed functional food products (HemoHIM, HemoTonic) showed the protection and recovery of the immune functions in the UV-irradiated skin. It is suggested that these products may be used as a new functional food or cosmetic material for the protection of skin damage and the promotion of recovery

  11. Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats.

    Science.gov (United States)

    Osborne, Brittany F; Caulfield, Jasmine I; Solomotis, Samantha A; Schwarz, Jaclyn M

    2017-10-01

    The current experiments examined the impact of early-life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal-dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal-dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal-dependent context pre-exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL-1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL-1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL-1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL-6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal-dependent learning deficits at this young age. These findings underscore the need to consider age and associated on-going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early-life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221-1236, 2017. © 2017 Wiley Periodicals, Inc.

  12. Photoperiod history differentially impacts reproduction and immune function in adult Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Pyter, Leah M

    2009-12-01

    Seasonal changes in numerous aspects of mammalian immune function arise as a result of the annual variation in environmental day length (photoperiod), but it is not known if absolute photoperiod or relative change in photoperiod drives these changes. This experiment tested the hypothesis that an individual's history of exposure to day length determines immune responses to ambiguous, intermediate-duration day lengths. Immunological (blood leukocytes, delayed-type hypersensitivity reactions [DTH]), reproductive, and adrenocortical responses were assessed in adult Siberian hamsters (Phodopus sungorus) that had been raised initially in categorically long (15-h light/day; 15L) or short (9L) photoperiods and were subsequently transferred to 1 of 7 cardinal experimental photoperiods between 9L and 15L, inclusive. Initial photoperiod history interacted with contemporary experimental photoperiods to determine reproductive responses: 11L, 12L, and 13L caused gonadal regression in hamsters previously exposed to 15L, but elicited growth in hamsters previously in 9L. In hamsters with a 15L photoperiod history, photoperiods history, DTH responses were largely unaffected by increases in day length. Enhancement and suppression of blood leukocyte concentrations occurred at 13L in hamsters with photoperiod histories of 15L and 9L, respectively; however, prior exposure to 9L imparted marked hysteresis effects, which suppressed baseline leukocyte concentrations. Cortisol concentrations were only enhanced in 15L hamsters transferred to 9L and, in common with DTH, were unaffected by photoperiod treatments in hamsters with a 9L photoperiod history. Photoperiod history acquired in adulthood impacts immune responses to photoperiod, but manifests in a markedly dissimilar fashion as compared to the reproductive system. Prior photoperiod exposure has an enduring impact on the ability of the immune system to respond to subsequent changes in day length.

  13. Human study of the herbal preparation(HemoHIM) on enhancement of immune and hematopoietic functions

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hee-Jeong; Park, Jong-Nam; Jeon, Sun-Hee [Eulji Univ. Hospital, Daejeon (Korea, Republic of)

    2006-01-15

    This study was aimed to evaluate the human efficacy of the herbal preparation(HemoHIM) on the immune and hematopoiesis enhancement in sub-healthy volunteers. It was conducted as a double-blind, placebo-controlled human study. The sub-healthy volunteers with peripheral White Blood Cell (WBC) counts below 5000/μl were recruited and randomly allocated to 3 groups and administered with HemoHIM 6g/day, HemoHIM 12g/day, or placebo throughout the test. Peripheral blood was collected 4 times before or after the administration and analyzed for the hematological and serum biochemical values, immune cell activities, antioxidant status of plasma. The data of 38 volunteers were finally included in the analysis. Although there were no statistical significances, a trend was observed that the dose and duration of HemoHIM administration was correlated to the increased number of immune cells (white blood cells and lymphocytes). NK cell activity was increased significantly in the male group administered with HemoHIM 6g/day. The cytokines involved in immune activation (IL-2, IFN-γ, IL-6) were significantly increased or showed the trends of increases in HemoHIM administered groups, while IL-4 involved in allergy and asthma was not changed or showed the trends of decreases in HemoHIM administered groups. On the other hand, the antioxidant biomarkers such as total GSH, MDA, and TAS, were not affected by HemoHIM administration. The toxicological safety of HemoHIM administration was confirmed by the serum biochemical analysis of liver and kidney function markers and the questionnaire of HemoHIM administration and the consultation with the doctor, which showed no side effects of HemoHIM administration. The results of this study may provide the basic data for further clinical study on HemoHIM.

  14. Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Hoeger, Birgit [Environmental Toxicology, University of Konstanz, P.O. Box X918, D-78457 Constance (Germany); Heuvel, Michael R. van den [Forest Research, Private Bag 3020, Sala St., Rotorua (New Zealand); Hitzfeld, Bettina C. [Swiss Agency for the Environment, Forests and Landscape (SAEFL), Substances, Soil, Biotechnology Division, Section Substances, 3003 Bern (Switzerland); Dietrich, Daniel R. [Environmental Toxicology, University of Konstanz, P.O. Box X918, D-78457 Constance (Germany)]. E-mail: daniel.dietrich@uni-konstanz.de

    2004-12-20

    In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune

  15. Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Hoeger, Birgit; Heuvel, Michael R. van den; Hitzfeld, Bettina C.; Dietrich, Daniel R.

    2004-01-01

    In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune

  16. Impact of enteral nutrition on postoperative immune function and nutritional status.

    Science.gov (United States)

    Wang, F; Hou, M X; Wu, X L; Bao, L D; Dong, P D

    2015-06-10

    We studied the effects of enteral nutrition (EN) support initiated 1 week before surgery on postoperative nutritional status, immune function, and inflammatory response in gastric cancer patients. A total of 200 gastric cancer patients were randomly divided into two groups: EN starting 1 week before surgery (study group) and EN starting early after surgery (control group). The two groups received EN support, following different therapeutic schedules, until the 9th day after operation. In the patients, body weight, skinfold thickness, upper-arm circumference, white blood cell count, albumin, prealbumin, C-reactive protein, peripheral immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets, interleukin-6, and tumor necrosis factor-α were measured 10 days before and after surgery and on the first day after surgery. There was no statistically significant difference in the results of recovery time of passage of gas by anus, abdominal distension, stomachache, blood glucose, hepatic and renal functions, and electrolytes between the two groups of patients (P > 0. 05). Adverse reactions occurred to both groups at 1 and 2 days after operation. Such conditions was improved after the intravenous drip rate was adjusted. The albumin and prealbumin levels of the patients in both groups decreased at 1 day after operation (P gastric cancer patients can improve their postoperative nutritional status and immune function, can reduce inflammatory response, and is more conducive to the recovery of patients.

  17. The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis

    Directory of Open Access Journals (Sweden)

    Daisuke Hirayama

    2017-12-01

    Full Text Available Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.

  18. Qualitative analysis of a stochastic epidemic model with specific functional response and temporary immunity

    Science.gov (United States)

    Hattaf, Khalid; Mahrouf, Marouane; Adnani, Jihad; Yousfi, Noura

    2018-01-01

    In this paper, we propose a stochastic delayed epidemic model with specific functional response. The time delay represents temporary immunity period, i.e., time from recovery to becoming susceptible again. We first show that the proposed model is mathematically and biologically well-posed. Moreover, the extinction of the disease and the persistence in the mean are established in the terms of a threshold value R0S which is smaller than the basic reproduction number R0 of the corresponding deterministic system.

  19. 3,3′-Diindolylmethane Stimulates Murine Immune Function In Vitro and In Vivo*

    OpenAIRE

    Xue, Ling; Pestka, James J.; Li, Maoxiang; Firestone, Gary L; Bjeldanes, Leonard F.

    2007-01-01

    3,3′-Diindolylmethane (DIM), a major condensation product of indole-3-carbinol (I3C), exhibits chemopreventive properties in animal models of cancer. Recent studies have shown that DIM stimulates interferon-gamma (IFN-γ) production and potentiates the IFN-γ signaling pathway in human breast cancer cells via a mechanism that includes increased expression of the IFN-γ receptor. The goal of this study was to test the hypothesis that DIM modulates the murine immune function. Specifically, the eff...

  20. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke

    DEFF Research Database (Denmark)

    Ruscher, Karsten; Kuric, Enida; Liu, Yawei

    2013-01-01

    cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1......After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after......,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3...

  1. Functional Analysis of the Tomato Immune Receptor Ve1 through Domain Swaps with Its Non-Functional Homolog Ve2

    Science.gov (United States)

    Rovenich, Hanna; Song, Yin; Liebrand, Thomas W. H.; Masini, Laura; van den Berg, Grardy C. M.; Joosten, Matthieu H. A. J.; Thomma, Bart P. H. J.

    2014-01-01

    Resistance in tomato against race 1 strains of the fungal vascular wilt pathogens Verticillium dahliae and V. albo-atrum is mediated by the Ve locus. This locus comprises two closely linked inversely oriented genes, Ve1 and Ve2, which encode cell surface receptors of the extracellular leucine-rich repeat receptor-like protein (eLRR-RLP) type. While Ve1 mediates Verticillium resistance through monitoring the presence of the recently identified V. dahliae Ave1 effector, no functionality for Ve2 has been demonstrated in tomato. Ve1 and Ve2 contain 37 eLRRs and share 84% amino acid identity, facilitating investigation of Ve protein functionality through domain swapping. In this study it is shown that Ve chimeras in which the first thirty eLRRs of Ve1 were replaced by those of Ve2 remain able to induce HR and activate Verticillium resistance, and that deletion of these thirty eLRRs from Ve1 resulted in loss of functionality. Also the region between eLRR30 and eLRR35 is required for Ve1-mediated resistance, and cannot be replaced by the region between eLRR30 and eLRR35 of Ve2. We furthermore show that the cytoplasmic tail of Ve1 is required for functionality, as truncation of this tail results in loss of functionality. Moreover, the C-terminus of Ve2 fails to activate immune signaling as chimeras containing the C-terminus of Ve2 do not provide Verticillium resistance. Furthermore, Ve1 was found to interact through its C-terminus with the eLRR-containing receptor-like kinase (eLRR-RLK) interactor SOBIR1 that was recently identified as an interactor of eLRR-RLP (immune) receptors. Intriguingly, also Ve2 was found to interact with SOBIR1. PMID:24505431

  2. Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

    Science.gov (United States)

    Bilbo, Staci D

    2013-05-01

    Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Abnormal immune system development and function in schizophrenia helps reconcile diverse findings and suggests new treatment and prevention strategies.

    Science.gov (United States)

    Anders, Sherry; Kinney, Dennis K

    2015-08-18

    Extensive research implicates disturbed immune function and development in the etiology and pathology of schizophrenia. In addition to reviewing evidence for immunological factors in schizophrenia, this paper discusses how an emerging model of atypical immune function and development helps explain a wide variety of well-established - but puzzling - findings about schizophrenia. A number of theorists have presented hypotheses that early immune system programming, disrupted by pre- and perinatal adversity, often combines with abnormal brain development to produce schizophrenia. The present paper focuses on the hypothesis that disruption of early immune system development produces a latent immune vulnerability that manifests more fully after puberty, when changes in immune function and the thymus leave individuals more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Complementing neurodevelopmental models, this hypothesis integrates findings on many contributing factors to schizophrenia, including prenatal adversity, genes, climate, migration, infections, and stress, among others. It helps explain, for example, why (a) schizophrenia onset is typically delayed until years after prenatal adversity, (b) individual risk factors alone often do not lead to schizophrenia, and (c) schizophrenia prevalence rates actually tend to be higher in economically advantaged countries. Here we discuss how the hypothesis explains 10 key findings, and suggests new, potentially highly cost-effective, strategies for treatment and prevention of schizophrenia. Moreover, while most human research linking immune factors to schizophrenia has been correlational, these strategies provide ethical ways to experimentally test in humans theories about immune function and schizophrenia. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. The paradoxical effect of low reward probabilities in suboptimal choice.

    Science.gov (United States)

    Fortes, Inês; Pinto, Carlos; Machado, Armando; Vasconcelos, Marco

    2018-04-01

    When offered a choice between 2 alternatives, animals sometimes prefer the option yielding less food. For instance, pigeons and starlings prefer an option that on 20% of the trials presents a stimulus always followed by food, and on the remaining 80% of the trials presents a stimulus never followed by food (the Informative Option), over an option that provides food on 50% of the trials regardless of the stimulus presented (the Noninformative Option). To explain this suboptimal behavior, it has been hypothesized that animals ignore (or do not engage with) the stimulus that is never followed by food in the Informative Option. To assess when pigeons attend to the stimulus usually not followed by food, we increased the probability of reinforcement, p, in the presence of that stimulus. Across 2 experiments, we found that the value of the Informative Option decreased with p. To account for the results, we added to the Reinforcement Rate Model (and also to the Hyperbolic Discounting Model) an engagement function, f(p), that specified the likelihood the animal attends to a stimulus followed by reward with probability p, and then derived the model predictions for 2 forms of f(p), a linear function, and an all-or-none threshold function. Both models predicted the observed findings with a linear engagement function: The higher the probability of reinforcement after a stimulus, the higher the probability of engaging the stimulus, and, surprisingly, the less the value of the option comprising the stimulus. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  5. Consequences of bisphenol a perinatal exposure on immune responses and gut barrier function in mice.

    Science.gov (United States)

    Malaisé, Yann; Ménard, Sandrine; Cartier, Christel; Lencina, Corinne; Sommer, Caroline; Gaultier, Eric; Houdeau, Eric; Guzylack-Piriou, Laurence

    2018-01-01

    The potent immunomodulatory effect of the endocrine disruptor bisphenol A during development and consequences during life span are of increasing concern. Particular interests have been raised from animal studies regarding the risk of developing food intolerance and infection. We aimed to identify immune disorders in mice triggered by perinatal exposure to bisphenol A. Gravid mice were orally exposed to bisphenol (50 μg/kg body weight/day) from day 15 of pregnancy until weaning. Gut barrier function, local and systemic immunity were assessed in adult female offspring. Mice perinatally exposed to bisphenol showed a decrease in ileal lysozyme expression and a fall of fecal antimicrobial activity. In offspring mice exposed to bisphenol, an increase in colonic permeability was observed associated with an increase in interferon-γ level and a drop of colonic IgA + cells and fecal IgA production. Interestingly, altered frequency of innate lymphoid cells type 3 occurred in the small intestine, with an increase in IgG response against commensal bacteria in sera. These effects were related to a defect in dendritic cell maturation in the lamina propria and spleen. Activated and regulatory T cells were decreased in the lamina propria. Furthermore, perinatal exposure to bisphenol promoted a sharp increase in interferon-γ and interleukin-17 production in the intestine and elicited a T helper 17 profile in the spleen. To conclude, perinatal exposure to bisphenol weakens protective and regulatory immune functions in the intestine and at systemic level in adult offspring. The increased susceptibility to inflammatory response is an interesting lead supporting bisphenol-mediated adverse consequences on food reactions and infections.

  6. Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

    Science.gov (United States)

    Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

    2013-01-01

    Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

  7. Effects of ration level on immune functions in chinook salmon (Oncorhynchus tshawytscha)

    Science.gov (United States)

    Alcorn, S.W.; Pascho, R.J.; Murray, A.L.; Shearer, K.D.

    2003-01-01

    The relationship between nutritional status and disease resistance in cultured salmonids can be affected by dietary manipulations. Careful attention to feeding levels may be important to avoid imbalances in nutrient levels that could ultimately impair a fish's ability to resist infectious microorganisms. In the current study, fish in three feed-level groups were fed an experimental diet either to satiation, 64% of satiation or 40% of satiation. A fourth group of fish were fed a commercial diet at the 64% of satiation level and served as controls. To evaluate certain indices of disease resistance in the test and control fish, a panel of assays was employed to measure humoral and cellular immune functions 30, 39 and 54 weeks after starting the dietary treatments. The panel included measures of blood hematocrit and leucocrit levels, plasma protein concentration and serum lysozyme and complement activity. Cellular analyses included differential blood leucocyte counts, NBT reduction and phagocytosis by pronephros macrophages and myeloperoxidase activity of pronephros neutrophils. No differences were observed in those indices between fish tested from the control-diet group (commercial diet fed at the 64% rate) and fish tested from the 64% feed-level group, except that fish fed the commercial diet had a greater concentration of plasma protein. Leucocrit values and plasma protein concentrations tended to increase among the experimental feed groups as the ration increased from 40% to satiation. More importantly, phagocytic activity by anterior kidney leucocytes was found to be inversely proportional to the feed level. Whereas the results of this study provide evidence that the salmonid immune system may be fairly robust with regard to available metabolic energy, the significant changes observed in phagocytic cell activity suggest that some cellular immune functions may be affected by the feed level.

  8. Effects of methylmercury exposure on the immune function of juvenile common loons (Gavia immer)

    Science.gov (United States)

    Kenow, K.P.; Grasman, K.A.; Hines, R.K.; Meyer, M.W.; Gendron-Fitzpatrick, A.; Spalding, M.G.; Gray, B.R.

    2007-01-01

    We conducted a dose-response laboratory study to quantify the level of exposure to dietary Hg, delivered as methylmercury chloride (CH3HgCl), that is associated with suppressed immune function in captive-reared common loon (Gavia immer) chicks. We used the phytohemagglutinin (PHA) skin test to assess T-lymphocyte function and the sheep red blood cell (SRBC) hemagglutination test to measure antibody-mediated immunity. The PHA stimulation index among chicks receiving dietary Hg treatment did not differ significantly from those of chicks on the control diet (p = 0.15). Total antibody (immunoglobulin [Ig] M [primary antibody] + IgG [secondary response]) production to the SRBC antigen in chicks treated with dietary methylmercury (MeHg), however, was suppressed (p = 0.04) relative to chicks on control diets. Analysis indicated suppression of total Ig production (p = 0.025 with comparisonwise ?? level = 0.017) between control and 0.4 ??g Hg/g wet food intake treatment groups. Furthermore, the control group exhibited a higher degree of variability in antibody response compared to the Hg groups, suggesting that in addition to reducing the mean response, Hg treatment reduced the normal variation attributable to other biological factors. We observed bursal lymphoid depletion in chicks receiving the 1.2 ??g Hg/g treatment (p = 0.017) and a marginally significant effect (p = 0.025) in chicks receiving the 0.4 ??g Hg/g diet. These findings suggest that common loon chick immune systems may be compromised at an ecologically relevant dietary exposure concentration (0.4 ??g Hg/g wet wt food intake). We also found that chicks hatched from eggs collected from low-pH lakes exhibited higher levels of lymphoid depletion in bursa tissue relative to chicks hatched from eggs collected from neutral-pH lakes. ?? 2007 SETAC.

  9. Anti-Tribbles Pseudokinase 2 (TRIB2)-Immunization Modulates Hypocretin/Orexin Neuronal Functions.

    Science.gov (United States)

    Tanaka, Susumu; Honda, Yoshiko; Honda, Makoto; Yamada, Hisao; Honda, Kazuki; Kodama, Tohru

    2017-01-01

    Recent findings showed that 16%-26% of narcolepsy patients were positive for anti-tribbles pseudokinase 2 (TRIB2) antibody, and the intracerebroventricular administration of immunoglobulin-G purified from anti-TRIB2 positive narcolepsy patients caused hypocretin/orexin neuron loss. We investigated the pathophysiological role of TRIB2 antibody using TRIB2-immunized rats and hypocretin/ataxin-3 transgenic (ataxin-3) mice. Plasma, cerebrospinal fluid (CSF), and hypothalamic tissues from TRIB2-immunized rats were collected. Anti-TRIB2 titers, hypocretin contents, mRNA expressions, the cell count of hypocretin neurons, and immunoreactivity of anti-TRIB2 antibodies on hypocretin neurons were investigated. The plasma from ataxin-3 mice was also used to determine the anti-TRIB2 antibody titer changes following the loss of hypocretin neurons. TRIB2 antibody titers increased in the plasma and CSF of TRIB2-immunized rats. The hypothalamic tissue immunostained with the sera from TRIB2-immunized rats revealed positive signals in the cytoplasm of hypcretin neurons. While no changes were found regarding hypothalamic hypocretin contents or cell counts, but there were significant decreases of the hypocretin mRNA level and release into the CSF. The plasma from over 26-week-old ataxin-3 mice, at the advanced stage of hypocretin cell destruction, showed positive reactions against TRIB2 antigen, and positive plasma also reacted with murine hypothalamic hypocretin neurons. Our results suggest that the general activation of the immune system modulates the functions of hypocretin neurons. The absence of a change in hypocretin cell populations suggested that factors other than anti-TRIB2 antibody play a part in the loss of hypocretin neurons in narcolepsy. The increased anti-TRIB2 antibody after the destruction of hypocretin neurons suggest that anti-TRIB2 antibody in narcolepsy patients is the consequence rather than the inciting cause of hypocretin cell destruction. © Sleep Research

  10. Stimulatory effect of low dose radiation on the immune function in tumor-bearing mice

    International Nuclear Information System (INIS)

    Zhang Ying; Li Xiujuan; Li Xiuyi; Liu Shuzheng

    1999-01-01

    Objective: The author aims at investigating the effect of whole body irradiation (WBI) with low dose radiation on immune function in tumor-bearing mice. Methods: C57BL/6J mine implanted with Lewis lung carcinoma cells in the right thighs were used as an experimental animal model. WBI with 75 mGy X-rays was given at the 10 th day after implantation and immunological parameters were detected 18 hours after irradiation. The immunological parameters included the spontaneous incorporation of 3 H-TdR into thymocytes, the number of splenocytes, the reaction of splenocytes to ConA and LPS, the splenic production of IL-2, the cytotoxic activities of natural killer (NK) and lymphokine activated killer cells (LAK) as well as specific cytotoxic T lymphocytes (CTL). Results: The immunological parameters of irradiated tumor-bearing mice were significantly increased compared with those of sham-irradiated tumor-bearing mice (P<0.05∼0.01). Conclusion: Low dose radiation could significantly increase the immune function of tumor-bearing mice, and this stimulatory effect may be of some potential significance in tumor therapy

  11. Impact of perioperative blood transfusion on immune function and prognosis in colorectal cancer patients.

    Science.gov (United States)

    Qiu, Li; Wang, Dao-Rong; Zhang, Xiang-Yun; Gao, Shan; Li, Xiao-Xia; Sun, Gong-Ping; Lu, Xiao-Bo

    2016-04-01

    To investigate the impacts of perioperative blood transfusion on the immune function and prognosis in colorectal cancer (CC) patients. A retrospective analysis was conducted in 1404 CC patients, including 1223 sporadic colorectal cancer (SCC) patients and 181 hereditary colorectal cancer (HCC) patients. Among them, 701 SCC and 102 HCC patients received perioperative blood transfusion. The amount of T lymphocyte subsets and natural killer (NK) cells was measured. All patients received a 10-year follow-up and relapse, metastasis and curative conditions were recorded. In SCC group, mortality, local recurrence and distant metastasis rate of transfused patients were significantly higher than non-transfused patients (all P transfused patients than non-transfused patients (P = 0.002). SCC patients transfused with ≥3 U of blood had significantly higher mortality than patients transfused with blood transfusion in SCC and HCC patients (all P blood transfusion (P blood transfusion had markedly lower 10-year survival rates as compared with those who did not receive (both P transfused with ≥3 U of blood had remarkably lower survival rates compared with SCC patients transfused with blood transfusion could impact immune function, increased postoperative mortality, local recurrence rate and distant metastasis rate in CC patients; and survival rate of CC patients is negatively related to blood transfusion volume. Copyright © 2016. Published by Elsevier Ltd.

  12. Brain immune cell composition and functional outcome after cerebral ischemia: Comparison of two mouse strains

    Directory of Open Access Journals (Sweden)

    Hyun Ah eKim

    2014-11-01

    Full Text Available Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stroke outcome is more severe in C57Bl/6 than FVB mice. Male mice of each strain underwent sham surgery or 1 h occlusion of the middle cerebral artery followed by 23 h of reperfusion. Despite no difference in infarct size, C57Bl/6 mice displayed markedly greater functional deficits than FVB mice after stroke, as assessed by neurological scoring and hanging wire test. Total numbers of CD45+ leukocytes tended to be larger in the brains of C57Bl/6 than FVB mice after stroke, but there were marked differences in leukocyte composition between the two mouse strains. The inflammatory response in C57Bl/6 mice primarily involved T and B lymphocytes, whereas neutrophils, monocytes and macrophages were more prominent in FVB mice. Our data are consistent with the concept that functional outcome after stroke is dependent on the immune cell composition which develops following ischemic brain injury.

  13. In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush)

    Science.gov (United States)

    Ottinger, Christopher A.; Honeyfield, Dale C.; Densmore, Christine L.; Iwanowicz, Luke R.

    2014-01-01

    In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP – biologically inactive form) to thiamine pyrophosphate (TPP – biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state.

  14. In vitro immune functions in thiamine-replete and -depleted lake trout (Salvelinus namaycush).

    Science.gov (United States)

    Ottinger, Christopher A; Honeyfield, Dale C; Densmore, Christine L; Iwanowicz, Luke R

    2014-05-01

    In this study we examined the impacts of in vivo thiamine deficiency on lake trout leukocyte function measured in vitro. When compared outside the context of individual-specific thiamine concentrations no significant differences were observed in leukocyte bactericidal activity or in concanavalin A (Con A), and phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune functions into context with the ratio of in vivo liver thiamine monophosphate (TMP--biologically inactive form) to thiamine pyrophosphate (TPP--biologically active form) proved to be the best indicator of thiamine depletion impacts as determined using regression modeling. These observed relationships indicated differential effects on the immune measures with bactericidal activity exhibiting an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated mitogenesis exhibiting no significant relationships. In addition, these relationships showed considerable complexity which included the consistent observation of a thiamine-replete subgroup with characteristics similar to those seen in the leukocytes from thiamine-depleted fish. When considered together, our observations indicate that lake trout leukocytes experience cell-type specific impacts as well as an altered physiologic environment when confronted with a thiamine-limited state. Published by Elsevier Ltd.

  15. Segmentation precedes face categorization under suboptimal conditions

    NARCIS (Netherlands)

    Van Den Boomen, Carlijn; Fahrenfort, Johannes J; Snijders, Tineke M; Kemner, Chantal

    2015-01-01

    Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain,

  16. Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Xiu-Ping Xu

    2018-01-01

    Conclusions: Our findings suggest that MFN2 may regulate T cell immune functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent a potential therapeutic target for T cell immune dysfunction-related diseases.

  17. On the Origins of Suboptimality in Human Probabilistic Inference

    Science.gov (United States)

    Acerbi, Luigi; Vijayakumar, Sethu; Wolpert, Daniel M.

    2014-01-01

    Humans have been shown to combine noisy sensory information with previous experience (priors), in qualitative and sometimes quantitative agreement with the statistically-optimal predictions of Bayesian integration. However, when the prior distribution becomes more complex than a simple Gaussian, such as skewed or bimodal, training takes much longer and performance appears suboptimal. It is unclear whether such suboptimality arises from an imprecise internal representation of the complex prior, or from additional constraints in performing probabilistic computations on complex distributions, even when accurately represented. Here we probe the sources of suboptimality in probabilistic inference using a novel estimation task in which subjects are exposed to an explicitly provided distribution, thereby removing the need to remember the prior. Subjects had to estimate the location of a target given a noisy cue and a visual representation of the prior probability density over locations, which changed on each trial. Different classes of priors were examined (Gaussian, unimodal, bimodal). Subjects' performance was in qualitative agreement with the predictions of Bayesian Decision Theory although generally suboptimal. The degree of suboptimality was modulated by statistical features of the priors but was largely independent of the class of the prior and level of noise in the cue, suggesting that suboptimality in dealing with complex statistical features, such as bimodality, may be due to a problem of acquiring the priors rather than computing with them. We performed a factorial model comparison across a large set of Bayesian observer models to identify additional sources of noise and suboptimality. Our analysis rejects several models of stochastic behavior, including probability matching and sample-averaging strategies. Instead we show that subjects' response variability was mainly driven by a combination of a noisy estimation of the parameters of the priors, and by

  18. On the origins of suboptimality in human probabilistic inference.

    Directory of Open Access Journals (Sweden)

    Luigi Acerbi

    2014-06-01

    Full Text Available Humans have been shown to combine noisy sensory information with previous experience (priors, in qualitative and sometimes quantitative agreement with the statistically-optimal predictions of Bayesian integration. However, when the prior distribution becomes more complex than a simple Gaussian, such as skewed or bimodal, training takes much longer and performance appears suboptimal. It is unclear whether such suboptimality arises from an imprecise internal representation of the complex prior, or from additional constraints in performing probabilistic computations on complex distributions, even when accurately represented. Here we probe the sources of suboptimality in probabilistic inference using a novel estimation task in which subjects are exposed to an explicitly provided distribution, thereby removing the need to remember the prior. Subjects had to estimate the location of a target given a noisy cue and a visual representation of the prior probability density over locations, which changed on each trial. Different classes of priors were examined (Gaussian, unimodal, bimodal. Subjects' performance was in qualitative agreement with the predictions of Bayesian Decision Theory although generally suboptimal. The degree of suboptimality was modulated by statistical features of the priors but was largely independent of the class of the prior and level of noise in the cue, suggesting that suboptimality in dealing with complex statistical features, such as bimodality, may be due to a problem of acquiring the priors rather than computing with them. We performed a factorial model comparison across a large set of Bayesian observer models to identify additional sources of noise and suboptimality. Our analysis rejects several models of stochastic behavior, including probability matching and sample-averaging strategies. Instead we show that subjects' response variability was mainly driven by a combination of a noisy estimation of the parameters of the

  19. Improvement of Intestinal Immune Cell Function by Lactic Acid Bacteria for Dairy Products

    Directory of Open Access Journals (Sweden)

    Tomonori Kamiya

    2016-12-01

    Full Text Available Lactic acid bacteria (LAB form a major component of gut microbiota and are often used as probiotics for fermented foods, such as yoghurt. In this study, we aimed to evaluate immunomodulatory activity of LAB, especially that of Lactobacillus bulgaricus ME-552 (ME552 and Streptococcus thermophilus ME-553 (ME553. In vivo/in vitro assay was performed in order to investigate their effects on T cell function. After oral administration of ME553 to C57BL/6 mice, the amount of both interferon γ (IFN-γ and interleukin 17 (IL-17 produced by cluster of differentiation (CD 4+ T cells from Peyer’s patches (PPs were significantly enhanced. On the other hand, ME552 only up-regulated the production of IL-17 from PP cells. The extent of induction for IFN-γ production differed between ME552 and ME553. These results suggest that LAB modulate T cell effector functions and mucosal immunity.

  20. Improvement of Intestinal Immune Cell Function by Lactic Acid Bacteria for Dairy Products.

    Science.gov (United States)

    Kamiya, Tomonori; Watanabe, Yohei; Makino, Seiya; Kano, Hiroshi; Tsuji, Noriko M

    2016-12-23

    Lactic acid bacteria (LAB) form a major component of gut microbiota and are often used as probiotics for fermented foods, such as yoghurt. In this study, we aimed to evaluate immunomodulatory activity of LAB, especially that of Lactobacillus bulgaricus ME-552 (ME552) and Streptococcus thermophilus ME-553 (ME553). In vivo/in vitro assay was performed in order to investigate their effects on T cell function. After oral administration of ME553 to C57BL/6 mice, the amount of both interferon γ (IFN-γ) and interleukin 17 (IL-17) produced by cluster of differentiation (CD) 4⁺ T cells from Peyer's patches (PPs) were significantly enhanced. On the other hand, ME552 only up-regulated the production of IL-17 from PP cells. The extent of induction for IFN-γ production differed between ME552 and ME553. These results suggest that LAB modulate T cell effector functions and mucosal immunity.

  1. Studies on the control mechanism and the degenerative immune function of dendritic cells using radiation

    International Nuclear Information System (INIS)

    Yee, Sung Tae; Kim, Jong Jin; Choi, Ji Na; Park, Jung Eun; Jeong, Young Ran

    2010-05-01

    Dendritic cells are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and costimulatory molecule expression of spleen or bone marrow-derived CD11c + DCs of C57BL/6 mice. In the first year, we compared various function of dendritic cells isolated from young and gamma-irradiated 57BL/6 mice(5 weeks after γ-radiation) for the development of aging models using radiation. In the second year, we also compared the function of spleen- and bone marrow-derived dendritic cells of young(2-3 months) and old(23-24 months) 57BL/6 mice. And we studied the differences of spleen- and bone marrow-derived dendritic cells of young and gamma-irradiated 57BL/6 mice(2, 4, 6 months after γ-radiation) for the development of aging models in third year. And we obtained various differences between spleen- and bone marrow-derived dendritic cells of normal and old(23-24 months) or γ-irradiated 57BL/6 mice. It is possible to use our results as age-associated model for modulation of the declined immunity and hematopoiesis for treatment of cancer, adult diseases and stress in aging. Such studies on the mechanism of aging model would further lead to new avenues for the development of functional foods which effect such as pathogenesis, inflammatory and autoimmune disorders. It will contributed to activation of related industry conforming quality and diversity of radiation industry. The techniques developed in our research may provide novel therapeutic modalities for age-associated immune dysfunctions

  2. Studies on the control mechanism and the degenerative immune function of dendritic cells using radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yee, Sung Tae; Kim, Jong Jin; Choi, Ji Na; Park, Jung Eun; Jeong, Young Ran [Sunchon National University, Sunchon (Korea, Republic of)

    2010-05-15

    Dendritic cells are actively used as cellular adjuvant in cancer immunotherapy. However, although DC immunotherapies primarily target the elderly population, little is known about the effect of aging on DC functions. Here, we compared the T-cell stimulation, cytokine production, and costimulatory molecule expression of spleen or bone marrow-derived CD11c{sup +} DCs of C57BL/6 mice. In the first year, we compared various function of dendritic cells isolated from young and gamma-irradiated 57BL/6 mice(5 weeks after {gamma}-radiation) for the development of aging models using radiation. In the second year, we also compared the function of spleen- and bone marrow-derived dendritic cells of young(2-3 months) and old(23-24 months) 57BL/6 mice. And we studied the differences of spleen- and bone marrow-derived dendritic cells of young and gamma-irradiated 57BL/6 mice(2, 4, 6 months after {gamma}-radiation) for the development of aging models in third year. And we obtained various differences between spleen- and bone marrow-derived dendritic cells of normal and old(23-24 months) or {gamma}-irradiated 57BL/6 mice. It is possible to use our results as age-associated model for modulation of the declined immunity and hematopoiesis for treatment of cancer, adult diseases and stress in aging. Such studies on the mechanism of aging model would further lead to new avenues for the development of functional foods which effect such as pathogenesis, inflammatory and autoimmune disorders. It will contributed to activation of related industry conforming quality and diversity of radiation industry. The techniques developed in our research may provide novel therapeutic modalities for age-associated immune dysfunctions

  3. Functions of innate immune cells and commensal bacteria in gut homeostasis.

    Science.gov (United States)

    Kayama, Hisako; Takeda, Kiyoshi

    2016-02-01

    The intestinal immune system remains unresponsive to beneficial microbes and dietary antigens while activating pro-inflammatory responses against pathogens for host defence. In intestinal mucosa, abnormal activation of innate immunity, which directs adaptive immune responses, causes the onset and/or progression of inflammatory bowel diseases. Thus, innate immunity is finely regulated in the gut. Multiple innate immune cell subsets have been identified in both murine and human intestinal lamina propria. Some innate immune cells play a key role in the maintenance of gut homeostasis by preventing inappropriate adaptive immune responses while others are associated with the pathogenesis of intestinal inflammation through development of Th1 and Th17 cells. In addition, intestinal microbiota and their metabolites contribute to the regulation of innate/adaptive immune responses. Accordingly, perturbation of microbiota composition can trigger intestinal inflammation by driving inappropriate immune responses. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  4. Functionalized iron oxide nanoparticles for controlling the movement of immune cells

    Science.gov (United States)

    White, Ethan E.; Pai, Alex; Weng, Yiming; Suresh, Anil K.; van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

    2015-04-01

    Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were

  5. Immune Checkpoint Function of CD85j in CD8 T Cell Differentiation and Aging

    Directory of Open Access Journals (Sweden)

    Claire E. Gustafson

    2017-06-01

    Full Text Available Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging. Here, we show that CD85j is mainly expressed by terminally differentiated effector (TEMRAs CD8 T cells, which increase with age, in cytomegalovirus (CMV infection and in males. CD85j+ CMV-specific cells demonstrate clonal expansion. However, TCR diversity is similar between CD85j+ and CD85j− compartments, suggesting that CD85j does not directly impact the repertoire of antigen-specific cells. Further phenotypic and functional analyses revealed that CD85j identifies a specific subset of CMV-responsive CD8 T cells that coexpress a marker of senescence (CD57 but retain polyfunctional cytokine production and expression of cytotoxic mediators. Blocking CD85j binding enhanced proliferation of CMV-specific CD8 T cells upon antigen stimulation but did not alter polyfunctional cytokine production. Taken together, these data demonstrate that CD85j characterizes a population of “senescent,” but not exhausted antigen-specific effector CD8 T cells and indicates that CD85j is an important checkpoint regulator controlling expansion of virus-specific T cells during aging. Inhibition of CD85j activity may be a mechanism to promote stronger CD8 T cell effector responses during immune aging.

  6. Acute brief heat stress in late gestation alters neonatal calf innate immune functions.

    Science.gov (United States)

    Strong, R A; Silva, E B; Cheng, H W; Eicher, S D

    2015-11-01

    Heat stress, as one of the environmental stressors affecting the dairy industry, compromises the cow milk production, immune function, and reproductive system. However, few studies have looked at how prenatal heat stress (HS) affects the offspring. The objective of this study was to evaluate the effect of HS during late gestation on calf immunity. Calves were born to cows exposed to evaporative cooling (CT) or HS (cyclic 23-35°C) for 1 wk at 3 wk before calving. Both bull and heifer calves (CT, n=10; HS, n=10) were housed in similar environmental temperatures after birth. Both CT and HS calves received 3.78 L of pooled colostrum within 12 h after birth and were fed the same diet throughout the study. In addition to tumor necrosis factor α, IL-1β, IL-1 receptor antagonist (IL-1RA), and toll-like receptor (TLR)2, and TLR4 mRNA expression, the expression of CD14(+) and CD18(+) cells, and DEC205(+) dendritic cells were determined in whole blood samples at d 0, 3, 7, 14, 21, and 28. The neutrophil to lymphocyte ratio, differential cell counts, and the hematocrit were also determined. During late gestation, the HS cows had greater respiration rates, rectal temperatures, and tended to spend more time standing compared with the CT cows. The HS calves had less expression of tumor necrosis factor-α and TLR2 and greater levels of IL-1β, IL-1RA, and TLR4 compared with CT calves. The HS calves also had a greater percentage of CD18(+) cells compared with the CT calves. Additionally, a greater percentage of neutrophils and lesser percentage of lymphocytes were in the HS calves compared with the CT calves. The results indicate that biomarkers of calves' immunity are affected in the first several weeks after birth by HS in the dam during late gestation. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Suboptimal palliative sedation in primary care: an exploration.

    Science.gov (United States)

    Pype, Peter; Teuwen, Inge; Mertens, Fien; Sercu, Marij; De Sutter, An

    2018-02-01

    Palliative sedation is a therapeutic option to control refractory symptoms in terminal palliative patients. This study aims at describing the occurrence and characteristics of suboptimal palliative sedations in primary care and at exploring the way general practitioners (GPs) experience suboptimal palliative sedation in their practice. We conducted a mixed methods study with a quantitative prospective survey in primary care and qualitative semi-structured interviews with GPs. The research team defined suboptimal palliative sedation as a time interval until deep sleep >1.5 h and/ or >2 awakenings after the start of the unconsciousness. Descriptive statistics were calculated on the quantitative data. Thematic analysis was used to analyse interview transcripts. We registered 63 palliative sedations in 1181 home deaths, 27 forms were completed. Eleven palliative sedations were suboptimal: eight due to the long time span until deep sleep; three due the number of unintended awakenings. GPs' interview analysis revealed two major themes: the shifting perception of failure and the burden of responsibility. Suboptimal palliative sedation occurs frequently in primary palliative care. Efficient communication towards family members is needed to prevent them from having unrealistic expectations and to prevent putting pressure on the GP to hasten the procedure. Sharing the burden of decision-making during the procedure with other health care professionals might diminish the heavy responsibility as perceived by GPs.

  8. Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Clovis S. Palmer

    2018-01-01

    Full Text Available An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of “inflammaging”, a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV+ individuals.

  9. Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

    Science.gov (United States)

    David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

    2017-07-01

    Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

  10. Effect of gavage of rhubarb preparation on immune function in patients with sepsis

    Directory of Open Access Journals (Sweden)

    Chao YIN

    2016-01-01

    Full Text Available Objectives  To study the effect of nasointestinal infusion of rhubarb preparation on general inflammatory reaction and immune function in sepsis patients. Methods  The patients with sepsis admitted to our hospital from August 2012 to November 2014 was randomized to placebo group (n=36 and treatment group (n=32. The placebo group was treated conventionally, while the treatment group received the rhubarb preparation through nasal tube. The differences in the clinical symptoms, inflammatory cytokines, immunological indexes were compared between two groups. Results  There was no significant difference in clinical indexes between two groups before the treatment (P>0.05. The time of gastric retention, first defecation, bowel sounds recovery, abdominal pain, and abdominal distension relief were shortened (P<0.05. The contents of TNF-α, IL-1β, and IL-6 were reduced significantly on day 8 and 28 after therapy (P<0.01 in the treatment group, but the level of IL-10 was elevated obviously on days 3 and 8 after therapy (P<0.01. Significant improvements in CD3+, CD4+, CD4+/CD8+ and HLA-DR/ CD14+ were observed at days 3, 8 and 28 after therapy (P<0.05, though the improvement of HLA-DR/CD14+ was seen only on day 8 after therapy (P<0.05. Conclusion  Rhubarb can improve the gastrointestinal function and immune function, and reduce release of inflammatory cytokines in sepsis patients, thus producing the positive role in the treatment of sepsis. DOI: 10.11855/j.issn.0577-7402.2015.12.15

  11. IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

    Science.gov (United States)

    Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

    2014-09-01

    Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

  12. Functional analysis of the human cytomegalovirus immune evasion protein, pUS322kDa

    International Nuclear Information System (INIS)

    Zhao Yiqiang; Biegalke, Bonita J.

    2003-01-01

    Human cytomegalovirus (HCMV) is an important opportunistic pathogen that infrequently causes disease in individuals with mature immune systems. The HCMV US3 gene encodes a 22-kDa protein that interferes with immune recognition of virally infected cells. The 22-kDa US3 protein binds to major histocompatibility complex (MHC) class I complexes, retaining them in the endoplasmic reticulum (ER), thereby decreasing the presentation of viral antigen to cytotoxic T cells. Our studies demonstrate that correct folding of the ER lumenal domain of the US3 protein is essential, but insufficient for interactions with MHC class I complexes. We demonstrate a requirement for the transmembrane domain of the 22-kDa US3 protein, confirming the results of others, and also show that the cytosolic carboxyl-terminal tail influences the function of the protein. Anchoring of the ER-lumenal immunoglobulin-like fold of the US3 protein to the membrane of the endoplasmic reticulum is critical for the binding and retention of MHC class I complexes

  13. Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily.

    Science.gov (United States)

    Nelson, Christopher A; Epperson, Megan L; Singh, Sukrit; Elliott, Jabari I; Fremont, Daved H

    2015-08-28

    Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. Herein we propose to call this unique structural scaffolding the PIE (Poxvirus Immune Evasion) domain. PIE domain containing proteins are abundant in chordopoxvirinae, with our analysis identifying 20 likely PIE subfamilies among 33 representative genomes spanning 7 genera. For example, cowpox strain Brighton Red appears to encode 10 different PIEs: vCCI, A41, C8, M2, T4 (CPVX203), and the SECRET proteins CrmB, CrmD, SCP-1, SCP-2, and SCP-3. Characterized PIE proteins all appear to be nonessential for virus replication, and all contain signal peptides for targeting to the secretory pathway. The PIE subfamilies differ primarily in the number, size, and location of structural embellishments to the beta-sandwich core that confer unique functional specificities. Reported ligands include chemokines, GM-CSF, IL-2, MHC class I, and glycosaminoglycans. We expect that the list of ligands and receptors engaged by the PIE domain will grow as we come to better understand how this versatile structural architecture can be tailored to manipulate host responses to infection.

  14. Association study of functional genetic variants of innate immunity related genes in celiac disease

    Directory of Open Access Journals (Sweden)

    Martín J

    2005-08-01

    Full Text Available Abstract Background Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. Methods We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. Results The TDT analysis for IL-1α, IL-1β, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. Conclusion Our results suggest that the analysed polymorphisms of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.

  15. Are there differences in immune function between continental and insular birds?

    NARCIS (Netherlands)

    Matson, K.D.

    2006-01-01

    Generally, immune system architecture varies with different environments, which presumably reflect different pathogen pressures. Specifically, populations from relatively disease-free, oceanic islands are expected to exhibit reorganized immune systems, which might be characterized by attenuated

  16. Anthrax Lethal Toxin Impairs Innate Immune Functions of Alveolar Macrophages and Facilitates Bacillus anthracis Survival

    National Research Council Canada - National Science Library

    Ribot, Wilson J; Panchal, Rekha G; Brittingham, Katherine C; Ruthel, Gordon; Kenny, Tara A; Lane, Douglas; Curry, Bob; Hoover, Timothy A; Friedlander, Arthur M; Bavari, Sina

    2006-01-01

    Alveolar macrophages (AM) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses...

  17. Suboptimal control for drag reduction in turbulent pipe flow

    International Nuclear Information System (INIS)

    Choi, Jung Il; Sung, Hyung Jin; Xu, Chun Xiao

    2001-01-01

    A suboptimal control law in turbulent pipe flow is derived and tested. Two sensing variables ∂ρ/∂θ / w and ∂ν θ /∂r / w are applied with two actuations φ θ and φ γ . To test the suboptimal control law, direct numerical simulations of turbulent pipe flow at Re τ =150 are performed. When the control law is applied, a 13∼23% drag reduction is achieved. The most effective drag reduction is made at the pair of ∂υ θ /∂r / w and φ γ . An impenetrable virtual wall concept is useful for analyzing the near-wall suction and blowing. The virtual wall concept is useful for analyzing the near-wall behavior of the controlled flow. Comparison of the present suboptimal control with that of turbulent channel flow reveals that the curvature effect is insignificant

  18. Long-term effect of postoperative irradiation on the immune functions in patients with mammary carcinoma

    International Nuclear Information System (INIS)

    Toivanen, A.; Nordman, E.

    1981-01-01

    The effect of postoperative irradiation on the immune functions of 13 patients with breast carcinoma is reported, using as parameters the peipheral blood lymphocyte count, percentages of E and EAC rosette forming cells, and lymphocyte proliferative responses to PHA, Con A and PPD. After irradiation the number of peripheral blood lymphocytes was reduced during 8 months. The percentages of E and EAC rosette forming cells were not altered during the observation time of 7 to 36 months. In the proliferative responses of lymphocytes to PHA, Con A and PPD, the postoperative irradiation caused a decrease which, regarding PHA and Con A, lasted up to 8 months and then recovered. The decrease in the proliferative responses to PPD was stronger and lasted during the whole observation time. In the mitogenic responses of patients with recurrent or disseminating disease no difference could be demonstrated as compared with the patients living recurrence-free. (Auth.)

  19. Modulation of Immune Function in Rats Using Oligosaccharides Extracted from Palm Kernel Cake.

    Science.gov (United States)

    Faseleh Jahromi, Mohammd; Shokryazdan, Parisa; Idrus, Zulkifli; Ebrahimi, Rohollah; Bashokouh, Fatemeh; Liang, Juan Boo

    2017-01-01

    To investigate the prebiotic and immunomodulatory effects of PKC extract (OligoPKC) a total of 24 male rats were randomly assigned to three treatment groups receiving basal diet (control), basal diet containing 0.5% OligoPKC, or basal diet containing 1% OligoPKC for four weeks. We found that OligoPKC had no significant effect on the tested growth parameters. However, it increased the size of the total and beneficial bacterial populations while reducing pathogen populations. OligoPKC increased the concentration of immunoglobulins in the serum and cecal contents of rats. It also enhanced the antioxidant capacity of the liver while reducing lipid peroxidation in liver tissue. OligoPKC affected the expression of genes involved in immune system function in the intestine. Therefore, OligoPKC could be considered a potential mannan-based prebiotic for humans and animals due to its beneficial effects on the health and well-being of the model rats.

  20. In vitro uptake and immune functionality of digested Rosemary extract delivered through food grade vehicles.

    Science.gov (United States)

    Arranz, E; Guri, A; Fornari, T; Mendiola, J A; Reglero, G; Corredig, M

    2017-07-01

    The digestion, absorption, uptake and bioavailability of a rosemary supercritical fluid extract encapsulated in oil in water emulsion were studied. Two emulsions with opposite surface charge were prepared, containing 7% canola oil, and either 2% lactoferrin or whey protein isolate. When absorption and uptake of carnosic acid and carnosol were followed on Caco-2 cell monolayers, there were no differences with protein type. However, when co-cultures of HT-29 MTX were employed, the presence of mucus caused a higher retention of carnosic acid in the apical layer for lactoferrin emulsions. The immune activity of the bioavailable fractions collected from cell absorption experiments was tested ex vivo on murine splenocytes. Although transport through the intestinal barrier models was low, the bioavailable fractions showed a significant effect on splenocytes proliferation. These results demonstrated the potential of using rosemary supercritical extract through protein stabilized oil in water emulsions, as a food with immunomodulatory functionality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

    Science.gov (United States)

    Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

    2012-06-01

    A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

  2. Sacral Nerve Stimulation for Constipation: Suboptimal Outcome and Adverse Events

    DEFF Research Database (Denmark)

    Maeda, Yasuko; Lundby, Lilli; Buntzen, Steen

    2010-01-01

    Sacral nerve stimulation is an emerging treatment for patients with severe constipation. There has been no substantial report to date on suboptimal outcomes and complications. We report our experience of more than 6 years by focusing on incidents and the management of reportable events.......Sacral nerve stimulation is an emerging treatment for patients with severe constipation. There has been no substantial report to date on suboptimal outcomes and complications. We report our experience of more than 6 years by focusing on incidents and the management of reportable events....

  3. Effects of Suboptimal Bidding in Combinatorial Auctions

    Science.gov (United States)

    Schneider, Stefan; Shabalin, Pasha; Bichler, Martin

    Though the VCG auction assumes a central place in the mechanism design literature, there are a number of reasons for favoring iterative combinatorial auction designs. Several promising ascending auction formats have been developed throughout the past few years based on primal-dual and subgradient algorithms and linear programming theory. Prices are interpreted as a feasible dual solution and the provisional allocation is interpreted as a feasible primal solution. iBundle( 3) (Parkes and Ungar 2000), dVSV (de Vries et al. 2007) and the Ascending Proxy auction (Ausubel and Milgrom 2002) result in VCG payoffs when the coalitional value function satisfies the buyer submodularity condition and bidders bid straightforward, which is an expost Nash equilibrium in that case. iBEA and CreditDebit auctions (Mishra and Parkes 2007) do not even require the buyer submodularity condition and achieve the same properties for general valuations. In many situations, however, one cannot assume bidders to bid straightforward and it is not clear from the theory how these non-linear personalized price auctions (NLPPAs) perform in this case. Robustness of auctions with respect to different bidding behavior is therefore a critical issue for any application. We have conducted a large number of computational experiments to analyze the performance of NLPPA designs with respect to different bidding strategies and different valuation models. We compare the results of NLPPAs to those of the VCG auction and those of iterative combinatorial auctions with approximate linear prices, such as ALPS (Bichler et al. 2009) and the Combinatorial Clock auction (Porter et al. 2003).

  4. A Simulated Heat Wave Has Diverse Effects on Immune Function and Oxidative Physiology in the Corn Snake (Pantherophis guttatus).

    Science.gov (United States)

    Stahlschmidt, Z R; French, S S; Ahn, A; Webb, A; Butler, M W

    Animals will continue to encounter increasingly warm environments, including more frequent and intense heat waves. Yet the physiological consequences of heat waves remain equivocal, potentially because of variation in adaptive plasticity (reversible acclimation) and/or aspects of experimental design. Thus, we measured a suite of physiological variables in the corn snake (Pantherophis guttatus) after exposure to field-parameterized, fluctuating temperature regimes (moderate temperature and heat wave treatments) to address two hypotheses: (1) a heat wave causes physiological stress, and (2) thermal performance of immune function exhibits adaptive plasticity in response to a heat wave. We found little support for our first hypothesis because a simulated heat wave had a negative effect on body mass, but it also reduced oxidative damage and did not affect peak performance of three immune metrics. Likewise, we found only partial support for our second hypothesis. After exposure to a simulated heat wave, P. guttatus exhibited greater performance breadth and reduced temperature specialization (the standardized difference between peak performance and performance breadth) for only one of three immune metrics and did so in a sex-dependent manner. Further, a simulated heat wave did not elicit greater performance of any immune metric at higher temperatures. Yet a heat wave likely reduced innate immune function in P. guttatus because each metric of innate immune performance in this species (as in most vertebrates) was lower at elevated temperatures. Together with previous research, our study indicates that a heat wave may have complex, modest, and even positive physiological effects in some taxa.

  5. Bacillus Coagulans Enhance the Immune Function of the Intestinal Mucosa of Yellow Broilers

    Directory of Open Access Journals (Sweden)

    L Xu

    Full Text Available ABSTRACT This experiment was conducted to investigate the effects of Bacillus coagulans on the growth performance and immune functions of the intestinal mucosa of yellow broilers. Three hundred and sixty one-day-old yellow chicks were randomly allocated to four treatments groups with six replicates of 15 chicks each. The broilers were randomly subjected to one of the following treatments for 28 days: control group (group1, fed a basal diet and three treatments (group 2, 3, 4 fed the basal diet supplemented with 100, 200, or 300 mg/kg Bacillus coagulans , respectively. The results showed that for 28 days, compared with the control diet, the dietary addition of 200 mg/kg Bacillus coagulans significantly decreased the feed/gain ratio (F/G (p<0.05, improved the thymus index, spleen index and bursa index (p<0.05, increased the villus height to crypt depth ratio (V/C in the duodenum (p<0.05, increased the number of secretory immunoglobulin (sIgA positive cells ( p<0.05. The dietary addition of 200 mg/kg Bacillus coagulans promoted a significant increase in Lactobacillus spp. populations and suppressed Escherichia coli replication in cecum, compared with the control (p<0.05. Moreover, the dietary addition of 200 mg/kg Bacillus coagulans also significantly enhanced the levels of interferon alpha (IFNα, toll-like receptor (TLR3, and melanoma differentiation-associated protein 5(MDA5 in the duodenum (p<0.05. In conclusion, the dietary addition of Bacillus coagulans significantly improved broiler performance, and enhanced the intestinal mucosal barrier and immune function. The optimal dosage of Bacillus coagulans for yellow broilers was determined as 2×108 cfu/kg.

  6. Effects of zinc-methionine on growth performance, intestinal flora and immune function in pigeon squabs.

    Science.gov (United States)

    Wang, Y; Yi, L; Zhao, M L; Wu, J Q; Wang, M Y; Cheng, X C

    2014-01-01

    1. Different concentrations of zinc-methionine (Zn-Met) were given to pigeon squabs, and the resulting effects on growth, immune functions and intestinal microflora were investigated from hatching to 28 d of age. A total of 180 artificially hatched pigeon squabs were randomly allotted to each of three treatments with three replicates of 20 squabs. The three treatments given were either one ml (2 mg/ml) Zn-Met, one ml (10 mg/ml) Zn-Met or one ml 0.9% NaCl solution. 2. The results showed that Zn-Met improved the growth performance of squabs. The average daily and average weekly weight gain was significantly greater in squabs treated with Zn-Met than in the control group. 3. The group given 2 and 10 mg supplemental Zn-Met had heavier thymus, spleen and bursa of Fabricius than the control group at d 28. 4. Maternal antibody titres against Newcastle disease haemagglutination inhibition and alpha-naphthyl acetate esterase were significantly higher in squabs treated with supplemental 2 and 10 mg Zn-Met compared to the control group at d 14 and d 28. 5. Additionally, the squabs given supplemental 2 mg Zn-Met exhibited significantly higher Bacillaceae, Lactobacillus, Enterococcus and Bifidobacterium populations at d 14 and d 28, but lower Escherichia coli populations at d 28 compared to the control group. On the contrary, Lactobacillus, Enterococcus and Bifidobacterium populations were significantly decreased with 10 mg Zn-Met at d 28. 6. This study indicates that supplementation with Zn-Met has a positive effect on growth performance, immune function and regulation of intestinal flora in pigeons. An inclusion level of 2 mg seems to be better than 10 mg Zn-Met per day per bird.

  7. Wheat homologs of yeast ATG6 function in autophagy and are implicated in powdery mildew immunity.

    Science.gov (United States)

    Yue, Jieyu; Sun, Hong; Zhang, Wei; Pei, Dan; He, Yang; Wang, Huazhong

    2015-04-01

    Autophagy-related ATG6 proteins are pleiotropic proteins functioning in autophagy and the phosphatidylinositol 3-phosphate-signaling pathways. Arabidopsis ATG6 regulates normal plant growth, pollen development and germination, and plant responses to biotic/abiotic stresses. However, the ATG6 functions in wheat (Triticum aestivum L.), an important food crop, are lacking. We identified three members, TaATG6a-6c, of the ATG6 family from common wheat. TaATG6a, 6b and 6c were localized on homeologous chromosomes 3DL, 3BL and 3AL, respectively, of the allo-hexaploid wheat genome, and evidence was provided for their essential role in autophagy. The TaATG6a-GFP fusion protein was found in punctate pre-autophagosomal structures. The expression of each TaATG6 gene restored the accumulation of autophagic bodies in atg6-mutant yeast. Additionally, TaATG6 knockdown plants showed impaired constitutive and pathogen-induced autophagy and growth abnormalities under normal conditions. We also examined the expression patterns of wheat ATG6s for clues to their physiological roles, and found that their expression was induced by the fungus Blumeria graminis f. sp. tritici (Bgt), the causal agent of powdery mildew, and by abiotic stress factors. A role for TaATG6s in wheat immunity to powdery mildew was further implied when knockdowns of TaATG6s weakly compromised the broad-spectrum powdery mildew resistance gene Pm21-triggered resistance response and, conversely and significantly, enhanced the basal resistance of susceptible plants. In addition, leaf cell death was sometimes induced by growth-retarded small Bgt mycelia on susceptible TaATG6 knockdown plants after a long period of interaction. Thus, we provide an important extension of the previous characterization of plant ATG6 genes in wheat, and observed a role for autophagy genes in wheat immune responses to fungal pathogens. Three wheat ATG6s were identified and shown to be essential for autophagy biogenesis. Wheat ATG6s are

  8. Francisella tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel Activity.

    Science.gov (United States)

    Shakerley, Nicole L; Chandrasekaran, Akshaya; Trebak, Mohamed; Miller, Barbara A; Melendez, J Andrés

    2016-02-19

    As an innate defense mechanism, macrophages produce reactive oxygen species that weaken pathogens and serve as secondary messengers involved in immune function. The Gram-negative bacterium Francisella tularensis utilizes its antioxidant armature to limit the host immune response, but the mechanism behind this suppression is not defined. Here we establish that F. tularensis limits Ca(2+) entry in macrophages, thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild type (live vaccine strain) or catalase-deficient F. tularensis (ΔkatG) show distinct profiles in their H2O2 scavenging rates, 1 and 0.015 pm/s, respectively. Murine alveolar macrophages infected with ΔkatG display abnormally high basal intracellular Ca(2+) concentration that did not increase further in response to H2O2. Additionally, ΔkatG-infected macrophages displayed limited Ca(2+) influx in response to ionomycin, as a result of ionophore H2O2 sensitivity. Exogenously added H2O2 or H2O2 generated by ΔkatG likely oxidizes ionomycin and alters its ability to transport Ca(2+). Basal increases in cytosolic Ca(2+) and insensitivity to H2O2-mediated Ca(2+) entry in ΔkatG-infected cells are reversed by the Ca(2+) channel inhibitors 2-aminoethyl diphenylborinate and SKF-96365. 2-Aminoethyl diphenylborinate but not SKF-96365 abrogated ΔkatG-dependent increases in macrophage actin remodeling and IL-6 secretion, suggesting a role for H2O2-mediated Ca(2+) entry through the transient receptor potential melastatin 2 (TRPM2) channel in macrophages. Indeed, increases in basal Ca(2+), actin polymerization, and IL-6 production are reversed in TRPM2-null macrophages infected with ΔkatG. Together, our findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species to temper macrophage TRPM2-mediated Ca(2+) signaling and limit host immune function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. A biocultural perspective on fictive kinship in the Andes: social support and women's immune function in El Alto, Bolivia.

    Science.gov (United States)

    Hicks, Kathryn

    2014-09-01

    This article examines the influence of emotional and instrumental support on women's immune function, a biomarker of stress, in the city of El Alto, Bolivia. It tests the prediction that instrumental support is protective of immune function for women living in this marginal environment. Qualitative and quantitative ethnographic methods were employed to assess perceived emotional and instrumental support and common sources of support; multiple linear regression analysis was used to model the relationship between social support and antibodies to the Epstein-Barr virus. These analyses provided no evidence that instrumental social support is related to women's health, but there is some evidence that emotional support from compadres helps protect immune function. © 2014 by the American Anthropological Association.

  10. Nanoparticle-based B-cell targeting vaccines: Tailoring of humoral immune responses by functionalization with different TLR-ligands.

    Science.gov (United States)

    Zilker, Claudia; Kozlova, Diana; Sokolova, Viktoriya; Yan, Huimin; Epple, Matthias; Überla, Klaus; Temchura, Vladimir

    2017-01-01

    Induction of an appropriate type of humoral immune response during vaccination is essential for protection against viral and bacterial infections. We recently observed that biodegradable calcium phosphate (CaP) nanoparticles coated with proteins efficiently targeted and activated naïve antigen-specific B-cells in vitro. We now compared different administration routes for CaP-nanoparticles and demonstrated that intramuscular immunization with such CaP-nanoparticles induced stronger immune responses than immunization with monovalent antigen. Additional functionalization of the CaP-nanoparticles with TRL-ligands allowed modulating the IgG subtype response and the level of mucosal IgA antibodies. CpG-containing CaP-nanoparticles were as immunogenic as a virus-like particle vaccine. Functionalization of CaP-nanoparticles with T-helper cell epitopes or CpG also allowed overcoming lack of T-cell help. Thus, our results indicate that CaP-nanoparticle-based B-cell targeting vaccines functionalized with TLR-ligands can serve as a versatile platform for efficient induction and modulation of humoral immune responses in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

    Science.gov (United States)

    Canetta, S; Bolkan, S; Padilla-Coreano, N; Song, L J; Sahn, R; Harrison, N L; Gordon, J A; Brown, A; Kellendonk, C

    2016-07-01

    Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

  12. Sub-optimal control of fuzzy linear dynamical systems under granular differentiability concept.

    Science.gov (United States)

    Mazandarani, Mehran; Pariz, Naser

    2018-05-01

    This paper deals with sub-optimal control of a fuzzy linear dynamical system. The aim is to keep the state variables of the fuzzy linear dynamical system close to zero in an optimal manner. In the fuzzy dynamical system, the fuzzy derivative is considered as the granular derivative; and all the coefficients and initial conditions can be uncertain. The criterion for assessing the optimality is regarded as a granular integral whose integrand is a quadratic function of the state variables and control inputs. Using the relative-distance-measure (RDM) fuzzy interval arithmetic and calculus of variations, the optimal control law is presented as the fuzzy state variables feedback. Since the optimal feedback gains are obtained as fuzzy functions, they need to be defuzzified. This will result in the sub-optimal control law. This paper also sheds light on the restrictions imposed by the approaches which are based on fuzzy standard interval arithmetic (FSIA), and use strongly generalized Hukuhara and generalized Hukuhara differentiability concepts for obtaining the optimal control law. The granular eigenvalues notion is also defined. Using an RLC circuit mathematical model, it is shown that, due to their unnatural behavior in the modeling phenomenon, the FSIA-based approaches may obtain some eigenvalues sets that might be different from the inherent eigenvalues set of the fuzzy dynamical system. This is, however, not the case with the approach proposed in this study. The notions of granular controllability and granular stabilizability of the fuzzy linear dynamical system are also presented in this paper. Moreover, a sub-optimal control for regulating a Boeing 747 in longitudinal direction with uncertain initial conditions and parameters is gained. In addition, an uncertain suspension system of one of the four wheels of a bus is regulated using the sub-optimal control introduced in this paper. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  13. Sub-optimal breastfeeding and its associated factors in rural ...

    African Journals Online (AJOL)

    Similarly, not attending formal education, low birth order and lack of knowledge about exclusive breastfeeding were also negatively associated with exclusive breastfeeding practice. Conclusion: In this study, sub-optimal breast feeding was found to be high. Delayed initiation and non-exclusive breastfeeding practices were ...

  14. Suboptimality of Sales Promotions and Improvement Through Channel Coordination

    NARCIS (Netherlands)

    B. Wierenga (Berend); H. Soethoudt (Han)

    2002-01-01

    textabstractThis paper deals with sales promotions in the form of consumer price discounts in fast-moving consumer goods. First, we show analytically that suboptimality is to be expected with respect to the size of the consumer price discount. This is due to the separate decision making of the

  15. Altered time structure of neuro-endocrine-immune system function in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Carughi Stefano

    2010-06-01

    TcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. Conclusion The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system

  16. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  17. Toxic effects of dietary methylmercury on immune function and hematology in American kestrels (Falco sparverius)

    Science.gov (United States)

    Fallacara, Dawn M.; Halbrook, Richard S.; French, John B.

    2011-01-01

    Fifty-nine adult male American kestrels (Falco sparverius) were assigned to one of three diet formulations including 0 (control), 0.6, and 3.9 μg/g (dry wt) methylmercury (MeHg). Kestrels received their diets daily for 13 weeks to assess the effects of dietary MeHg on immunocompetence. Immunotoxic endpoints included assessment of cell-mediated immunity (CMI) using the phytohemagglutinin (PHA) skin-swelling assay and primary and secondary antibody-mediated immune responses (IR) via the sheep red blood cell (SRBC) hemagglutination assay. Select hematology and histology parameters were evaluated to corroborate the results of functional assays and to assess immunosuppression of T and B cell-dependent components in spleen tissue. Kestrels in the 0.6 and 3.9 μg/g MeHg groups exhibited suppression of CMI, including lower PHA stimulation indexes (p = 0.019) and a 42 to 45% depletion of T cell-dependent splenic lymphoid tissue (p = 0.006). Kestrels in the 0.6 μg/g group exhibited suppression of the primary IR to SRBCs (p = 0.014). MeHg did not have a noticeable effect on the secondary IR (p = 0.166). Elevation of absolute heterophil counts (p p p = 0.003) was apparent in the 3.9 μg/g group at week 12. Heterophilia, or the excess of heterophils in peripheral blood above normal ranges, was apparent in seven of 17 (41%) kestrels in the 3.9 μg/g group and was indicative of an acute inflammatory response or physiological stress. This study revealed that adult kestrels were more sensitive to immunotoxic effects of MeHg at environmentally relevant dietary concentrations than they were to reproductive effects as previously reported.

  18. Effect of depression on the immune function and tumor load in patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Hai-Bo Shi

    2017-06-01

    Full Text Available Objective: To study the correlation between depression and immune function as well as tumor load in patients with advanced gastric cancer. Methods: 98 patients diagnosed with advanced gastric cancer in our hospital between May 2013 and September 2016 were selected and divided into depression group (n=39 with HAMD scores >50 and non-depression group with HAMD scores≤50 (n=39, serum was collected to detect the levels of cytokines interleukin-2 (IL-2, IL-4, IL-10, IL-17, interferon-γ (IFN-γ and transforming growth factor β1 (TGF- β1 as well as tumor markers carcinoembryonic antigen (CEA, carbohydrate antigen 199 (CA199, CA724, TK-1 and sLAG-3, and gastric cancer tissues were collected to determine the expression of cell cycle-related proteins CyclinD1, CDK4 and E2F. Results: Serum IL-2, IFN-γ and IL-17 levels of depression group were significantly lower than those of non-depression group (P<0.05 while IL-4, IL-10, TGF-β1, CEA, CA199, CA724, TK-1 and sLAG-3 levels were significantly higher than those of non-depression group (P<0.05; CyclinD1, CDK4 and E2F protein expression in tumor tissues of depression group were significantly higher than those of non-depression group (P<0.05. Conclusions: Depression can inhibit the anti-tumor immune response in patients with advanced gastric cancer, and then promote cancer cell proliferation and increase tumor load.

  19. Evaluation of long-term effects of 50-Hz magnetic fields on immune functions in humans

    Energy Technology Data Exchange (ETDEWEB)

    Touitou, Y.; Auzeby, A.; Camus, F. [Faculty of Medicine Pierre et Marie Curie, 75 - Paris (France); Lambrozo, J.; Souques, M.; Verrier, A. [Gaz de France (EDF/GDF), SEM, 75 - Paris (France)

    2006-07-01

    The relationship between exposure to 50-Hz magnetic fields (E.L.F.) and human health is of increasing interest since this exposure has been implicated in many different diseases including cancers in epidemiological studies, though the results are controversial. The identification of possible mechanisms of interaction between E.L.F. and biological systems that could provide a biological plausibility to the observed effects has failed so far. In this study we investigate the possible chronic effects of exposure to E.L.F. in humans. We examine the circadian rhythm of CD{sub 3}, CD{sub 4}, CD{sub 8}, Nk cells and B cells in 15 men (38.0{+-}8.9 yrs) exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 {mu}T. The results are compared to those for 15 unexposed men similar in a (39.4 {+-}1.2 yrs), with the same synchronization and physical activity who served as controls (individual exposures ranged from 0.004 to 0.092 {mu}T). Blood samples were taken hourly from 2000 to 0800. This work shows that subjects exposed over a long period (up to 20 years) and on a daily basis to magnetic fields experienced no changes in their plasma immune variables. Our data suggest therefore that magnetic fields have no cumulative effects on immune functions, at least for the variables under study. (authors)

  20. Effect of depression on the immune function and tumor load in patients with advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Shi

    2017-01-01

    Objective:To study the correlation between depression and immune function as well as tumor load in patients with advanced gastric cancer.Methods: 98 patients diagnosed with advanced gastric cancer in our hospital between May 2013 and September 2016 were selected and divided into depression group (n=39) with HAMD scores >50 and non-depression group with HAMD scores≤50 (n=39), serum was collected to detect the levels of cytokines interleukin-2 (IL-2), IL-4, IL-10, IL-17, interferon-γ (IFN-γ) and transforming growth factorβ1 (TGF-β1) as well as tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), CA724, TK-1 and sLAG-3, and gastric cancer tissues were collected to determine the expression of cell cycle-related proteins CyclinD1, CDK4 and E2F.Results:Serum IL-2, IFN-γand IL-17 levels of depression group were significantly lower than those of non-depression group (P<0.05) while IL-4, IL-10, TGF-β1, CEA, CA199, CA724, TK-1 and sLAG-3 levels were significantly higher than those of non-depression group (P<0.05);CyclinD1, CDK4 and E2F protein expression in tumor tissues of depression group were significantly higher than those of non-depression group (P<0.05).Conclusions:Depression can inhibit the anti-tumor immune response in patients with advanced gastric cancer, and then promote cancer cell proliferation and increase tumor load.

  1. Lipid mobilization, immune function and the paradigm of vitamin E in transition cows.

    Directory of Open Access Journals (Sweden)

    Ioannis Politis

    2016-06-01

    Full Text Available The number of metabolic disorders that dairy cows have to cope during the transition to lactation can be divided in three main categories. The first category includes disorders related to abnormal energy metabolism (ketosis, fatty liver, acidosis. The second and the third categories include disorders related to mineral metabolism (milk fever and disorders related directly or indirectly to impaired immune function (mastitis, metritis, retained placenta, respectively. Among the many physiological changes during the transition period, perhaps the most crucial, is an increase in the concentration of plasma non-esterified fatty acids (NEFA. A portion of this increase in NEFA is obligatory and it is under hormonal control while another portion is the result of a situation known as negative energy balance (difference between energy consumed and energy spent. In this presentation I will present data from a collaborative study between the University of Milan and the Agricultural University of Athens which proves that negative correlations exist between blood concentrations of NEFA and β-hydroxybutyrate with α-tocopherol. The adipose tissue contains two main categories of cells: adipocytes and immunocompetent cells mainly monocytes/macrophages. Our research has tested the hypothesis that a cross-talk exists between adipocytes and monocytes/macrophages and this cross-talk is mediated by fatty acids released by adipocytes especially during the transition period. Results indicate that all fatty acids tested (myristic, palmitic, palmitoleic, stearic and oleic upregulate the expression of numerous pro-inflammatory genes by both monocytes but neutrophils, as well. The longer the carbon chain, the most potent is the effect.  Another hypothesis that we have tested is that vitamin E can interfere and block the cross talk between adipocytes and immunocompetent cells. Against this notion, α-tocopherol does not interfere with the effect of fatty acids on

  2. Stromal cell contributions to the homeostasis and functionality of the immune system.

    Science.gov (United States)

    Mueller, Scott N; Germain, Ronald N

    2009-09-01

    A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response.

  3. Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety.

    Directory of Open Access Journals (Sweden)

    Luba Sominsky

    Full Text Available Neonatal exposure of rodents to an immune challenge alters a variety of behavioural and physiological parameters in adulthood. In particular, neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p. exposure produces robust increases in anxiety-like behaviour, accompanied by persistent changes in hypothalamic-pituitary-adrenal (HPA axis functioning. Altered autonomic nervous system (ANS activity is an important physiological contributor to the generation of anxiety. Here we examined the long term effects of neonatal LPS exposure on ANS function and the associated changes in neuroendocrine and behavioural indices. ANS function in Wistar rats, neonatally treated with LPS, was assessed via analysis of tyrosine hydroxylase (TH in the adrenal glands on postnatal days (PNDs 50 and 85, and via plethysmographic assessment of adult respiratory rate in response to mild stress (acoustic and light stimuli. Expression of genes implicated in regulation of autonomic and endocrine activity in the relevant brain areas was also examined. Neonatal LPS exposure produced an increase in TH phosphorylation and activity at both PNDs 50 and 85. In adulthood, LPS-treated rats responded with increased respiratory rates to the lower intensities of stimuli, indicative of increased autonomic arousal. These changes were associated with increases in anxiety-like behaviours and HPA axis activity, alongside altered expression of the GABA-A receptor α2 subunit, CRH receptor type 1, CRH binding protein, and glucocorticoid receptor mRNA levels in the prefrontal cortex, hippocampus and hypothalamus. The current findings suggest that in addition to the commonly reported alterations in HPA axis functioning, neonatal LPS challenge is associated with a persistent change in ANS activity, associated with, and potentially contributing to, the anxiety-like phenotype. The findings of this study reflect the importance of changes in the perinatal microbial environment on the ontogeny of

  4. Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety.

    Science.gov (United States)

    Sominsky, Luba; Fuller, Erin A; Bondarenko, Evgeny; Ong, Lin Kooi; Averell, Lee; Nalivaiko, Eugene; Dunkley, Peter R; Dickson, Phillip W; Hodgson, Deborah M

    2013-01-01

    Neonatal exposure of rodents to an immune challenge alters a variety of behavioural and physiological parameters in adulthood. In particular, neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) exposure produces robust increases in anxiety-like behaviour, accompanied by persistent changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. Altered autonomic nervous system (ANS) activity is an important physiological contributor to the generation of anxiety. Here we examined the long term effects of neonatal LPS exposure on ANS function and the associated changes in neuroendocrine and behavioural indices. ANS function in Wistar rats, neonatally treated with LPS, was assessed via analysis of tyrosine hydroxylase (TH) in the adrenal glands on postnatal days (PNDs) 50 and 85, and via plethysmographic assessment of adult respiratory rate in response to mild stress (acoustic and light stimuli). Expression of genes implicated in regulation of autonomic and endocrine activity in the relevant brain areas was also examined. Neonatal LPS exposure produced an increase in TH phosphorylation and activity at both PNDs 50 and 85. In adulthood, LPS-treated rats responded with increased respiratory rates to the lower intensities of stimuli, indicative of increased autonomic arousal. These changes were associated with increases in anxiety-like behaviours and HPA axis activity, alongside altered expression of the GABA-A receptor α2 subunit, CRH receptor type 1, CRH binding protein, and glucocorticoid receptor mRNA levels in the prefrontal cortex, hippocampus and hypothalamus. The current findings suggest that in addition to the commonly reported alterations in HPA axis functioning, neonatal LPS challenge is associated with a persistent change in ANS activity, associated with, and potentially contributing to, the anxiety-like phenotype. The findings of this study reflect the importance of changes in the perinatal microbial environment on the ontogeny of physiological processes.

  5. TiO{sub 2} nanoparticle-induced ROS correlates with modulated immune cell function

    Energy Technology Data Exchange (ETDEWEB)

    Maurer-Jones, Melissa A.; Christenson, Jenna R.; Haynes, Christy L., E-mail: chaynes@umn.edu [University of Minnesota, Department of Chemistry (United States)

    2012-12-15

    Design of non-toxic nanoparticles will be greatly facilitated by understanding the nanoparticle-cell interaction mechanism on a cell function level. Mast cells are important cells for the immune system's first line of defense, and we can utilize their exocytotic behavior as a model cellular function as it is a conserved process across cell types and species. Perturbations in exocytosis can also have implications for whole organism health. One proposed mode of toxicity is nanoparticle-induced reactive oxygen species (ROS), particularly for titanium dioxide (TiO{sub 2}) nanoparticles. Herein, we have correlated changes in ROS with the perturbation of the critical cell function of exocytosis, using UV light to induce greater levels of ROS in TiO{sub 2} exposed cells. The primary culture mouse peritoneal mast cells (MPMCs) were exposed to varying concentrations of TiO{sub 2} nanoparticles for 24 h. ROS content was determined using 2,7-dihydrodichlorofluorescein diacetate (DCFDA). Cellular viability was determined with the MTT and Trypan blue assays, and exocytosis was measured by the analytical electrochemistry technique of carbon-fiber microelectrode amperometry. MPMCs exposed to TiO{sub 2} nanoparticles experienced a dose-dependent increase in total ROS content. While there was minimal impact of ROS on cellular viability, there is a correlation between ROS amount and exocytosis perturbation. As nanoparticle-induced ROS increases, there is a significant decrease (45 %) in the number of serotonin molecules being released during exocytosis, increase (26 %) in the amount of time for each exocytotic granule to release, and decrease (28 %) in the efficiency of granule trafficking and docking. This is the first evidence that nanoparticle-induced ROS correlates with chemical messenger molecule secretion, possibly making a critical connection between functional impairment and mechanisms contributing to that impairment.

  6. Efficacy of screening immune system function in at-risk newborns

    OpenAIRE

    Pavlovski, Christopher J

    2014-01-01

    This paper explores the introduction of a screening test to highlight impaired immune system status for newborn infants and its efficacy as a preventative clinical measure. Moreover, it is suggested that screening of the infantile immune system has the potential to highlight susceptibility to a range of infant and childhood diseases, bestowing an opportunity to introduce early intervention to reduce the incidence of these diseases. Development of the neonatal immune system is an important hea...

  7. T cell immunity

    OpenAIRE

    Emel Bülbül Başkan

    2013-01-01

    Since birth, our immune system is constantly bombarded with self-antigens and foreign pathogens. To stay healthy, complex immune strategies have evolved in our immune system to maintain self-tolerance and to defend against foreign pathogens. Effector T cells are the key players in steering the immune responses to execute immune functions. While effector T cells were initially identified to be immune promoting, recent studies unraveled negative regulatory functions of effector T cells...

  8. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  9. Effects of blood transportation on human peripheral mononuclear cell yield, phenotype and function: implications for immune cell biobanking.

    Directory of Open Access Journals (Sweden)

    Anita Posevitz-Fejfár

    Full Text Available Human biospecimen collection, processing and preservation are rapidly emerging subjects providing essential support to clinical as well as basic researchers. Unlike collection of other biospecimens (e.g. DNA and serum, biobanking of viable immune cells, such as peripheral blood mononuclear cells (PBMC and/or isolated immune cell subsets is still in its infancy. While certain aspects of processing and freezing conditions have been studied in the past years, little is known about the effect of blood transportation on immune cell survival, phenotype and specific functions. However, especially for multicentric and cooperative projects it is vital to precisely know those effects. In this study we investigated the effect of blood shipping and pre-processing delay on immune cell phenotype and function both on cellular and subcellular levels. Peripheral blood was collected from healthy volunteers (n = 9: at a distal location (shipped overnight and in the central laboratory (processed immediately. PBMC were processed in the central laboratory and analyzed post-cryopreservation. We analyzed yield, major immune subset distribution, proliferative capacity of T cells, cytokine pattern and T-cell receptor signal transduction. Results show that overnight transportation of blood samples does not globally compromise T- cell subsets as they largely retain their phenotype and proliferative capacity. However, NK and B cell frequencies, the production of certain PBMC-derived cytokines and IL-6 mediated cytokine signaling pathway are altered due to transportation. Various control experiments have been carried out to compare issues related to shipping versus pre-processing delay on site. Our results suggest the implementation of appropriate controls when using multicenter logistics for blood transportation aiming at subsequent isolation of viable immune cells, e.g. in multicenter clinical trials or studies analyzing immune cells/subsets. One important conclusion might

  10. Aged Garlic Extract Modifies Human Immunity.

    Science.gov (United States)

    Percival, Susan S

    2016-02-01

    Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification. The purpose of this review was to summarize the influence of aged garlic extract (AGE) on the immune system. The author's laboratory is interested in AGE's effects on cell proliferation and activation and inflammation and to learn whether those changes might affect the occurrence and severity of colds and flu. Healthy human participants (n = 120), between 21 and 50 y of age, were recruited for a randomized, double-blind, placebo-controlled parallel-intervention study to consume 2.56 g AGE/d or placebo supplements for 90 d during the cold and flu season. Peripheral blood mononuclear cells were isolated before and after consumption, and γδ-T and NK cell function was assessed by flow cytometry. The effect on cold and flu symptoms was determined by using daily diary records of self-reported illnesses. After 45 d of AGE consumption, γδ-T and NK cells proliferated better and were more activated than cells from the placebo group. After 90 d, although the number of illnesses was not significantly different, the AGE group showed reduced cold and flu severity, with a reduction in the number of symptoms, the number of days participants functioned suboptimally, and the number of work/school days missed. These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation. This trial was registered at clinicaltrials.gov as NCT01390116. © 2016 American Society for Nutrition.

  11. Thermal sensitivity of immune function: evidence against a generalist-specialist trade-off among endothermic and ectothermic vertebrates

    Science.gov (United States)

    Butler, Michael W.; Stahlschmidt, Zachary R.; Ardia, Daniel R.; Davies, Scott; Davis, Jon; Guillette, Louis J.; Johnson, Nicholas; McCormick, Stephen D.; McGraw, Kevin J.; DeNardo, Dale F.

    2013-01-01

    Animal body temperature (Tbody) varies over daily and annual cycles, affecting multiple aspects of biological performance in both endothermic and ectothermic animals. Yet a comprehensive comparison of thermal performance among animals varying in Tbody (mean and variance) and heat production is lacking. Thus, we examined the thermal sensitivity of immune function (a crucial fitness determinant) in Vertebrata, a group encompassing species of varying thermal biology. Specifically, we investigated temperature-related variation in two innate immune performance metrics, hemagglutination and hemolysis, for 13 species across all seven major vertebrate clades. Agglutination and lysis were temperature dependent and were more strongly related to the thermal biology of species (e.g., mean Tbody) than to the phylogenetic relatedness of species, although these relationships were complex and frequently surprising (e.g., heterotherms did not exhibit broader thermal performance curves than homeotherms). Agglutination and lysis performance were positively correlated within species, except in taxa that produce squalamine, a steroidal antibiotic that does not lyse red blood cells. Interestingly, we found the antithesis of a generalist-specialist trade-off: species with broader temperature ranges of immune performance also had higher peak performance levels. In sum, we have uncovered thermal sensitivity of immune performance in both endotherms and ectotherms, highlighting the role that temperature and life history play in immune function across Vertebrata.

  12. Effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer

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    Qi Pan

    2017-09-01

    Full Text Available Objective: To investigate the effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer. Methods: A total of 90 breast cancer patients in our hospital were randomly divided into control group (45 cases and observation group (45 cases. The two groups received CAF chemotherapy, and the observation group was additionally given Kanglaite injection (200 mL/d for 2 weeks continuously. Both groups had chemotherapy for 6 courses. The effect on myelosuppression, immune function and tumor markers levels was detected and compared before and after treatment in two groups. Results: After treatment, myelosuppression was found in both groups, and the levels of leukocyte, hemoglobin and platelet decreased significantly compared with before treatment (P0.05, and the levels of immune function indexes (CD3+, CD4+, CD4+/ CD8+ of the observation group were significantly higher than those in the control group (P<0.05) . After treatment, the levels of two tumor markers (CEA, CA15-3 decreased significantly than before treatment in both groups (P<0.05, and the decrease amplitude in the observation group was higher than that in the control group (P<0.05. Conclusions: Kanglaite combined with chemotherapy has evident therapeutic effect on breast cancer. It can alleviate the myelosuppression caused by chemotherapy, improve immune function, and reduce the concentration of tumor markers in patients with breast cancer.

  13. Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM.

    Science.gov (United States)

    Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee; Yee, Sung-Tae

    2008-01-01

    The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-gamma and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans. Copyright (c) 2007 John Wiley & Sons, Ltd.

  14. The Effects of Tacrolimus on T-Cell Proliferation Are Short-Lived: A Pilot Analysis of Immune Function Testing

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    Benjamin L. Laskin, MD, MS

    2017-08-01

    Conclusions. T-cell proliferation is currently not suitable to measure immunosuppression because sample processing diminishes observable effects. Future immune function testing should focus on fresh samples with minimal washing steps. Our results also emphasize the importance of adherence to immunosuppressive treatment, because T-cell proliferation recovered substantially after even brief discontinuation of tacrolimus.

  15. Effects of indomethacin suppositories on serum amylase, inflammatory factors and immune function after endoscopic retrograde cholangiopancreatography

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    Xiao-Bin Peng

    2016-10-01

    Full Text Available Objective: To explore the effects of indomethacin suppositories on serum amylase, inflammatory factors and immune function after endoscopic retrograde cholangiopancreatography (ERCP. Methods: A total of 85 patients with common bile duct stones or obstructive jaundice were divided into the observation group (n=45 and the control group (n=40 according to the different treatment methods, both two groups patients were treated with ERCP, patients in the observation group was given indomethacin suppositories 50 mg preoperative 30 min. Serum amylase, inflammatory factors and T cell subsets were detected preoperative, postoperative 6 h and postoperative 24 h. Inflammatory factors including interleukin -10 (IL-10, interleukin -6 (IL-6, tumor necrosis factor alpha (TNF-α and interleukin-4 (IL-4. T cell subsets including CD3+ , CD4+ , CD8+ and calculated CD4+ / CD8+ . Results: In both two groups, postoperative 6 h, 24 h serum amylase were significantly higher than before surgery; in the observation group, the postoperative 6 h, 24 h serum amylase were significantly lower than in the control group at the same time point and the differences were statistically significant (P<0.05. Both two groups’ postoperative 6 h, 24 h serum proinflammatory factor IL-6 and TNF-α increased first and then decreased, both were significantly higher than before surgery; both two groups’ postoperative 6 h, 24 h serum anti-inflammatory factor IL-10 and IL-4 gradually increased, both were significantly higher than before surgery, and the differences were statistically significant (P<0.05; In the observation group, antiinflammatory factor IL-10 and IL-4 significantly increased while pro-inflammatory factor IL-6 and TNF-α significantly decreased compared with the control group at the same time point 6 h and 24 h after surgery, the difference between the two groups was statistically significant (P<0.05. Both two groups’ postoperative 6 h, 24 h T cell subsets CD3+ , CD4+ , CD4

  16. Immuno-regulatory function of indoleamine 2,3 dioxygenase through modulation of innate immune responses.

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    Malihe-Sadat Poormasjedi-Meibod

    Full Text Available Successful long-term treatment of type-1 diabetes mainly relies on replacement of β-cells via islet transplantation. Donor shortage is one of the main obstacles preventing transplantation from becoming the treatment of choice. Although animal organs could be an alternative source for transplantation, common immunosuppressive treatments demonstrate low efficacy in preventing xenorejection. Immunoprotective effects of indoleamine 2,3-dioxygenase (IDO on T-cell mediated allorejection has been extensively studied. Our studies revealed that IDO expression by fibroblasts, induced apoptosis in T-cells while not affecting non-immune cell survival/function. Since macrophages play a pivotal role in xenograft rejection, herein we investigated the effect of IDO-induced tryptophan deficiency/kynurenine accumulation on macrophage function/survival. Moreover, we evaluated the local immunosuppressive effect of IDO on islet-xenograft protection. Our results indicated that IDO expression by bystander fibroblasts significantly reduced the viability of primary macrophages via apoptosis induction. Treatment of peritoneal macrophages by IDO-expressing fibroblast conditioned medium significantly reduced their proinflammatory activity through inhibition of iNOS expression. To determine whether IDO-induced tryptophan starvation or kynurenine accumulation is responsible for macrophage apoptosis and inhibition of their proinflammatory activity, Raw264.7 cell viability and proinflammatory responses were evaluated in tryptophan deficient medium or in the presence of kynurenine. Tryptophan deficiency, but not kynurenine accumulation, reduced Raw264.7 cell viability and suppressed their proinflammatory activity. Next a three-dimensional islet-xenograft was engineered by embedding rat islets within either control or IDO-expressing fibroblast-populated collagen matrix. Islets morphology and immune cell infiltration were then studied in the xenografts transplanted into the C57

  17. Radionuclide activity and the immune system functioning in residents of radiation contaminated areas

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    V. L. Sokolenko

    2015-09-01

    Full Text Available The objective of this research is to assess the relation of radioactive contamination degree to immune system functioning, in the absence or presence of additional potential immunosuppressants. To achieve the objective, during the period of 1995–2015 we examined 250 people, students of Cherkasy State University, who lived in the areas of enhanced radiation monitoring before. Also we evaluated the additional impact of the emotional stress caused by examinations on examined students. Indicators of cellular immunity were determined by immunophenotyping and dyeing using Romanowsky-Giemsa method. The level of immunoglobulins in blood serum was determined by radial immunodiffusion (Mancini method. The level of cortisol in blood serum was determined by immunoenzyme method. We have found that in absence of the emotional stress among residents of the areas contaminated with radionuclides, cortisol level remained at the upper limit of homeostatic norm. There is an average positive correlation between the activity of radionuclides in the territories of residence and the level of cortisol. There are marked average positive correlations between the activity of radionuclides and the level of neutrophils, and low positive correlations with the levels of IgG and IgM in blood serum. Average negative correlations between the activity of radionuclides and the following parameters are also observed: absolute and relative number of functionally mature T-lymphocytes with phenotype CD3+, absolute and relative number of their helper subpopulation CD4+, absolute and relative number of natural killer cells with phenotype CD16+; and strong negative correlations with immunoregulatory index CD4+/CD8+. Cortisol level shows the similar correlation with the same parameters, but correlation coefficient is lower. Under conditions of additional stress, caused by emotional load during the examinations, cortisol level significantly increases. This enhanced previously discovered

  18. Deconstructing and constructing innate immune functions using molecular sensors and actuators

    Science.gov (United States)

    Coutinho, Kester; Inoue, Takanari

    2016-05-01

    White blood cells such as neutrophils and macrophages are made competent for chemotaxis and phagocytosis -- the dynamic cellular behaviors that are hallmarks of their innate immune functions -- by the reorganization of complex biological circuits during differentiation. Conventional loss-of-function approaches have revealed that more than 100 genes participate in these cellular functions, and we have begun to understand the intricate signaling circuits that are built up from these gene products. We now appreciate: (1) that these circuits come in a variety of flavors -- so that we can make a distinction between genetic circuits, metabolic circuits and signaling circuits; and (2) that they are usually so complex that the assumption of multiple feedback loops, as well as that of crosstalk between seemingly independent pathways, is now routine. It has not escaped our notice, however, that just as physicists and electrical engineers have long been able to disentangle complex electric circuits simply by repetitive cycles of probing and measuring electric currents using a voltmeter, we might similarly be able to dissect these intricate biological circuits by incorporating equivalent approaches in the fields of cell biology and bioengineering. Existing techniques in biology for probing individual circuit components are unfortunately lacking, so that the overarching goal of drawing an exact circuit diagram for the whole cell -- complete with kinetic parameters for connections between individual circuit components -- is not yet in near sight. My laboratory and others have thus begun the development of a new series of molecular tools that can measurably investigate the circuit connectivity inside living cells, as if we were doing so on a silicon board. In these proceedings, I will introduce some of these techniques, provide examples of their implementation, and offer a perspective on directions moving forward.

  19. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  20. Immune function genes CD99L2, JARID2 and TPO show association with autism spectrum disorder

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    Ramos Paula S

    2012-06-01

    Full Text Available Abstract Background A growing number of clinical and basic research studies have implicated immunological abnormalities as being associated with and potentially responsible for the cognitive and behavioral deficits seen in autism spectrum disorder (ASD children. Here we test the hypothesis that immune-related gene loci are associated with ASD. Findings We identified 2,012 genes of known immune-function via Ingenuity Pathway Analysis. Family-based tests of association were computed on the 22,904 single nucleotide polymorphisms (SNPs from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE repository. Several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, we observed significant associations in the CD99 molecule-like 2 region (CD99L2, rs11796490, P = 4.01 × 10-06, OR = 0.68 (0.58-0.80, in the jumonji AT rich interactive domain 2 (JARID2 gene (rs13193457, P = 2.71 × 10-06, OR = 0.61 (0.49-0.75, and in the thyroid peroxidase gene (TPO (rs1514687, P = 5.72 × 10-06, OR = 1.46 (1.24-1.72. Conclusions This study suggests that despite the lack of a general enrichment of SNPs in immune function genes in ASD children, several novel genes with known immune functions are associated with ASD.

  1. Molecular mechanism and function of CD40/CD40L engagement in the immune system.

    Science.gov (United States)

    Elgueta, Raul; Benson, Micah J; de Vries, Victor C; Wasiuk, Anna; Guo, Yanxia; Noelle, Randolph J

    2009-05-01

    During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.

  2. Functional analysis of tomato immune receptor Ve1 and recognition of Verticillium effector Ave1

    NARCIS (Netherlands)

    Zhang, Z.

    2013-01-01

    Similar to the animal innate immune system, plants employ extracellular leucine rich repeat (eLRR)-containing cell surface receptors to recognize conserved molecular structures that are derived from microbial pathogens. A number of these immune receptors, as well as the corresponding pathogen

  3. MECHANISMS OF ANTIINFECTIOUS FUNCTIONS OF INNATE IMMUNITY: ROLE OF TOLL-LIKE RECEPTORS

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    S. I. Suskov

    2012-01-01

    Full Text Available This review describes the main role of toll-like receptors of innate immunity for pathogen recognition; signaling; production of inflammatory response. Also Interrelation of innate and adaptive Immunity in conditions of pathology and organ transplantation were considered. 

  4. Modulation of the chicken immune cell function by dietary polyunsaturated fatty acids

    NARCIS (Netherlands)

    Sijben, J.W.C.

    2002-01-01

    Polyunsaturated fatty acids (PUFA) possess a wide range of biological properties, including immunomodulation. The amount, type, and ratio of dietary PUFA determine the types of fatty acids that are incorporated into immune cell membranes. Consequently, the physiological properties of immune cells

  5. Evaluation of immunomodulation by lactobacillus casei shirota: immune function, autoimmunity and gene expression

    NARCIS (Netherlands)

    Baken, A.; Ezendam, J.; Gremmer, E.R.; Klerk, de A.; Pennings, J.L.A.; Matthee, B.; Peijnenburg, A.A.C.M.; Loveren, van H.

    2006-01-01

    Lactic acid bacteria are claimed to have immunomodulating effects. Stimulation as well as suppression of T helper (Th)1 mediated immune responses, have been described for various strains. Experiments involving Lactobacillus casei Shirota (LcS) detected mainly enhancement of innate immune responses

  6. Leishmania exosomes and other virulence factors: Impact on innate immune response and macrophage functions.

    Science.gov (United States)

    Atayde, Vanessa Diniz; Hassani, Kasra; da Silva Lira Filho, Alonso; Borges, Andrezza Raposo; Adhikari, Anupam; Martel, Caroline; Olivier, Martin

    2016-11-01

    Leishmania parasites are the causative agents of the leishmaniases, a collection of vector-borne diseases that range from simple cutaneous to fatal visceral forms. Employing potent immune modulation mechanisms, Leishmania is able to render the host macrophage inactive and persist inside its phagolysosome. In the last few years, the role of exosomes in Leishmania-host interactions has been increasingly investigated. For instance, it was reported that Leishmania exosome release is augmented following temperature shift, a condition mimicking parasite's entry into its mammalian host. Leishmania exosomes were found to strongly affect macrophage cell signaling and functions, similarly to whole parasites. Importantly, these vesicles were shown to be pro-inflammatory, capable to recruit neutrophils at their inoculation site exacerbating the pathology. In this review, we provide the most recent insights on the role of exosomes and other virulence factors, especially the surface protease GP63, in Leishmania-host interactions, deepening our knowledge on leishmaniasis and paving the way for the development of new therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Functional Implications of the IL-23/IL-17 Immune Axis in Schizophrenia.

    Science.gov (United States)

    Debnath, Monojit; Berk, Michael

    2017-12-01

    The aetiology of schizophrenia seems to stem from complex interactions amongst environmental, genetic, metabolic, immunologic and oxidative components. Chronic low-grade inflammation has been persistently linked to schizophrenia, and this has primarily been based on the findings derived from Th1/Th2 cytokine balance. While the IL-23/IL-17 axis plays crucial role in the pathogenesis of several immune-mediated disorders, it has remained relatively unexplored in neuropsychiatric disorders. Altered levels of cytokines related to IL-23/IL-17 axis have been observed in schizophrenia patients in a few studies. In addition, other indirect factors known to confer schizophrenia risk like complement activation and altered gut microbiota are shown to modulate the IL-23/IL-17 axis. These preliminary observations provide crucial clues about the functional implications of IL-23/IL-17 axis in schizophrenia. In this review, an attempt has been made to highlight the biology of IL-23/IL-17 axis and its relevance to schizophrenia risk and pathogenesis. Given the pathogenic potential of the IL-23/IL-17 axis, therapeutic targeting of this axis may be a promising approach to benefit patients suffering from this devastating disorder.

  8. Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

    Science.gov (United States)

    Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

    2015-10-01

    Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

  9. The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity.

    Science.gov (United States)

    Xiao, Yichuan; Zou, Qiang; Xie, Xiaoping; Liu, Ting; Li, Haiyan S; Jie, Zuliang; Jin, Jin; Hu, Hongbo; Manyam, Ganiraju; Zhang, Li; Cheng, Xuhong; Wang, Hui; Marie, Isabelle; Levy, David E; Watowich, Stephanie S; Sun, Shao-Cong

    2017-05-01

    Dendritic cells (DCs) are crucial for mediating immune responses but, when deregulated, also contribute to immunological disorders, such as autoimmunity. The molecular mechanism underlying the function of DCs is incompletely understood. In this study, we have identified TANK-binding kinase 1 (TBK1), a master innate immune kinase, as an important regulator of DC function. DC-specific deletion of Tbk1 causes T cell activation and autoimmune symptoms and also enhances antitumor immunity in animal models of cancer immunotherapy. The TBK1-deficient DCs have up-regulated expression of co-stimulatory molecules and increased T cell-priming activity. We further demonstrate that TBK1 negatively regulates the induction of a subset of genes by type I interferon receptor (IFNAR). Deletion of IFNAR1 could largely prevent aberrant T cell activation and autoimmunity in DC-conditional Tbk1 knockout mice. These findings identify a DC-specific function of TBK1 in the maintenance of immune homeostasis and tolerance. © 2017 Xiao et al.

  10. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet

    Science.gov (United States)

    Mabuchi, Yuko; Frankel, Theresa L.

    2016-01-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons. PMID:27069640

  11. Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid.

    Science.gov (United States)

    Herzog, Rebecca; Kuster, Lilian; Becker, Julia; Gluexam, Tobias; Pils, Dietmar; Spittler, Andreas; Bhasin, Manoj K; Alper, Seth L; Vychytil, Andreas; Aufricht, Christoph; Kratochwill, Klaus

    2017-07-24

    Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.

  12. Functional similarities between pigeon 'milk' and mammalian milk: induction of immune gene expression and modification of the microbiota.

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    Meagan J Gillespie

    Full Text Available Pigeon 'milk' and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon 'milk'. Therefore, using a chicken model, we investigated the effect of pigeon 'milk' on immune gene expression in the Gut Associated Lymphoid Tissue (GALT and on the composition of the caecal microbiota. Chickens fed pigeon 'milk' had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon 'milk'-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon 'milk'-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon 'milk', as well as being directly seeded by bacteria present in pigeon 'milk'. Our results demonstrate that pigeon 'milk' has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon 'lactation' and mammalian lactation evolved independently but resulted in similarly functional products.

  13. Toxicity of cadmium in Japanese quail: Evaluation of body weight, hepatic and renal function, and cellular immune response

    International Nuclear Information System (INIS)

    Sant'Ana, M.G.; Moraes, R.; Bernardi, M.M.

    2005-01-01

    Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TNα and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure

  14. Analysis of the toxicity of gold nano particles on the immune system: effect on dendritic cell functions

    International Nuclear Information System (INIS)

    Villiers, Christian L.; Freitas, Heidi; Couderc, Rachel; Villiers, Marie-Bernadette; Marche, Patrice N.

    2010-01-01

    The effect of manufactured gold nanoparticles (NPs) on the immune system was analysed through their ability to perturb the functions of dendritic cells (DCs), a major actor of both innate and acquired immune responses. For this purpose, DCs were produced in culture from mouse bone marrow progenitors. The analysis of the viability of the cells after their incubation in the presence of gold NPs shows that these NPs are not cytotoxics even at high concentration. Furthermore, the phenotype of the DC is unchanged after the addition of NPs, indicating that there is no activation of the DC. However, the analysis of the cells at the intracellular level reveals important amounts of gold NPs amassing in endocytic compartments. Furthermore, the secretion of cytokines is significantly modified after such internalisation indicating a potential perturbation of the immune response.

  15. Suboptimal processor for anomaly detection for system surveillance and diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Ciftcioglu, Oe.; Hoogenboom, J.E.; Dam, H. van

    1989-06-01

    Anomaly detection for nuclear reactor surveillance and diagnosis is described. The residual noise obtained as a result of autoregressive (AR) modelling is essential to obtain high sensitivity for anomaly detection. By means of the method of hypothesis testing a suboptimal anomaly detection processor is devised for system surveillance and diagnosis. Experiments are carried out to investigate the performance of the processor, which is in particular of interest for on-line and real-time applications.

  16. Visually suboptimal bananas: How ripeness affects consumer expectation and perception.

    Science.gov (United States)

    Symmank, Claudia; Zahn, Susann; Rohm, Harald

    2018-01-01

    One reason for the significant amount of food that is wasted in developed countries is that consumers often expect visually suboptimal food as being less palatable. Using bananas as example, the objective of this study was to determine how appearance affects consumer overall liking, the rating of sensory attributes, purchase intention, and the intended use of bananas. The ripeness degree (RD) of the samples was adjusted to RD 5 (control) and RD 7 (more ripened, visually suboptimal). After preliminary experiments, a total of 233 participants were asked to judge their satisfaction with the intensity of sensory attributes that referred to flavor, taste, and texture using just-about-right scales. Subjects who received peeled samples were asked after tasting, whereas subjects who received unpeeled bananas judged expectation and, after peeling and tasting, perception. Expected overall liking and purchase intention were significantly lower for RD 7 bananas. Purchase intention was still significantly different between RD 5 and RD 7 after tasting, whereas no difference in overall liking was observed. Significant differences between RD 5 and RD 7 were observed when asking participants for their intended use of the bananas. Concerning the sensory attributes, penalty analysis revealed that only the firmness of the RD 7 bananas was still not just-about-right after tasting. The importance that consumers attribute to the shelf-life of food had a pronounced impact on purchase intention of bananas with different ripeness degree. In the case of suboptimal bananas, the results demonstrate a positive relationship between the sensory perception and overall liking and purchase intention. Convincing consumers that visually suboptimal food is still tasty is of high relevance for recommending different ways of communication. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

    Science.gov (United States)

    Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

    2017-11-01

    The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Functions of Calcium-Dependent Protein Kinases in Plant Innate Immunity

    Directory of Open Access Journals (Sweden)

    Xiquan Gao

    2014-03-01

    Full Text Available An increase of cytosolic Ca2+ is generated by diverse physiological stimuli and stresses, including pathogen attack. Plants have evolved two branches of the immune system to defend against pathogen infections. The primary innate immune response is triggered by the detection of evolutionarily conserved pathogen-associated molecular pattern (PAMP, which is called PAMP-triggered immunity (PTI. The second branch of plant innate immunity is triggered by the recognition of specific pathogen effector proteins and known as effector-triggered immunity (ETI. Calcium (Ca2+ signaling is essential in both plant PTI and ETI responses. Calcium-dependent protein kinases (CDPKs have emerged as important Ca2+ sensor proteins in transducing differential Ca2+ signatures, triggered by PAMPs or effectors and activating complex downstream responses. CDPKs directly transmit calcium signals by calcium binding to the elongation factor (EF-hand domain at the C-terminus and substrate phosphorylation by the catalytic kinase domain at the N-terminus. Emerging evidence suggests that specific and overlapping CDPKs phosphorylate distinct substrates in PTI and ETI to regulate diverse plant immune responses, including production of reactive oxygen species, transcriptional reprogramming of immune genes, and the hypersensitive response.

  19. Functions of Calcium-Dependent Protein Kinases in Plant Innate Immunity

    Science.gov (United States)

    Gao, Xiquan; Cox, Kevin L.; He, Ping

    2014-01-01

    An increase of cytosolic Ca2+ is generated by diverse physiological stimuli and stresses, including pathogen attack. Plants have evolved two branches of the immune system to defend against pathogen infections. The primary innate immune response is triggered by the detection of evolutionarily conserved pathogen-associated molecular pattern (PAMP), which is called PAMP-triggered immunity (PTI). The second branch of plant innate immunity is triggered by the recognition of specific pathogen effector proteins and known as effector-triggered immunity (ETI). Calcium (Ca2+) signaling is essential in both plant PTI and ETI responses. Calcium-dependent protein kinases (CDPKs) have emerged as important Ca2+ sensor proteins in transducing differential Ca2+ signatures, triggered by PAMPs or effectors and activating complex downstream responses. CDPKs directly transmit calcium signals by calcium binding to the elongation factor (EF)-hand domain at the C-terminus and substrate phosphorylation by the catalytic kinase domain at the N-terminus. Emerging evidence suggests that specific and overlapping CDPKs phosphorylate distinct substrates in PTI and ETI to regulate diverse plant immune responses, including production of reactive oxygen species, transcriptional reprogramming of immune genes, and the hypersensitive response. PMID:27135498

  20. Hungry pigeons make suboptimal choices, less hungry pigeons do not.

    Science.gov (United States)

    Laude, Jennifer R; Pattison, Kristina F; Zentall, Thomas R

    2012-10-01

    Hungry animals will often choose suboptimally by being attracted to reliable signals for food that occur infrequently (they gamble) over less reliable signals for food that occur more often. That is, pigeons prefer an option that 50 % of the time provides them with a reliable signal for the appearance of food but 50 % of the time provides them with a reliable signal for the absence of food (overall 50 % reinforcement) over an alternative that always provides them with a signal for the appearance of food 75 % of the time (overall 75 % reinforcement). The pigeons appear to choose impulsively for the possibility of obtaining the reliable signal for reinforcement. There is evidence that greater hunger is associated with greater impulsivity. We tested the hypothesis that if the pigeons were less hungry, they would be less impulsive and, thus, would choose more optimally (i.e., on the basis of the overall probability of reinforcement). We found that hungry pigeons choose the 50 % reinforcement alternative suboptimally but less hungry pigeons prefer the more optimal 75 % reinforcement. Paradoxically, pigeons that needed the food more received less of it. These findings have implications for how level of motivation may also affect human suboptimal choice (e.g., purchase of lottery tickets and playing slot machines).

  1. 17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients

    NARCIS (Netherlands)

    Wieten, R. W.; Goorhuis, A.; Jonker, E. F. F.; de Bree, G. J.; de Visser, A. W.; van Genderen, P. J. J.; Remmerswaal, E. B. M.; ten Berge, I. J. M.; Visser, L. G.; Grobusch, M. P.; van Leeuwen, E. M. M.

    2016-01-01

    The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen

  2. Use of calcitriol to maintain postpartum blood calcium and improve immune function in dairy cows.

    Science.gov (United States)

    Vieira-Neto, A; Lima, I R P; Lopes, F; Lopera, C; Zimpel, R; Sinedino, L D P; Jeong, K C; Galvão, K; Thatcher, W W; Nelson, C D; Santos, J E P

    2017-07-01

    Our objectives were to determine the effects of an injectable formulation of calcitriol on mineral metabolism and immune function in postpartum Holstein cows that received an acidogenic diet prepartum to minimize hypocalcemia. In experiment 1, cows within 6 h of calving received calcitriol (0, 200, or 300 μg) to determine the dose needed to increase plasma concentrations of Ca; 300 μg was sufficient to sustain Ca for at least 3 d. In experiment 2, multiparous cows were assigned randomly to receive only vehicle (control, n = 25) or 300 μg of calcitriol (n = 25) subcutaneously within the first 6 h after calving. Blood was sampled before treatment and 12 h later, then daily until 15 d in milk (DIM), and analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), total Mg (tMg), and total P (tP), metabolites, and hormones. Urine was sampled in the first 7 DIM and analyzed for concentrations of tCa, tMg, and creatinine. Neutrophil function was evaluated in the first week postpartum. Dry matter intake and production performance were evaluated for the first 36 DIM. Calcitriol administration increased concentrations of calcitriol in plasma within 12 h of application from 51 to 427 pg/mL, which returned to baseline within 5 d. Concentrations of iCa and tCa increased 24 h after treatment with calcitriol. Concentrations of iCa (control = 1.08 vs. calcitriol = 1.20 mM), tCa (control = 2.23 vs. calcitriol = 2.33 mM), and tP (control = 1.47 vs. calcitriol = 1.81 mM) remained elevated in cows treated with calcitriol until 3, 5, and 7 DIM, respectively, whereas concentration of tMg (control = 0.76 vs. calcitriol = 0.67 mM) was less in calcitriol cows than control cows until 3 DIM. Concentrations of parathyroid hormone decreased in calcitriol cows compared with control cows (control = 441 vs. calcitriol = 336 pg/mL). Calcitriol tended to increase plasma concentrations of β-hydroxybutyrate and serotonin, but concentrations of glucose, nonesterified fatty acids, and C

  3. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Ironson, Gail

    2001-01-01

    ... (immune measures that fight tumors and viruses). During the course of the three-year study, 60 women diagnosed with Stage 1 and 2 breast cancer will be recruited and assigned to a massage therapy (n=20...

  4. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Tronson, Gail

    2000-01-01

    ... (immune measures that fight tumors and viruses). During the course of the three-year study, 60 women diagnosed with Stage 1 and 2 breast cancer will be recruited and assigned to a massage therapy (n=20...

  5. [Effects of Early Enteral Immunonutrition on Postoperative Immune Function and Rehabilitation of Patients with Gastric Cancer and Nutritional Risk].

    Science.gov (United States)

    Peng, Chang-Bing; Li, Wen-Zhong; Xu, Rui; Zhuang, Wen

    2017-05-01

    To investigate the effects of early enteral immunonutrition on postoperative immune function and rehabilitation of gastric cancer patients with nutritional risk. New hospitalized patients with gastric cancer were evaluated the nutrient status based on NRS 2002. The patients who scored between 3 to 5 points were randomized into two groups(30 cases for each group), and those in experimental group were given 7-d early postoperative enteral immune nutrition, those in control group were given normal nutrition. The immune indexes (CD3 + , CD4 + , CD8 + and CD4 + /CD8 + ) and nutritional indexes(transferrin, pre-albumin, albumin) were measured before operation and at the 3 rd and 7 th day postoperatively. In addition, the first flatus time, gastrointestinal adverse reactions and complications, length of hospital stays were compared between the two groups. The level of CD4 + /CD8 + and transferrin, pre-albumin, albumin in experimental group were significantly higher than those in control group at the third and seventh day postoperatively ( P 0.05). Early enteral immunonutrition can effectively promote the recovery of nutritional status and immune function in gastric cancer patients with nutrition risk.

  6. Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood.

    Science.gov (United States)

    Pennings, Jeroen L A; Jennen, Danyel G J; Nygaard, Unni C; Namork, Ellen; Haug, Line S; van Loveren, Henk; Granum, Berit

    2016-01-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds that have widespread use in consumer and industrial applications. PFAS are considered environmental pollutants that have various toxic properties, including effects on the immune system. Recent human studies indicate that prenatal exposure to PFAS leads to suppressed immune responses in early childhood. In this study, data from the Norwegian BraMat cohort was used to investigate transcriptomics profiles in neonatal cord blood and their association with maternal PFAS exposure, anti-rubella antibody levels at 3 years of age and the number of common cold episodes until 3 years. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. The analyses identified a toxicogenomics profile of 52 PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes. This gene set contains several immunomodulatory genes (CYTL1, IL27) as well as other immune-associated genes (e.g. EMR4P, SHC4, ADORA2A). In addition, this study identified PPARD as a PFAS toxicogenomics marker. These markers can serve as the basis for further mechanistic or epidemiological studies. This study provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood and supports current views on PPAR- and NF-κB-mediated modes of action. The findings add to the available evidence that PFAS exposure is immunotoxic in humans and support regulatory policies to phase out these substances.

  7. Zymosan-induced immune challenge modifies the stress response of hypoxic air-breathing fish (Anabas testudineus Bloch): Evidence for reversed patterns of cortisol and thyroid hormone interaction, differential ion transporter functions and non-specific immune response.

    Science.gov (United States)

    Simi, S; Peter, Valsa S; Peter, M C Subhash

    2017-09-15

    Fishes have evolved physiological mechanisms to exhibit stress response, where hormonal signals interact with an array of ion transporters and regulate homeostasis. As major ion transport regulators in fish, cortisol and thyroid hormones have been shown to interact and fine-tune the stress response. Likewise, in fishes many interactions have been identified between stress and immune components, but the physiological basis of such interaction has not yet delineated particularly in air-breathing fish. We, therefore, investigated the responses of thyroid hormones and cortisol, ion transporter functions and non-specific immune response of an obligate air-breathing fish Anabas testudineus Bloch to zymosan treatment or hypoxia stress or both, to understand how immune challenge modifies the pattern of stress response in this fish. Induction of experimental peritonitis in these fish by zymosan treatment (200ngg -1 ) for 24h produced rise in respiratory burst and lysozomal activities in head kidney phagocytes. In contrast, hypoxia stress for 30min in immune-challenged fish reversed these non-specific responses of head kidney phagocytes. The decline in plasma cortisol in zymosan-treated fish and its further suppression by hypoxia stress indicate that immune challenge suppresses the cortisol-driven stress response of this fish. Likewise, the decline in plasma T 3 and T 4 after zymosan-treatment and the rise in plasma T 4 after hypoxia stress in immune-challenged fish indicate a critical role for thyroid hormone in immune-stress response due to its differential sensitivity to both immune and stress challenges. Further, analysis of the activity pattern of ion-dependent ATPases viz. Na + /K + -ATPase, H + /K + -ATPase and Na + /NH 4 + -ATPase indicates a functional interaction of ion transport system with the immune response as evident in its differential and spatial modifications after hypoxia stress in immune-challenged fish. The immune-challenge that produced differential

  8. Comprehensive Transcriptome Profiling and Functional Analysis of the Frog (Bombina maxima) Immune System

    Science.gov (United States)

    Zhao, Feng; Yan, Chao; Wang, Xuan; Yang, Yang; Wang, Guangyin; Lee, Wenhui; Xiang, Yang; Zhang, Yun

    2014-01-01

    Amphibians occupy a key phylogenetic position in vertebrates and evolution of the immune system. But, the resources of its transcriptome or genome are still little now. Bombina maxima possess strong ability to survival in very harsh environment with a more mature immune system. We obtained a comprehensive transcriptome by RNA-sequencing technology. 14.3% of transcripts were identified to be skin-specific genes, most of which were not isolated from skin secretion in previous works or novel non-coding RNAs. 27.9% of transcripts were mapped into 242 predicted KEGG pathways and 6.16% of transcripts related to human disease and cancer. Of 39 448 transcripts with the coding sequence, at least 1501 transcripts (570 genes) related to the immune system process. The molecules of immune signalling pathway were almost presented, several transcripts with high expression in skin and stomach. Experiments showed that lipopolysaccharide or bacteria challenge stimulated pro-inflammatory cytokine production and activation of pro-inflammatory caspase-1. These frog's data can remarkably expand the existing genome or transcriptome resources of amphibians, especially immunity data. The entity of the data provides a valuable platform for further investigation on more detailed immune response in B. maxima and a comparative study with other amphibians. PMID:23942912

  9. Targeting cFMS signaling to restore immune function and eradicate HIV reservoirs

    Science.gov (United States)

    Gerngross, Lindsey

    While combination anti-retroviral therapy (cART) has improved the length and quality of life of individuals living with HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HAND) has increased and remains a significant clinical concern. The neuropathogenesis of HAND is not completely understood, however, latent HIV infection in the central nervous system (CNS) and chronic neuroinflammation are believed to play a prominent role. CNS-associated macrophages and resident microglia are significant contributors to CNS inflammation and constitute the chief reservoir of HIV-1 infection in the CNS. Previous studies from our lab suggest monocyte/macrophage invasion of the CNS in HIV may be driven by altered monocyte/macrophage homeostasis. We have reported expansion of a monocyte subset (CD14+CD16 +CD163+) in peripheral blood of HIV+ patients that is phenotypically similar to macrophages/microglia that accumulate in the CNS as seen in post-mortem tissue. The factors driving the expansion of this monocyte subset are unknown, however, signaling through cFMS, a type III receptor tyrosine kinase (RTK), may play a role. Macrophage-colony stimulating factor (M-CSF), a ligand of cFMS, has been shown to be elevated in the cerebral spinal fluid (CSF) of individuals with the most severe form of HAND, HIV-associated dementia (HAD). M-CSF promotes a Macrophage-2-like phenotype and increases CD16 and CD163 expression in cultured monocytes. M-CSF has also been shown to increase the susceptibility of macrophages to HIV infection and enhance virus production. These findings, in addition to the known function of M-CSF in promoting macrophage survival, supports a role for M-CSF in the development and maintenance of macrophage viral reservoirs in tissues where these cells accumulate, including the CNS. Interestingly, a second ligand for cFMS, IL-34, was recently identified and reported to share some functions with M-CSF, suggesting that both ligands may contribute to HIV

  10. The study on the immunity restoring function of cWPROL in treating experimental radiation esophagitis

    International Nuclear Information System (INIS)

    Shen Li; Shan Baoen; Zhang Li; Lu Fuhe; Guo Xiujuan

    2007-01-01

    Objective: To study the restorative function of compound white peony root oral liquids (cWPROL) in treating rats' experimental acute radiation-induced esophagitis from the aspect of immunodeficiency. Methods: 128 Wistar rats were divided into eight groups. The radiation esophagitis was induced by 43 Gy 60 Co. Then the rats were treated with medicine in different ways. On every experimental point the absolute number and percentage of T lymphocyte subsets were analyzed by flow cytometry. The changes of the leukocyte in number and differential count were detected by haemocyte counting instrument. IgG and C3 in rats' serum were analyzed by immunological turbidimetry. Results: Radiation brought on decrease of experimental rats 'leukocyte count, the lymphocyte differential count, absolute count and absolute T lymphocyte subsets in the blood and the content of IgG and C3 with radiation esophagitis. cWPROL could increase the lymphocyte percentage compared that in with the radiated group 2. The preventive (high dose) could increase lymphocyte count while Western medicine decreased rats' leukocyte count, lymphocyte percentage and absolute count (P<0.05). The absolute T lymphocyte subsets in rats' peripheral blood increased in the group infused with cWPROL (high dose) (P<0.001). Compared with the radiated group 2 the absolute T lymphocyte subsets decreased significantly(P<0.001), and the content of complement C3 increased in the group infused with cWPROL (high dose) (P<0.05) but decreased in the group infused with Western medicine (P<0.01). Conclusion: cWPROL plays the role of restoring the cytoimmunity and immunity damaged by radiation in rats with radiation esophagitis. (authors)

  11. Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction.

    Directory of Open Access Journals (Sweden)

    Patrick S Mitchell

    2015-12-01

    Full Text Available Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host

  12. Six-SOMAmer Index Relating to Immune, Protease and Angiogenic Functions Predicts Progression in IPF.

    Directory of Open Access Journals (Sweden)

    Shanna L Ashley

    Full Text Available Biomarkers in easily accessible compartments like peripheral blood that can predict disease progression in idiopathic pulmonary fibrosis (IPF would be clinically useful regarding clinical trial participation or treatment decisions for patients. In this study, we used unbiased proteomics to identify relevant disease progression biomarkers in IPF.Plasma from IPF patients was measured using an 1129 analyte slow off-rate modified aptamer (SOMAmer array, and patient outcomes were followed over the next 80 weeks. Receiver operating characteristic (ROC curves evaluated sensitivity and specificity for levels of each biomarker and estimated area under the curve (AUC when prognostic biomarker thresholds were used to predict disease progression. Both logistic and Cox regression models advised biomarker selection for a composite disease progression index; index biomarkers were weighted via expected progression-free days lost during follow-up with a biomarker on the unfavorable side of the threshold.A six-analyte index, scaled 0 to 11, composed of markers of immune function, proteolysis and angiogenesis [high levels of ficolin-2 (FCN2, cathepsin-S (Cath-S, legumain (LGMN and soluble vascular endothelial growth factor receptor 2 (VEGFsR2, but low levels of inducible T cell costimulator (ICOS or trypsin 3 (TRY3] predicted better progression-free survival in IPF with a ROC AUC of 0.91. An index score ≥ 3 (group ≥ 2 was strongly associated with IPF progression after adjustment for age, gender, smoking status, immunomodulation, forced vital capacity % predicted and diffusing capacity for carbon monoxide % predicted (HR 16.8, 95% CI 2.2-126.7, P = 0.006.This index, derived from the largest proteomic analysis of IPF plasma samples to date, could be useful for clinical decision making in IPF, and the identified analytes suggest biological processes that may promote disease progression.

  13. Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.

    Science.gov (United States)

    Yamaguchi, Sachiko; Ogiue-Ikeda, Mari; Sekino, Masaki; Ueno, Shoogo

    2006-01-01

    We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.

  14. Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

    Science.gov (United States)

    Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M

    2015-10-01

    Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus

    Science.gov (United States)

    Op den Brouw, Marjoleine L; Binda, Rekha S; van Roosmalen, Mark H; Protzer, Ulrike; Janssen, Harry L A; van der Molen, Renate G; Woltman, Andrea M

    2009-01-01

    Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Myeloid dendritic cells (mDC) of patients with chronic HBV are impaired in their maturation and function, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. The mechanism responsible for altered mDC function remains unclear. The HBV-infected patients display large amounts of HBV particles and viral proteins in their circulation, especially the surface antigen HBsAg, which allows multiple interactions between the virus, its viral proteins and DC. To assess whether HBV directly influences mDC function, the effects of HBV and HBsAg on human mDC maturation and function were investigated in vitro. As already described for internalization of HBV by DC, the present study shows that peripheral blood-derived mDC of healthy controls also actively take up HBsAg in a time-dependent manner. Cytokine-induced maturation in the presence of HBV or HBsAg resulted in a significantly more tolerogenic mDC phenotype as demonstrated by a diminished up-regulation of costimulatory molecules and a decreased T-cell stimulatory capacity, as assessed by T-cell proliferation and interferon-γ production. In addition, the presence of HBV significantly reduced interleukin-12 production by mDC. These results show that both HBV particles and purified HBsAg have an immune modulatory capacity and may directly contribute to the dysfunction of mDC in patients with chronic HBV. The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity. PMID:18624732

  16. High frequency of sub-optimal semen quality in an unselected population of young men

    DEFF Research Database (Denmark)

    Andersen, A G; Jensen, T K; Carlsen, E

    2000-01-01

    for military service, this provided a unique opportunity to study the reproductive function in an unbiased population. Altogether 891 young men delivered a blood sample in which reproductive hormones were measured. From 708 of these men data were also obtained on semen quality and testis size. The median sperm...... immotile spermatozoa and follicle stimulating hormone. Possible causes for this high frequency of young men with suboptimal semen quality are obscure and need to be explored. Whether these findings apply for young male populations of comparable countries remains to be seen....

  17. Reproduction Alters Hydration State but Does Not Impact the Positive Effects of Dehydration on Innate Immune Function in Children's Pythons (Antaresia childreni).

    Science.gov (United States)

    Brusch, George A; Billy, Gopal; Blattman, Joseph N; DeNardo, Dale F

    Resource availability can impact immune function, with the majority of studies of such influences focusing on the allocation of energy investment into immune versus other physiological functions. When energy is a limited resource, performance trade-offs can result, compromising immunity. Dehydration is also considered a physiological challenge resulting from the limitation of a vital resource, yet previous research has found a positive relationship between dehydration and innate immune performance. However, these studies did not examine the effects of dehydration on immunity when there was another concurrent, substantial physiological challenge. Thus, we examined the impact of reproduction and water deprivation, individually and in combination, on immune performance in Children's pythons (Antaresia childreni). We collected blood samples from free-ranging A. childreni to evaluate osmolality and innate immune function (lysis, agglutination, bacterial growth inhibition) during the austral dry season, when water availability is limited and this species is typically reproducing. To examine how reproduction and water imbalance, both separately and combined, impact immune function, we used a laboratory-based 2 × 2 experiment. Our results demonstrate that A. childreni experience significant dehydration during the dry season and that, overall, osmolality, regardless of the underlying cause (seasonal rainfall, water deprivation, or reproduction), is positively correlated with increased innate immune performance.

  18. Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus genome

    Directory of Open Access Journals (Sweden)

    McGuire Michael J

    2012-01-01

    Full Text Available Abstract Background The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. Results The genome of Parapoxvirus ovis (Orf virus was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer. Conclusion A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration

  19. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, Moniek S. E.; Schmand, Ben; Wekking, Ellie M.; Hageman, Gerard; Deelman, Betto G.

    2003-01-01

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  20. Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy

    NARCIS (Netherlands)

    van Hout, MSE; Schmand, B; Wekking, EM; Hageman, G; Deelman, BG

    Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure

  1. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Rebecca J Faleiro

    2016-02-01

    Full Text Available Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of

  2. Effect of psychological intervention in the form of relaxation and guided imagery on cellular immune function in normal healthy subjects. An overview

    DEFF Research Database (Denmark)

    Zachariae, R; Kristensen, J S; Hokland, P

    1991-01-01

    The present study measured the effects of relaxation and guided imagery on cellular immune function. During a period of 10 days 10 healthy subjects were given one 1-hour relaxation procedure and one combined relaxation and guided imagery procedure, instructing the subjects to imagine their immune...... on the immune defense and could form the basis of further studies on psychological intervention and immunological status. Udgivelsesdato: 1990-null...

  3. Cost of reproduction in a long-lived bird: incubation effort reduces immune function and future reproduction

    OpenAIRE

    Hanssen, S A; Hasselquist, Dennis; Folstad, I; Erikstad, K E

    2005-01-01

    Life-history theory predicts that increased current reproductive effort should lead to a fitness cost. This cost of reproduction may be observed as reduced survival or future reproduction, and may be caused by temporal suppression of immune function in stressed or hard-working individuals. In birds, consideration of the costs of incubating eggs has largely been neglected in favour of the costs of brood rearing. We manipulated incubation demand in two breeding seasons (2000 and 2001) in female...

  4. The effects of probiotics, prebiotics and synbiotics on gut flora, immune function and blood characteristics of broilers

    OpenAIRE

    Akoy, Rebin Aswad Mirza

    2015-01-01

    Abstract The microbial populations in the gastrointestinal tracts of poultry play an important role in normal digestive processes and in maintaining animal health. The purpose of this study was to evaluate the effects of probiotics, prebiotics and synbiotics on the growth parameters, gut ecosystem, histology and immune function. In this study, four experiments one in vitro and three in vivo were conducted using specific pathogen free (SPF) and Hubbard broiler chickens. The first exper...

  5. Relationship between ways of nutritional support and immune function in patients with malignant obstructive jaundice after PTCD

    OpenAIRE

    YANG Shenghua

    2014-01-01

    ObjectiveTo investigate the clinical effect of different nutritional therapies on the immune function of patients with malignant obstructive jaundice after percutaneous transhepatic cholangiodrainage (PTCD). MethodsA total of 50 patients with malignant obstructive jaundice who were admitted to our hospital from January 2009 to March 2013 were randomly divided into two groups according to the admission order. The patients in group A (n=25) received enteral nutritional support after PTCD, and t...

  6. Relationship between ways of nutritional support and immune function in patients with malignant obstructive jaundice after PTCD

    Directory of Open Access Journals (Sweden)

    YANG Shenghua

    2014-11-01

    Full Text Available ObjectiveTo investigate the clinical effect of different nutritional therapies on the immune function of patients with malignant obstructive jaundice after percutaneous transhepatic cholangiodrainage (PTCD. MethodsA total of 50 patients with malignant obstructive jaundice who were admitted to our hospital from January 2009 to March 2013 were randomly divided into two groups according to the admission order. The patients in group A (n=25 received enteral nutritional support after PTCD, and those in group B (n=25 received total parenteral nutritional support after PTCD. Intra-group and inter-group comparisons were made in terms of jaundice clearance, nutritional indices, and body’s immune function on preoperative day 1 and postoperative day 7; comparison between the two groups was made by t test. ResultsAmong the 50 patients who underwent PTCD, 39 (78% had good drainage, while 11 (22% did not reach the expectation, of which, 5 (10% were in group A and 6 (12% in group B. In both groups, the nutritional indices on postoperative day 7 were significantly higher than those on preoperative day 1(P<0.05, but no significant difference in these indices was observed between group A and group B on postoperative day 7 (P>0.05. The immune function of patients in both groups was significantly improved following PTCD and nutritional support (P<0.05, but there was no significant difference between the two groups (P>0.05. Although the same scheme of nutritional support was used, there were 11 patients who did not achieve the expected jaundice clearance after PTCD and had limited improvement in immune function compared with those who had complete jaundice clearance (all P<0.05. ConclusionJaundice clearance is closely related to PTCD in patients with malignant obstructive jaundice, but not markedly associated with the ways of nutritional support.

  7. Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion.

    Science.gov (United States)

    Chen, Yu; Deng, Xiaoling; Deng, Junfang; Zhou, Jiehua; Ren, Yuping; Liu, Shengxuan; Prusak, Deborah J; Wood, Thomas G; Bao, Xiaoyong

    2016-12-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion. We also found both motifs prevent TRAF5 and TRAF6, the MAVS downstream adaptors, to be recruited to MAVS, while the motif 39-KEALSDGI-46 also blocks TRAF3 migrating to MAVS. In parallel, these TRAFs are important in activating transcription factors NF-kB and/or IRF-3 by hMPV. Our findings collectively demonstrate that M2-2 uses its PDZ motifs to launch the hMPV immune evasion through blocking the interaction of MAVS and its downstream TRAFs. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response.

    Science.gov (United States)

    Roberts, Mark L; Buchanan, Katherine L; Evans, Matthew R; Marin, Raul H; Satterlee, Daniel G

    2009-10-01

    The immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birds' humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.

  9. Effect of the Algaecide Palmitoleic Acid on the Immune Function of the Bay Scallop Argopecten irradians

    Directory of Open Access Journals (Sweden)

    Cheng Chi

    2016-05-01

    Full Text Available Palmitoleic acid (PA, an algicidal compound, is used against the toxin producing dinofagelate Alexandrium tamarense, however, its impact on the edible bay scallop (Argopecten irradians is still unclear. Therefore, we investigated the impacts of effective algicidal concentrations (20, 40, and 80 mg/L of PA on immune responses in A. irradians. Various immune parameters including acid phosphatase (ACP activity, superoxide dismutase (SOD, lysozyme, phagocytic activity, total protein, malondialdehyde (MDA level, and reactive oxygen species (ROS production and the expression of immune-related genes (PrxV, CLT-6, MT, and BD were measured at 3, 6, 12, 24, and 48 h post-exposure (hpe to PA. Lysozyme activity was lower in scallops at 12–48 hpe to 80 mg/L. SOD, ACP activity, ROS production, the total protein, and MDA level was higher at 12 to 48 hpe with different concentrations of PA. Phagocytic activity increased at 6–12 hpe to 40–80 mg/L of PA, but decreased at 24–48 hpe. The expressions of genes PrxV, CLT-6, MT and BD down-regulated at 3 hpe were observed, while differential expressions from 6–48 hpe with different concentrations of PA. The present study demonstrated that immersing A. irradians in PA at effective concentrations could result in differential effects on non-specific immune responses and expressions of immune-related genes.

  10. Combined acupuncture and general anesthesia on immune and cognitive function in elderly patients following subtotal gastrectomy for gastric cancer.

    Science.gov (United States)

    Wang, Ningke; Ou, Yangwen; Qing, Wenxiang

    2018-01-01

    This study investigated the effects of acupuncture combined with general anesthesia on postoperative immune and cognitive functions in elderly patients undergoing subtotal gastrectomy. We recruited 96 elderly patients who received anesthesia for subtotal gastrectomy and randomly divided them into control (n=48) and experimental (n=48) groups. The control group received general anesthesia and the experimental group received combined acupuncture and general anesthesia. We measured hemodynamic immediately before and after anesthesia induction, and immune observations before and after surgery. We found no significant differences in mean heart rate (HR), mean oxygen saturation (SpO2), and partial pressure of end-tidal carbon dioxide (PETCO2) in the perioperative period between the two groups. Mean arterial pressure (MAP) was lower in the experimental group than that in the control group (P0.05), but the incidence of delayed recovery and postoperative agitation were significantly lower in the experimental group compared with those in the control group (P<0.05). One day after surgery, the experimental group showed better protection of cognitive function than the control group (P<0.05). Overall, combined acupuncture and general anesthesia in elderly gastric cancer patients receiving subtotal gastrectomy showed more stable hemodynamics and fewer stress responses during surgery. Thus, combined acupuncture and general anesthesia can shorten the recovery time from anesthesia, have less negative effects on immune function and decrease the incidence of postoperative cognitive impairment.

  11. Cost of reproduction in a long-lived bird: incubation effort reduces immune function and future reproduction.

    Science.gov (United States)

    Hanssen, Sveinn Are; Hasselquist, Dennis; Folstad, Ivar; Erikstad, Kjell Einar

    2005-05-22

    Life-history theory predicts that increased current reproductive effort should lead to a fitness cost. This cost of reproduction may be observed as reduced survival or future reproduction, and may be caused by temporal suppression of immune function in stressed or hard-working individuals. In birds, consideration of the costs of incubating eggs has largely been neglected in favour of the costs of brood rearing. We manipulated incubation demand in two breeding seasons (2000 and 2001) in female common eiders (Somateria mollissima) by creating clutches of three and six eggs (natural range 3-6 eggs). The common eider is a long-lived sea-duck where females do not eat during the incubation period. Mass loss increased and immune function (lymphocyte levels and specific antibody response to the non-pathogenic antigens diphtheria and tetanus toxoid) was reduced in females incubating large clutches. The increased incubation effort among females assigned to large incubation demand did not lead to adverse effects on current reproduction or return rate in the next breeding season. However, large incubation demand resulted in long-term fitness costs through reduced fecundity the year after manipulation. Our data show that in eiders, a long-lived species, the cost of high incubation demand is paid in the currency of reduced future fecundity, possibly mediated by reduced immune function.

  12. [Changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia].

    Science.gov (United States)

    Ma, Wei-Yin; Peng, Shao; Zhang, Ting

    2017-04-01

    To investigate the changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia. Blood samples were collected from 30 children with recurrent pneumonia (recurrent pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and 30 healthy children (control group). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. The correlation between serum YKL-40 level and laboratory indices related to humoral immune function was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40 level for recurrent pneumonia. The recurrent pneumonia group had a significantly higher serum YKL-40 level than the acute pneumonia and control groups (Ppneumonia group had a significantly higher serum YKL-40 level than the control group (Ppneumonia group were significantly lower than in the acute pneumonia group (Ppneumonia was 0.958 (95%CI: 0.921-0.994). Humoral immune function is low in children with recurrent pneumonia. Serum YKL-40 may be involved in the occurrence of recurrent pneumonia and can be used as a reference index for diagnosing recurrent pneumonia.

  13. Transient receptor potential vanilloid 1 expression and function in splenic dendritic cells: a potential role in immune homeostasis.

    Science.gov (United States)

    Assas, Bakri M; Wakid, Majed H; Zakai, Haytham A; Miyan, Jaleel A; Pennock, Joanne L

    2016-03-01

    Neuro-immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance, triggering calcium-channel transient receptor potential vanilloid 1 (TRPV1) on sensory nerves induces the release of calcitonin-gene-related peptide (CGRP), a neuropeptide known to moderate dendritic cell activation and T helper cell type 1 polarization. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well-documented 'neural' ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen-presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown down-regulation of activation markers CD80/86 on dendritic cells, and up-regulation of interleukin-6 and interleukin-10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis. © 2015 John Wiley & Sons Ltd.

  14. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  15. Structural and functional annotation of human FAM26F: A multifaceted protein having a critical role in the immune system.

    Science.gov (United States)

    Malik, Uzma; Javed, Aneela; Ali, Amjad; Asghar, Kashif

    2017-01-15

    Human immune system is a complex amalgam of a greatly diverse ensemble comprising of various cellular and non-cellular components, including proteins. FAM26F (family with sequence similarity 26, member F) is a relatively recently identified gene reported to play important role in diverse immune responses. Numerous studies have reported FAM26F to be differentially expressed in several viral, bacterial and parasitic infections, in certain pathophysiological conditions such as heart and liver transplantation, and in several cancers. FAM26F has also been found to be upregulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various anticipated pathways including TLR3, TLR4 IFN-β and Dectin-1. Moreover, the synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing the therapeutic potential of FAM26F for NK sensitive tumors. Although a considerable amount of evidence is present regarding the potential role of FAM26F in immune modulation, the exact function and modulatory pathways of this gene are yet to be elucidated. We aimed to completely characterize FAM26F in order to apprehend its function and role in the immune responses. The results revealed human FAM26F to be located at chromosomal position 6q22.1. FAM26F mRNA contains 1141bp coding region encoding a 315 amino acid long, stable protein that has been well-conserved throughout evolution. It is a signal peptide deprived transmembrane protein that is secreted through non-classical pathway. The presence of a single well-conserved Ca_hom_mod domain indicated FAM26F to be a cation channel involved in the transport of molecules. A potential N-glycosylation and 14 phosphorylation sites were also predicted, along with four interacting partners of FAM26F. The secondary and tertiary structures of FAM26F were determined. Moreover, the presence of an immunoglobulin-like fold in FAM26F

  16. Defining immune engagement thresholds for in vivo control of virus-driven lymphoproliferation.

    Directory of Open Access Journals (Sweden)

    Cristina Godinho-Silva

    2014-06-01

    Full Text Available Persistent infections are subject to constant surveillance by CD8+ cytotoxic T cells (CTL. Their control should therefore depend on MHC class I-restricted epitope presentation. Many epitopes are described for γ-herpesviruses and form a basis for prospective immunotherapies and vaccines. However the quantitative requirements of in vivo immune control for epitope presentation and recognition remain poorly defined. We used Murid Herpesvirus-4 (MuHV-4 to determine for a latently expressed viral epitope how MHC class-I binding and CTL functional avidity impact on host colonization. Tracking MuHV-4 recombinants that differed only in epitope presentation, we found little latitude for sub-optimal MHC class I binding before immune control failed. By contrast, control remained effective across a wide range of T cell functional avidities. Thus, we could define critical engagement thresholds for the in vivo immune control of virus-driven B cell proliferation.

  17. Asian and Siberian ginseng as a potential modulator of immune function: an in vitro cytokine study using mouse macrophages.

    Science.gov (United States)

    Wang, Huamin; Actor, Jeffrey K; Indrigo, Jessica; Olsen, Margaret; Dasgupta, Amitava

    2003-01-01

    Ginseng is a widely used herbal product in China, other Asian countries, and in the Unites States. There is a traditional belief that ginseng stimulates immune functions. In this study, the innate effects of Asian and Siberian ginsengs on cytokines and chemokines produced by cultured macrophages were examined. The effects of Asian and Siberian ginseng on cytokines and chemokines produced by cultured macrophages were examined. Mouse macrophages (J774A.1) were incubated with Asian or Siberian ginseng at varying concentrations (1, 10, 100, and 1000 microg/ml) for 24 h and then harvested for RNA isolation. The expression levels of IL-1beta, IL-12, TNF-alpha, MIP-1 alpha, and MIP-2 mRNA were measured by quantitative PCR. Our data showed that Asian ginseng induced a statistically significant increase in IL-12 expression at both mRNA and protein levels. However, the minor twofold increase is probably biologically insignificant. No significant increase of IL-12 by Siberian ginseng was observed at any dose level studied. No significant change in IL-1beta, IL-15, TNF-alpha, or MIP-1alpha mRNA was observed by either Asian or Siberian ginseng treatment. Our data showed statistically significant differential regulation of IL-12 by Asian ginseng. Siberian ginseng did not show a statistically significant increase. We conclude that both Asian ginseng and Siberian ginseng cannot significantly stimulate innate macrophage immune functions that influence cellular immune responses. Therefore, contrary to the popular belief, Asian and Siberian ginseng may not stimulate immune function.

  18. [Changes and the impact on immune function of opioid-dependent subjects by Jitai tabelets during the withdrawal stage].

    Science.gov (United States)

    Li, X X; Fan, H Y; Sun, L; Liang, J C; Deng, Y P

    2017-04-10

    Objective: To detect the changes in the immune function of opioid-dependent subjects during the withdrawal stage through the administration of Jitai tablet. Methods: Subjects were treated as Jitai tablet alone, Jitai tablet plus buprenorphine and placebo, in a randomized,double-blind, placebo-controlled trial. Before and after the 14(th) day of withdrawal, levels of immunoglobulin (IgM, IgA, IgG), T cell subsets (CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+)) and cytokines (IL-2, IFN-γ, IL-4, IFN-γ/IL-4) were detected. Results: Compared with healthy people, immunity function before withdrawal among the opioid abusers showed higher levels of IgM, IL-2, IFN-γ, IL-4 and lower level of CD(3)(+)T, as (1.67±0.87) g/L, (14.44±13.50) % , (20.23±15.10) % , (1.97±1.59) % , (47.01±13.62) % , respectively, with difference statistically significant ( P 0.05). At the 14(th) day of withdrawal in placebo group, levels of IL-4 returned to normal while IFN-γ/IL-4 ratio increased by 3.43 times ( P 0.05). Compared with placebo group, fluctuation of IgG and IgM decreased in Jitai group during withdrawal period, together with a normal level of IgM at the 14(th) day. Level of IL-4 abnormally rose up by 0.54 times in Jitai tablet plus buprenorphine group, while IFN-γ/IL-4 ratio been switched back at the 14(th) day of withdrawal. Other immune indicators were not affected by medical interventions. Conclusion: We noticed that certain impairment of the immune function might be restored by Jitai tablet during the withdrawal period.

  19. Systematic identification of anti-interferon function on hepatitis C virus genome reveals p7 as an immune evasion protein.

    Science.gov (United States)

    Qi, Hangfei; Chu, Virginia; Wu, Nicholas C; Chen, Zugen; Truong, Shawna; Brar, Gurpreet; Su, Sheng-Yao; Du, Yushen; Arumugaswami, Vaithilingaraja; Olson, C Anders; Chen, Shu-Hua; Lin, Chung-Yen; Wu, Ting-Ting; Sun, Ren

    2017-02-21

    Hepatitis C virus (HCV) encodes mechanisms to evade the multilayered antiviral actions of the host immune system. Great progress has been made in elucidating the strategies HCV employs to down-regulate interferon (IFN) production, impede IFN signaling transduction, and impair IFN-stimulated gene (ISG) expression. However, there is a limited understanding of the mechanisms governing how viral proteins counteract the antiviral functions of downstream IFN effectors due to the lack of an efficient approach to identify such interactions systematically. To study the mechanisms by which HCV antagonizes the IFN responses, we have developed a high-throughput profiling platform that enables mapping of HCV sequences critical for anti-IFN function at high resolution. Genome-wide profiling performed with a 15-nt insertion mutant library of HCV showed that mutations in the p7 region conferred high levels of IFN sensitivity, which could be alleviated by the expression of WT p7 protein. This finding suggests that p7 protein of HCV has an immune evasion function. By screening a liver-specific ISG library, we identified that IFI6-16 significantly inhibits the replication of p7 mutant viruses without affecting WT virus replication. In contrast, knockout of IFI6-16 reversed the IFN hypersensitivity of p7 mutant virus. In addition, p7 was found to be coimmunoprecipitated with IFI6-16 and to counteract the function of IFI6-16 by depolarizing the mitochondria potential. Our data suggest that p7 is a critical immune evasion protein that suppresses the antiviral IFN function by counteracting the function of IFI6-16.

  20. A Functional Food Mixture “Protector” Reinforces the Protective Immune Parameters against Viral Flu Infection in Mice

    Directory of Open Access Journals (Sweden)

    Kenza A. Mansoor

    2018-06-01

    Full Text Available Background: Viral influenza infection causes serious health issues especially when an outbreak occurs. Although influenza virus vaccines are available and each year manufactures modify the vaccine depending on the expected mutated strain, it is still far from satisfactory, mainly in young children and older adults. Therefore, a product that can support and shape the immune system to protect against viral flu infections is highly essential. Methods: A functional food water-soluble mixture of pomegranate, red grape, dates, olive fruit, figs, and ginger extracts, termed herein “Protector”, was prepared and tested in stimulating/modulating the production of specific cytokines, and hemagglutinin inhibition (HAI antibodies following viral flu vaccination in mice. Results: A single intraperitoneal or multiple oral administration for 1–7 days of “Protector” significantly increased the production of interferon (IFN-γ and interleukin (IL-12 in blood, spleen, and lungs of mice. When “Protector” was orally administered for one week following a single vaccine injection (primary immunization or for two weeks (one week apart following double vaccine injections (secondary immunization, mice significantly produced higher titers of HAI antibodies. This increase in HAI antibodies was associated with Pillow-inducing significant and different changes in vaccine-induced IFN-γ, IL-12, IL-6 and IL-22 following primary and secondary immunizations. Conclusions: “Protector” administration reinforces the protective immune parameters against viral flu infection. Therefore, after performing preclinical toxicology studies and ensuring its safety, “Protector” should be considered a potential product to be tested in clinical trials to conclude its efficacy in reducing the devastating effects of flu infection in humans and its outbreaks.

  1. Optimal inference with suboptimal models: Addiction and active Bayesian inference

    Science.gov (United States)

    Schwartenbeck, Philipp; FitzGerald, Thomas H.B.; Mathys, Christoph; Dolan, Ray; Wurst, Friedrich; Kronbichler, Martin; Friston, Karl

    2015-01-01

    When casting behaviour as active (Bayesian) inference, optimal inference is defined with respect to an agent’s beliefs – based on its generative model of the world. This contrasts with normative accounts of choice behaviour, in which optimal actions are considered in relation to the true structure of the environment – as opposed to the agent’s beliefs about worldly states (or the task). This distinction shifts an understanding of suboptimal or pathological behaviour away from aberrant inference as such, to understanding the prior beliefs of a subject that cause them to behave less ‘optimally’ than our prior beliefs suggest they should behave. Put simply, suboptimal or pathological behaviour does not speak against understanding behaviour in terms of (Bayes optimal) inference, but rather calls for a more refined understanding of the subject’s generative model upon which their (optimal) Bayesian inference is based. Here, we discuss this fundamental distinction and its implications for understanding optimality, bounded rationality and pathological (choice) behaviour. We illustrate our argument using addictive choice behaviour in a recently described ‘limited offer’ task. Our simulations of pathological choices and addictive behaviour also generate some clear hypotheses, which we hope to pursue in ongoing empirical work. PMID:25561321

  2. Robotic fish tracking method based on suboptimal interval Kalman filter

    Science.gov (United States)

    Tong, Xiaohong; Tang, Chao

    2017-11-01

    Autonomous Underwater Vehicle (AUV) research focused on tracking and positioning, precise guidance and return to dock and other fields. The robotic fish of AUV has become a hot application in intelligent education, civil and military etc. In nonlinear tracking analysis of robotic fish, which was found that the interval Kalman filter algorithm contains all possible filter results, but the range is wide, relatively conservative, and the interval data vector is uncertain before implementation. This paper proposes a ptimization algorithm of suboptimal interval Kalman filter. Suboptimal interval Kalman filter scheme used the interval inverse matrix with its worst inverse instead, is more approximate nonlinear state equation and measurement equation than the standard interval Kalman filter, increases the accuracy of the nominal dynamic system model, improves the speed and precision of tracking system. Monte-Carlo simulation results show that the optimal trajectory of sub optimal interval Kalman filter algorithm is better than that of the interval Kalman filter method and the standard method of the filter.

  3. Risk of suboptimal iodine intake in pregnant Norwegian women.

    Science.gov (United States)

    Brantsæter, Anne Lise; Abel, Marianne Hope; Haugen, Margaretha; Meltzer, Helle Margrete

    2013-02-06

    Pregnant women and infants are exceptionally vulnerable to iodine deficiency. The aims of the present study were to estimate iodine intake, to investigate sources of iodine, to identify predictors of low or suboptimal iodine intake (defined as intakes below 100 μg/day and 150 μg/day) in a large population of pregnant Norwegian women and to evaluate iodine status in a sub-population. Iodine intake was calculated based on a validated Food Frequency Questionnaire in the Norwegian Mother and Child Cohort. The median iodine intake was 141 μg/day from food and 166 μg/day from food and supplements. Use of iodine-containing supplements was reported by 31.6%. The main source of iodine from food was dairy products, contributing 67% and 43% in non-supplement and iodine-supplement users, respectively. Of 61,904 women, 16.1% had iodine intake below 100 μg/day, 42.0% had iodine intake below 150 μg/day and only 21.7% reached the WHO/UNICEF/ICCIDD recommendation of 250 μg/day. Dietary behaviors associated with increased risk of low and suboptimal iodine intake were: no use of iodine-containing supplements and low intake of milk/yogurt, seafood and eggs. The median urinary iodine concentration measured in 119 participants (69 μg/L) confirmed insufficient iodine intake. Public health strategies are needed to improve and secure the iodine status of pregnant women in Norway.

  4. Suboptimal Choice in Pigeons: Stimulus Value Predicts Choice over Frequencies.

    Directory of Open Access Journals (Sweden)

    Aaron P Smith

    Full Text Available Pigeons have shown suboptimal gambling-like behavior when preferring a stimulus that infrequently signals reliable reinforcement over alternatives that provide greater reinforcement overall. As a mechanism for this behavior, recent research proposed that the stimulus value of alternatives with more reliable signals for reinforcement will be preferred relatively independently of their frequencies. The present study tested this hypothesis using a simplified design of a Discriminative alternative that, 50% of the time, led to either a signal for 100% reinforcement or a blackout period indicative of 0% reinforcement against a Nondiscriminative alternative that always led to a signal that predicted 50% reinforcement. Pigeons showed a strong preference for the Discriminative alternative that remained despite reducing the frequency of the signal for reinforcement in subsequent phases to 25% and then 12.5%. In Experiment 2, using the original design of Experiment 1, the stimulus following choice of the Nondiscriminative alternative was increased to 75% and then to 100%. Results showed that preference for the Discriminative alternative decreased only when the signals for reinforcement for the two alternatives predicted the same probability of reinforcement. The ability of several models to predict this behavior are discussed, but the terminal link stimulus value offers the most parsimonious account of this suboptimal behavior.

  5. Investment in constitutive immune function by north American elk experimentally maintained at two different population densities

    Science.gov (United States)

    Cynthia J. Downs; Kelley M. Stewart; Brian L. Dick; Daniel E Crocker

    2015-01-01

    Natural selection favors individuals that respond with effective and appropriate immune responses to macro or microparasites. Animals living in populations close to ecological carrying capacity experience increased intraspecific competition, and as a result are often in poor nutritional condition. Nutritional condition, in turn, affects the amount of endogenous...

  6. STRESS AND DIFFERENTIAL ALTERATIONS IN IMMUNE-SYSTEM FUNCTIONS - CONCLUSIONS FROM SOCIAL STRESS STUDIES IN ANIMALS

    NARCIS (Netherlands)

    BOHUS, B; KOOLHAAS, JM; DERUITER, AJH; HEIJNEN, CJ

    1991-01-01

    Psychosocial factors are implicated in the development, in the course of, and in the recovery from disease. The immune system may be a mediator of the disease. Studies with animal models using social interactions in rodents suggest that short- and long-term social stress does not invariably suppress

  7. Parasitic infections and immune function : Effect of helminth infections in a malaria endemic area

    NARCIS (Netherlands)

    Boef, Anna G.C.; May, Linda; van Bodegom, David; van Lieshout, Lisette; Verweij, Jaco J.; Maier, Andrea B.; Westendorp, Rudi G.J.; Eriksson, Ulrika K.

    According to the hygiene hypothesis, reduced exposure to infections could explain the rise of atopic diseases in high-income countries. Helminths are hypothesised to alter the host's immune response in order to avoid elimination and, as a consequence, also reduce the host responsiveness to potential

  8. SOME ASPECTS OF IMMUNE SYSTEM FUNCTIONING IN HEALTHY DONORS SUBJECTED TO XENOGENOUS EXPOSURE

    Directory of Open Access Journals (Sweden)

    O. O. Obukhova

    2006-01-01

    Full Text Available Abstract. In present work, we studied some interrelations between tobacco smoking and the processes of immune system stimulation in healthy blood donors. In our opinion, this issue is especially important for the big industrial center, with rather strong antigenic exposure of the organism. The levels of circulating immune complexes (CIC were used as a marker index which reflects specific antigen-antibody interactions during inflammation. According to the results obtained, the majority of persons who have high CIC levels were tobacco smokers (53.76%. Moreover, the percentage of persons with high CIC content, like as the mean values of this index is increased proportionally to the duration of smoking. A mixture of tobacco smoke components seems to exert direct toxic effect upon various compartments of the immune system and causes local irritation of bronchial tree, thus producing local and systemic inflammatory reaction. It is, possibly, an additional factor which determines activation of immune system, with a background of adverse antropogenic exposures typical to industrial centers. The data obtained allow us to affirm a toxic action of tobacco smoke upon the organism of smokers, with development of inflammatory reactions that are displayed as increased CIC levels at preclinical stage.

  9. Altered neurological function in mice immunized with early endosome antigen 1

    Directory of Open Access Journals (Sweden)

    Fritzler Marvin J

    2004-01-01

    Full Text Available Abstract Background Autoantibodies directed against the 160 kDa endosome protein early endosome antigen 1 (EEA1 are seen in patients with neurological diseases. To determine if antibodies to EEA1 have a neuropathological effect, mice from three major histocompatability haplotype backgrounds (H2q, H2b and H2d were immunized with EEA1 (amino acids 82–1411 that was previously shown to contain the target EEA1 epitopes. The mice were then subjected to five neuro-behavioural tests: grid walking, forelimb strength, open field, reaching and rotarod. Results The immunized SWR/J mice with sustained anti-EEA1 antibodies had significantly reduced forelimb strength than the control non-immune mice of the same strain, and BALB/CJ immune mice demonstrated significantly more forelimb errors on the grid walk test than the control group. Conclusions Antibodies to recombinant EEA1 in mice may mediate neurological deficits that are consistent with clinical features of some humans that spontaneously develop anti-EEA1 autoantibodies.

  10. Effect of Paris saponin on antitumor and immune function in U14 ...

    African Journals Online (AJOL)

    bearing mice, and reduced the serum IL-4 level. The Paris saponin can inhibit U14 cell growth and prolong survival time of mice; it is speculated that the Paris saponin may express its anti-tumor activity by improving the body's immune system.

  11. Quality and Timing of Stressors Differentially Impact on Brain Plasticity and Neuroendocrine-Immune Function in Mice

    Directory of Open Access Journals (Sweden)

    Sara Capoccia

    2013-01-01

    Full Text Available A growing body of evidence suggests that psychological stress is a major risk factor for psychiatric disorders. The basic mechanisms are still under investigation but involve changes in neuroendocrine-immune interactions, ultimately affecting brain plasticity. In this study we characterized central and peripheral effects of different stressors, applied for different time lengths, in adult male C57BL/6J mice. We compared the effects of repeated (7 versus 21 days restraint stress (RS and chronic disruption of social hierarchy (SS on neuroendocrine (corticosterone and immune function (cytokines and splenic apoptosis and on a marker of brain plasticity (brain-derived neurotrophic factor, BDNF . Neuroendocrine activation did not differ between SS and control subjects; by contrast, the RS group showed a strong neuroendocrine response characterized by a specific time-dependent profile. Immune function and hippocampal BDNF levels were inversely related to hypothalamic-pituitary-adrenal axis activation. These data show a fine modulation of the crosstalk between central and peripheral pathways of adaptation and plasticity and suggest that the length of stress exposure is crucial to determine its final outcome on health or disease.

  12. Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

    Science.gov (United States)

    Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

    2015-07-01

    Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Tumor necrosis factor receptor associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system

    Science.gov (United States)

    Walsh, Matthew C.; Lee, JangEun; Choi, Yongwon

    2016-01-01

    Summary Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of IL-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor (IRF) pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system, but also for maintaining immune tolerance, and more recent works have begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. PMID:26085208

  14. Effects of preoperative and postoperative enteral nutrition on postoperative nutritional status and immune function of gastric cancer patients.

    Science.gov (United States)

    Ding, Dayong; Feng, Ye; Song, Bin; Gao, Shuohui; Zhao, Jisheng

    2015-03-01

    Effects of preoperative one week enteral nutrition (EN) support on the postoperative nutritional status, immune function and inflammatory response of gastric cancer patients were investigated. 106 cases of gastric cancer patients were randomly divided into preoperative one week EN group (trial group) and early postoperative EN group (control group), which were continuously treated with EN support until the postoperative 9th day according to different treatment protocols. All the patients were checked for their body weight, skinfold thickness, upper arm circumference, white blood cell count (WBC), albumin (ALB), prealbumin (PA), C-reactive protein (CRP), humoral immunity (IgA, IgG), T cell subsets (CD4, CD8 and CD4/CD8), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), etc. on the preoperative and the postoperative 1st and 10th day, respectively. PA and IgG levels of the experimental group were higher than those of the control group on the postoperative 10th day, whereas IL-6 level of the experimental group was lower than that of the control group. EN support for preoperative gastric cancer patients will improve the postoperative nutritional status and immune function, alleviate inflammatory response, and facilitate the recovery of patients.

  15. [Effect of Supportan on nutritional status and immune function of late-staged gastric cancer patients undergoing chemotherapy].

    Science.gov (United States)

    Zhong, Hai-jun; Ying, Jie-er; Ma, Sheng-lin

    2006-09-01

    To evaluate the effect of Supportan, an enteral nutrition (EN) specific for tumor patients, on the nutritional status and immune function of late-staged gastric cancer patients undergoing chemotherapy. Sixty-six late-staged gastric cancer patients undergoing chemotherapy were randomly divided into EN group (n=33) and control group (n=33). During chemotherapy, the patients in EN group received Supportan and the patients in the control group received basic diet. On the 14th day before chemotherapy and after chemotherapy, nutritional status and cell immune indicators were evaluated. As for nutrition indicators, there were no significant differences in EN group before and after chemotherapy (P > 0.05). Total protein, hemoglobin, prealbumin and transferrin significantly decreased after chemotherapy compared with those before chemotherapy in the control group (Pnutrition in EN group were superior to that in the control group, however, the differences were not statistically significant. The incidences of nausea, vomiting and marrow inhibition in Supportan group was lower compared with those in the control group, but with no significant difference. Supportan can prevent malnutrition of the late-staged gastric cancer patients undergoing chemotherapy, and improve immune function and alleviate adverse effects of chemotherapy.

  16. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression.

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica D; Sari, Duygu; Torres-Gomez, Alvaro; Li, Lequn; Strauss, Laura; Lafuente, Esther M; Boussiotis, Vassiliki A

    2017-08-22

    Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children

    Science.gov (United States)

    Seppanen, Elke; Tan, Dino; Corscadden, Karli J.; Currie, Andrew J.; Richmond, Peter C.; Thornton, Ruth B.

    2018-01-01

    Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen nontypeable Haemophilus influenzae (NTHi). NTHi was a potent stimulator of inflammatory cytokine secretion from PBMC within 4 hours, with no difference in cytokine levels produced between PBMC from cases or controls. In the absence of antigen stimulation, otitis-prone children had more circulating Natural Killer (NK) cells (potitis-prone and non-otitis-prone children (potitis-prone children are functional and respond to NTHi. CD8+ T cells and NK cells from both cases and controls produced IFNγ in response to polyclonal stimulus (Staphylococcal enterotoxin B; SEB), with more IFNγ+ CD8+ T cells present in cases than controls (pOtitis-prone children had more circulating IFNγ-producing NK cells (potitis-prone children mounted innate and T cell-mediated responses to NTHi challenge that were comparable to healthy children. These data provide evidence that otitis-prone children do not have impaired functional cell mediated immunity. PMID:29621281

  18. Effects of Delayed Enteral Nutrition on Inflammatory Responses and Immune Function Competence in Critically Ill Patients with Prolonged Fasting.

    Science.gov (United States)

    Xi, Fengchan; Li, Ning; Geng, Yanxia; Gao, Tao; Zhang, Juanjuan; Jun, Tanshan; Lin, Zhiliang; Li, Weiqin; Zhu, Weiming; Yu, Wenkui; Li, Jieshou

    2014-05-01

    Although different studies suggest that early enteral nutrition (EEN) has benefits in reducing infectious complications, there is no data that addresses whether delayed enteral nutrition (EN) is detrimental and if it may have effects on inflammatory responses and immune function. Forty-five critically ill patients with long fasting were randomly allocated in two groups according to the type of nutritional support. The first group included patients assuming a standard enteral nutrition (EN, n = 22) and the second group assuming a parenteral nutrition (PN, n = 23). The daily nutritional amount was 25 kcal (105 kJ)/kg for all patients. The inflammatory markers white blood cells (WBC), C-reactive protein (CRP), TNF-α, IL-1-β, IL-6, IL-4, IL- 10 and the immune T-lymphocyte sub-populations CD3+, CD4+, CD8+, and HLA-DR+ were evaluated at day 1, and after 2, 3 and 7 days. IL-4, IL-10, CD3+, CD4+, CD8+ and the CD4+/CD8+ ratio were not statistically different between the two groups. WBC and TNF-α in EN patients were higher than those in PN after 3 and 7 days (P fasting increased systemic inflammatory responses, whereas EN could modify immune function, therefore reducing hospital stay and costs.

  19. Mucosal immunity in HIV infection: what can be done to restore gastrointestinal-associated lymphoid tissue function?

    Science.gov (United States)

    George, Michael D; Asmuth, David M

    2014-06-01

    This review describes the impact of HIV infection on gut-associated lymphoid tissue, the mechanisms for persistent gut-associated lymphoid tissue dysfunction despite effective antiretroviral therapy, and potential strategies to restore gut-associated lymphoid tissue function and promote immune reconstitution. Recent studies indicate that unresolved microbial translocation and intestinal dysbiosis may continue to promote enteropathy as well as HIV-associated and non-HIV-associated conditions in many HIV patients who otherwise maintain therapeutic control of systemic viral replication. Several novel therapeutic approaches to reduce intestinal inflammation and mitigate microbial translocation may hold promise for restoring gastrointestinal health and thereby increasing the efficacy of immune reconstitution in HIV-infected patients undergoing antiretroviral therapy.

  20. Effect of spirulina food supplement on blood morphological parameters, biochemical composition and on the immune function of sportsmen

    Directory of Open Access Journals (Sweden)

    K Milasius

    2009-07-01

    Full Text Available Of highest biological value are natural concentrates of optimally combined substances produced by nature. One of food supplements of this kind is dietary Spirulina produced by the Tianshi firm (China. It is a most rationally balanced food supplement of a high biological value; it satisfies the needs of the whole body, including its immune system. The aim of the current work was to assess the effect of the multicomponent natural food supplement Spirulina on the physical development, blood morphological, biochemical picture and immune function of sportsmen. Materials and Methods: The study cohort comprised 12 high performance sportsmen (age 20-22 years. They were using tablets of Spirulina, a dietary product for 14 days. Physical development was determined with the aid of standard methods. The general blood picture was analyzed with the aid of a Micros-60 hematological analyzer (company ABX DIAGNOSTICS, France. Lymphocytes and their subsets were analysed by flow cytometery (FACSCalibur, Becton Dickinson Immunocytometry Systems (BDIS, USA and the absolute and percentage values were calculated. To evaluate immune function lymphocyte blasttransformation response to mitogens was studied. Results: Investigations carried out on endurance-training sportsmen showed that a 14-d administration of Spirulina exerted a positive effect on blood morphological composition indices and its biochemical changes. The results of our study confirm the positive effect of Spirulina food supplement on the quantitative parameters of immune system. Part of the study cohort after weeks showed a tendency of normalizing CD3 , CD3 CD4 lympocite count: positive changes were still present two weeks following the interruption of Spirulina intake

  1. Natural functional SNPs in miR-155 alter its expression level, blood cell counts and immune responses

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    Congcong Li

    2016-08-01

    Full Text Available miR-155 has been confirmed to be a key factor in immune responses in humans and other mammals. Therefore, investigation of variations in miR-155 could be useful for understanding the differences in immunity between individuals. In this study, four SNPs in miR-155 were identified in mice (Mus musculus and humans (Homo sapiens. In mice, the four SNPs were closely linked and formed two miR-155 haplotypes (A and B. Ten distinct types of blood parameters were associated with miR-155 expression under normal conditions. Additionally, 4 and 14 blood parameters were significantly different between these two genotypes under normal and lipopolysaccharide (LPS stimulation conditions, respectively. Moreover, the expression levels of miR-155, the inflammatory response to LPS stimulation and the lethal ratio following Salmonella typhimurium infection were significantly increased in mice harboring the AA genotype. Further, two SNPs, one in the loop region and the other near the 3' terminal of pre-miR-155, were confirmed to be responsible for the differential expression of miR-155 in mice. Interestingly, two additional SNPs, one in the loop region and the other in the middle of miR-155*, modulated the function of miR-155 in humans. Predictions of secondary RNA structure using RNAfold showed that these SNPs affected the structure of miR-155 in both mice and humans. Our results provide novel evidence of the natural functional SNPs of miR-155 in both mice and humans, which may affect the expression levels of mature miR-155 by modulating its secondary structure. The SNPs of human miR-155 may be considered as causal mutations for some immune-related diseases in the clinic. The two genotypes of mice could be used as natural models for studying the mechanisms of immune diseases caused by abnormal expression of miR-155 in humans.

  2. Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

    KAUST Repository

    Frei dit Frey, Nicolas

    2014-06-30

    Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways.

  3. Single-walled carbon nanotubes disturbed the immune and metabolic regulation function 13-weeks after a single intratracheal instillation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Hong, Young-Shick [Division of Food and Nutrition, Chonnam National University, Yongbong-Ro, Buk-Gu, Gwangju 500-757 (Korea, Republic of); Lee, Byoung-Seok [Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Jeong, Uiseok; Kim, Younghun [Department of Chemical Engineering, Kwangwoon University, Seoul 139-701 (Korea, Republic of)

    2016-07-15

    Due to their unique physicochemical properties, the potential health effects of single-walled carbon nanotubes (SWCNTs) have attracted continuous attention together with their extensive application. In this study, we aimed to identify local and systemic health effects following pulmonary persistence of SWCNTs. As expected, SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation (50, 100, and 200 μg/kg). In the lung, the total number of cells and the percentages of lymphocytes and neutrophils significantly increased at 200 μg/kg compared to the control, and the Th1-polarized immune response was induced accompanying enhanced expression of tissue damage-related genes and increased release of chemokines. Additionally, SWCNTs enhanced the expression of antigen presentation-related proteins on the surface of antigen-presenting cells, however, maturation of dendritic cells was inhibited by their persistence. As compared to the control, a significant increase in the percentage of neutrophils and a remarkable decrease of BUN and potassium level were observed in the blood of mice treated with the highest dose. This was accompanied by the down-regulation of the expression of antigen presentation-related proteins on splenocytes. Moreover, protein and glucose metabolism were disturbed with an up-regulation of fatty acid β-oxidation. Taken together, we conclude that SWCNTs may induce adverse health effects by disturbing immune and metabolic regulation functions in the body. Therefore, careful application of SWCNTs is necessary for the enforcement of safety in nano-industries. - Highlights: • We evaluated local and systemic health effects following persistence of SWCNTs. • SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation. • Th1-polarized immune response was induced in the lung. • The expression of antigen presentation-related proteins was altered. • Immune and metabolic regulation function were disturbed.

  4. Effects of methotrexate combined with hydroxychloroquine sulfate and prednisone acetate on inflammatory response, immune function and liver and renal function in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Jiang-Li Xia

    2017-11-01

    Full Text Available Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SLE. Methods: A total of 80 cases of SLE patients according to the random data table were divided into the control group (n=40 and observation group (n=40, the control group were treated with hydroxychloroquine sulfate and prednisone treatment, on the basis of treatment of the control group, patients in the observation group in the control group were treated with methotrexate, the levels of inflammatory factors, immune function, liver and kidney function indexes in the two groups between the before treatment and after treatment were compared. Results: Comparison of the levels before treatment, the difference of the CRP, WBC, ESR, IgA, IgG, complement C3, complement C4, ALT, AST, SCr and BUN levels were not statistically significant. After treatment, the levels of CRP, ESR, IgA, IgG, ALT, AST, SCr and BUN in the observation group were significantly lower than those in the control group, and the difference was statistically significant. The levels of WBC and complement C4 in the observation group [(5.18±1.08伊10 9 /L, (0.22±0.05 g/L] were significantly higher than those in the control group [(4.51±0.52伊10 9 /L, (0.18±0.03 g/L], and there was no significant difference in the level of complement C3 between the two groups after treatment. Conclusion: Methotrexate combined with hydroxychloroquine sulfate and prednisone for the treatment of SLE can effectively reduce inflammation, improve immune function, has little effect on kidney function, high safety, which has an important clinical value.

  5. Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.S. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Swart, R.L. de [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands); Timmerman, H.H.; Loveren, H. van [National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Osterhaus, A.D.M.E. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands)

    1995-12-31

    Complex mixtures of lipophilic contaminants have been shown to affect certain top predators in the aquatic food chain, including seals. A recent demonstration that harbor seals (Phoca vitulina) fed Baltic Sea herring displayed impaired natural killer cell activity and T-lymphocyte function represented the first demonstration of immunotoxicity induced by ambient levels of contaminants in the environment. While these animals had a lower ability to respond to immunizations with inactivated vaccines, specific antibody responses, and in vitro antigen-specific lymphoproliferative responses, obvious constraints limited the ability to extend these results with host resistance tests or an evaluation of thymus and other lymphoid organs. The authors therefore set up a parallel study by exposing pregnant laboratory rats to the same Baltic herring contaminant mixture as received the seals. They then examined immune function parameters and host resistance to virus infection. As in the seals, rat pups of the Baltic group had impaired T-lymphocyte function. In addition, thymus cells and/or their precursors appeared to be targeted, as their numbers and function were reduced in the rats. Following challenge with rat cytomegalovirus in a host resistance study, rat pups in the Baltic group had impaired natural killer cell responses to the virus infection, and lower specific CD8 + (cytotoxic T-lymphocyte) responses following in vitro stimulation. By extrapolation, these results suggest that the impaired immune responses observed in the Baltic group of seals may lead to a less effective defense against virus infections in marine mammals inhabiting polluted coastal waters. Toxicological profiles and results of both the captive seal and laboratory rat experiments tend to implicate the 2,3,7,8-TCDD-like PCB, dioxin and furan congeners in the immunosuppression, and point to a major role for the PCBs.

  6. IRAK-M regulation and function in host defense and immune homeostasis

    Directory of Open Access Journals (Sweden)

    Leah L.N. Hubbard

    2010-06-01

    Full Text Available Antigen presenting cells (APCs of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs. Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R superfamily. However, TLR/IL-1R induction of pro-inflammatory mediators must be regulated to prevent excessive inflammation and tissue damage. One molecule of recent interest that is known to inhibit TLR/IL-1R signaling is interleukin-1 receptor associated kinase (IRAK-M, also known as IRAK-3. IRAK-M is expressed in a number of immune and epithelial cells types, and through its inhibition of pro-inflammatory cytokine production, IRAK-M can regulate immune homeostasis and tolerance in a number of infectious and non-infectious diseases. Furthermore, use of IRAK-M deficient animals has increased our understanding of the importance of IRAK-M in regulating immune responsiveness to a variety of pathogens. Although IRAK-M expression is typically induced through TLR signaling, IRAK-M can also be expressed in response to various endogenous and exogenous soluble factors as well as cell surface and intracellular signaling molecules. This review will focus on clinical scenarios in which expression of IRAK-M is beneficial (as in early sepsis and those situations where IRAK-M expression is harmful to the host (as in cancer and following bone marrow transplant. There is strong rationale for therapeutic targeting of IRAK-M for clinical benefit. However, effective targeting will require a greater understanding of the transcriptional regulation of this gene.

  7. Perturbation of cellular immune functions in cigarette smokers and protection by palm oil vitamin E supplementation

    Directory of Open Access Journals (Sweden)

    Jubri Zakiah

    2013-01-01

    Full Text Available Abstract Background Cigarette smoke contains free radicals and an have adverse effect to the immune system. Supplementation of palm oil vitamin E (palmvitee, is known has antioxidant properties is thought to be beneficial for system immune protection against free radicals activity. The objective of the study was to determine the effect of palmvitee supplementation on immune response in smokers. Methods This study involved a group of smokers and nonsmokers who received 200 mg/day palmvitee and placebo for the control group. Blood samples were taken at 0, 12 and 24 weeks of supplementation. Plasma tocopherol and tocotrienol were determined by HPLC, lymphocyte proliferation by lymphocyte transformation test (LTT and enumeration of lymphocytes T and B cells by flow cytometry. Statistical analysis was performed by Mann–Whitney U-test for non-parametric data distribution and correlation among the variables was examined by Spearman. Results Plasma tocopherol and tocotrienol were increased in vitamin E supplemented group as compared to placebo group. Urine cotinine levels and serum α1-antitrypsin were significantly higher in smokers compared to nonsmokers. Lymphocyte proliferation induced by PHA showed an increasing trend with palmvitee supplementation in both smokers and nonsmokers. Natural killer cells were decreased; CD4+ cells and B cells were increased in smokers compared to nonsmokers but were unaffected with vitamin E supplementation except in the percentage of B cells which were increased in nonsmokers supplemented palmvitee compared to placebo. CD4+/CD8+ ratio was increased in smokers compared to nonsmokers. The high TWBC count observed in smokers correlated with the increased CD4+ and B cells. Conclusions Smoking caused alterations in certain immune parameters and palmvitee supplementation tended to cause an increase in lymphocytes transformation test but had no effect on CD3+, CD4+, CD8+, NK cells and B cells except B cells percentage

  8. Blood metal levels and metal-influenced immune functions of harbour seals in captivity

    Energy Technology Data Exchange (ETDEWEB)

    Kakuschke, Antje [GKSS Research Centre, Institute for Coastal Research, Max-Planck-Strasse 1, 21502 Geesthacht (Germany)], E-mail: antje.kakuschke@gkss.de; Valentine-Thon, Elizabeth [Department of Immunology, Laboratory Center Bremen, Friedrich-Karl-Strasse 22, 28205 Bremen (Germany); Griesel, Simone [GKSS Research Centre, Institute for Coastal Research, Max-Planck-Strasse 1, 21502 Geesthacht (Germany); Rosenberger, Tanja [Seal Centre Friedrichskoog e.V., 25718 Friedrichskoog (Germany); Mundry, Roger [Research and Technology Centre Westcoast (FTZ), University of Kiel, Hafentoern 1, 25761 Buesum (Germany); Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig (Germany); Siebert, Ursula [Research and Technology Centre Westcoast (FTZ), University of Kiel, Hafentoern 1, 25761 Buesum (Germany); Prange, Andreas [GKSS Research Centre, Institute for Coastal Research, Max-Planck-Strasse 1, 21502 Geesthacht (Germany)

    2008-04-15

    Immunological blood parameters and the effects of environmental pollutants on the immune system are important to assess the health status of seals. Animals living permanently in seal centres are useful for development and validation of diagnostic tools for free-ranging animals. In this study, parameters of cellular immunity as well as metal concentrations in blood and metal influence on cell proliferation of seven seals from a seal centre were investigated repeatedly using multi-element analysis and a lymphocyte proliferation assay. The metal concentrations, except for tin and chromium, were in general comparable to those of free-ranging animals of the North Sea. The unstimulated and mitogen-stimulated lymphocyte proliferation showed strong intra- and inter-individual variability, which reflected variability in activation of the immune status. Furthermore, both immunosuppressive and stimulative influences of metals on lymphocytes were found. Summarising, the methods used in this investigation provided useful information on these animals, and their application to free-ranging animals can be recommended.

  9. Blood metal levels and metal-influenced immune functions of harbour seals in captivity

    International Nuclear Information System (INIS)

    Kakuschke, Antje; Valentine-Thon, Elizabeth; Griesel, Simone; Rosenberger, Tanja; Mundry, Roger; Siebert, Ursula; Prange, Andreas

    2008-01-01

    Immunological blood parameters and the effects of environmental pollutants on the immune system are important to assess the health status of seals. Animals living permanently in seal centres are useful for development and validation of diagnostic tools for free-ranging animals. In this study, parameters of cellular immunity as well as metal concentrations in blood and metal influence on cell proliferation of seven seals from a seal centre were investigated repeatedly using multi-element analysis and a lymphocyte proliferation assay. The metal concentrations, except for tin and chromium, were in general comparable to those of free-ranging animals of the North Sea. The unstimulated and mitogen-stimulated lymphocyte proliferation showed strong intra- and inter-individual variability, which reflected variability in activation of the immune status. Furthermore, both immunosuppressive and stimulative influences of metals on lymphocytes were found. Summarising, the methods used in this investigation provided useful information on these animals, and their application to free-ranging animals can be recommended

  10. SAP: structure, function, and its roles in immune-related diseases.

    Science.gov (United States)

    Xi, Dan; Luo, TianTian; Xiong, Haowei; Liu, Jichen; Lu, Hao; Li, Menghao; Hou, Yuqing; Guo, Zhigang

    2015-01-01

    Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Real-time discrete suboptimal control for systems with input and state delays: Experimental tests on a dehydration process.

    Science.gov (United States)

    Rodríguez-Guerrero, Liliam; Santos-Sánchez, Omar-Jacobo; Cervantes-Escorcia, Nicolás; Romero, Hugo

    2017-11-01

    This article presents a suboptimal control strategy with finite horizon for affine nonlinear discrete systems with both state and input delays. The Dynamic Programming Approach is used to obtain the suboptimal control sequence, but in order to avoid the computation of the Bellman functional, a numerical approximation of this function is proposed in every step. The feasibility of our proposal is demonstrated via an experimental test on a dehydration process and the obtained results show a good performance and behavior of this process. Then in order to demonstrate the benefits of using this kind of control strategy, the results are compared with a non optimal control strategy, particularly with respect to results produced by an industrial Proportional Integral Derivative (PID) Honeywell controller, which is tuned using the Ziegler-Nichols method. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  12. Risk-Based Maintenance Assessment in the Manufacturing Industry: Minimisation of Suboptimal Prioritisation

    Directory of Open Access Journals (Sweden)

    Ratnayake R.M. Chandima

    2017-03-01

    Full Text Available Manufacturing firms continuously strive to increase the efficiency and effectiveness in the maintenance management processes. Focus is placed on eliminating the unexpected failures which cause unnecessary costs and the production losses. Risk-based maintenance (RBM strategies enable to address the above through the identification of probability and consequences of potential failures whilst providing a way for prioritisation of maintenance actions based on the risk of possible failures. Such prioritisations enable to identify the optimal maintenance strategy, intervals of maintenance tasks, and optimal level of spare parts inventory. However, the risk assessment activities are performed with the support of a risk matrix. Suboptimal classifications and/or prioritisations arise due to the inherent nature of the risk matrix. This is caused by the fact that there are no means to incorporate actual circumstances at the boundary of the input ranges or at the levels of linguistic data and risk categories. In this paper, a risk matrix is first developed in collaboration with one of the manufacturing firms in Poland. Then, it illustrates the use of fuzzy logic for minimisation of suboptimal prioritisation and/or classifications using a fuzzy inference system (FIS together with illustrative membership functions and a rule base. Finally, an illustrative risk assessment is also demonstrated to illustrate the methodology.

  13. Design Of Real-Time Implementable Distributed Suboptimal Control: An LQR Perspective

    KAUST Repository

    Jaleel, Hassan

    2017-09-29

    We propose a framework for multiagent systems in which the agents compute their control actions in real time, based on local information only. The novelty of the proposed framework is that the process of computing a suboptimal control action is divided into two phases: an offline phase and an online phase. In the offline phase, an approximate problem is formulated with a cost function that is close to the optimal cost in some sense and is distributed, i.e., the costs of non-neighboring nodes are not coupled. This phase is centralized and is completed before the deployment of the system. In the online phase, the approximate problem is solved in real time by implementing any efficient distributed optimization algorithm. To quantify the performance loss, we derive upper bounds for the maximum error between the optimal performance and the performance under the proposed framework. Finally, the proposed framework is applied to an example setup in which a team of mobile nodes is assigned the task of establishing a communication link between two base stations with minimum energy consumption. We show through simulations that the performance under the proposed framework is close to the optimal performance and the suboptimal policy can be efficiently implemented online.

  14. Semaphorin7A and its receptors: pleiotropic regulators of immune cell function, bone homeostasis, and neural development.

    Science.gov (United States)

    Jongbloets, Bart C; Ramakers, Geert M J; Pasterkamp, R Jeroen

    2013-03-01

    Semaphorins form a large, evolutionary conserved family of cellular guidance signals. The semaphorin family contains several secreted and transmembrane proteins, but only one GPI-anchored member, Semaphorin7A (Sema7A). Although originally identified in immune cells, as CDw108, Sema7A displays widespread expression outside the immune system. It is therefore not surprising that accumulating evidence supports roles for this protein in a wide variety of biological processes in different organ systems and in disease. Well-characterized biological effects of Sema7A include those during bone and immune cell regulation, neuron migration and neurite growth. These effects are mediated by two receptors, plexinC1 and integrins. However, most of what is known today about Sema7A signaling concerns Sema7A-integrin interactions. Here, we review our current knowledge of Sema7A function and signaling in different organ systems, highlighting commonalities between the cellular effects and signaling pathways activated by Sema7A in different cell types. Furthermore, we discuss a potential role for Sema7A in disease and provide directions for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Ultrastructural and functional characterization of circulating hemocytes from Galleria mellonella larva: Cell types and their role in the innate immunity.

    Science.gov (United States)

    Wu, Gongqing; Liu, Yi; Ding, Ying; Yi, Yunhong

    2016-08-01

    Galleria mellonella larvae have been widely used as a model to study the virulence of various human pathogens. Hemocytes play important roles in the innate immune response of G. mellonella. In this study, the hemocytes of G. mellonella larvae were analyzed by transmission electron microscope, light microscope, and cytochemistry. The cytological and morphological analyses revealed four types of hemocytes; Plasmatocytes, granular cells, spherule cells and oenocytoids. Differential hemocyte counts showed that under our conditions plasmatocytes and granular cells were the most abundant circulating cell types in the hemolymph. We also investigated the role of different types of hemocytes in the cellular and humoral immune defenses. The in-vivo experiment showed that plasmatocytes, granular cells and oenocytoids phagocytized FITC-labelled Escherichia coli bacteria in larvae of G. mellonella, whereas the granular cells exhibited the strongest phagocytic ability against these microbial cells. After incubation with L-DOPA, plasmatocytes, granular cells and oenocytoids are stained brown, indicating the presence of phenoloxidase activity. These results shed new light on our understanding of the immune function of G. mellonella hemocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Imbalance of intestinal immune function in piglets infected by porcine circovirus type 2 during the fetal period.

    Science.gov (United States)

    Mao, Yu; Li, Jin Jun; Liu, Yuan; Dong, Wei; Pang, Pei; Deng, Zhi Bang

    2017-03-01

    Porcine circovirus type 2- (PCV2-) associated reproductive disorders and enteritis have commonly been observed on PCV2-contaminated pig farms in recent years. In order to investigate disorders of intestinal immunity in piglets infected by PCV2 during the fetal period, 9 PCV2b-infected piglets and 6 non-infected piglets at one day of age were selected and euthanised prior to suckling. Samples of mesenteric lymph nodes (MLNs) and duodena were collected to investigate factors related to intestinal immunity and to detect lymphocytic apoptosis. The results indicated that there were no significant changes in the levels of IL-2, IL-10 and transforming growth factor-β (TGF-β) in the PCV2b-infected piglets but IFN-γ levels were significantly lower (P < 0.01) and IL-4 levels were significantly higher (P < 0.05) in infected piglets than in the controls. Furthermore, lymphocytic apoptosis increased in PCV2b-infected piglets and CD4+ to CD8+ ratios were lower in these piglets than in the controls. These findings suggest vertical transmission of PCV2b to fetuses, leading to an imbalance of intestinal immune function in piglets.

  17. Characterization of Ixodes ricinus Fibrinogen-Related Proteins (Ixoderins Discloses Their Function in the Tick Innate Immunity

    Directory of Open Access Journals (Sweden)

    Helena Honig Mondekova

    2017-12-01

    Full Text Available Ticks are important vectors of serious human and animal disease-causing organisms, but their innate immunity can fight invading pathogens and may have the ability to reduce or block transmission to mammalian hosts. Lectins, sugar-binding proteins, can distinguish between self and non-self-oligosaccharide motifs on pathogen surfaces. Although tick hemolymph possesses strong lectin activity, and several lectins have already been isolated and characterized, little is known about the implementation of these molecules in tick immunity. Here, we have described and functionally characterized fibrinogen-related protein (FReP lectins in Ixodes ticks. We have shown that the FReP family contains at least 27 genes (ixoderins, ixo that could, based on phylogenetic and expression analyses, be divided into three groups with differing degrees of expansion. By using RNA interference-mediated gene silencing (RNAi we demonstrated that IXO-A was the main lectin in tick hemolymph. Further, we found that ixoderins were important for phagocytosis of Gram-negative bacteria and yeasts by tick hemocytes and that their expression was upregulated upon injection of microbes, wounding, or after blood feeding. However, although the tick hemocytes could swiftly phagocytose Borrelia afzelii spirochetes, their transmission and burst of infection in mice was not altered. Our results demonstrate that tick ixoderins are crucial immune proteins that work as opsonins in the tick hemolymph, targeting microbes for phagocytosis or lysis.

  18. CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity.

    Science.gov (United States)

    Zaccard, Colleen R; Watkins, Simon C; Kalinski, Pawel; Fecek, Ronald J; Yates, Aarika L; Salter, Russell D; Ayyavoo, Velpandi; Rinaldo, Charles R; Mailliard, Robbie B

    2015-02-01

    The ability of dendritic cells (DC) to mediate CD4(+) T cell help for cellular immunity is guided by instructive signals received during DC maturation, as well as the resulting pattern of DC responsiveness to the Th signal, CD40L. Furthermore, the professional transfer of antigenic information from migratory DC to lymph node-residing DC is critical for the effective induction of cellular immune responses. In this study we report that, in addition to their enhanced IL-12p70 producing capacity, human DC matured in the presence of inflammatory mediators of type 1 immunity are uniquely programmed to form networks of tunneling nanotube-like structures in response to CD40L-expressing Th cells or rCD40L. This immunologic process of DC reticulation facilitates intercellular trafficking of endosome-associated vesicles and Ag, but also pathogens such HIV-1, and is regulated by the opposing roles of IFN-γ and IL-4. The initiation of DC reticulation represents a novel helper function of CD40L and a superior mechanism of intercellular communication possessed by type 1 polarized DC, as well as a target for exploitation by pathogens to enhance direct cell-to-cell spread. Copyright © 2015 by The American Association of Immunologists, Inc.

  19. The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease.

    Science.gov (United States)

    Iijima, Hideki; Shinzaki, Shinichiro; Takehara, Tetsuo

    2012-11-01

    This review summarizes the recent literature about the roles of vitamins D and K in bone metabolism and immunity-mediated inflammatory processes in inflammatory bowel diseases (IBDs). The levels of vitamins D and K are lower than normal in patients with IBD, especially in Crohn's disease. Although vitamins D and K are important for the maintenance of bone mineral density in non-IBD patients, an association between vitamins D or K and bone metabolism is not apparent in IBD patients. Recent studies showed that vitamins D and K are suggested to have immune-suppressive effects, both in animal models of colitis and human trials. In particular, vitamin D suppresses dendritic and T-cell functions by inhibiting the production of proinflammatory cytokines. Insufficiency of vitamin D is associated with the activated phenotype of IBD. Vitamins D and K potentially contribute to the maintenance of bone health in IBD, but this effect may be diminished by other factors such as steroid use, reduced exposure to sunlight, and inflammatory cytokines. Vitamin D and possibly vitamin K are suggested to be involved in the suppression of immune-mediated inflammation and modulation of disease activity.

  20. Perfluoroalkyl and Polyfluoroalkyl Substances and Indicators of Immune Function in Children Aged 12 – 19 years: NHANES

    Science.gov (United States)

    Stein, Cheryl R.; McGovern, Kathleen J.; Pajak, Ashley M.; Maglione, Paul J.; Wolff, Mary S.

    2016-01-01

    Background Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are immunotoxic in laboratory studies. Humans studies of immune effects are inconsistent. Using the U.S. National Health and Nutrition Examination Survey (NHANES) we examined PFAS serum concentration and indicators of prevalent immune function among 12 to 19 year old children. Methods In this cross-sectional study we examined PFAS serum concentration in relation to measles, mumps, and rubella antibody concentrations in NHANES 1999 – 2000 and 2003 – 2004 (n=1,191) and to allergic conditions and allergic sensitization in NHANES 2005 – 2006 (n=640). Results In adjusted, survey-weighted models, a doubling of perfluorooctane sulfonate (PFOS) concentration among seropositive children was associated with a 13.3% (95% CI −19.9, −6.2) decrease in rubella antibody concentration and a 5.9% decrease in mumps antibody concentration (95% CI −9.9, −1.6). We observed no adverse association between exposure and current allergic conditions, including asthma. Children with higher PFOS concentration were less likely to be sensitized to any allergen (OR 0.74, 95% CI 0.58, 0.95). Conclusion Increased exposure to several PFAS was associated with lower levels to mumps and rubella antibody concentrations, especially among seropositive individuals. These lower antibody concentrations may indicate a less robust response to vaccination or greater waning of vaccine-derived immunity over time. PMID:26492286

  1. Identification, structure, and function of a novel type VI secretion peptidoglycan glycoside hydrolase effector-immunity pair.

    Science.gov (United States)

    Whitney, John C; Chou, Seemay; Russell, Alistair B; Biboy, Jacob; Gardiner, Taylor E; Ferrin, Michael A; Brittnacher, Mitchell; Vollmer, Waldemar; Mougous, Joseph D

    2013-09-13

    Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs among Gram-negative bacteria, the number of experimentally validated substrate effector proteins mediating these interactions remains small. Here, employing an informatics approach, we define novel families of T6S peptidoglycan glycoside hydrolase effectors. Consistent with the known intercellular self-intoxication exhibited by the T6S pathway, we observe that each effector gene is located adjacent to a hypothetical open reading frame encoding a putative periplasmically localized immunity determinant. To validate our sequence-based approach, we functionally investigate a representative family member from the soil-dwelling bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in a T6SS-dependent manner and that it confers a fitness advantage in growth competition assays with Pseudomonas putida. In addition, we determined the 1.4 Å x-ray crystal structure of this effector in complex with its cognate immunity protein. The structure reveals the effector shares highest overall structural similarity to a glycoside hydrolase family associated with peptidoglycan N-acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside hydrolase effector families may comprise significant enzymatic diversity. Our structural analyses also demonstrate that self-intoxication is prevented by the immunity protein through direct occlusion of the effector active site. This work significantly expands our current understanding of T6S effector diversity.

  2. Identification, Structure, and Function of a Novel Type VI Secretion Peptidoglycan Glycoside Hydrolase Effector-Immunity Pair*

    Science.gov (United States)

    Whitney, John C.; Chou, Seemay; Russell, Alistair B.; Biboy, Jacob; Gardiner, Taylor E.; Ferrin, Michael A.; Brittnacher, Mitchell; Vollmer, Waldemar; Mougous, Joseph D.

    2013-01-01

    Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs among Gram-negative bacteria, the number of experimentally validated substrate effector proteins mediating these interactions remains small. Here, employing an informatics approach, we define novel families of T6S peptidoglycan glycoside hydrolase effectors. Consistent with the known intercellular self-intoxication exhibited by the T6S pathway, we observe that each effector gene is located adjacent to a hypothetical open reading frame encoding a putative periplasmically localized immunity determinant. To validate our sequence-based approach, we functionally investigate a representative family member from the soil-dwelling bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in a T6SS-dependent manner and that it confers a fitness advantage in growth competition assays with Pseudomonas putida. In addition, we determined the 1.4 Å x-ray crystal structure of this effector in complex with its cognate immunity protein. The structure reveals the effector shares highest overall structural similarity to a glycoside hydrolase family associated with peptidoglycan N-acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside hydrolase effector families may comprise significant enzymatic diversity. Our structural analyses also demonstrate that self-intoxication is prevented by the immunity protein through direct occlusion of the effector active site. This work significantly expands our current understanding of T6S effector diversity. PMID:23878199

  3. Suboptimal Criterion Learning in Static and Dynamic Environments.

    Directory of Open Access Journals (Sweden)

    Elyse H Norton

    2017-01-01

    Full Text Available Humans often make decisions based on uncertain sensory information. Signal detection theory (SDT describes detection and discrimination decisions as a comparison of stimulus "strength" to a fixed decision criterion. However, recent research suggests that current responses depend on the recent history of stimuli and previous responses, suggesting that the decision criterion is updated trial-by-trial. The mechanisms underpinning criterion setting remain unknown. Here, we examine how observers learn to set a decision criterion in an orientation-discrimination task under both static and dynamic conditions. To investigate mechanisms underlying trial-by-trial criterion placement, we introduce a novel task in which participants explicitly set the criterion, and compare it to a more traditional discrimination task, allowing us to model this explicit indication of criterion dynamics. In each task, stimuli were ellipses with principal orientations drawn from two categories: Gaussian distributions with different means and equal variance. In the covert-criterion task, observers categorized a displayed ellipse. In the overt-criterion task, observers adjusted the orientation of a line that served as the discrimination criterion for a subsequently presented ellipse. We compared performance to the ideal Bayesian learner and several suboptimal models that varied in both computational and memory demands. Under static and dynamic conditions, we found that, in both tasks, observers used suboptimal learning rules. In most conditions, a model in which the recent history of past samples determines a belief about category means fit the data best for most observers and on average. Our results reveal dynamic adjustment of discrimination criterion, even after prolonged training, and indicate how decision criteria are updated over time.

  4. Reoperation for suboptimal outcomes after deep brain stimulation surgery.

    Science.gov (United States)

    Ellis, Tina-Marie; Foote, Kelly D; Fernandez, Hubert H; Sudhyadhom, Atchar; Rodriguez, Ramon L; Zeilman, Pamela; Jacobson, Charles E; Okun, Michael S

    2008-10-01

    To examine a case series of reoperations for deep brain stimulation (DBS) leads in which clinical scenarios revealed suboptimal outcome from a previous operation. Suboptimally placed DBS leads are one potential reason for unsatisfactory results after surgery for Parkinson's disease (PD), essential tremor (ET), or dystonia. In a previous study of patients who experienced suboptimal results, 19 of 41 patients had misplaced leads. Similarly, another report commented that lead placement beyond a 2- to 3-mm window resulted in inadequate clinical benefit, and, in 1 patient, revision improved outcome. The goal of the current study was to perform an unblinded retrospective chart review of DBS patients with unsatisfactory outcomes who presented for reoperation. Patients who had DBS lead replacements after reoperation were assessed with the use of a retrospective review of an institutional review board-approved movement disorders database. Cases of reoperation for suboptimal clinical benefit were included, and cases of replacement of DBS leads caused by infection or hardware malfunction were excluded. Data points studied included age, disease duration, diagnosis, motor outcomes (the Unified Parkinson Disease Rating Scale III in PD, the Tremor Rating Scale in ET, and the Unified Dystonia Rating Scale in dystonia), quality of life (Parkinson's Disease Questionnaire-39 in PD), and the Clinician Global Impression scale. The data from before and after reoperation were examined to determine the estimated impact of repeat surgery. There were 11 patients with PD, 7 with ET, and 4 with dystonia. The average age of the PD group was 52 years, the disease duration was 10 years, and the average vector distance of the location of the active DBS contact was adjusted 5.5 mm. Six patients (54%) with PD had preoperative off medication on DBS Unified Parkinson Disease Rating Scale scores that could be compared with postoperative off medication on DBS scores. The average improvement across this

  5. Work-Recreation Balance, Health-Promoting Lifestyles and Suboptimal Health Status in Southern China: A Cross-Sectional Study

    OpenAIRE

    Wu, Shengwei; Xuan, Zhengzheng; Li, Fei; Xiao, Wei; Fu, Xiuqiong; Jiang, Pingping; Chen, Jieyu; Xiang, Lei; Liu, Yanyan; Nie, Xiaoli; Luo, Ren; Sun, Xiaomin; Kwan, Hiuyee; Zhao, Xiaoshan

    2016-01-01

    Suboptimal health status (SHS)—an intermediate state between health and illness—refers to functional somatic symptoms that are medically undiagnosed. Although SHS has become a great challenge for global public health, very little about its etiology and mechanisms are known. Work-recreation balance is a part of work−life balance, and is related to stress which greatly influences health status. We therefore carried out a cross-sectional investigation between 2012 and 2013 within a clustered sam...

  6. BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: Impact of mineral and vitamin status on beef cattle immune function and health.

    Science.gov (United States)

    Kegley, E B; Ball, J J; Beck, P A

    2016-12-01

    The importance of optimal mineral and vitamin nutrition on improving immune function and health has been recognized in the preceding decades. In the southeast, beef cattle are raised predominantly on forages that may be limiting in nutrients for optimal health, especially trace minerals such as Cu, Zn, and Se. Clinical deficiencies of these nutrients produce classic symptoms that are common to several nutrient deficiencies (e.g., slow growth and unthrifty appearance); however, subclinical deficiencies are more widespread and more difficult to detect, yet may result in broader economic losses. Dietary mineral concentrations often considered adequate for maximum growth, reproductive performance, or optimal immune function have been found to be insufficient at times of physiological stress (weaning, transport, comingling, etc.), when feed intake is reduced. The impacts of these deficiencies on beef cattle health are not apparent until calves have been subjected to these stressors. Health problems that are exacerbated by mineral or vitamin deficiencies include bovine respiratory disease, footrot, retained placenta, metritis, and mastitis. Many micronutrients have antioxidant properties through being components of enzymes and proteins that benefit animal health. In dairy cattle, high levels of supplemental Zn are generally associated with reduced somatic cell counts and improved foot health, possibly reflecting the importance of Zn in maintaining effective epithelial barriers. Neutrophils isolated from ruminants deficient in Cu or Se have reduced ability to kill ingested bacteria in vitro. Supplemental vitamin E, in its role as an intracellular antioxidant has been shown to decrease morbidity in stressed calves. There is more understanding of the important biological role that these nutrients play in the functioning of the complex and multifaceted immune system. However, there is still much to be learned about determining the micronutrient status of herds (and hence

  7. Effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Yi-Qun He; Fa-Qun He; Shao-Long Wang

    2017-01-01

    Objective:To study the effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy.Methods:Patients with advanced cervical cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between May 2014 and June 2016 were selected, HAMA scores and HAMD scores were used to assess anxiety and depression and divide the patients into control group, depression group, anxiety group and depression + anxiety group. The contents of monoamine neurotransmitters and immune cytokines in serum as well as the expression of immune transcription factors in peripheral blood mononuclear cells were detected.Results:Serum NE, E, 5-HT, 5-HIAA and DOPAC contents of depression group and depression + anxiety group were significantly lower than those of control group, and serum NE, E, 5-HT, 5-HIAA and DOPAC contents of anxiety group were significantly higher than those of control group; peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression group, anxiety group and depression + anxiety group were significantly lower than those of control group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of control group; peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression + anxiety group were significantly lower than those of depression group and anxiety group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of depression group and anxiety group. Conclusion: Anxiety and depression in patients with cervical cancer chemotherapy can affect the secretion of monoamine neurotransmitters, the differentiation of CD4+T cell subsets and the antitumor immune response mediated by them.

  8. Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host Immune Function and Reduces Nosema ceranae Infections

    Science.gov (United States)

    Li, Wenfeng; Evans, Jay D.; Huang, Qiang; Rodríguez-García, Cristina; Liu, Jie; Hamilton, Michele; Grozinger, Christina M.; Webster, Thomas C.; Su, Songkun

    2016-01-01

    ABSTRACT Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd), which is a negative regulator of host immune function. Our studies found that nkd mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown of nkd transcripts in Nosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host nkd gene can activate honey bee immune responses, suppress the reproduction of N. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration. IMPORTANCE Given the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors

  9. Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host Immune Function and Reduces Nosema ceranae Infections.

    Science.gov (United States)

    Li, Wenfeng; Evans, Jay D; Huang, Qiang; Rodríguez-García, Cristina; Liu, Jie; Hamilton, Michele; Grozinger, Christina M; Webster, Thomas C; Su, Songkun; Chen, Yan Ping

    2016-11-15

    Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd), which is a negative regulator of host immune function. Our studies found that nkd mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown of nkd transcripts in Nosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host nkd gene can activate honey bee immune responses, suppress the reproduction of N. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration. Given the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors. Here, we demonstrate

  10. ImprimatinC1, a novel plant immune-priming compound, functions as a partial agonist of salicylic acid.

    Science.gov (United States)

    Noutoshi, Yoshiteru; Jikumaru, Yusuke; Kamiya, Yuji; Shirasu, Ken

    2012-01-01

    Plant activators are agrochemicals that protect crops from pathogens. They confer durable resistance to a broad range of diseases by activating intrinsic immune mechanisms in plants. To obtain leads regarding useful compounds, we have screened a chemical library using an established method that allows selective identification of immune-priming compounds. Here, we report the characterisation of one of the isolated chemicals, imprimatinC1, and its structural derivative imprimatinC2. ImprimatinC1 functions as a weak analogue of salicylic acid (SA) and activates the expression of defence-related genes. However, it lacks antagonistic activity toward jasmonic acid. Structure-activity relationship analysis suggests that imprimatinC1 and C2 can be metabolised to 4-chlorobenzoic acid and 3,4-chlorobenzoic acid, respectively, to function in Arabidopsis. We also found that imprimatinC1 and C2 and their potential functional metabolites acted as partial agonists of SA. Thus, imprimatinC compounds could be useful tools for dissecting SA-dependent signal transduction pathways.

  11. Sexual selection by female immunity against paternal antigens can fix loss of function alleles

    OpenAIRE

    Ghaderi, Darius; Springer, Stevan A.; Ma, Fang; Cohen, Miriam; Secrest, Patrick; Taylor, Rachel E.; Varki, Ajit; Gagneux, Pascal

    2011-01-01

    Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(−/−) mutation and immunized to express anti-Neu5G...

  12. Sick and tired: how molecular regulators of human sleep schedules and duration impact immune function.

    Science.gov (United States)

    Kurien, Philip A; Chong, S Y Christin; Ptáček, Louis J; Fu, Ying-Hui

    2013-10-01

    Why do we need to sleep? What regulates when we sleep? And what dictates the number of hours we require? These are often viewed as three separate biological questions. Here, we propose they share molecular etiologies, whereby regulators of sleep schedules and sleep duration also govern the physiological purposes of sleep. To support our hypothesis, we review Mendelian human genetic variants sufficient to advance sleep-wake onset (PER2) and shorten sleep length (DEC2), and evaluate their emerging roles in immune responses that may rely on a sound night of slumber. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Cancer Stem Cell-Secreted Macrophage Migration Inhibitory Factor Stimulates Myeloid Derived Suppressor Cell Function and Facilitates Glioblastoma Immune Evasion

    DEFF Research Database (Denmark)

    Otvos, Balint; Silver, Daniel J; Mulkearns-Hubert, Erin E

    2016-01-01

    Shifting the balance away from tumor-mediated immune suppression toward tumor immune rejection is the conceptual foundation for a variety of immunotherapy efforts currently being tested. These efforts largely focus on activating antitumor immune responses but are confounded by multiple immune cel...

  14. Emerging functions of natural IgM and its Fc receptor FCMR in immune homeostasis

    Directory of Open Access Journals (Sweden)

    Hongsheng eWang

    2016-03-01

    Full Text Available Most natural IgM antibodies are encoded by germline Ig sequences and are produced in large quantities by both mice and humans in the absence of intentional immunization. Natural IgM are reactive with many conserved epitopes, including those shared by microorganisms and autoantigens. As a result, these antibodies play important roles in clearing intruding pathogens, as well as apoptotic/necrotic cells and otherwise damaged tissues. While natural IgM binds to target structures with low affinity due to a lack of significant selection by somatic hypermutation, its pentameric structure with 10 antigen binding sites enables these antibodies to bind multivalent target antigens with high avidity. Opsonization of antigen complexed with IgM is mediated by cell surface Fc receptors. While the existence of Fc alpha/mu receptor has been known for some time, only recently has the Fc receptor specific for IgM (FCMR been identified. In this review, we focus on our current understandings of how natural IgM and FCMR regulate the immune system and maintain homeostasis under physiological and pathological conditions.

  15. The impact of psychological stress on immune function in the athletic population.

    Science.gov (United States)

    Clow, A; Hucklebridge, F

    2001-01-01

    In many ways, the physiological and immune consequences of acute bursts of physical exercise parallel the effect of an acute psychological stressor. Similarly, the net effects of endurance training resemble chronic psychological stress, whereas the physiological milieu associated with overtraining resembles that of melancholic depression. We suggest that the prolonged psychological stress often associated with athletic training and competition may make athletes more vulnerable to the negative health effects of training. Furthermore, a relationship between anxiety and life events on susceptibility to injury is well documented. Individual differences in self-confidence and self-esteem are also known to relate to the occurrence of injury as well as recovery from injury. We suggest that these two observations may be linked. It is the purpose of this paper to review the most recent evidence that psychological stress does impact upon the balance of the immune system in such a way as to be relevant to health outcomes and that the athletic population, in particular those with low self-esteem, may be especially vulnerable due to the probable synergistic effects of both physical and psychological stress.

  16. In Vitro Evaluation of Colloidal Silver on Immune Function: Anti lymphoproliferative Activity

    International Nuclear Information System (INIS)

    Franco-Molina, M. A.; Mendoza-Gamboa, E.; Zarate-Trivino, D. G.; Coronado-Cerda, E.E.; Alcocer-Gonzalez, J. M.; Resendez-Perez, D.; Rodriguez-Salazar, M.C.; Rivera-Morales, L.G.; Tamez-Guerra, R.; Rodriguez-Padilla, C.

    2016-01-01

    Colloidal silver (AgC) is currently used by humans and it can be internalized through inhalation, injection, ingestion, and dermal contact. However, there is limited information about immunological activity; more investigations using colloidal silver are needed. In the present study, the effects of AgC (17.5 ng/m L) on immunological parameters (proliferation and immuno phenotyping) using human peripheral blood mononuclear cells (PBMC) and macrophages (phagocytosis) and cytotoxicity on leukemia and lymphoma cancer cell lines (1.75 to 17.5 ng/m L) were investigated. AgC was observed to significantly ρ) decrease interleukin-2 (I L-2) production and proliferation induced by phytohemagglutinin or concanavalin A in PBMC without affecting its cell viability but with cytotoxic effect on cancer cells. IL-2, IL-4, IL-6, IL-10, INF-γ, and IL_-17 A cytokines production and CD3"+, CD3"-CD19"+, CD3"+CD4"+, CD3"+CD8"+, and CD16"+CD56"+ PBMC phenotypes were not affected by AgC. The present study demonstrates that colloidal silver is harmless and nontoxic to the immune system cells and its ability to interfere with the immune response by decreasing cell proliferation when stimulated with mitogens demonstrated the anti lymphoproliferative potential of AgC

  17. Daidzein enhances immune function in late lactation cows under heat stress.

    Science.gov (United States)

    Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting

    2014-01-01

    Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.

  18. In Vitro Evaluation of Colloidal Silver on Immune Function: Antilymphoproliferative Activity

    Directory of Open Access Journals (Sweden)

    M. A. Franco-Molina

    2016-01-01

    Full Text Available Colloidal silver (AgC is currently used by humans and it can be internalized through inhalation, injection, ingestion, and dermal contact. However, there is limited information about immunological activity; more investigations using colloidal silver are needed. In the present study, the effects of AgC (17.5 ng/mL on immunological parameters (proliferation and immunophenotyping using human peripheral blood mononuclear cells (PBMC and macrophages (phagocytosis and cytotoxicity on leukemia and lymphoma cancer cell lines (1.75 to 17.5 ng/mL were investigated. AgC was observed to significantly (p<0.05 decrease interleukin-2 (IL-2 production and proliferation induced by phytohemagglutinin or concanavalin A in PBMC without affecting its cell viability but with cytotoxic effect on cancer cells. IL-2, IL-4, IL-6, IL-10, INF-γ, and IL-17A cytokines production and CD3+, CD3−CD19+, CD3+CD4+, CD3+CD8+, and CD16+CD56+ PBMC phenotypes were not affected by AgC. The present study demonstrates that colloidal silver is harmless and nontoxic to the immune system cells and its ability to interfere with the immune response by decreasing cell proliferation when stimulated with mitogens demonstrated the antilymphoproliferative potential of AgC.

  19. Estimating Herd Immunity to Amphibian Chytridiomycosis in Madagascar Based on the Defensive Function of Amphibian Skin Bacteria

    Directory of Open Access Journals (Sweden)

    Molly C. Bletz

    2017-09-01

    Full Text Available For decades, Amphibians have been globally threatened by the still expanding infectious disease, chytridiomycosis. Madagascar is an amphibian biodiversity hotspot where Batrachochytrium dendrobatidis (Bd has only recently been detected. While no Bd-associated population declines have been reported, the risk of declines is high when invasive virulent lineages become involved. Cutaneous bacteria contribute to host innate immunity by providing defense against pathogens for numerous animals, including amphibians. Little is known, however, about the cutaneous bacterial residents of Malagasy amphibians and the functional capacity they have against Bd. We cultured 3179 skin bacterial isolates from over 90 frog species across Madagascar, identified them via Sanger sequencing of approximately 700 bp of the 16S rRNA gene, and characterized their functional capacity against Bd. A subset of isolates was also tested against multiple Bd genotypes. In addition, we applied the concept of herd immunity to estimate Bd-associated risk for amphibian communities across Madagascar based on bacterial antifungal activity. We found that multiple bacterial isolates (39% of all isolates cultured from the skin of Malagasy frogs were able to inhibit Bd. Mean inhibition was weakly correlated with bacterial phylogeny, and certain taxonomic groups appear to have a high proportion of inhibitory isolates, such as the Enterobacteriaceae, Pseudomonadaceae, and Xanthamonadaceae (84, 80, and 75% respectively. Functional capacity of bacteria against Bd varied among Bd genotypes; however, there were some bacteria that showed broad spectrum inhibition against all tested Bd genotypes, suggesting that these bacteria would be good candidates for probiotic therapies. We estimated Bd-associated risk for sampled amphibian communities based on the concept of herd immunity. Multiple amphibian communities, including those in the amphibian diversity hotspots, Andasibe and Ranomafana, were

  20. Estimating Herd Immunity to Amphibian Chytridiomycosis in Madagascar Based on the Defensive Function of Amphibian Skin Bacteria.

    Science.gov (United States)

    Bletz, Molly C; Myers, Jillian; Woodhams, Douglas C; Rabemananjara, Falitiana C E; Rakotonirina, Angela; Weldon, Che; Edmonds, Devin; Vences, Miguel; Harris, Reid N

    2017-01-01

    For decades, Amphibians have been globally threatened by the still expanding infectious disease, chytridiomycosis. Madagascar is an amphibian biodiversity hotspot where Batrachochytrium dendrobatidis ( Bd ) has only recently been detected. While no Bd -associated population declines have been reported, the risk of declines is high when invasive virulent lineages become involved. Cutaneous bacteria contribute to host innate immunity by providing defense against pathogens for numerous animals, including amphibians. Little is known, however, about the cutaneous bacterial residents of Malagasy amphibians and the functional capacity they have against Bd . We cultured 3179 skin bacterial isolates from over 90 frog species across Madagascar, identified them via Sanger sequencing of approximately 700 bp of the 16S rRNA gene, and characterized their functional capacity against Bd . A subset of isolates was also tested against multiple Bd genotypes. In addition, we applied the concept of herd immunity to estimate Bd -associated risk for amphibian communities across Madagascar based on bacterial antifungal activity. We found that multiple bacterial isolates (39% of all isolates) cultured from the skin of Malagasy frogs were able to inhibit Bd . Mean inhibition was weakly correlated with bacterial phylogeny, and certain taxonomic groups appear to have a high proportion of inhibitory isolates, such as the Enterobacteriaceae, Pseudomonadaceae, and Xanthamonadaceae (84, 80, and 75% respectively). Functional capacity of bacteria against Bd varied among Bd genotypes; however, there were some bacteria that showed broad spectrum inhibition against all tested Bd genotypes, suggesting that these bacteria would be good candidates for probiotic therapies. We estimated Bd -associated risk for sampled amphibian communities based on the concept of herd immunity. Multiple amphibian communities, including those in the amphibian diversity hotspots, Andasibe and Ranomafana, were estimated to be

  1. Boron Affects Immune Function Through Modulation of Splenic T Lymphocyte Subsets, Cytokine Secretion, and Lymphocyte Proliferation and Apoptosis in Rats.

    Science.gov (United States)

    Jin, Erhui; Li, Shenghe; Ren, Man; Hu, Qianqian; Gu, Youfang; Li, Kui

    2017-08-01

    This study demonstrated the mechanisms of boron effects in a rat model and provided a scientific basis for the rational of boron use. These findings were achieved by investigating the effects of boron (10, 20, 40, 80, 160, 320, and 640 mg/L in drinking water or 1.5, 3, 6, 12, 24, 48, and 96 mg/kg BW) on rat serum immunoglobulins (IgGs), splenic cytokines, lymphocyte subsets, as well as on lymphocyte proliferation and apoptosis. Addition of 20 (3) and 40 (6) mg/L (mg/kg BW) of boron to drinking water significantly increased rat serum IgG concentrations, splenic IFN-γ and IL-4 expression as well as the number of splenic CD3 + , CD4 + and proliferating cell nuclear antigen (PCNA) + cells. Supplementation of drinking water with 40 mg/L (6 mg/kg BW) boron also markedly increased splenic IL-2 expression and the CD4 + /CD8 + cell ratio and reduced splenic CD8 + cell number. Supplementation with 80 mg/L (12 mg/kg BW) boron significantly increased CD3 + and PCNA + cell numbers (P boron markedly reduced the serum IgG concentrations; splenic IL-2 and IL-10 expression; the number of CD3 + , CD4 + and PCNA + cells; and increased the number of splenic CD8 + and caspase-3 + cells and promoted caspase-3 expression in CD3 + cells. In conclusion, these findings suggest that the supplementation of rat drinking water with 20(3) and 40(6) mg/L (mg/kg BW) boron can markedly enhance humoral and cellular immune functions, while boron concentrations above 320 mg/L (48 mg/kg BW) can have an inhibitory effect or even toxicity on immune functions. These results exhibit a U-shaped response characteristic of low and high doses of boron supplementation on immune function and imply that proper boron supplementation in food for humans and animals could be used as an immunity regulator.

  2. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment.

    Science.gov (United States)

    Phillips, Dennis R; Clark, Kevin D

    2017-01-01

    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms.

  3. Sub-optimal vitamin B-12 levels among ART-naïve HIV-positive individuals in an urban cohort in Uganda.

    Science.gov (United States)

    Semeere, Aggrey S; Nakanjako, Damalie; Ddungu, Henry; Kambugu, Andrew; Manabe, Yukari C; Colebunders, Robert

    2012-01-01

    Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART) naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals' Joint AIDS Program (MJAP) or the Infectious Diseases Institute (IDI) clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200-900). Sub-optimal vitamin B-12 levels (ART (CD4ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub-optimal vitamin B-12, and explore the role of vitamin B-12 supplementation in immune recovery.

  4. Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion.

    Science.gov (United States)

    Albacker, Lee A; Wu, Jeremy; Smith, Peter; Warmuth, Markus; Stephens, Philip J; Zhu, Ping; Yu, Lihua; Chmielecki, Juliann

    2017-01-01

    Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

  5. Effects of experimentally elevated traffic noise on nestling white-crowned sparrow stress physiology, immune function and life history.

    Science.gov (United States)

    Crino, Ondi L; Johnson, Erin E; Blickley, Jessica L; Patricelli, Gail L; Breuner, Creagh W

    2013-06-01

    Roads have been associated with behavioral and physiological changes in wildlife. In birds, roads decrease reproductive success and biodiversity and increase physiological stress. Although the consequences of roads on individuals and communities have been well described, the mechanisms through which roads affect birds remain largely unexplored. Here, we examine one mechanism through which roads could affect birds: traffic noise. We exposed nestling mountain white-crowned sparrows (Zonotrichia leucophrys oriantha) to experimentally elevated traffic noise for 5 days during the nestling period. Following exposure to traffic noise we measured nestling stress physiology, immune function, body size, condition and survival. Based on prior studies, we expected the traffic noise treatment to result in elevated stress hormones (glucocorticoids), and declines in immune function, body size, condition and survival. Surprisingly, nestlings exposed to traffic noise had lower glucocorticoid levels and improved condition relative to control nests. These results indicate that traffic noise does affect physiology and development in white-crowned sparrows, but not at all as predicted. Therefore, when evaluating the mechanisms through which roads affect avian populations, other factors (e.g. edge effects, pollution and mechanical vibration) may be more important than traffic noise in explaining elevated nestling stress responses in this species.

  6. Effects of Light Intensity on Growth, Anti-Stress Ability and Immune Function in Yellow Feathered Broilers

    Directory of Open Access Journals (Sweden)

    YL Guo

    Full Text Available ABSTRACT An experiment was conducted to investigate the effects of light intensity on growth, anti-stress ability, and immune function of yellow feathered broilers. A total of 480 one-day-old male Lingnan yellow feathered broilers were randomly allocated to 4 treatments based on light intensity (1, 5, 20 and 80 lx with 8 replicates of 15 chicks each. The experiment lasted for 63 days. Compared with those under high light intensity, broilers exposed to low light intensity had higher (p<0.05 total antioxidant capacity (T-AOC, glutathione peroxidase (GSH-Px, a-Naphthylacetate esterase (ANAE+, antibody titer, but lower (p<0.05 malonaldehyde (MDA levels and heterophil/lymphocyte ratio (H/L. There was a linear effect for T-AOC(p=0.002, GSH-Px(p≤0.047, MDA (p=0.003, H/L(p≤0.014, ANAE+ (p≤0.044, and antibody titer (p≤0.021 with T-AOC, GSH-Px, ANAE+, and antibody titer increased significantly as light intensity decreased, whereas MDA and H/L were decreased with the decrease in light intensity. These results suggested that broilers under low light intensity could have similar performance, better anti-stress ability, stronger immune function, and more efficient in energy usage as compared with those exposed to high light intensity environment.

  7. Effects of Aromatherapy Massage on Pregnant Women's Stress and Immune Function: A Longitudinal, Prospective, Randomized Controlled Trial.

    Science.gov (United States)

    Chen, Pao-Ju; Chou, Cheng-Chen; Yang, Luke; Tsai, Yu-Lun; Chang, Yue-Cune; Liaw, Jen-Jiuan

    2017-10-01

    This study's aims are to examine the effects of aromatherapy massage on women's stress and immune function during pregnancy. This longitudinal, prospective, randomized controlled trial recruited 52 healthy pregnant women from a prenatal clinic in Taipei using convenience sampling. The participants were randomly assigned to the intervention (n = 24) or control (n = 28) group using Clinstat block randomization. The intervention group received 70 min of aromatherapy massage with 2% lavender essential oil every other week (10 times in total) for 20 weeks; the control group received only routine prenatal care. In both groups, participants' salivary cortisol and immunoglobulin A (IgA) levels were collected before and after the intervention group received aromatherapy massage (every month from 16 to 36 weeks gestation) and were analyzed using enzyme-linked immunosorbent assay. The pregnant women in the intervention group had lower salivary cortisol (p aromatherapy massage than those in the control group, which did not receive massage treatment. Comparing the long-term effects of aromatherapy massage on salivary IgA levels between groups at different times, the study found that the pretest salivary IgA levels at 32 (p = 0.002) and 36 (p aromatherapy massage could significantly decrease stress and enhance immune function in pregnant women. The findings can guide clinicians or midwives in providing aromatherapy massage to women throughout the pregnancy.

  8. Exercise training reveals trade-offs between endurance performance and immune function, but does not influence growth, in juvenile lizards.

    Science.gov (United States)

    Husak, Jerry F; Roy, Jordan C; Lovern, Matthew B

    2017-04-15

    Acquired energetic resources allocated to a particular trait cannot then be re-allocated to a different trait. This often results in a trade-off between survival and reproduction for the adults of many species, but such a trade-off may be manifested differently in juveniles not yet capable of reproduction. Whereas adults may allocate resources to current and/or future reproduction, juveniles can only allocate to future reproduction. Thus, juveniles should allocate resources toward traits that increase survival and their chances of future reproductive success. We manipulated allocation of resources to performance, via endurance exercise training, to examine trade-offs among endurance capacity, immune function and growth in juvenile green anole lizards. We trained male and female captive anoles on a treadmill for 8 weeks, with increasing intensity, and compared traits with those of untrained individuals. Our results show that training enhanced endurance capacity equally in both sexes, but immune function was suppressed only in females. Training had no effect on growth, but males had higher growth rates than females. Previous work showed that trained adults have enhanced growth, so juvenile growth is either insensitive to stimulation with exercise, or they are already growing at maximal rates. Our results add to a growing body of literature indicating that locomotor performance is an important part of life-history trade-offs that are sex and age specific. © 2017. Published by The Company of Biologists Ltd.

  9. The Effects of Combined Exercise on Health-Related Fitness, Endotoxin, and Immune Function of Postmenopausal Women with Abdominal Obesity.

    Science.gov (United States)

    Park, Sung-Mo; Kwak, Yi-Sub; Ji, Jin-Goo

    2015-01-01

    This study was conducted to examine the effects of combined exercise on health-related fitness, endotoxin concentrations, and immune functions of postmenopausal women with abdominal obesity. 20 voluntary participants were recruited and they were randomly allocated to the combined exercise group (n = 10) or the control group (n = 10). Visceral obesity was defined as a visceral-to-subcutaneous fat ratio ≥ 0.4 based on computed tomography (CT) results. Body composition, exercise stress testing, fitness measurement, CT scan, and blood variables were analyzed to elucidate the effects of combined exercise. The SPSS Statistics 18.0 program was used to calculate means and standard deviations for all variables. Significant differences between the exercise group and control group were determined with 2-way ANOVA and paired t-tests. The exercise group's abdominal obesity was mitigated due to visceral fat reduction; grip strength, push-ups, and oxygen uptake per weight improved; and HDL-C and IgA level also increased, while TNF-α, CD14, and endotoxin levels decreased. Lowered TNF-α after exercise might have an important role in the obesity reduction. Therefore, we can conclude that combined exercise is effective in mitigating abdominal obesity, preventing metabolic diseases, and enhancing immune function.

  10. The effects of an instant haw beverage on lipid levels, antioxidant enzyme and immune function in hyperlipidemia patients.

    Science.gov (United States)

    Chen, Jidi; Xue, Bin; Li, Keji; Shi, Jingda; Krempin, D; Zhu, M; Garland, C

    2002-05-01

    To determine the effectiveness of an instant haw beverage in regulating lipid disturbance, enhancing antioxidant enzyme activity and immune function. Data was collected from 60 hyperlipidemic subjects. In this crossover design, each subject randomly received either the instant haw beverage (100 ml corresponding to 3 g of haw powder or 30 g of fresh haw fruit plus the carrier-guar gum plus some starch) or placebo (guar gum 1.5 g plus some starch as the carrier of the beverage) twice daily. Each supplementation lasted 31 days with a 28-day washout period between treatments. The instant haw beverage significantly reduced total serum cholesterol (9.6%), triglyceride (12.1%), LDLC (18%) while significantly increased SOD activities (7.5%). The placebo was shown to have positive results in some of the lipid profiles, though the effects of the instant haw beverage demonstrated greater significance. Serum triglyceride levels were significantly decreased and SOD activity significantly increased only as subjects were supplemented with the instant haw beverage while no significant changes were seen with placebo. Supplementation with the instant haw beverage positively affects blood lipid profile, antioxidant status and immune function in individuals with hyperlipidemia.

  11. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells

    International Nuclear Information System (INIS)

    Feagins, Alicia R.; Basler, Christopher F.

    2015-01-01

    Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. The EBOV VP24 and MARV VP40 proteins inhibit IFN signaling, albeit by different mechanisms. Here we demonstrate that LLOV VP35 suppresses Sendai virus induced IFN regulatory factor 3 (IRF3) phosphorylation, IFN-α/β production, and PKR phosphorylation. Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function. These activities parallel EBOV IFN inhibitory functions. EBOV and LLOV VP35 and VP24 proteins also inhibit IFN responses in bat cells. These data suggest that LLOV infection will block innate immune responses in a manner similar to EBOV. - Highlights: • Lloviu virus (LLOV) is a new member of the filovirus family. • LLOV VP35 blocks IRF3 phosphorylation, IFN-α/β production and PKR phosphorylation. • LLOV VP24 inhibits IFN responses by targeting phospho-STAT1 KPNA interaction. • Infection by LLOV may block innate immune responses in a manner similar to EBOV.

  12. Early Enteral Combined with Parenteral Nutrition Treatment for Severe Traumatic Brain Injury: Effects on Immune Function, Nutritional Status and Outcomes.

    Science.gov (United States)

    Fan, Mingchao; Wang, Qiaoling; Fang, Wei; Jiang, Yunxia; Li, Liandi; Sun, Peng; Wang, Zhihong

    2016-11-20

    Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN) with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patients with severe traumatic brain injury (STBI). Methods A prospective randomized control trial was carried out from January 2009 to May 2012 in Neurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow Coma Scale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were admi- nistrated EN, PN or EN+PN treatments respectively. The indexes of nutritional status, immune function, complications and clinical outcomes were examined and compared statistically. Results There were 120 patients enrolled in the study, with 40 pationts in each group. In EN+PN group, T lymthocyte subsets CD3+%, CD4+%, ratio of CD3+/CD25+, ratio of CD4+/CD8+, the plasma levels of IgA, IgM, and IgG at 20 days after nutritional treatment were significantly increased compared to the baseline(t=4.32-30.00, Pnutritional status, the serum total protein, albumin, prealbumin and hemoglobin were significantly higher in the EN (t=5.87-11.91; Pnutrition treatment. The serum prealbumin was higher in EN+PN group than that in EN group (t=2.08; Pnutritional status, decrease complications and improve the clinical outcomes in patients with severe traumatic brain injury.

  13. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

    Science.gov (United States)

    Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

    2015-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

  14. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells

    Energy Technology Data Exchange (ETDEWEB)

    Feagins, Alicia R.; Basler, Christopher F., E-mail: chris.basler@mssm.edu

    2015-11-15

    Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. The EBOV VP24 and MARV VP40 proteins inhibit IFN signaling, albeit by different mechanisms. Here we demonstrate that LLOV VP35 suppresses Sendai virus induced IFN regulatory factor 3 (IRF3) phosphorylation, IFN-α/β production, and PKR phosphorylation. Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function. These activities parallel EBOV IFN inhibitory functions. EBOV and LLOV VP35 and VP24 proteins also inhibit IFN responses in bat cells. These data suggest that LLOV infection will block innate immune responses in a manner similar to EBOV. - Highlights: • Lloviu virus (LLOV) is a new member of the filovirus family. • LLOV VP35 blocks IRF3 phosphorylation, IFN-α/β production and PKR phosphorylation. • LLOV VP24 inhibits IFN responses by targeting phospho-STAT1 KPNA interaction. • Infection by LLOV may block innate immune responses in a manner similar to EBOV.

  15. Energy expenditures & physical activity in rats with chronic suboptimal nutrition.

    Science.gov (United States)

    Rising, Russell; Lifshitz, Fima

    2006-01-31

    Sub-optimally nourished rats show reduced growth, biochemical and physiological changes. However, no one has assessed metabolic rate adaptations in rats subjected to chronic suboptimal nutrition (CSN). In this study energy expenditure (EE; kcal/100 g body weight) and physical activity (PA; oscillations in weight/min/kg body weight) were assessed in rats subjected to three levels of CSN. Body weight gain was diminished (76.7 +/- 12.0 and 61.6 +/- 11.0 g) in rats fed 70 and 60% of the ad-libitum fed controls which gained more weight (148.5 +/- 32.3 g). The rats fed 80% gained weight similarly to controls (136.3 +/- 10.5 g). Percent Fat-free body mass was reduced (143.8 +/- 8.7 and 142.0 +/- 7.6 g) in rats fed 70 and 60% of ad-libitum, but not in those fed 80% (200.8 +/- 17.5 g) as compared with controls (201.6 +/- 33.4 g). Body fat (g) decreased in rats fed 80% (19.7 +/- 5.3), 70% (15.3 +/- 3.5) and 60% (9.6 +/- 2.7) of ad-libitum in comparison to controls (26.0 +/- 6.7). EE and PA were also altered by CSN. The control rats increased their EE and PA during the dark periods by 1.4 +/- 0.8 and 1.7 +/- 1.1 respectively, as compared with light the period; whereas CSN rats fed 80 and 70% of ad-libitum energy intake had reduced EE and PA during the dark periods as compared with the light period EE(7.5 +/- 1.4 and 7.8 +/- 0.6 vs. 9.0 +/- 1.2 and 9.7 +/- 0.8; p vs. 4.1 +/- 0.9 and 2.4 +/- 0.4; p vs. 0.95 +/- 0.03 and 0.91 +/- 0.05 p light (7.1 +/- 1.4) and dark period (6.2 +/- 1.0) EE and PA (3.4 +/- 0.9 and 2.5 +/- 0.5 respectively) were reduced in rats fed 60% of ad-libitum energy intake. CSN rats adapt to mild energy restriction by reducing body fat, EE and PA mainly during the dark period while growth proceeds and lean body mass is preserved. At higher levels of energy restrictions there is decreased growth, body fat and lean mass. Moreover EE and PA are also reduced during both light and dark periods.

  16. Energy expenditures & physical activity in rats with chronic suboptimal nutrition

    Directory of Open Access Journals (Sweden)

    Lifshitz Fima

    2006-01-01

    Full Text Available Abstract Background Sub-optimally nourished rats show reduced growth, biochemical and physiological changes. However, no one has assessed metabolic rate adaptations in rats subjected to chronic suboptimal nutrition (CSN. In this study energy expenditure (EE; kcal/100 g body weight and physical activity (PA; oscillations in weight/min/kg body weight were assessed in rats subjected to three levels of CSN. Results Body weight gain was diminished (76.7 ± 12.0 and 61.6 ± 11.0 g in rats fed 70 and 60% of the ad-libitum fed controls which gained more weight (148.5 ± 32.3 g. The rats fed 80% gained weight similarly to controls (136.3 ± 10.5 g. Percent Fat-free body mass was reduced (143.8 ± 8.7 and 142.0 ± 7.6 g in rats fed 70 and 60% of ad-libitum, but not in those fed 80% (200.8 ± 17.5 g as compared with controls (201.6 ± 33.4 g. Body fat (g decreased in rats fed 80% (19.7 ± 5.3, 70% (15.3 ± 3.5 and 60% (9.6 ± 2.7 of ad-libitum in comparison to controls (26.0 ± 6.7. EE and PA were also altered by CSN. The control rats increased their EE and PA during the dark periods by 1.4 ± 0.8 and 1.7 ± 1.1 respectively, as compared with light the period; whereas CSN rats fed 80 and 70% of ad-libitum energy intake had reduced EE and PA during the dark periods as compared with the light period EE(7.5 ± 1.4 and 7.8 ± 0.6 vs. 9.0 ± 1.2 and 9.7 ± 0.8; p Conclusion CSN rats adapt to mild energy restriction by reducing body fat, EE and PA mainly during the dark period while growth proceeds and lean body mass is preserved. At higher levels of energy restrictions there is decreased growth, body fat and lean mass. Moreover EE and PA are also reduced during both light and dark periods.

  17. Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

    Science.gov (United States)

    Lustgarten, Michael S; Fielding, Roger A

    2017-12-15

    Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and qMetabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle

  18. The Effects of Opium Addiction on the Immune System Function in Patients with Fungal Infection.

    Science.gov (United States)

    Ayatollahi-Mousavi, Seyyed Amin; Asadikaram, Gholamreza; Nakhaee, Nouzar; Izadi, Alireza; Keikha, Nasser

    2016-01-01

    The use of narcotics such as opium exposes addicts as susceptible targets of different diseases so that they might easily be exposed to different diseases such as fungal infections. The present study aimed to investigate the effects of addiction to opium and fungal infection on plasma levels of certain cytokines including interleukin-4 (IL-4), IL-6, IL-17, Interferon gamma (IFN-γ) and transforming growth factor-β (TGF-β). Present study included 72 individuals who were divided into 4 groups: 1) opium-addicted with fungal infection; 2) opium-addicted without fungal infection; 3) non-opium-addicted with fungal infection; and 4) normal individuals (non-opium-addicted and non-fungal infection). The fungal samples, after being detected and confirmed by a physician, were prepared based on clinical symptoms and then analyzed by direct smear and culture method. The measurement of the plasma level of cytokines was done by enzyme-linked immunosorbent assay (ELISA) method. The comparison of the mean of the plasma level of cytokines showed that addiction to opium and fungal infection had significant effect on the plasma levels of IL-17, IFN-γ, TGF-β cytokines in all studied groups. The interaction of addiction to opium and fungal infection was only significant in the case of plasma level of IL-6. Addiction to opium and fungal infection, either separately or simultaneously, poses significant effect on the immune system and causes disorders in the cytokine network and the immune system and also provides a suitable environment for fungal infection.

  19. Emerging roles for IL-15 in the activation and function of T-cells during immune stimulation

    Directory of Open Access Journals (Sweden)

    Anthony SM

    2015-02-01

    Full Text Available Scott M Anthony, Kimberly S Schluns Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Interleukin (IL-15 is a cytokine that promotes the development and homeostasis of a group of lymphocytes; however, IL-15 is also significantly upregulated in response to pathogen infections and in autoimmune diseases. With its ability to promote T-cell proliferation and survival and influence migration and effector functions, elevated IL-15 can impact T-cell responses in numerous ways. Nonetheless, the importance of IL-15 during early infection and autoimmunity is unclear. Furthermore, the mechanisms regulating IL-15 responses in both inflammatory situations and during the steady state are still being elucidated. The mechanisms by which IL-15 mediate responses are unique among cytokines. IL-15 associates with IL-15Rα within cells where it can either be transpresented to neighboring cells or cleaved into a soluble cytokine/receptor complex. Increased production of soluble (sIL-15Rα/IL-15 complexes is seen upon different types of immune stimulation, suggesting that these are circumstance when sIL-15 complexes are most likely to act. How common this response is remains unclear, as the production of sIL-15 complexes has only been recently appreciated. This review sets out to emphasize how IL-15 is frequently increased in response to pathogen infections and during autoimmunity and inflammatory conditions. Since pathogen infections and inflammatory diseases share signaling pathways that induce sIL-15 complexes, including pattern recognition receptors and type I interferon, sIL-15 complexes may be generated in more situations than realized. While there are multiple cellular targets of IL-15, this review primarily focuses on how T-cells are likely affected by IL-15 during immune activation and describes evidence

  20. Adaptive suboptimal second-order sliding mode control for microgrids

    Science.gov (United States)

    Incremona, Gian Paolo; Cucuzzella, Michele; Ferrara, Antonella

    2016-09-01

    This paper deals with the design of adaptive suboptimal second-order sliding mode (ASSOSM) control laws for grid-connected microgrids. Due to the presence of the inverter, of unpredicted load changes, of switching among different renewable energy sources, and of electrical parameters variations, the microgrid model is usually affected by uncertain terms which are bounded, but with unknown upper bounds. To theoretically frame the control problem, the class of second-order systems in Brunovsky canonical form, characterised by the presence of matched uncertain terms with unknown bounds, is first considered. Four adaptive strategies are designed, analysed and compared to select the most effective ones to be applied to the microgrid case study. In the first two strategies, the control amplitude is continuously adjusted, so as to arrive at dominating the effect of the uncertainty on the controlled system. When a suitable control amplitude is attained, the origin of the state space of the auxiliary system becomes attractive. In the other two strategies, a suitable blend between two components, one mainly working during the reaching phase, the other being the predominant one in a vicinity of the sliding manifold, is generated, so as to reduce the control amplitude in steady state. The microgrid system in a grid-connected operation mode, controlled via the selected ASSOSM control strategies, exhibits appreciable stability properties, as proved theoretically and shown in simulation.

  1. Robust Adaptive LCMV Beamformer Based On An Iterative Suboptimal Solution

    Directory of Open Access Journals (Sweden)

    Xiansheng Guo

    2015-06-01

    Full Text Available The main drawback of closed-form solution of linearly constrained minimum variance (CF-LCMV beamformer is the dilemma of acquiring long observation time for stable covariance matrix estimates and short observation time to track dynamic behavior of targets, leading to poor performance including low signal-noise-ratio (SNR, low jammer-to-noise ratios (JNRs and small number of snapshots. Additionally, CF-LCMV suffers from heavy computational burden which mainly comes from two matrix inverse operations for computing the optimal weight vector. In this paper, we derive a low-complexity Robust Adaptive LCMV beamformer based on an Iterative Suboptimal solution (RAIS-LCMV using conjugate gradient (CG optimization method. The merit of our proposed method is threefold. Firstly, RAIS-LCMV beamformer can reduce the complexity of CF-LCMV remarkably. Secondly, RAIS-LCMV beamformer can adjust output adaptively based on measurement and its convergence speed is comparable. Finally, RAIS-LCMV algorithm has robust performance against low SNR, JNRs, and small number of snapshots. Simulation results demonstrate the superiority of our proposed algorithms.

  2. Depression of leukocyte protein synthesis, immune function and growth performance induced by high environmental temperature in broiler chickens

    Science.gov (United States)

    Kamel, Nancy N.; Ahmed, Ayman M. H.; Mehaisen, Gamal M. K.; Mashaly, Magdi M.; Abass, Ahmed O.

    2017-09-01

    In tropical and semitropical regions, raising broiler chickens out of their thermal comfort zone can cause an added economic loss in the poultry industry. The cause for the deleterious effects on immunity and growth performance of broilers under high environmental temperatures is still poorly understood. Therefore, the aim of the current investigation was to evaluate the effect of heat stress on leukocytes protein synthesis and immune function as a possible direct cause of low performance in broiler chickens under such condition. In this study, 300 one-day-old male broiler chicks (Cobb500™) were randomly assigned into 2 groups with 5 replicates of 30 chicks each. From 21 to 42 days of age, one group was exposed to non-stressed condition at 24 °C and 50% relative humidity (control group), while the other group was exposed to heat stress at 35 °C and 50% relative humidity (HS group). At 42 days of age, blood samples were collected from each group to evaluate stress indicators, immune function, and leukocytes protein synthesis. Production performance was also recorded. Noteworthy, protein synthesis in leukocytes was significantly ( P < 0.05) inhibited in HS group by 38% compared to control group. In contrast, the phosphorylation level on threonine 56 site (Thr56) of eukaryotic elongation factor (eEF2), which indicates the suppression of protein translation process through altering the protein elongation phase, was significantly threefold higher in HS group than in control ( P < 0.05). In addition, an increase in stress indicators was markedly ( P < 0.05) presented in the HS birds by twofold increase in heterophil/lymphocyte (H/L) ratio and threefold increase in plasma corticosterone level compared to control. Furthermore, the immune function was significantly ( P < 0.05) suppressed in HS birds than control (0.99 vs. 1.88 mg/mL plasma IgG, 89.2 vs. 148.0 μg/mL plasma IgM, 4.80 vs. 7.20 antibody titer against SRBC, and 1.38 vs. 3.39 stimulation index of lymphocyte

  3. PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-control Study of U.S. Military Service Members

    Science.gov (United States)

    2013-06-24

    other relevant exposures which may influ- ence DNA methylation , such as dietary factors ( folate , vitamin B12 intake) (Fenech, 2001; Piyathilake and...ARTICLE published: 24 June 2013 doi: 10.3389/fpsyt.2013.00056 PTSD and DNA methylation in select immune function gene promoter regions: a repeated measures...largely unknown. Dis- tinct expression signatures for PTSD have been found, in particular for immune activation transcripts. DNA methylation may be

  4. Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum.

    Science.gov (United States)

    Mann, Elizabeth R; Bernardo, David; English, Nicholas R; Landy, Jon; Al-Hassi, Hafid O; Peake, Simon T C; Man, Ripple; Elliott, Timothy R; Spranger, Henning; Lee, Gui Han; Parian, Alyssa; Brant, Steven R; Lazarev, Mark; Hart, Ailsa L; Li, Xuhang; Knight, Stella C

    2016-02-01

    Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4(+)FoxP3(+)IL-10(+) (regulatory) T cells. There were enhanced proportions of CD103(+)Sirpα(-) DC in the colon, with increased proportions of CD103(+)Sirpα(+) DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103(+)Sirpα(+) DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103(+) DC, in particular CD103(+)Sirpα(+) DC. However, expression of ILT3 was associated with CD103(-) DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. [Induction of glutathione and activation of immune functions by low-dose, whole-body irradiation with gamma-rays].

    Science.gov (United States)

    Kojima, Shuji

    2006-10-01

    We first examined the relation between the induction of glutathione and immune functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing mice. The total glutathione level of the splenocytes transiently increased soon after irradiation and reached a maximum at around 4 h postirradiation. Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A significantly high splenocyte proliferative response was also recognized 4 h postirradiation. Natural killer (NK) activity was also increased significantly in a similar manner. The time at which the response reached the maximum coincided well with that of maximum total glutathione levels of the splenocytes in the gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced the proliferative response and NK activity in a dose-dependent manner. The inhibitory effects of radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after inoculation) significantly delayed the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body gamma-ray irradiation on immune balance was examined to elucidate the mechanism underlying the antitumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after radiation, concomitant with an increase in that of the helper T cell population. The IFN-gamma level in splenocyte culture prepared from EST-bearing mice was significantly increased 48 h after radiation, although the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by radiation. These results suggest that low-dose gamma-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to an inhibition of tumor growth.

  6. Functional Expression of Programmed Death-Ligand 1 (B7-H1 by Immune Cells and Tumor Cells

    Directory of Open Access Journals (Sweden)

    Rachel M. Gibbons Johnson

    2017-08-01

    Full Text Available The programmed death-1 (PD-1 and its ligand PD-L1 (B7-H1 signaling pathway has been the focus of much enthusiasm in the fields of tumor immunology and oncology with recent FDA approval of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies durvalumab, atezolimuab, and avelumab. These therapies, referred to here as PD-L1/PD-1 checkpoint blockade therapies, are designed to block the interaction between PD-L1, expressed by tumor cells, and PD-1, expressed by tumor-infiltrating CD8+ T cells, leading to enhanced antitumor CD8+ T cell responses and tumor regression. The influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined for antitumor CD8+ T cell responses. Although PD-L1 expression by tumor cells has been used as a biomarker in selection of patients for PD-L1/PD-1 checkpoint blockade therapies, patients whose tumor cells lack PD-L1 expression often respond positively to PD-L1/PD-1 checkpoint blockade therapies. This suggests that PD-L1 expressed by non-malignant cells may also contribute to antitumor immunity. Here, we review the functions of PD-L1 expressed by immune cells in the context of CD8+ T cell priming, contraction, and differentiation into memory populations, as well as the role of PD-L1 expressed by tumor cells in regulating antitumor CD8+ T cell responses.

  7. Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases

    DEFF Research Database (Denmark)

    Xanthoulea, Sofia; Pasparakis, Manolis; Kousteni, Stavroula

    2004-01-01

    Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses. Due to its pleiotropic activities, the amplitude and duration of TNF function must be tightly regulated. One of the mechanisms that may have evolved...... to modulate TNF function is the proteolytic cleavage of its cell surface receptors. In humans, mutations affecting shedding of the p55TNF receptor (R) have been linked with the development of the TNFR-associated periodic syndromes, disorders characterized by recurrent fever attacks and localized inflammation....... Here we show that knock-in mice expressing a mutated nonsheddable p55TNFR develop Toll-like receptor-dependent innate immune hyperreactivity, which renders their immune system more efficient at controlling intracellular bacterial infections. Notably, gain of function for antibacterial host defenses...

  8. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I.

    Science.gov (United States)

    Sippel, Trisha R; White, Jason; Nag, Kamalika; Tsvankin, Vadim; Klaassen, Marci; Kleinschmidt-DeMasters, B K; Waziri, Allen

    2011-11-15

    The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell-derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell-mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients.

  9. Pressure Induced Changes in Adaptive Immune Function in Belugas (Delphinapterus leucas; implications for dive physiology and health

    Directory of Open Access Journals (Sweden)

    Laura A Thompson

    2016-09-01

    Full Text Available Increased pressure, associated with diving, can alter cell function through several mechanisms and has been shown to impact immune functions performed by peripheral blood mononuclear cells (PBMC in humans. While marine mammals possess specific adaptations which protect them from dive related injury, it is unknown how their immune system is adapted to the challenges associated with diving. The purpose of this study was to measure PBMC activation (IL2R expression and Concanavalin A induced lymphocyte proliferation (BrdU incorporation in belugas following in vitro pressure exposures during baseline, Out of Water Examination (OWE and capture/release conditions. Beluga blood samples (n=4 were obtained from animals at the Mystic Aquarium and from free ranging animals in Alaska (n=9. Human blood samples (n=4 (Biological Specialty Corporation were run for comparison. In vivo catecholamines and cortisol were measured in belugas to characterize the neuroendocrine response. Comparison of cellular responses between controls and pressure exposed cells, between conditions in belugas, between belugas and humans as well as between dive profiles, were run using mixed generalized linear models (α=0.05. Cortisol was significantly higher in wild belugas and OWE samples as compared with baseline for aquarium animals. Both IL2R expression and proliferation displayed significant pressure induced changes, and these responses varied between conditions in belugas. Both belugas and humans displayed increased IL2R expression, while lymphocyte proliferation decreased for aquarium animals and increased for humans and wild belugas. Results suggest beluga PBMC function is altered during diving and changes may represent dive adaptation as the response differs from humans, a non-dive adapted mammal. In addition, characteristics of a dive (i.e., duration, depth as well as neuroendocrine activity can alter the response of beluga cells, potentially impacting the ability of animals

  10. Effects of montelukast sodium combined with pidotimod on acute phase protein and immune function in children with acute bronchitis

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2017-08-01

    Full Text Available Objective: To observe the effects of montelukast sodium combined with pidotimod on acute phase protein (APP and indexes of immunologic function in pediatric acute bronchitis treatment. Methods: A total of 180 cases children with acute bronchitis acted as research objects were randomly divided into control group (n=65 and observation group (n=63. On the basis of conventional therapy, control group was treated by plus pidotimod. On this base, observation group was treated with montelukast sodium. The changes of acute phase proteins (CRP, HP, a1-AAG and CER and immune function (CD3+ , CD4+ , CD8+ and CD4+ /CD8+ levels before and after treatment were observed after 2 months. Results: Before treatment, CRP, HP, a1-AAG, CER, CD3+ , CD4+ , CD8+ and CD4+ /CD8+ levels of two groups had no statistically significant difference; CRP, HP, a1-AAG, CER, and CD8+ levels of control and observation groups decreased significantly after treatment, the decreases of observation group were more obvious than that of control group, and the levels after treatment were significantly lower than that of control groups. The levels of CD3+ , CD4+ and CD4+ /CD8+ in two groups after treatment were significantly higher than those before treatment. For observation group, the levels of CD3+ , CD4+ and CD4+ /CD8+ increased more significantly after treatment, which were significantly higher than that of the control group. Conclusion: Using Montelukast sodium combined with pidotimod can effectively reduce the children's acute phase protein levels, improve immune function, which has clinical value for the treatment of children with acute bronchitis.

  11. High contaminant loads in Lake Apopka's riparian wetland disrupt gene networks involved in reproduction and immune function in largemouth bass.

    Science.gov (United States)

    Martyniuk, Christopher J; Doperalski, Nicholas J; Prucha, Melinda S; Zhang, Ji-Liang; Kroll, Kevin J; Conrow, Roxanne; Barber, David S; Denslow, Nancy D

    2016-09-01

    Lake Apopka (FL, USA) has elevated levels of some organochlorine pesticides in its sediments and a portion of its watershed has been designated a US Environmental Protection Agency Superfund site. This study assessed reproductive endpoints in Florida largemouth bass (LMB) (Micropterus salmoides floridanus) after placement into experimental ponds adjacent to Lake Apopka. LMB collected from a clean reference site (DeLeon Springs) were stocked at two periods of time into ponds constructed in former farm fields on the north shore of the lake. LMB were stocked during early and late oogenesis to determine if there were different effects of contamination on LMB that may be attributed to their reproductive stage. LMB inhabiting the ponds for ~4months had anywhere from 2 to 800 times higher contaminant load for a number of organochlorine pesticides (e.g. p, p'-DDE, methoxychlor) compared to control animals. Gonadosomatic index and plasma vitellogenin were not different between reproductively-stage matched LMB collected at reference sites compared to those inhabiting the ponds. However, plasma 17β-estradiol was lower in LMB inhabiting the Apopka ponds compared to ovary stage-matched LMB from the St. Johns River, a site used as a reference site. Sub-network enrichment analysis revealed that genes related to reproduction (granulosa function, oocyte development), endocrine function (steroid metabolism, hormone biosynthesis), and immune function (T cell suppression, leukocyte accumulation) were differentially expressed in the ovaries of LMB placed into the ponds. These data suggest that (1) LMB inhabiting the Apopka ponds showed disrupted reproduction and immune responses and that (2) gene expression profiles provided site-specific information by discriminating LMB from different macro-habitats. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Effects of Trauma-Hemorrhage and IL-6 Deficiency on Splenic Immune Function in a Murine Trauma Model

    Directory of Open Access Journals (Sweden)

    P. Mommsen

    2012-01-01

    Full Text Available Splenic immune function is known to be depressed following hemorrhage. The present study investigates the effects of femoral shaft fracture, isolated or in combination with hemorrhage, on early stage cytokine production capacity of splenocytes and observes the role of IL-6 under these conditions. Male IL-6 knockout (IL-6−/− and wild-type mice (WT were randomly divided into three groups: sham (S, isolated femoral fracture (Fx, and femoral fracture + volume controlled hemorrhage (TH-Fx (=6 per group. Animals were sacrificed four hours after induction of hemorrhage and fracture. Cytokine release (TNF-α, IL-6, and IL-10 of isolated and LPS-stimulated splenocytes was determined by cytometric bead array. Femoral fracture with or without hemorrhage caused a suppression of in vitro cytokine production capacity of splenocytes at an early posttraumatic stage in WT and IL-6−/−. In the absence of IL-6, the profile of splenic cytokine secretion is significantly altered, identifying this cytokine as a potential therapeutic target to modulate the posttraumatic immune response.

  13. The effects of music listening after a stressful task on immune functions, neuroendocrine responses, and emotional states in college students.

    Science.gov (United States)

    Hirokawa, Eri; Ohira, Hideki

    2003-01-01

    The purpose of this study was to examine the effects of listening to high-uplifting or low-uplifting music after a stressful task on (a) immune functions, (b) neuroendocrine responses, and (c) emotional states in college students. Musical selections that were evaluated as high-uplifting or low-uplifting by Japanese college students were used as musical stimuli. Eighteen Japanese subjects performed stressful tasks before they experienced each of these experimental conditions: (a) high-uplifting music, (b) low-uplifting music, and (c) silence. Subjects' emotional states, the Secretory IgA (S-IgA) level, active natural killer (NK) cell level, the numbers of T lymphocyte CD4+, CD8+, CD16+, dopamine, norepinephrine, and epinephrine levels were measured before and after each experimental condition. Results indicated low-uplifting music had a trend of increasing a sense of well-being. High-uplifting music showed trends of increasing the norepinephrine level, liveliness, and decreasing depression. Active NK cells were decreased after 20 min of silence. Results of the study were inconclusive, but high-uplifting and low-uplifting music had different effects on immune, neuroendocrine, and psychological responses. Classification of music is important to research that examines the effects of music on these responses. Recommendations for future research are discussed.

  14. [Effect of self-foot reflexology massage on depression, stress responses and immune functions of middle aged women].

    Science.gov (United States)

    Lee, Yun-Mi

    2006-02-01

    This study was aimed to identify the effects of a self-foot reflexology massage on depression, stress responses and functions of the immune system of middle-aged women. This study was a one group pretest-posttest experimental design and the data was collected from August 1st, 2004 to May 31st, 2005. The subjects consisted of 46 middle-aged women (40 - 64 years) who were recruited from the Community Health Center in Busan city. Subjects were not treated for 4 weeks, subsequently they were trained in self foot reflexology massage for 2 weeks, and then they did their own daily for 6 weeks (2 days at the research center, 5 days at home). The outcome variables were measured 4 times, at baseline, pre training, after training, and after the intervention. The collected data was analyzed using repeated measure ANOVA by the SPSS/WIN program. There was a statistically significant difference in depression, perceived stress, systolic blood pressure, natural-killer cells and Ig G. However, there was not a statistically significant difference in diastolic blood pressure, pulse or serum cortisol. These results suggest that a self-foot reflexology massage could be utilized as an effective nursing intervention to reduce depression and stress responses, and to strengthen immune systems in middle-aged women.

  15. Processing of whey modulates proliferative and immune functions in intestinal epithelial cells.

    Science.gov (United States)

    Nguyen, Duc Ninh; Sangild, Per T; Li, Yanqi; Bering, Stine B; Chatterton, Dereck E W

    2016-02-01

    Whey protein concentrate (WPC) is often subjected to heat treatment during industrial processing, resulting in protein denaturation and loss of protein bioactivity. We hypothesized that WPC samples subjected to different degrees of thermal processing are associated with different levels of bioactive proteins and effects on proliferation and immune response in intestinal epithelial cells (IEC). The results showed that low-heat-treated WPC had elevated levels of lactoferrin and transforming growth factor-β2 compared with that of standard WPC. The level of aggregates depended on the source of whey, with the lowest level being found in WPC derived from acid whey. Following acid activation, WPC from acid whey enhanced IEC proliferation compared with WPC from sweet whey or nonactivated WPC. Low-heat-treated WPC from acid whey induced greater secretion of IL-8 in IEC than either standard WPC from acid whey or low-heat-treated WPC from sweet whey. Following acid activation (to activate growth factors), low-heat-treated WPC from sweet whey induced higher IL-8 levels in IEC compared with standard WPC from sweet whey. In conclusion, higher levels of bioactive proteins in low-heat-treated WPC, especially from acid whey, may enhance proliferation and cytokine responses of IEC. These considerations could be important to maintain optimal bioactivity of infant formulas, including their maturational and immunological effects on the developing intestine. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  17. Effect of general anesthesia combined with epidural anesthesia on the postoperative immune function, stress state and coagulation function in patients with laparoscopic cholecystectomy

    Directory of Open Access Journals (Sweden)

    Yun-Long Zhao

    2017-05-01

    Full Text Available Objective: To study the effect of general anesthesia combined with epidural anesthesia on the postoperative immune function, stress state and coagulation function in patients with laparoscopic cholecystectomy. Methods: 98 patients undergoing selective laparoscopic cholecystectomy in our hospital between May 2014 and August 2016 were selected and randomly divided into the combined anesthesia group who accepted the general anesthesia combined with epidural anesthesia and the general anesthesia group who accepted the total intravenous anesthesia (n=49, peripheral blood was collected after operation to detect the number of CD3+CD4+CD8-T cells, CD3+CD4-CD8+T cells, CD16+CD56+NK cells and CD3- CD19+B cells, serum was collected to detect the levels of stress-related endocrine hormones norepinephrine (NE, cortisol (Cor, insulin (Ins, C-peptide (C-P, free triiodothyronine (FT3, free thyroxine (FT4 as well as coagulation function indexes rostaglandin I2 (PGI2, thromboxane A2 (TXA2, 6-ketone-prostaglandin F1α (6-K-PGI1α and thromboxane B2 (TXB2. Results: The number of CD3+CD4+CD8-T cells, CD3+CD4-CD8+T cells, CD16+CD56+NK cells and CD3-CD19+B cells in peripheral blood of combined anesthesia group were significantly higher than those of intravenous anesthesia group (P<0.05; serum NE, Cor, Ins, C-P, FT3, FT4, TXA2 and TXB2 levels of combined anesthesia group were significantly lower than those of intravenous anesthesia group (P<0.05 while PGI2 and 6-K-PGI1α levels were significantly higher than those of intravenous anesthesia group (P<0.05. Conclusions: General anesthesia combined with epidural anesthesia can improve the postoperative immune function, stress state and hypercoagulable state in patients with laparoscopic cholecystectomy.

  18. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Wang, Yong [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Weng, Zhiping; Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Harrod, Kevin S. [Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S., E-mail: treena@uab.edu [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2016-10-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice

  19. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A.; Harrod, Kevin S.; Deshane, Jessy S.; Athar, Mohammad

    2016-01-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4 +/+ wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4 +/− heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca ++ homeostasis. ATO induces Ca ++ -dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca ++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4 +/− mice. • Changes in macrophage

  20. Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

    Science.gov (United States)

    Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

    2018-05-31

    New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

  1. Stress effect on humoral and cell mediated immune response: Indispensable part of corticosterone and cytokine in neutrophil function

    Directory of Open Access Journals (Sweden)

    Sakthivel Srinivasan

    2016-01-01

    Conclusion: This result further concludes that prior immunization of SRBC in animal’s act as a vaccination, which helps to prevent noise stress induced impairment in immune system. Orally administered I. tinctoria prevented noise altered immune system. These results also concluded that I. tinctoria supplementation could act as an immunomodulators and suggesting its therapeutic efficacy as an antistressor.

  2. Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients.

    Science.gov (United States)

    Ma, Li; Zhou, Zeping; Zhang, Donglei; Yang, Shaoguang; Wang, Jinhong; Xue, Feng; Yang, Yanhui; Yang, Renchi

    2012-05-01

    Human umbilical cord matrix/Wharton's jelly (hUC)-derived mesenchymal stem cells (MSC) have been shown to have marked therapeutic effects in a number of inflammatory diseases and autoimmune diseases in humans based on their potential for immunosuppression and their low immunogenicity. Currently, no data are available on the effectiveness of UC-MSC transplantation in immune thrombocytopenia (ITP) patients. It was the objective of this study to assess the effect of allogeneic UC-MSCs on ITP patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BM-MNCs) from ITP patients and healthy controls were co-cultured with UC-MSCs for three days and seven days, respectively. Flow cytometry and ELISA were applied to assess the various parameters. In PBMCs from ITP patients, the proliferation of autoreactive T, B lymphocytes and destruction of autologous platelets were dramatically suppressed by UC-MSCs. UC-MSCs not only suppressed co-stimulatory molecules CD80, CD40L and FasL expression but also in shifting Th1/Th2/Treg cytokines profile in ITP patients. UC-MSCs obviously reversed the dysfunctions of megakaryocytes by promoting platelet production and decreasing the number of living megakaryocytes as well as early apoptosis. In addition, the level of thrombopoietin was increased significantly. Our clinical study showed that UC-MSCs play a role in alleviating refractory ITP by increasing platelet numbers. These findings suggested that UC-MSCs transplantation might be a potential therapy for ITP.

  3. The receptor kinase CERK1 has dual functions in symbiosis and immunity signalling.

    Science.gov (United States)

    Zhang, Xiaowei; Dong, Wentao; Sun, Jongho; Feng, Feng; Deng, Yiwen; He, Zuhua; Oldroyd, Giles E D; Wang, Ertao

    2015-01-01

    The establishment of symbiotic interactions between mycorrhizal fungi, rhizobial bacteria and their legume hosts involves a common symbiosis signalling pathway. This signalling pathway is activated by Nod factors produced by rhizobia and these are recognised by the Nod factor receptors NFR1/LYK3 and NFR5/NFP. Mycorrhizal fungi produce lipochitooligosaccharides (LCOs) similar to Nod factors, as well as short-chain chitin oligomers (CO4/5), implying commonalities in signalling during mycorrhizal and rhizobial associations. Here we show that NFR1/LYK3, but not NFR5/NFP, is required for the establishment of the mycorrhizal interaction in legumes. NFR1/LYK3 is necessary for the recognition of mycorrhizal fungi and the activation of the symbiosis signalling pathway leading to induction of calcium oscillations and gene expression. Chitin oligosaccharides also act as microbe associated molecular patterns that promote plant immunity via similar LysM receptor-like kinases. CERK1 in rice has the highest homology to NFR1 and we show that this gene is also necessary for the establishment of the mycorrhizal interaction as well as for resistance to the rice blast fungus. Our results demonstrate that NFR1/LYK3/OsCERK1 represents a common receptor for chitooligosaccharide-based signals produced by mycorrhizal fungi, rhizobial bacteria (in legumes) and fungal pathogens. It would appear that mycorrhizal recognition has been conserved in multiple receptors across plant species, but additional diversification in certain plant species has defined other signals that this class of receptors can perceive. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  4. Effect of Zi Gui decoction on immune function in {sup 60}Co {gamma}-ray irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Qiujun, Lu; Shafei, Huang; Xipeng, Zhou; Jiayun, Song; Zhongxiong, Tang [Dept. of Pharmacology, Institute of Radiation Medicine, Beijing (China)

    1995-02-01

    Zi Gui decoction (ZG), a complex preparation of traditional Chinese herbal medicine, mainly consists of Radix Angelicae and Radix Astragali. The effects of ZG on mitogen induced proliferation IL-1 and -2 production, natural killer (NK) cell activity in {sup 60}Co {gamma}-ray irradiated mice is investigated. After 5 Gy whole body irradiation. mice were treated i.g. with ZG (1.2, 1.8 g/kg/day) for 20 days. An enhancement in Con A- and LPS-induced proliferations of splenocytes from the two dosage groups were observed. There were marked increases in IL-1 activity in peritoneal macrophage culturesa and IL-2 activity in splenocyte cultures from irradiated mice treated with ZG. The two dosage groups also showed significant potentiation of NK cell activity against YAC-1 target cells. The above results indicated that ZG could promote the recovery of immune functions in {gamma}-ray irradiated mice.

  5. EFFECT OF POLYPHENOLIC COMPOUNDS ISOLATED FROM CARTHAMUS TINCTORIUS AND CALENDULA OFFICINALIS L., ON FUNCTIONAL ACTIVITY OF IMMUNE CELLS UNDER CONDITIONS OF CYTOSTATIC IMMUNOSUPPRESSION

    Directory of Open Access Journals (Sweden)

    N. V. Masnaya

    2013-01-01

    Full Text Available The purpose of the study – to study the effect of polyphenolic compounds extracted from the flowers of safflower oil and calendula, the functional activity of immune cells in cytotoxic immune suppression.Conventional methods determined the total number of splenocytes, relative (% and absolute (106, the number of antibody-forming cells (AFC in the spleen of mice by local hemolysis by Cunningham.Evaluated the effect of compounds of natural origin on the cellular immune response in the delayed-type hypersensitivity (DTH. Phagocytic activity of peritoneal macrophages was determined by the method based on the intensity of their capture ink particles. We studied the functional activity of peritoneal macrophages by NBT test (spontaneous and stimulated. Studies were conducted on male mice Category 1 (conventional linear mouse line CBA/CaLac aged 2–2.5 months, weighing 20–22 g. After the introduction mice line CBA/CaLac of polyphenolic compounds derived from flowers of Carthamus tinctorius and flowers of Calendula officinalis L. during the 5-day course in dose 50 mg/kg was observed stimulation of the humoral immune response (total number of splenocytes, the number of antibodies in the spleen cells and the functional activity of macrophages and Immunomodulating effect on the humoral immunity and the functional activity of macrophages after a single injection of cyclophosphamide in dose 250 mg/kg. Immunotropic activity of polyphenolic compounds is higher than that those of the reference product of tincture of Echinacea purpurea.

  6. Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

    Directory of Open Access Journals (Sweden)

    Xavier Chauchet

    2016-01-01

    Full Text Available Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy.

  7. Influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function of elderly patients with advanced lung cancer

    International Nuclear Information System (INIS)

    Jiang Tinghui; Wu Shiyan; Chen Yue; Zhang Qingquan; Zhang Weiwei; Shen Xubo; Wang Qianyao

    2010-01-01

    Objective: To investigate the influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function in elderly patients with advanced lung cancer and to establish a comprehensive therapeutic pattern which is effective and economical with lower side-effects. Methods: A total of 60 aged patients with lung cancer were randomly and equally divided into two groups with 30 patients in each group. Patients in group A were purely treated with traditional Chinese medicine and patients in group B were treated with a combination of interventional chemotherapy and traditional Chinese medicine. And two therapeutic courses (6-8 weeks) were conducted in both groups. The serum T-lymphocyte subsets levels of CD3, CD4, CD8, CD4/CD8, NK cells and CD4 + CD25 + Treg cell levels were estimated with flow cytometry. The results were statistically analyzed. Results: No significant difference in serum levels of T cell subsets and CD4 + CD25 + Treg cell levels existed between the two groups, both before and after the treatment (P > 0.05). However, after the treatment the CD4 + CD25 + Treg cell level in group B was significantly lower than that in group A (P < 0.05). The short-term effective rate and the total clinical benefit rate in group B were 40% and 73.3% respectively, which were much better than those in group A (20% and 63.3% respectively). Conclusion: Interventional chemotherapy combined with traditional Chinese medicine will not damage the immune function of elderly patients with advanced lung cancer, on the contrary, the combination therapy, through effectively reducing the suppressor T cell level,shows excellent short-term effect. It indicates that interventional chemotherapy combined with Chinese medicine is an effective comprehensive therapeutic mode for elderly patients with advanced lung cancer. (authors)

  8. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis.

    Science.gov (United States)

    Chen, Kang; Chen, Hao; Faas, Marijke M; de Haan, Bart J; Li, Jiahong; Xiao, Ping; Zhang, Hao; Diana, Julien; de Vos, Paul; Sun, Jia

    2017-08-01

    Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice. Female nonobese diabetic mice were weaned to long- and short-chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic-gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T-cell responses, as evidenced by increased CD25 + Foxp3 + CD4 + regulatory T cells, decreased IL17A + CD4 + Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase-1-p20-IL-1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide as well as short-chain fatty acid production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli. Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut-pancreatic immunity, barrier function, and microbiota homeostasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Effect of Micronutrient and Probiotic Fortified Yogurt on Immune-Function of Anti-Retroviral Therapy Naive HIV Patients  

    Directory of Open Access Journals (Sweden)

    J. Dik F. Habbema

    2011-10-01

    Full Text Available Background: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving the immune-function of HIV patients. Objective: Assess the impact of micronutrient supplemented probiotic yogurt on the immune function of HIV patients. Design: We performed a randomized, double blind, controlled trial with CD4 count as primary outcome among HIV patients naïve to anti-retroviral treatment. Secondary outcomes included hematological parameters, incidence of diarrhea and clinical symptoms. A total of 112 HIV patients were randomized to receive a micronutrient fortified yogurt with (n = 55 or without additional probiotic Lactobacillus rhamnosus GR-1 (n = 57 for four weeks. Results: An average decline in CD4 count of −70 cells/μL (95% CI: −154 to −15 was observed in the micronutrient, probiotic group versus a decrease of −63 cells/μL (95% CI: −157 to −30 in the micronutrient control group (p = 0.9. Additional probiotic supplementation was well tolerated and not associated with adverse events. No difference between groups was detected in incidence of diarrhea or clinical symptoms. An improvement of hemoglobin levels was observed for all subjects, based upon a mean difference from baseline of 1.4 g/L (SD = 6 (p = 0.02. Conclusion: The addition of probiotics to a micronutrient fortified yogurt was well tolerated by HIV patients but was not associated with a further increase in CD4 count after one month.

  10. Lead effects on development and function of bone marrow-derived dendritic cells promote Th2 immune responses

    International Nuclear Information System (INIS)

    Gao Donghong; Mondal, Tapan K.; Lawrence, David A.

    2007-01-01

    Although lead (Pb) has significant effects on the development and function of macrophages, B cells, and T cells and has been suggested to promote allergic asthma in mice and humans, Pb modulation of bone marrow (BM)-derived dendritic cells (DCs) and the resultant DC effects on Th1 and Th2 development have not been examined. Accordingly, we cultured BM cells with murine granulocyte macrophage-colony stimulating factor (mGM-CSF) ± PbCl 2 . At day 10, culture supernatant (SN) and non-adherent cells were harvested for analysis. Additionally, day 10 non-adherent BM-DCs were harvested and recultured with mGM-CSF + LPS ± Pb for 2 days. The day 10 Pb exposure significantly inhibited BM-DC generation, based on CD11c expression. Although fewer DCs were generated with Pb, the existing Pb-exposed DCs had significantly greater MHC-II expression than did the non-Pb-exposed DCs. However, these differences diminished upon LPS stimulation. After LPS stimulation, CD80, CD86, CD40, CD54, and MHC-II were all up-regulated on both Pb-DCs and DCs, but Pb-DCs expressed significantly less CD80 than did DCs. The CD86:CD80 ratio suggests a Pb-DC potential for Th2 cell development. After LPS stimulation, IL-6, IL-10, IL-12 (p70), and TNF-α levels significantly increased with both Pb-DCs and DCs, but Pb-DCs produced significantly less cytokines than did DCs, except for IL-10, which further supports Pb-DC preferential skewing toward type-2 immunity. In vitro studies confirm that Pb-DCs have the ability to polarize antigen-specific T cells to Th2 cells. Pb-DCs also enhanced allogeneic and autologous T cell proliferation in vitro, and in vivo studies suggested that Pb-DCs inhibited Th1 effects on humoral and cell-mediated immunity. The Pb effect was mainly on DCs, rather than on T cells, and Pb's modification of DC function appears to be the main cause of Pb's promotion of type-2-related immunity, which may relate to Pb's enhanced activation of the Erk/MAP kinase pathway

  11. The influence of recovery and training phases on body composition, peripheral vascular function and immune system of professional soccer players.

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    Simon Reinke

    Full Text Available Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4+/-4.2 kg to 72.2+/-3.9 kg was observed, but an increase of fat mass from 10.3+/-5.6 kg to 11.1+/-5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3+/-3.4 and 26.0+/-6.3 ml/100 ml/min respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0+/-2.7 and 33.9+/-7.6 ml/100 ml/min during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by i

  12. A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.

    Science.gov (United States)

    Shah, Javeed A; Musvosvi, Munyaradzi; Shey, Muki; Horne, David J; Wells, Richard D; Peterson, Glenna J; Cox, Jeffery S; Daya, Michelle; Hoal, Eileen G; Lin, Lin; Gottardo, Raphael; Hanekom, Willem A; Scriba, Thomas J; Hatherill, Mark; Hawn, Thomas R

    2017-08-15

    The molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood. To identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis. We used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis-induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection. We identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2 + CD4 + T-cell frequency and proliferation. This genotype was also associated with increased susceptibility to latent tuberculosis infection. TOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG

  13. Sub-optimal vitamin B-12 levels among ART-naive HIV-positive individuals in an urban cohort in Uganda.

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    Aggrey S Semeere

    Full Text Available Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals' Joint AIDS Program (MJAP or the Infectious Diseases Institute (IDI clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200-900. Sub-optimal vitamin B-12 levels (<300 pg/ml were found in 75/204 (36.8%. Twenty-one of 204 (10.3% had vitamin B-12 deficiency (<200 pg/ml while 54/204 (26.5% had marginal depletion (200-300 pg/ml. Irritable mood was observed more among individuals with sub-optimal vitamin B-12 levels (OR 2.5, 95% CI; 1.1-5.6, P=0.03. Increasing MCV was associated with decreasing serum B-12 category; 86.9 fl (± 5.1 vs. 83 fl (± 8.4 vs. 82 fl (± 8.4 for B-12 deficiency, marginal and normal B-12 categories respectively (test for trend, P=0.017. Compared to normal B-12, individuals with vitamin B-12 deficiency had a longer known duration of HIV infection: 42.2 months (± 27.1 vs. 29.4 months (± 23.8; P=0.02. Participants eligible for ART (CD4<350 cells/µl with sub-optimal B-12 had a higher mean rate of CD4 decline compared to counterparts with normal B-12; 118 (± 145 vs. 22 (± 115 cells/µl/year, P=0.01 respectively. The prevalence of a sub-optimal vitamin B-12 was high in this HIV-infected, ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub-optimal

  14. Epitope-based vaccines with the Anaplasma marginale MSP1a functional motif induce a balanced humoral and cellular immune response in mice.

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    Paula S Santos

    Full Text Available Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based a