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Sample records for neonatal immune function

  1. Season of birth shapes neonatal immune function

    DEFF Research Database (Denmark)

    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...

  2. 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.

  3. The effect of maternal helminth infection on maternal and neonatal immune function and immunity to tuberculosis.

    Directory of Open Access Journals (Sweden)

    Dawit Gebreegziabiher

    Full Text Available BACKGROUND: M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis. OBJECTIVE: To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB. METHODS: In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB infections using Kato-Katz and QFT-GIT tests, respectively. IFN-γ and IL-4 ELISpot on Cord blood Mononuclear Cells, and total IgE and TB specific IgG ELISA on cord blood plasma was performed to investigate the possible effect of maternal helminth and/or latent TB co-infection on maternal and neonatal immune function and immunity to TB. RESULT: The prevalence of helminth infections in pregnant women was 27% (n = 23, with Schistosoma mansoni the most common helminth species observed (20% of women were infected. Among the total of 85 study participants 25.8% were QFT-GIT positive and 17% had an indeterminate result. The mean total IgE value of cord blood was significantly higher in helminth positive than negative women (0.76 vs 0.47, p = 0.042. Cross placental transfer of TB specific IgG was significantly higher in helminth positive (21.9 ± 7.9 than negative (12.3 ± 5.1, p = 0.002 Latent TB Infection positive participants. The IFN-γ response of CBMCs to ESAT-6/CFP-10 cocktail (50 vs 116, p = 0.018 and PPD (58 vs 123, p = 0.02 was significantly lower in helminth positive than negative participants. There was no significant difference in IL-4 response of CBMCs between helminth negative and positive participants. CONCLUSIONS: Maternal helminth infection had a significant association with the IFN-γ response of CBMCs, total IgE and cross placental transfer of TB specific IgG. Therefore, further studies should be conducted to determine the effect of these

  4. Neonatal innate immunity - A translational perspective

    NARCIS (Netherlands)

    Belderbos, M.E.

    2012-01-01

    Human newborns are highly susceptible to infections, which appears to be due to immaturity of the neonatal innate immune system. At birth, neonatal innate immune responses are characterized by decreased Th1-polarizing responses, whereas generation of Th2-polarizing and regulatory responses is

  5. Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

    Science.gov (United States)

    Spann, Marisa N; Monk, Catherine; Scheinost, Dustin; Peterson, Bradley S

    2018-03-14

    Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior. SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for

  6. Neonatal pertussis, cocooning and maternal immunization.

    Science.gov (United States)

    Swamy, Geeta K; Wheeler, Sarahn M

    2014-09-01

    The rising incidence of whooping cough, a highly contagious infection caused by Bordetella pertussis, is particularly significant for young infants who have the highest risk for morbidity and mortality. The pertussis resurgence has led to a shift in primary prevention relying on childhood vaccination to a cocooning strategy, that is, vaccination of close contacts of newborn infants (new mothers, fathers, grandparents, siblings, caretakers, etc.), thereby reducing pertussis exposure. Immunization of women during pregnancy rather than during the immediate postpartum period (the initial cocooning recommendation) appears to be a better approach by directly providing protection through transplacental transfer of maternal vaccine-induced antibodies. This article describes neonatal pertussis, cocooning as a means of reducing neonatal exposure to pertussis and maternal immunization as a means of protecting young infants against pertussis infection.

  7. Immunity to rotavirus in conventional neonatal calves.

    OpenAIRE

    Vonderfecht, S L; Osburn, B I

    1982-01-01

    The local and systemic humoral immune responses to rotavirus were studied in six conventional neonatal calves. Attenuated bovine rotavirus was administered either orally or directly into an isolated intestinal loop. The parameters monitored were neutralizing rotavirus antibody in serum, immunofluorescent and neutralizing rotavirus antibody in intestinal loop washings, and rotavirus antibody-producing cells in intestinal mucosa. An antibody response was observed in the serum and intestinal sec...

  8. Immunity to rotavirus in conventional neonatal calves.

    Science.gov (United States)

    Vonderfecht, S L; Osburn, B I

    1982-11-01

    The local and systemic humoral immune responses to rotavirus were studied in six conventional neonatal calves. Attenuated bovine rotavirus was administered either orally or directly into an isolated intestinal loop. The parameters monitored were neutralizing rotavirus antibody in serum, immunofluorescent and neutralizing rotavirus antibody in intestinal loop washings, and rotavirus antibody-producing cells in intestinal mucosa. An antibody response was observed in the serum and intestinal secretions from one calf only. Viral replication was not detected in the isolated intestinal loop. Rotavirus antibody-producing cells were found in the intestinal mucosa of five calves. Double staining revealed that most of these cells produced antibody of the immunoglobulin A class. The conclusions were: (i) a previously described system to detect rotavirus antibody-producing cells can be used to study immune responses in neonatal calves, (ii) the class or subclass of antibody in rotavirus antibody-producing cells can be determined by double immunofluorescent staining, (iii) neonatal calves respond to rotavirus inoculation with a local immunoglobulin A response, and (iv) most of the rotavirus antibody-producing cells are located in the mucosa of the proximal small intestine.

  9. Dietary Nucleotides Supplementation Improves the Intestinal Development and Immune Function of Neonates with Intra-Uterine Growth Restriction in a Pig Model.

    Directory of Open Access Journals (Sweden)

    Lianqiang Che

    Full Text Available The current study aimed to determine whether dietary nucleotides supplementation could improve growth performance, intestinal development and immune function of intra-uterine growth restricted (IUGR neonate using pig as animal model. A total of 14 pairs of normal birth weight (NBW and IUGR piglets (7 days old were randomly assigned to receive a milk-based control diet (CON diet or diet supplemented with nucleotides (NT diet for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, microbial populations, peripheral immune cells, expression of intestinal innate immunity and barrier-related genes and proteins. Compared with NBW piglets, IUGR piglets had significantly lower average daily dry matter intake and body weight gain (P<0.05. Moreover, IUGR markedly decreased the villous height and villi: crypt ratio in duodenum (P<0.05, as well as the maltase activity in jejunum (P<0.05. In addition, IUGR significantly decreased the serum concentrations of IgA, IL-1βand IL-10 (P<0.05, as well as the percentage of peripheral lymphocytes (P<0.05. Meanwhile, the down-regulation of innate immunity-related genes such as TOLLIP (P<0.05, TLR-9 (P = 0.08 and TLR-2 (P = 0.07 was observed in the ileum of IUGR relative to NBW piglets. Regardless of birth weight, however, feeding NT diet markedly decreased (P<0.05 feed conversion ratio, increased the villous height in duodenum (P<0.05, activities of lactase and maltase in jejunum (P<0.05, count of peripheral leukocytes (P<0.05, serum concentrations of IgA and IL-1β as well as gene expressions of TLR-9, TLR-4 and TOLLIP in ileum (P<0.05. In addition, expressions of tight junction proteins (Claudin-1 and ZO-1 in ileum were markedly increased by feeding NT diet relative to CON diet (P<0.05. These results indicated that IUGR impaired growth performance, intestinal and immune function, but dietary nucleotides supplementation

  10. Treatment of neonatal sepsis with intravenous immune globulin

    DEFF Research Database (Denmark)

    Brocklehurst, Peter; Farrell, Barbara; King, Andrew

    2011-01-01

    Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...... suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality....

  11. Treatment of neonatal sepsis with intravenous immune globulin

    DEFF Research Database (Denmark)

    Brocklehurst, Peter; Farrell, Barbara; King, Andrew

    2011-01-01

    Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...

  12. Stress/aggressiveness-induced immune changes are altered in adult rats submitted to neonatal malnutrition.

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    Barreto-Medeiros, Jairza; Queiros-Santos, Adenilda; Cabral-Filho, José Eulálio; Ferreira E Silva, Wylla Tatiana; Leandro, Carol Góis; Deiró, Tereza Cristina; Manhaes-de-Castro, Raul; Machado Barbosa de-Castro, Célia Maria

    2007-01-01

    Neonatal malnutrition induces metabolic and endocrine changes that have beneficial effects on the neonatal in the short term but, in the longer term, these alterations lead to maladaptations. We investigated the effect of neonatal malnutrition on immune responses in adult rats submitted or not to an aggressiveness test. Male Wistar rats were distributed to one of two groups according to their mothers' diet during lactation: the well-nourished group (group C, n = 42, receiving 23% of protein) and the malnourished group (group MN, n = 42, receiving 8% of protein). After weaning, all rats received normoproteic diet. Ninety days after birth, each group was subdivided into three subgroups: control rats (n = 14, respectively), aggressive rats (n = 14, respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma corticosterone concentration was measured after FS sessions. Leukocyte counts and humoral immunity were evaluated. In neonatal malnourished animals, FS-induced stress reduced plasma corticosterone concentration. Intraspecific aggressiveness induced alterations in leukocyte counts and antibody titers 7 and 15 days after immunization. Neonatal malnourished animals showed no changes in the immune parameters evaluated. Expression of intraspecific aggressiveness activates the immune system. Neonatal malnutrition seems to have a long-lasting effect on components of both neuroendocrine and immune functions.

  13. Picornavirus-Induced Airway Mucosa Immune Profile in Asymptomatic Neonates

    DEFF Research Database (Denmark)

    Wolsk, Helene M.; Følsgaard, Nilofar V.; Birch, Sune

    2016-01-01

    , and regulatory immune paths. The association between immune mediator levels and viruses was tested by conventional statistics and partial least square discriminant analysis. Picornaviruses were detected in 58 neonates (10.2%) and other viruses in 10 (1.8%). A general up-regulation of immune mediators was found...... in the neonates with picornavirus (P partial least square discriminant analysis). The association was pronounced for type 1- and type 2-related markers and was unaffected by comprehensive confounder adjustment. Detection of picornavirus and bacteria was associated with an additive general up...

  14. Immune Response to Intrapharyngeal LPS in Neonatal and Juvenile Mice

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    Lee, Seakwoo; Gibbs, Kevin; Lopez, Armando; Collaco, Joseph M.; Neptune, Enid; Soloski, Mark J.; Scott, Alan; D’Alessio, Franco

    2015-01-01

    Neonates and infants have a higher morbidity and mortality associated with lower respiratory tract illnesses compared with older children. To identify age-related and longitudinal differences in the cellular immune response to acute lung injury (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel, minimally invasive aspiration technique. Neonatal and juvenile mice received between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA expression from lung homogenates was quantified, and lung morphometry and injury scores were performed. LPS-treated neonatal mice underwent adoptive transfer with adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure, neonatal lungs were slower to resolve inflammation and expressed lower mRNA levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced lung inflammation and improved weight gain. These findings underscore several vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the importance of age-related differences in Tregs and their response to ALI during early postnatal development. PMID:25068533

  15. Tetanus toxoid immunization to reduce mortality from neonatal tetanus.

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    Blencowe, Hannah; Lawn, Joy; Vandelaer, Jos; Roper, Martha; Cousens, Simon

    2010-04-01

    Neonatal tetanus remains an important and preventable cause of neonatal mortality globally. Large reductions in neonatal tetanus deaths have been reported following major increases in the coverage of tetanus toxoid immunization, yet the level of evidence for the mortality effect of tetanus toxoid immunization is surprisingly weak with only two trials considered in a Cochrane review. To review the evidence for and estimate the effect on neonatal tetanus mortality of immunization with tetanus toxoid of pregnant women, or women of childbearing age. We conducted a systematic review of multiple databases. Standardized abstraction forms were used. Individual study quality and the overall quality of evidence were assessed using an adaptation of the GRADE approach. Meta-analyses were performed. Only one randomised controlled trial (RCT) and one well-controlled cohort study were identified, which met inclusion criteria for meta-analysis. Immunization of pregnant women or women of childbearing age with at least two doses of tetanus toxoid is estimated to reduce mortality from neonatal tetanus by 94% [95% confidence interval (CI) 80-98%]. Additionally, another RCT with a case definition based on day of death, 3 case-control studies and 1 before-and-after study gave consistent results. Based on the consistency of the mortality data, the very large effect size and that the data are all from low/middle-income countries, the overall quality of the evidence was judged to be moderate. This review uses a standard approach to provide a transparent estimate of the high impact of tetanus toxoid immunization on neonatal tetanus.

  16. Perinatal Environmental Effects on the Neonatal Immune System

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich

    2014-01-01

    are thought to be programmed in utero supporting a role of the early environment. The aim of the present PhD thesis was to study if known risk factors are imprinted in the immune system of newborns. The hypotheses were that cesarean section and season of birth would influence the immune signature in early...... that the seasonal-related maternal exposome is reflected in the newborn immune system. These data supports the notion that environmental factors imprints immunological variation already in the perinatal life. In conclusion, studies on early immunological priming may be critical in order to understanding early...... disease programming and subsequent to be able to direct future research on disease preventative strategies. We identified mode of delivery and birth season as important risk factors acting on the perinatal immune system. Collectively, our results suggest that the neonatal immune system may be imprinted...

  17. Early Life Microbiota, Neonatal Immune Maturation and Hematopoiesis

    DEFF Research Database (Denmark)

    Kristensen, Matilde Bylov

    Emerging epidemiologic data supports the hypothesis that early life colonization is a key player in development of a balanced immune system. Events in early life, as birth mode and infant diet, are shown to influence development of immune related diseases, like asthma, diabetes and inflammatory...... studies show a role for various myeloid derived and immune suppressive cellular subsets in the newborn. In the present work we showed the presence of a prominent group of CD11b+Gr-1+ cells in the neonate murine spleen. The presence of these cells were dependent on the colonizing microbiota, as germfree...... bowl disease, later in life. The intestinal epithelium makes up a physical and biochemical barrier between the bacteria in the gut lumen and the immune cells in the submocusal tissue. This monolayer of intestinal epithelial cells (IEC) makes up an extremely large surface and is highly important...

  18. Relationships between maternal malaria and malarial immune responses in mothers and neonates

    DEFF Research Database (Denmark)

    Rasheed, F N; Bulmer, J N; De Francisco, A

    1995-01-01

    Immune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection....... Maternal and cord malarial IgG levels correlated (P ... and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation...

  19. Sex-specific effects of neonatal exposures to low levels of cadmium through maternal milk on development and immune functions of juvenile and adult rats

    International Nuclear Information System (INIS)

    Pillet, Stephane; Rooney, Andrew A.; Bouquegneau, Jean-Marie; Cyr, Daniel G.; Fournier, Michel

    2005-01-01

    Cadmium (Cd) is a major environmental contaminant. Although immunotoxic effects have been associated with Cd exposure, the inconsistency of experimental results underlines the need of an experimental approach more closely related to environmental conditions. We investigated the effects of exposing neonatal Sprague-Dawley rats to environmentally relevant doses of Cd through maternal milk. Dams received 10 parts per billion (ppb) or 5 parts per million (ppm) Cd chloride (CdCl 2 ) in drinking water from parturition until the weaning of the pups. Half of the offspring was sampled at weaning time. The remaining juvenile rats received water without addition of Cd until adulthood. Cd accumulation in kidneys of juvenile rats fed from dams exposed to Cd indicated the transfer of the metal from mother to pups through maternal milk. This neonatal exposure resulted in decreased body, kidney and spleen weights of just weaned females but not of males. This effect was more pronounced in the less exposed females fed from dams exposed to 10 ppb Cd, which also displayed lower hepatic metallothionein-1 (MT-1) mRNA levels. The effect of Cd exposure on body and organ weights did not persist to adulthood. In contrast, we observed gender-specific effects of neonatal Cd exposure on the cytotoxic activity of splenic NK-cells of both juvenile and adult rats. Cd also strongly inhibited the proliferative response of Con A-stimulated thymocytes in both male and female adult rats 5 weeks after the cessation of Cd exposure. These immunotoxic effects were observed at doses much lower than those reported to produce similar effects when exposure occurred during adulthood. In conclusion, neonatal exposures to environmentally relevant levels of Cd through maternal milk represent a critical hazard liable to lead to both transitory and persistent immunotoxic effects

  20. Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

    Directory of Open Access Journals (Sweden)

    Mark R. Schleiss

    2013-01-01

    Full Text Available Fetal and neonatal infections caused by human cytomegalovirus (CMV are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies.

  1. Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

    Science.gov (United States)

    Schleiss, Mark R.

    2013-01-01

    Fetal and neonatal infections caused by human cytomegalovirus (CMV) are important causes of morbidity and occasional mortality. Development of a vaccine against congenital CMV infection is a major public health priority. Vaccine design is currently focused on strategies that aim to elicit neutralizing antibody and T-cell responses, toward the goal of preventing primary or recurrent infection in women of child-bearing age. However, there has been relatively little attention given to understanding the mechanisms of immune protection against acquisition of CMV infection in the fetus and newborn and how this information might be exploited for vaccine design. There has similarly been an insufficient study of what deficits in the immune response to CMV, both for mother and fetus, may increase susceptibility to congenital infection and disease. Protection of the fetus against vertical transmission can likely be achieved by protection of the placenta, which has its own unique immunological milieu, further complicating the analysis of the correlates of protective immunity. In this review, the current state of knowledge about immune effectors of protection against CMV in the maternal, placental, and fetal compartments is reviewed. A better understanding of immune responses that prevent and/or predispose to infection will help in the development of novel vaccine strategies. PMID:24023565

  2. Immunizations, neonatal jaundice, and animal-induced injuries.

    Science.gov (United States)

    Morris, Shaine A; Bernstein, Henry H

    2004-08-01

    Published studies during the past year about three topics important to the pediatric clinician-- immunizations, neonatal jaundice, and animal-induced injuries-are concisely reviewed. Recent updates regarding vaccines including the questionable link with autism, implementation of universal influenza vaccination for young children, the efficacy of pneumococcal vaccine against invasive disease, and new information on pertussis, varicella, hepatitis A, hepatitis B, measles, and rotavirus vaccination are discussed. No association between measles/mumps/rubella vaccine or thimerosal-containing pertussis vaccine and autism is evident. Universal influenza vaccination for children 6 to 23 months of age will be recommended for the 2004-2005 flu season, and this implementation should reduce significant school absenteeism as well as complications seen last year including encephalopathy, seizures, respiratory failure, and pneumonia. Pneumococcal vaccine significantly reduces rates of invasive pneumococcal vaccine in healthy and HIV-infected children, although it does not appear to greatly affect otitis media rates. A reduction in post-vaccine febrile seizures appears to be present since the introduction of acellular pertussis vaccine. Multiple outbreaks in varicella have been reported since the introduction of the varicella vaccine, and a booster vaccination may be necessary in the future. Methods for detecting and preventing severe neonatal hyperbilirubinemia are reviewed, as well as anticipated recommendations from the American Academy of Pediatrics for the detection and management of hyperbilirubinemia. High bilirubin levels in preterm infants may result in hearing dysfunction and developmental impairment. The American Academy of Pediatrics has recommended a higher level of monitoring for newborn jaundice and treatment of hyperbilirubinemia in an effort to prevent kernicterus and sequelae from elevated bilirubin levels, including post-discharge follow-up appointment by day 3

  3. Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

    DEFF Research Database (Denmark)

    Jensen, Michael L.; Thymann, Thomas; Cilieborg, Malene Skovsted

    2014-01-01

    strong downregulation of genes related to inflammation and innate immune response to microbiota and marked upregulation of genes related to amino acid metabolism, in particular threonine, glucose transport systems, and cell cycle in 5-day-old ANTI pigs. In a follow-up experiment, 5 days of antibiotics......Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad......-spectrum antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either antibiotics (oral...

  4. Monounsaturated fats and immune function

    Directory of Open Access Journals (Sweden)

    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

  5. Pertussis Antibody Transfer to Preterm Neonates After Second- Versus Third-Trimester Maternal Immunization.

    Science.gov (United States)

    Eberhardt, Christiane S; Blanchard-Rohner, Geraldine; Lemaître, Barbara; Combescure, Christophe; Othenin-Girard, Véronique; Chilin, Antonina; Petre, Jean; Martinez de Tejada, Begoña; Siegrist, Claire-Anne

    2017-04-15

    Preterm infants are most vulnerable to pertussis. Whether they might benefit from maternal immunization is unknown. Extending our previous results in term neonates, this observational study demonstrates that second- rather than third-trimester maternal vaccination results in higher birth anti-pertussis toxin titers in preterm neonates. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  6. Pertussis Antibody Transfer to Preterm Neonates After Second- Versus Third-Trimester Maternal Immunization

    OpenAIRE

    Eberhardt, Christiane S.; Blanchard-Rohner, Geraldine; Lema?tre, Barbara; Combescure, Christophe; Othenin-Girard, V?ronique; Chilin, Antonina; Petre, Jean; Martinez de Tejada, Bego?a; Siegrist, Claire-Anne

    2017-01-01

    Abstract Preterm infants are most vulnerable to pertussis. Whether they might benefit from maternal immunization is unknown. Extending our previous results in term neonates, this observational study demonstrates that second- rather than third-trimester maternal vaccination results in higher birth anti?pertussis toxin titers in preterm neonates.

  7. Fetal/neonatal allo-immune thrombocytopenia (FNAIT): past, present, and future.

    NARCIS (Netherlands)

    Serrarens-Janssen, V.M.; Semmekrot, B.A.; Novotny, V.M.J.; Porcelijn, L.; Lotgering, F.K.; Delemarre, F.M.C.; Steegers, E.A.P.

    2008-01-01

    We reviewed the English, American, and German literature for articles describing the prevalence, clinical presentation, outcome, therapeutic options, and screening possibilities for fetal/neonatal allo-immune thrombocytopenia (FNAIT), published between January 1950 and March 2007. The reported

  8. Prenatal buprenorphine exposure and neonatal neurobehavioral functioning.

    Science.gov (United States)

    Velez, Martha L; McConnell, Krystle; Spencer, Nancy; Montoya, Lina; Tuten, Michelle; Jansson, Lauren M

    2017-12-07

    Assessments of effects of prenatal opioid exposure on the neonate have consisted principally of evaluations of neonatal abstinence syndrome (NAS) to determine the need for pharmacotherapy. The purpose of this study was to comprehensively evaluate the effects of gestational maternal buprenorphine maintenance on newborn neurobehavioral functioning. Maternal substance use history and psychosocial demographics that can contribute to the neurobehavioral functioning of the infant were explored. Infants were assessed using the NICU Network Neurobehavioral Scale (NNNS) to measure their neurologic and behavioral functioning and signs of stress/abstinence on days 3, 14 and 30 of life. Participants were 41 pregnant buprenorphine-maintained women and their infants. Maternal buprenorphine dose at delivery was negatively correlated with infant quality of movement and self-regulation, and positively correlated with the central nervous system parameters of stress/abstinence at day 3 of life. As maternal buprenorphine dose increased, the mean morphine dose that the infant required for NAS treatment significantly increased. No differences were found when comparing the NNNS domain scores between infants who required pharmacotherapy for NAS versus those who did not at day 3 of life. Buprenorphine exposure during pregnancy can alter neonatal neurobehavioral and physiological responses to stimuli. A systematic evaluation of the newborn's functional domains above NAS assessment alone is crucial to address the challenges created by neurobehavioral dysregulation associated with substance exposure, improve caregiver/infant interaction and developmental trajectory. Comprehensive pre/postnatal treatment of buprenorphine-maintained mothers can lead to healthier outcomes for the dyad. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Breast Milk Oligosaccharides: Structure-Function Relationships in the Neonate

    Science.gov (United States)

    Smilowitz, Jennifer T.; Lebrilla, Carlito B.; Mills, David A.; German, J. Bruce; Freeman, Samara L.

    2015-01-01

    In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-function knowledge is enhancing our understanding of early nutrition in the neonate. PMID:24850388

  10. Immune Function and Psychological Stress.

    Science.gov (United States)

    1986-11-13

    Immune Function and Psychological Stress S17MI ONR Contract N00014-85-K-0565 Introduction B Although the evidence for a psychosocial stres - illness...membranes with secretions containing immunoglobulins . The predominant immunogloblin of the SIS is IgA, although smaller amounts of IgG, IgM, IgD, and...Report - 2 November 13, 1986 esting, there were several major deficiences in their study; first, only total immunoglobulin of the IgA isotype was

  11. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  12. Vitamin C and Immune Function

    Directory of Open Access Journals (Sweden)

    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.

  13. Neonatal Immune Adaptation of the Gut and Its Role during Infections

    Directory of Open Access Journals (Sweden)

    Emilie Tourneur

    2013-01-01

    Full Text Available The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis. Contact with potent immunostimulatory molecules starts immediately at birth, and the discrimination between commensal bacteria and invading pathogens is essential to avoid an inappropriate immune stimulation and/or host infection. The dysregulation of these tight interactions between host and microbiota can be responsible for important health disorders, including inflammation and sepsis. This review summarizes the molecular events leading to the establishment of postnatal immune tolerance and how pathogens can avoid host immunity and induce neonatal infections and sepsis.

  14. Neonatal Fc Receptor Expression in Dendritic Cells Mediates Protective Immunity Against Colorectal Cancer

    Science.gov (United States)

    Baker, Kristi; Rath, Timo; Flak, Magdalena B.; Arthur, Janelle C.; Chen, Zhangguo; Glickman, Jonathan N.; Zlobec, Inti; Karamitopoulou, Eva; Stachler, Matthew D.; Odze, Robert D.; Lencer, Wayne I.; Jobin, Christian; Blumberg, Richard S.

    2014-01-01

    SUMMARY Cancers arising in mucosal tissues account for a disproportionately large fraction of malignancies. IgG and the neonatal Fc receptor for IgG (FcRn) have an important function in the mucosal immune system which we have now shown extends to the induction of CD8+ T cell-mediated anti-tumor immunity. We demonstrate that FcRn within dendritic cells (DC) was critical for homeostatic activation of mucosal CD8+ T cells which drove protection against the development of colorectal cancers and lung metastases. FcRn-mediated tumor protection was driven by DC activation of endogenous tumor-reactive CD8+ T cells via the cross-presentation of IgG complexed antigens (IgG IC) as well as the induction of cytotoxicity-promoting cytokine secretion, particularly interleukin-12 (IL-12), both of which were independently triggered by the FcRn–IgG IC interaction in murine and human DC. FcRn thus has a primary role within mucosal tissues in activating local immune responses that are critical for priming efficient anti-tumor immunosurveillance. PMID:24290911

  15. Immune function in acute stress.

    Science.gov (United States)

    Segal, A B; Bruno, S; Forte, W C N

    2006-01-01

    The aim of this study was to evaluate immune function in acute stress in medical students before academic examinations. Twenty-five medical students were selected because they presented intense acute stress, evaluated by the presence of the following classic signs: cold hands, intense sudoresis in the extremities, generalized sudoresis, paleness, tachycardia, confused reasoning, nervous irritability, diarrhea, and sleep disorders in the hours preceding the examination (agitated sleep, insomnia). Immediately before the examination, peripheral blood was collected from the 25 students presenting acute stress to analyze T and B cells, CD4+ and CD8+ cells, immunoglobulins, and C3 and C4 complement components, as well as phagocytic activity in neutrophils and monocytes. These investigations were repeated in the same students in situations free of acute stress. The results of the two samples collected from each student were compared. The means and standard deviations showed no significant differences for any of the parameters analyzed (p> or =0.01). We conclude that acute stress did not cause changes in the lymphocyte subpopulations, phagocytic activity of neutrophils and monocytes, serum immunoglobulins, or C3 and C4 complement components in students participating in the present study. In conditions of basal chronic stress, acute stress may cause alterations in immune function.

  16. Neonates with reduced neonatal lung function have systemic low-grade inflammation

    DEFF Research Database (Denmark)

    Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus

    2015-01-01

    , TNF-α, and CXCL8, confirmed a uniform upregulated inflammatory profile in children with reduced forced expiratory volume at 0.5 seconds (P = .02). Adjusting for body mass index at birth, maternal smoking, older children in the home, neonatal bacterial airway colonization, infections 14 days before...... of the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort who had completed neonatal lung function testing at age 4 weeks. Associations between neonatal lung function indices and inflammatory biomarkers were investigated by conventional statistics and unsupervised principal component analysis...

  17. Immune function in Amazonian horticulturalists.

    Science.gov (United States)

    Blackwell, Aaron D; Trumble, Benjamin C; Maldonado Suarez, Ivan; Stieglitz, Jonathan; Beheim, Bret; Snodgrass, J Josh; Kaplan, Hillard; Gurven, Michael

    2016-07-01

    Amazonian populations are exposed to diverse parasites and pathogens, including protozoal, bacterial, fungal and helminthic infections. Yet much knowledge of the immune system is based on industrialised populations where these infections are relatively rare. This study examines distributions and age-related differences in 22 measures of immune function for Bolivian forager-horticulturalists and US and European populations. Subjects were 6338 Tsimane aged 0-90 years. Blood samples collected between 2004-2014 were analysed for 5-part blood differentials, C-reactive protein, erythrocyte sedimentation rate (ESR) and total immunoglobulins E, G, A and M. Flow cytometry was used to quantify naïve and non-naïve CD4 and CD8 T cells, natural killer cells, and B cells. Compared to reference populations, Tsimane have elevated levels of most immunological parameters, particularly immunoglobulins, eosinophils, ESR, B cells, and natural killer cells. However, monocytes and basophils are reduced and naïve CD4 cells depleted in older age groups. Tsimane ecology leads to lymphocyte repertoires and immunoglobulin profiles that differ from those observed in industrialised populations. These differences have consequences for disease susceptibility and co-vary with patterns of other life history traits, such as growth and reproduction.

  18. Gene-based neonatal immune priming potentiates a mucosal adenoviral vaccine encoding mycobacterial Ag85B.

    Science.gov (United States)

    Dai, Guixiang; Rady, Hamada F; Huang, Weitao; Shellito, Judd E; Mason, Carol; Ramsay, Alistair J

    2016-12-07

    Tuberculosis remains a major public health hazard worldwide, with neonates and young infants potentially more susceptible to infection than adults. BCG, the only vaccine currently available, provides some protection against tuberculous meningitis in children but variable efficacy in adults, and is not safe to use in immune compromised individuals. A safe and effective vaccine that could be given early in life, and that could also potentiate subsequent booster immunization, would represent a significant advance. To test this proposition, we have generated gene-based vaccine vectors expressing Ag85B from Mycobacterium tuberculosis (Mtb) and designed experiments to test their immunogenicity and protective efficacy particularly when given in heterologous prime-boost combination, with the initial DNA vaccine component given soon after birth. Intradermal delivery of DNA vaccines elicited Th1-based immune responses against Ag85B in neonatal mice but did not protect them from subsequent aerosol challenge with virulent Mtb H37Rv. Recombinant adenovirus vectors encoding Ag85B, given via the intranasal route at six weeks of age, generated moderate immune responses and were poorly protective. However, neonatal DNA priming following by mucosal boosting with recombinant adenovirus generated strong immune responses, as evidenced by strong Ag85B-specific CD4+ and CD8+ T cell responses, both in the lung-associated lymph nodes and the spleen, by the quality of these responding cells (assessed by their capacity to secrete multiple antimicrobial factors), and by improved protection, as indicated by reduced bacterial burden in the lungs following pulmonary TB challenge. These results suggest that neonatal immunization with gene-based vaccines may create a favorable immunological environment that potentiates the pulmonary mucosal boosting effects of a subsequent heterologous vector vaccine encoding the same antigen. Our data indicate that immunization early in life with mycobacterial

  19. Senecavirus A infection in market weight gilts, sows and neonates with subsequent protective immunity

    Science.gov (United States)

    Objective: The objectives of this study were to 1) characterize SVA infection in market weight pigs, late-gestation sows, and neonates and 2) examine protective immunity in late-gestation gilts Materials and Methods: For Part 1 of the study 15 gilts were inoculated with SVA, bled regularly for 2 we...

  20. Senecavirus A infection in sows, neonates, and market weight gilts with subsequent protective immunity

    Science.gov (United States)

    Objective: The objectives of this study were to 1) characterize SVA infection late-gestation sows, neonates, and market weight gilts and 2) examine protective immunity in late-gestation gilts Methods: For Part 1, 15 market weight gilts were inoculated with SVA, bled regularly, and clinical observat...

  1. Neonatal and Infantile Immune Responses to Encapsulated Bacteria and Conjugate Vaccines

    Directory of Open Access Journals (Sweden)

    Peter Klein Klouwenberg

    2008-01-01

    Full Text Available Encapsulated bacteria are responsible for the majority of mortality among neonates and infants. The major components on the surface of these bacteria are polysaccharides which are important virulence factors. Immunity against these components protects against disease. However, most of the polysaccharides are thymus-independent (TI-2 antigens which induce an inadequate immune response in neonates and infants. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children. These and several other approaches in current vaccine development will be discussed.

  2. Perinatal Environmental Effects on the Neonatal Immune System

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich

    2014-01-01

    that the seasonal-related maternal exposome is reflected in the newborn immune system. These data supports the notion that environmental factors imprints immunological variation already in the perinatal life. In conclusion, studies on early immunological priming may be critical in order to understanding early...... are thought to be programmed in utero supporting a role of the early environment. The aim of the present PhD thesis was to study if known risk factors are imprinted in the immune system of newborns. The hypotheses were that cesarean section and season of birth would influence the immune signature in early...... life. Both are known to be associated with disease. We analyzed the distribution of circulating immune cells from cord blood in the children part of the ongoing unselected COPSAC2010 birth cohort by multi-color flow cytometry. Moreover, airway mucosal cytokines and chemokines of 1-month-old children...

  3. Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

    International Nuclear Information System (INIS)

    Ordonhez Rigato, Paula; Maciel, Milton; Goldoni, Adriana Leticia; Piubelli, Orlando; Alves de Brito, Cyro; Fusaro, Ana Elisa; Eurico de Alencar, Liciana Xavier; August, Thomas; Torres Azevedo Marques, Ernesto; Silva Duarte, Alberto Jose da; Sato, Maria Notomi

    2010-01-01

    Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-γ, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

  4. Identification of a human neonatal immune-metabolic network associated with bacterial infection.

    Science.gov (United States)

    Smith, Claire L; Dickinson, Paul; Forster, Thorsten; Craigon, Marie; Ross, Alan; Khondoker, Mizanur R; France, Rebecca; Ivens, Alasdair; Lynn, David J; Orme, Judith; Jackson, Allan; Lacaze, Paul; Flanagan, Katie L; Stenson, Benjamin J; Ghazal, Peter

    2014-08-14

    Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

  5. Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs.

    Science.gov (United States)

    Vlasova, Anastasia N; Paim, Francine C; Kandasamy, Sukumar; Alhamo, Moyasar A; Fischer, David D; Langel, Stephanie N; Deblais, Loic; Kumar, Anand; Chepngeno, Juliet; Shao, Lulu; Huang, Huang-Chi; Candelero-Rueda, Rosario A; Rajashekara, Gireesh; Saif, Linda J

    2017-01-01

    Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103 + and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates

  6. Influence of maternal antibodies on active pertussis toxoid immunization of neonatal mice and piglets.

    Science.gov (United States)

    Polewicz, Monika; Gracia, Aleksandra; Buchanan, Rachelle; Strom, Stacy; Halperin, Scott A; Potter, Andrew A; Babiuk, Lorne A; Gerdts, Volker

    2011-10-13

    Whooping cough caused by infection with Bordetella pertussis, is a serious illness in infants and young children. Mortality due to whooping cough is being reported in infants too young to be immunized as well as those who have not completed their series of vaccinations. One of the major factors that interferes with successful active immunization in early life is the presence of maternal antibodies (MatAbs). Using the mouse and pig models, we evaluated the effect of maternal antibodies on active immunization with pertussis toxoid (PTd) and explored strategies to overcome this interference. Our results indicate that passively transferred maternal antibodies interfered with active immunization using pertussis toxoid. The level of passively transferred antibodies directly correlated with the level of interference observed. However, this interference could be overcome by using a second booster immunization or by co-formulating the toxoid with novel adjuvants. These results support the need for novel vaccine formulations that are optimized for the neonate and that can be used not only to modulate the inherently biased neonatal immune system but also to prime the response in the presence of passively transferred maternal antibodies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    Science.gov (United States)

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  8. Siblings Promote a Type 1/Type 17-oriented immune response in the airways of asymptomatic neonates

    DEFF Research Database (Denmark)

    Wolsk, Helene Mygind; Chawes, Bo L.; Følsgaard, Nilofar V.

    2016-01-01

    effect. These findings may represent an in-utero immune priming effect of the fetal immune system caused by previous pregnancies as the effect was attenuated with time since last childbirth or presence of unidentified microbes, but further studies are needed to confirm our findings.......-related mediators. This was supported by the PCA showing a highly significant difference between children with vs. without siblings: ppriming effect was inversely...... associated with time since last childbirth: p=0.0015. CONCLUSIONS: Siblings mediate a Type 1/Type 17-related immune-stimulatory effect in the airways of asymptomatic neonates, also after adjustment for pathogenic bacteria and viruses, indicating that siblings exert a transferable early immune modulatory...

  9. Immune cells and non-immune cells with immune function in mammalian cochleae.

    Science.gov (United States)

    Hu, Bo Hua; Zhang, Celia; Frye, Mitchell D

    2017-12-20

    The cochlea has an immune environment dominated by macrophages under resting conditions. When stressed, circulating monocytes enter the cochlea. These immune mediators, along with cochlear resident cells, organize a complex defense response against pathological challenges. Since the cochlea has minimal exposure to pathogens, most inflammatory conditions in the cochlea are sterile. Although the immune response is initiated for the protection of the cochlea, off-target effects can cause collateral damage to cochlear cells. A better understanding of cochlear immune capacity and regulation would therefore lead to development of new therapeutic treatments. Over the past decade, there have been many advances in our understanding of cochlear immune capacity. In this review, we provide an update and overview of the cellular components of cochlear immune capacity with a focus on macrophages in mammalian cochleae. We describe the composition and distribution of immune cells in the cochlea and suggest that phenotypic and functional characteristics of macrophages have site-specific diversity. We also highlight the response of immune cells to acute and chronic stresses and comment on the potential function of immune cells in cochlear homeostasis and disease development. Finally, we briefly review potential roles for cochlear resident cells in immune activities of the cochlea. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

    Science.gov (United States)

    Roger, Thierry; Schneider, Anina; Weier, Manuela; Sweep, Fred C G J; Le Roy, Didier; Bernhagen, Jürgen; Calandra, Thierry; Giannoni, Eric

    2016-02-23

    The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

  11. 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

  12. 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.

  13. 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.

  14. Mental resilience, perceived immune functioning, and health

    Directory of Open Access Journals (Sweden)

    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

  15. Macrophages in Homeostatic Immune Function

    Directory of Open Access Journals (Sweden)

    Jonathan eJantsch

    2014-05-01

    Full Text Available Macrophages are not only involved in inflammatory and anti-infective processes, but also play an important role in maintaining tissue homeostasis. In this review, we summarize recent evidence investigating the role of macrophages in controlling angiogenesis, metabolism and salt and water balance. Particularly, we summarize the importance of macrophage tonicity enhancer binding protein (TonEBP, also termed nuclear factor of activated T-cells 5 [NFAT5] expression in the regulation of salt and water homeostasis. Further understanding of homeostatic macrophage function may lead to new therapeutic approaches to treat ischemia, hypertension and metabolic disorders.

  16. Role of Polyamines in Immune Cell Functions

    Directory of Open Access Journals (Sweden)

    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.

  17. Effects of smoking in pregnancy on neonatal lung function

    OpenAIRE

    Milner, A.; Marsh, M.; Ingram, D.; Fox, G.; Susiva, C.

    1999-01-01

    AIMS—To assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking.
METHODS—Lung function tests were carried out within 72 hours of delivery in infants born to 100 non-smoking and 189 smoking mothers. Lung growth was assessed by plethysmography and lung mechanics using the single breath occlusion technique and oesophageal balloon/ pneumotachography. Antenatal maternal serum cotin...

  18. Stratum corneum maturation. A review of neonatal skin function.

    Science.gov (United States)

    Chiou, Y B; Blume-Peytavi, U

    2004-01-01

    The importance of the stratum corneum and its barrier function for infants, especially for newborns, is clinically evident. Research regarding the maturation of the stratum corneum in neonates, i.e. when full barrier function is obtained, has produced varying results. Based on transepidermal water loss and percutaneous absorption studies, term infants seem to possess stratum corneum with adult barrier properties. Additionally, postnatal life is thought to accelerate stratum corneum maturation, so that even preterm infants have barrier function similar to term infants at 2-3 weeks of gestational age. However, a look at other parameters, such as skin thickness, skin pH and stratum corneum hydration, shows that neonatal skin is always adjusting to the extrauterine environment in contrast to the steady state of adult skin. This suggests that barrier stabilization may be dependent on achieving a balance between different parameters. However, it is still in question, which parameters, what balance and what timing. This paper provides an up-to-date overview on the neonatal skin barrier based on the review of current literature. Copyright 2004 S. Karger AG, Basel

  19. Zinc as a Gatekeeper of Immune Function

    OpenAIRE

    Wessels, Inga; Maywald, Martina; Rink, Lothar

    2017-01-01

    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, underly...

  20. Effect of chromium tripicolinate supplementation on porcine immune response during the periparturient and neonatal period.

    Science.gov (United States)

    van de Ligt, J L G; Lindemann, M D; Harmon, R J; Monegue, H J; Cromwell, G L

    2002-02-01

    A total of 36 gilts were used to assess the effects of Cr tripicolinate supplementation on immune response in sows and their offspring during the periparturient and neonatal period. Gilts were raised from weaning to reproductive age on diets with either 0 (-Cr) or 200 (+Cr) ppb supplemental Cr from CrPic. Subsequently, 22 gilts (9 -Cr and 13 +Cr) in parity 1 and 16 sows in parity 2 (7 -Cr and 9 +Cr) underwent immune status testing. Only sows that completed all procedures in parity 1 were included in parity 2. Sows were immunized with ovalbumin about 3 wk (d 0), and again 14 d later for gilts, prior to anticipated farrowing, and serum was collected on d 0 and at 14-d intervals for a total of four samples. Serum was collected from five to six pigs/litter at 24 h after birth, three or six pigs/litter the day after weaning (25 d of age) in parity 1, and three pigs/litter the day of weaning (20 d of age) in parity 2. Milk was collected at 1 h (colostrum), 6.5 d (early), and 19 d (late) after farrowing. The only effect of Cr on total immunoglobulin (Ig) concentration was on sow serum IgG (21.7 and 24.1 mg/mL for -Cr and +Cr, respectively; P = 0.08) and IgM (11.0 and 12.5 mg/mL; P = 0.06) on d 0. No effect (P > 0.15) of Cr was observed on the IgG antibody response to ovalbumin, but Cr was associated (P < 0.10) with a decreased IgM antibody response to ovalbumin beginning on d 14. In parity 2, colostral total IgG increased (80.6 and 92.4 mg/mL for parity 1 and 2, respectively; P = 0.06), which was reflected in the neonates at 24 h after birth (33.6 and 39.7 mg/mL; P = 0.01) and at weaning (7.3 and 13.3 mg/mL; P < 0.001). Supplementation of Cr tripicolinate had minimal effects on humoral antibody response of the dam or its transfer to the neonate; however, parity greatly influenced the concentrations of immunoglobulins in the milk and their transfer to the neonate.

  1. Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge

    Directory of Open Access Journals (Sweden)

    Erin Jane Campbell

    2015-03-01

    Full Text Available Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS, during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13 were exposed to either LPS or saline (0.05mg/kg, i.p on postnatal days (PND 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.

  2. Zinc as a Gatekeeper of Immune Function

    Directory of Open Access Journals (Sweden)

    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.

  3. Neutrophil functions in late preterm neonates with respiratory ...

    African Journals Online (AJOL)

    Further studies are recommended to elucidate the exact mechanisms by which RDS can affect neutrophil functions and whether these effects are associated with increased incidence of infections. Keywords: Neutrophils, function, respiratory distress syndrome, late preterm, innate immunity, infections, adhesion molecules ...

  4. Effect of oral antigen and antibody exposure at birth on subsequent immune status. A study in neonatal pigs.

    Science.gov (United States)

    Haverson, Karin; Corfield, Gaynor; Jones, Philip H; Kenny, Martin; Fowler, Jenny; Bailey, Mick; Stokes, Christopher R; Miller, Bevis G

    2009-01-01

    The purpose of this work was to investigate the effects of early low-level exposure to either antigen or antibody alone on subsequent immune responses in entirely immunologically naïve animals. This is impossible in species with a permeable placenta such as rodents or humans, where both antigen and antibody can be transferred in utero. It is, however, possible in pigs, due to the impermeable placenta of the sow. Thus, neonatal piglets were used for this study. Newborn piglets were exposed to ovalbumin (OVA) at dosages similar to those used in rodents to sensitise, as well as to serum containing anti-OVA antibodies. Both single low doses of OVA (10 and 1,000 mg per animal) induced classical oral tolerance following a systemic challenge: both doses reduced specific systemic IgG responses and tertiary in vitro recall proliferative responses by splenocytes and especially by mesenteric lymph node (MLN) cells. Additionally, dietary challenge had phenotypic effects on helper T cells in MLN, which could be reversed by OVA at birth. In contrast, giving antibody as serum collected from hyperimmune or orally tolerant pigs had no functional effects. Overall, our data support the hypothesis that contrary to previous work in rodents, very early exposure of neonatal pigs to a single small dose of antigen can reduce subsequent immune responses. This may have implications for human health. However, although these data point to a reducing/regulatory effect of low doses of antigen in very young animals, they cannot be extrapolated directly to allergy. (c) 2009 S. Karger AG, Basel.

  5. Functional photoacoustic tomography for neonatal brain imaging: developments and challenges

    Science.gov (United States)

    Hariri, Ali; Tavakoli, Emytis; Adabi, Saba; Gelovani, Juri; Avanaki, Mohammad R. N.

    2017-03-01

    Transfontanelle ultrasound imaging (TFUSI) is a routine diagnostic brain imaging method in infants who are born prematurely, whose skull bones have not completely fused together and have openings between them, so-called fontanelles. Open fontanelles in neonates provide acoustic windows, allowing the ultrasound beam to freely pass through. TFUSI is used to rule out neurological complications of premature birth including subarachnoid hemorrhage (SAH), intraventricular (IVH), subependimal (SEPH), subdural (SDH) or intracerebral (ICH) hemorrhages, as well as hypoxic brain injuries. TFUSI is widely used in the clinic owing to its low cost, safety, accessibility, and noninvasive nature. Nevertheless, the accuracy of TFUSI is limited. To address several limitations of current clinical imaging modalities, we develop a novel transfontanelle photoacoustic imaging (TFPAI) probe, which, for the first time, should allow for non-invasive structural and functional imaging of the infant brain. In this study, we test the feasibility of TFPAI for detection of experimentally-induced intra ventricular and Intraparenchymal hemorrhage phantoms in a sheep model with a surgically-induced cranial window which will serve as a model of neonatal fontanelle. This study is towards using the probe we develop for bedside monitoring of neonates with various disease conditions and complications affecting brain perfusion and oxygenation, including apnea, asphyxia, as well as for detection of various types of intracranial hemorrhages (SAH, IVH, SEPH, SDH, ICH).

  6. Immune functions of the garment workers.

    Science.gov (United States)

    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.

  7. Parasitism, host immune function, and sexual selection.

    Science.gov (United States)

    Møller, A P; Christe, P; Lux, E

    1999-03-01

    Parasite-mediated sexual selection may arise as a consequence of 1) females avoiding mates with directly transmitted parasites, 2) females choosing less-parasitized males that provide parental care of superior quality, or 3) females choosing males with few parasites in order to obtain genes for parasite resistance in their offspring. Studies of specific host-parasite systems and comparative analyses have revealed both supportive and conflicting evidence for these hypotheses. A meta-analysis of the available evidence revealed a negative relationship between parasite load and the expression of male secondary sexual characters. Experimental studies yielded more strongly negative relationships than observations did, and the relationships were more strongly negative for ectoparasites than for endoparasites. There was no significant difference in the magnitude of the negative effect for species with and without male parental care, or between behavioral and morphological secondary sexual characters. There was a significant difference between studies based on host immune function and those based on parasite loads, with stronger effects for measures of immune function, suggesting that the many negative results from previous analyses of parasite-mediated sexual selection may be explained because relatively benign parasites were studied. The multivariate analyses demonstrating strong effect sizes of immune function in relation to the expression of secondary sexual characters, and for species with male parental care as compared to those without, suggest that parasite resistance may be a general determinant of parasite-mediated sexual selection.

  8. Evaluation of several approaches to immunize parents of neonates against B. pertussis.

    Science.gov (United States)

    Frère, Julie; De Wals, Philippe; Ovetchkine, Philippe; Coïc, Léna; Audibert, François; Tapiero, Bruce

    2013-12-09

    Parental immunization ("cocooning") is a potentially effective strategy to protect neonates against Bordetella pertussis. The objective of this study was to evaluate three approaches to parental immunization: (1) current practice (single dTap dose to adolescents, one additional dose recommended in adults); (2) promotion of vaccination in the maternity ward, with vaccine offered in the community; and (3) promotion and administration of vaccine in the maternity ward. We conducted a two-phase study of postpartum women in a tertiary care obstetric-pediatric hospital in Montreal, Canada. In Phase I, mothers completed a standardized questionnaire regarding pertussis knowledge, attitudes and immunization status. Interviews provided information on cocooning and pertussis vaccination, and invited parents to receive the vaccine in the community. In phase II, information was provided (no questionnaire) with vaccination offered in the maternity ward before discharge. Phase I included 101 participants; Phase II, 244. Baseline knowledge on infant disease severity and adult vaccine recommendations was poor. Only 6% of women were considered protected. In Phase I, 56.3% and 62.5% of eligible mothers and fathers, respectively, were willing to receive the vaccine; only 5.4% and 8.7% were immunized in the community. In Phase II, 53.1% and 62.6% of mothers and fathers, respectively, would accept vaccination; 46.9% of mothers and 60.5% of fathers were immunized onsite (pvaccine in the maternity ward is an effective approach to promote cocooning and increase vaccine uptake. The generalizability and cost effectiveness of this strategy should be investigated further. Copyright © 2013. Published by Elsevier Ltd.

  9. Innate immune responses to human rotavirus in the neonatal gnotobiotic piglet disease model.

    Science.gov (United States)

    González, Ana M; Azevedo, Marli S P; Jung, Kwonil; Vlasova, Anastasia; Zhang, Wei; Saif, Linda J

    2010-10-01

    Intestinal and systemic dendritic cell (DC) frequencies, serum and small intestinal content cytokines and uptake/binding of human rotavirus (HRV) virus-like particles (VLP) were studied in HRV acutely infected or mock-inoculated neonatal gnotobiotic piglets. Intestinal, mesenteric lymph node (MLN) and splenic plasmacytoid DCs (pDCs), conventional DCs (cDCs) and macrophages/monocytes were assessed by flow cytometry. In infected pigs, serum and small intestinal content interferon-α (IFN-α) were highest, interleukin-12 (IL-12) was lower and IL-10, tumour necrosis factor-α and IL-6 were minimal. Compared with mock-inoculated piglets, frequencies of total intestinal DCs were higher; splenic and MLN DC frequencies were lower. Most intestinal pDCs, but few cDCs, were IFN-α(+) and intestinal macrophages/monocytes were negative for IFN-α. Serum IFN-α levels and IFN-α(+) intestinal pDCs were highly correlated, suggesting IFN-α production in vivo by intestinal pDCs (r=0·8; Pintestinal pDCs and cDCs, but not intestinal macrophages/monocytes, of HRV-infected piglets showed significantly lower VLP uptake/binding compared with mock-inoculated piglets, suggesting higher activation of pDCs and cDCs in infected piglets. Both intestinal pDCs and cDCs were activated (IFN-α(+) and lower VLP binding) after HRV infection, suggesting their role in induction of HRV-specific immunity. Dose-effects of HRV on serum IFN-α and IFN-α(+) DCs were studied by infecting piglets with 100-fold higher HRV dose. A high dose increased parameters associated with inflammation (diarrhoea, intestinal pathology) but serum IFN-α and IFN-α(+) DCs were similar between both groups. The pDCs have both anti- and pro-inflammatory functions. Stimulation of the anti-inflammatory effects of pDCs after the high dose, without increasing their pro-inflammatory impacts, may be critical to reduce further immunopathology during HRV infection. © 2010 The Authors. Immunology © 2010 Blackwell Publishing Ltd.

  10. Potential role of the intestinal microbiota of the mother in neonatal immune education.

    Science.gov (United States)

    Donnet-Hughes, Anne; Perez, Pablo F; Doré, Joël; Leclerc, Marion; Levenez, Florence; Benyacoub, Jalil; Serrant, Patrick; Segura-Roggero, Iris; Schiffrin, Eduardo J

    2010-08-01

    Mucosal dendritic cells are at the heart of decision-making processes that dictate immune reactivity to intestinal microbes. They ensure tolerance to commensal bacteria and a vigorous immune response to pathogens. It has recently been demonstrated that the former involves a limited migration of bacterially loaded dendritic cells from the Peyer's patches to the mesenteric lymph nodes. During lactation, cells from gut-associated lymphoid tissue travel to the breast via the lymphatics and peripheral blood. Here, we show that human peripheral blood mononuclear cells and breast milk cells contain bacteria and their genetic material during lactation. Furthermore, we show an increased bacterial translocation from the mouse gut during pregnancy and lactation and the presence of bacterially loaded dendritic cells in lactating breast tissue. Our observations show bacterial translocation as a unique physiological event, which is increased during pregnancy and lactation. They suggest endogenous transport of intestinally derived bacterial components within dendritic cells destined for the lactating mammary gland. They also suggest neonatal immune imprinting by milk cells containing commensal-associated molecular patterns.

  11. Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis.

    Science.gov (United States)

    Sherman, Michael P; Zaghouani, Habib; Niklas, Victoria

    2015-01-01

    The conceptual framework for a gut-brain axis has existed for decades. The Human Microbiome Project is responsible for establishing intestinal dysbiosis as a mediator of inflammatory bowel disease, obesity, and neurodevelopmental disorders in adults. Recent advances in metagenomics implicate gut microbiota and diet as key modulators of the bidirectional signaling pathways between the gut and brain that underlie neurodevelopmental and psychiatric disorders in adults. Evidence linking intestinal dysbiosis to neurodevelopmental disease outcomes in preterm infants is emerging. Recent clinical studies show that intestinal dysbiosis precedes late-onset neonatal sepsis and necrotizing enterocolitis in intensive care nurseries. Moreover, strong epidemiologic evidence links late-onset neonatal sepsis and necrotizing enterocolitis in long-term psychomotor disabilities of very-low-birth-weight infants. The notion of the gut-brain axis thereby supports that intestinal microbiota can indirectly harm the brain of preterm infants. In this review, we highlight the anatomy and physiology of the gut-brain axis and describe transmission of stress signals caused by immune-microbial dysfunction in the gut. These messengers initiate neurologic disease in preterm infants. Understanding neural and humoral signaling through the gut-brain axis will offer insight into therapeutic and dietary approaches that may improve the outcomes of very-low-birth-weight infants.

  12. 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

  13. 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

  14. The innate immune response to lower respiratory tract E. Coli infection and the role of the CCL2-CCR2 axis in neonatal mice.

    Science.gov (United States)

    McGrath-Morrow, Sharon A; Ndeh, Roland; Collaco, Joseph M; Poupore, Amy K; Dikeman, Dustin; Zhong, Qiong; Singer, Benjamin D; D'Alessio, Franco; Scott, Alan

    2017-09-01

    Neonates have greater morbidity/mortality from lower respiratory tract infections (LRTI) compared to older children. Lack of conditioning of the pulmonary immune system due to limited environmental exposures and/or infectious challenges likely contributes to the increase susceptibility in the neonate. In this study, we sought to gain insights into the nature and dynamics of the neonatal pulmonary immune response to LRTI using a murine model. Wildtype (WT) and Ccr2 -/- C57BL/6 neonatal and juvenile mice received E. coli or PBS by direct pharyngeal aspiration. Flow cytometry was used to measure immune cell dynamics and identify cytokine-producing cells. Real-time PCR and ELISA were used to measure cytokine/chemokine expression. Innate immune cell recruitment in response to E. coli-induced LRTI was delayed in the neonatal lung compared to juvenile lung. Lung clearance of bacteria was also significantly delayed in the neonate. Ccr2 -/- neonates, which lack an intact CCL2-CCR2 axis, had higher mortality after E. coli challenged than Ccr2 +/+ neonates. A greater percentage of CD8 + T cells and monocytes from WT neonates challenged with E. coli produced TNF compared to controls. The pulmonary immune response to E. coli-induced LRTI differed significantly between neonatal and juvenile mice. Neonates were more susceptible to increasing doses of E. coli and exhibited greater mortality than juveniles. In the absence of an intact CCL2-CCR2 axis, susceptibility to LRTI-induced mortality was further increased in neonatal mice. Taken together these findings underscore the importance of age-related differences in the innate immune response to LRTI during early stages of postnatal life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dietary supplementation of mannan-oligosaccharide enhances neonatal immune responses in chickens during natural exposure to Eimeria spp

    Directory of Open Access Journals (Sweden)

    Nava Gerardo M

    2009-03-01

    Full Text Available Abstract Background Control and eradication of intestinal infections caused by protozoa are important biomedical challenges worldwide. Prophylactic control of coccidiosis has been achieved with the use of anticoccidial drugs; however, the increase in anticoccidial resistance has raised concerns about the need for new alternatives for the control of coccidial infections. In fact, new strategies are needed to induce potent protective immune responses in neonatal individuals. Methods The effects of a dietary supplementation of mannan-oligosaccharide (yeast cell wall; YCW on the local, humoral and cell-mediated immune responses, and intestinal replication of coccidia were evaluated in a neonatal animal model during natural exposure to Eimeria spp. A total of 840 one-day-old chicks were distributed among four dietary regimens: A Control diet (no YCW plus anticoccidial vaccine; B Control diet plus coccidiostat; C YCW diet plus anticoccidial vaccination; and D YCW diet plus coccidiostat. Weight gain, feed consumption and immunological parameters were examined within the first seven weeks of life. Results Dietary supplementation of 0.05% of YCW increased local mucosal IgA secretions, humoral and cell-mediated immune responses, and reduced parasite excretion in feces. Conclusion Dietary supplementation of yeast cell wall in neonatal animals can enhance the immune response against coccidial infections. The present study reveals the potential of YCW as adjuvant for modulating mucosal immune responses.

  16. Basics of Functional Echocardiography in Children and Neonates

    Directory of Open Access Journals (Sweden)

    Cécile Tissot

    2017-12-01

    Full Text Available Functional echocardiography has become an invaluable tool in the pediatric and neonatal intensive care unit. “Point-of-care,” “target,” or “focus” echocardiography allows bedside cardiac ultrasound evaluation of the hemodynamic status of the patient, helps in directing treatment, thus improves patients care. In order to be able to perform functional echocardiography, it is essential to understand the principles of ultrasound, to know the echocardiographic equipment and settings necessary to acquire the images. This article focuses therefore on the basics of cardiac ultrasound. It is meant to give an overview of two-dimensional echocardiographic views, M-mode imaging and Doppler echocardiography for neonatologists and pediatric intensivists. It is richly illustrated for better understanding with some examples of clinical applications of functional echocardiography in the intensive care setting.

  17. Cryopreserved neonatal hepatocytes may be a source for transplantation: Evaluation of functionality toward clinical use.

    Science.gov (United States)

    Lee, Charlotte A; Dhawan, Anil; Iansante, Valeria; Lehec, Sharon; Khorsandi, Shirin E; Filippi, Celine; Walker, Simon; Fernandez-Dacosta, Raquel; Heaton, Nigel; Bansal, Sanjay; Mitry, Ragai R; Fitzpatrick, Emer

    2018-03-01

    Neonatal livers are a potential source of good-quality hepatocytes for clinical transplantation. We compared viability and function of neonatal hepatocytes (NHs) and adult hepatocytes (AHs) and report their clinical use both intraportally and in alginate microbeads. Following isolation from donor livers, hepatocyte function was assessed using albumin, alpha-1-antitrypsin, and factor VII. Metabolic function was investigated by measuring resorufin conjugation, ammonia metabolism, uridine diphosphate glucuronosyltransferase enzyme activity, and cytochrome P450 (CYP) function following induction. Activation of the instant blood-mediated inflammatory reaction by NHs and AHs was investigated using an in vitro blood perfusion model, and tissue factor expression was analyzed using real-time polymerase chain reaction (RT-PCR). Clinical hepatocyte transplantation (HT) was undertaken using standard protocols. Hepatocytes were isolated from 14 neonatal livers, with an average viability of 89.4% ± 1.8% (mean ± standard error of the mean) and average yield of 9.3 × 10 6 ± 2.0 × 10 6 cells/g. Hepatocytes were isolated from 14 adult livers with an average viability of 78.6% ± 2.4% and yield 2.2 × 10 6 ± 0.5 × 10 5 cells/g. NHs had significantly higher viability after cryopreservation than AHs, with better attachment efficiency and less plasma membrane leakage. There were no differences in albumin, alpha-1-antitrypsin, and factor VII synthesis between NHs and AHs (P > 0.05). Neonatal cells had inducible phase 1 enzymes as assessed by CYP function and functional phase 2 enzymes, in which activity was comparable to AHs. In an in vitro blood perfusion model, AHs elicited increased thrombus formation with a greater consumption of platelets and white cells compared with NHs (28.3 × 10 9 versus 118.7 × 10 9 and 3.3 × 10 9 versus 6.6 × 10 9 ; P < 0.01). Intraportal transplantation and intraperitoneal transplantation of alginate encapsulated hepatocytes was safe, and

  18. Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate immune responses to human rotavirus in neonatal gnotobiotic pigs.

    Directory of Open Access Journals (Sweden)

    Anastasia N Vlasova

    significantly decreased MNC proliferation, suggesting that probiotics control excessive lymphoproliferative reactions upon VirHRV challenge. We conclude that in the neonatal Gn pig disease model, selected probiotics contribute to immunomaturation, regulate immune homeostasis and modulate vaccine and virulent HRV effects, thereby moderating HRV diarrhea.

  19. 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.

  20. Functional Classification of Immune Regulatory Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Rubinstein, Rotem [Albert Einstein College of Medicine, Bronx, NY (United States); Ramagopal, Udupi A. [Albert Einstein College of Medicine, Bronx, NY (United States); Nathenson, Stanley G. [Albert Einstein College of Medicine, Bronx, NY (United States); Almo, Steven C. [Albert Einstein College of Medicine, Bronx, NY (United States); Fiser, Andras [Albert Einstein College of Medicine, Bronx, NY (United States)

    2013-05-01

    Members of the immunoglobulin superfamily (IgSF) control innate and adaptive immunity and are prime targets for the treatment of autoimmune diseases, infectious diseases, and malignancies. We describe a computational method, termed the Brotherhood algorithm, which utilizes intermediate sequence information to classify proteins into functionally related families. This approach identifies functional relationships within the IgSF and predicts additional receptor-ligand interactions. As a specific example, we examine the nectin/nectin-like family of cell adhesion and signaling proteins and propose receptor-ligand interactions within this family. We were guided by the Brotherhood approach and present the high-resolution structural characterization of a homophilic interaction involving the class-I MHC-restricted T-cell-associated molecule, which we now classify as a nectin-like family member. The Brotherhood algorithm is likely to have a significant impact on structural immunology by identifying those proteins and complexes for which structural characterization will be particularly informative.

  1. Intense exercise training and immune function.

    Science.gov (United States)

    Gleeson, Michael; Williams, Clyde

    2013-01-01

    Regular moderate exercise reduces the risk of infection compared with a sedentary lifestyle, but very prolonged bouts of exercise and periods of intensified training are associated with increased infection risk. In athletes, a common observation is that symptoms of respiratory infection cluster around competitions, and even minor illnesses such as colds can impair exercise performance. There are several behavioral, nutritional and training strategies that can be adopted to limit exercise-induced immunodepression and minimize the risk of infection. Athletes and support staff can avoid transmitting infections by avoiding close contact with those showing symptoms of infection, by practicing good hand, oral and food hygiene and by avoiding sharing drinks bottles and cutlery. Medical staff should consider appropriate immunization for their athletes particularly when travelling to international competitions. The impact of intensive training stress on immune function can be minimized by getting adequate sleep, minimizing psychological stress, avoiding periods of dietary energy restriction, consuming a well-balanced diet that meets energy and protein needs, avoiding deficiencies of micronutrients (particularly iron, zinc, and vitamins A, D, E, B6 and B12), ingesting carbohydrate during prolonged training sessions, and consuming - on a daily basis - plant polyphenol containing supplements or foodstuffs and Lactobacillus probiotics. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  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. 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

    (n-3) PUFA influence immune function in adults and may also affect immune maturation during development. This randomized trial is, to our knowledge, the first to investigate whether fish oil supplementation in late infancy modifies immune responses. The study was a 2 x 2 intervention in 64 health...

  4. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

    Directory of Open Access Journals (Sweden)

    Daniel H. Libraty

    2014-01-01

    Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

  5. Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor FcγRIIB expression on B cells

    Directory of Open Access Journals (Sweden)

    Duarte Alberto JS

    2010-03-01

    Full Text Available Abstract Background Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. Results Maternal immunization with OVA showed increased levels of FcγRIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-γ-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced FcγRIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. Conclusion Maternal immunization upregulates the inhibitory FcγRIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

  6. Functional characteristics of neonatal rat β cells with distinct markers

    DEFF Research Database (Denmark)

    Martens, G A; Motté, E; Kramer, G

    2014-01-01

    twofold lower expression of malate/aspartate-NADH shuttle and most glycolytic enzymes. Genome-wide profiling situated neonatal β cells at a developmental crossroad: they showed advanced endocrine differentiation when specifically analyzed for their mRNA/protein level of classical neuroendocrine markers....... On the other hand, discrete neonatal β cell subpopulations still expressed mRNAs/proteins typical for developing/proliferating tissues. One example, delta-like 1 homolog (DLK1) was used to investigate whether neonatal β cells with basal hyperactivity corresponded to a more immature subset with high DLK1......Neonatal β cells are considered developmentally immature and hence less glucose responsive. To study the acquisition of mature glucose responsiveness, we compared glucose-regulated redox state, insulin synthesis, and secretion of β cells purified from neonatal or 10-week-old rats...

  7. Wideband acoustic immittance for assessing middle ear functioning for preterm neonates in the neonatal intensive care unit

    Directory of Open Access Journals (Sweden)

    Nandel Gouws

    2017-06-01

    Full Text Available Background: The primary aim of newborn hearing screening is to detect permanent hearing loss. Because otoacoustic emissions (OAEs and automated auditory brainstem response (AABR are sensitive to hearing loss, they are often used as screening tools. On the other hand, false-positive results are most often because of transient outer- and middle ear conditions. Wideband acoustic immittance (WAI, which includes physical measures known as reflectance and absorbance, has shown potential for accurate assessment of middle ear function in young infants. Objective: The main objective of this study was to determine the feasibility of WAI as a diagnostic tool for assessing middle ear functioning in preterm neonates in the neonatal intensive care unit (NICU designed for premature and ill neonates. A further objective was to indicate the difference between the reflectance values of tones and click stimuli. Method: Fifty-six at-risk neonates (30 male and 26 female, with a mean age at testing of 35.6 weeks (range: 32–37 weeks and a standard deviation of 1.6 from three private hospitals, who passed both the distortion product otoacoustic emission (DPOAE and AABR tests, were evaluated prior to discharge from the NICU. Neonates who presented with abnormal DPOAE and AABR results were excluded from the study. WAI was measured by using chirp and tone stimuli. In addition to reflectance, the reflectance area index (RAI values were calculated. Results: Both tone and chirp stimuli indicated high-power reflectance values below a frequency of 1.5 kHz. Median reflectance reached a minimum of 0.67 at 1 kHz – 2 kHz but increased to 0.7 below 1 kHz and 0.72 above 2 kHz for the tone stimuli. For chirp stimuli, the median reflectance reached a minimum of 0.51 at 1 kHz – 2 kHz but increased to 0.68 below 1 kHz and decreased to 0.5 above 2 kHz. A comparison between the present study and previous studies on WAI indicated a substantial variability across all frequency ranges

  8. The Neonatal Window of Opportunity: Setting the Stage for Life-Long Host-Microbial Interaction and Immune Homeostasis.

    Science.gov (United States)

    Torow, Natalia; Hornef, Mathias W

    2017-01-15

    The existence of a neonatal window was first highlighted by epidemiological studies that revealed the particular importance of this early time in life for the susceptibility to immune-mediated diseases in humans. Recently, the first animal studies emerged that present examples of early-life exposure-triggered persisting immune events, allowing a detailed analysis of the factors that define this particular time period. The enteric microbiota and the innate and adaptive immune system represent prime candidates that impact on the pathogenesis of immune-mediated diseases and are known to reach a lasting homeostatic equilibrium following a dynamic priming period after birth. In this review, we outline the postnatal establishment of the microbiota and maturation of the innate and adaptive immune system and discuss examples of early-life exposure-triggered immune-mediated diseases that start to shed light on the critical importance of the early postnatal period for life-long immune homeostasis. Copyright © 2017 by The American Association of Immunologists, Inc.

  9. 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...... 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......) 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...

  10. 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.

  11. 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

  12. Modulation of immune functions by oestrogens. Part II

    Directory of Open Access Journals (Sweden)

    Jacek R. Wilczyński

    2010-06-01

    Full Text Available One of the most important functions of oestrogens is modulation of the immune system. By interactionswith specific oestrogen receptors ERα and ERβ these sex steroid hormones are capable of regulating manyaspects of both natural and adaptive immunity. Aging and the hypoestrogenic state can therefore influenceimmunological functions. Use of drugs belonging to SERM or isoflavons could also modify immune response inpost-menopausal women. All those phenomena might influence the risk of cancer initiation and the naturalcourse of tumour growth.

  13. Functional connectivity disruption in neonates with prenatal marijuana exposure

    Directory of Open Access Journals (Sweden)

    Karen eGrewen

    2015-11-01

    Full Text Available Prenatal marijuana exposure (PME is linked to neurobehavioral and cognitive impairments, however findings in childhood and adolescence are inconsistent. Type-1 cannabinoid receptors (CB1R modulate fetal neurodevelopment, mediating PME effects on growth of functional circuitry sub-serving behaviors critical for academic and social success. The purpose of this study was to investigate the effects of prenatal marijuana on development of early brain functional circuitry prior to prolonged postnatal environmental influences. We measured resting state functional connectivity during unsedated sleep in infants at 2-6 weeks (+MJ: 20 with PME in combination with nicotine, alcohol, opiates, and/or SSRI; -MJ: 23 exposed to the same other drugs without marijuana, CTR: 20 drug free controls. Connectivity of subcortical seed regions with high fetal CB1R expression was examined. Marijuana-specific differences were observed in insula and three striatal connections: anterior insula – cerebellum, right caudate – cerebellum, right caudate – right fusiform gyrus/inferior occipital, left caudate – cerebellum. +MJ neonates had hypoconnectivity in all clusters compared with -MJ and CTR groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use. Compared with CTRs, both +MJ and -MJ groups demonstrated hyperconnectivity of left amygdala seed with orbital frontal cortex and hypoconnectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits.

  14. Thyroid function testing in neonates born to women with hypothyroidism.

    Science.gov (United States)

    McGovern, Matthew; Reyani, Zahra; O'Connor, Pamela; White, Martin; Miletin, Jan

    2016-12-01

    Our aim was to assess the utility of serum thyroxine and thyroid stimulating hormone performed at 10-14 days of life in diagnosing congenital hypothyroidism (CH) in babies born to mothers with hypothyroidism. This was a retrospective study of all babies born in a tertiary referral centre for neonatology over a 12-month period. Infants who had thyroid function testing (TFT) checked at 10-14 days of life because of maternal hypothyroidism during the period of study were included. The results of the newborn bloodspot and day 10-14 TFT were recorded along with whether or not patients were subsequently treated. Of the 319 patients included in the study, only two patients were found to have CH and in both cases the newborn blood spot had been abnormal. No extra cases of CH were detected from the thyroid test at 10-14 days and this practice should be discontinued due to the robust nature of existing newborn screening programmes. What is Known: • Congenital hypothyroidism(CH) is the commonest preventable cause of childhood intellectual impairment. • Family history of hypothyroidism has been implicated as a risk factor for CH. • CH has formed part of newborn screening since the 1970s. What is New: • There is no research recommending thyroid function testing at 10-14 days of life to detect CH in neonates born to mothers with hypothyroidism. • Thyroid function testing at 10-14 days of life does not improve diagnostic yield for CH in babies born to mothers with hypothyroidism. • Newborn blood spot remains the mainstay for accurate and timely diagnosis of CH.

  15. Design of a Functional Training Prototype for Neonatal Resuscitation

    Directory of Open Access Journals (Sweden)

    Sivaramakrishnan Rajaraman

    2014-11-01

    Full Text Available Birth Asphyxia is considered to be one of the leading causes of neonatal mortality around the world. Asphyxiated neonates require skilled resuscitation to survive the neonatal period. The project aims to train health professionals in a basic newborn care using a prototype with an ultimate objective to have one person at every delivery trained in neonatal resuscitation. This prototype will be a user-friendly device with which one can get trained in performing neonatal resuscitation in resource-limited settings. The prototype consists of a Force Sensing Resistor (FSR that measures the pressure applied and is interfaced with Arduino® which controls the Liquid Crystal Display (LCD and Light Emitting Diode (LED indication for pressure and compression counts. With the increase in population and absence of proper medical care, the need for neonatal resuscitation program is not well addressed. The proposed work aims at offering a promising solution for training health care individuals on resuscitating newborn babies under low resource settings.

  16. Assessment of renal functional maturation and injury in preterm neonates during the first month of life.

    Science.gov (United States)

    Gubhaju, Lina; Sutherland, Megan R; Horne, Rosemary S C; Medhurst, Alison; Kent, Alison L; Ramsden, Andrew; Moore, Lynette; Singh, Gurmeet; Hoy, Wendy E; Black, M Jane

    2014-07-15

    Worldwide, approximately 10% of neonates are born preterm. The majority of preterm neonates are born when the kidneys are still developing; therefore, during the early postnatal period renal function is likely reflective of renal immaturity and/or injury. This study evaluated glomerular and tubular function and urinary neutrophil gelatinase-associated lipocalin (NGAL; a marker of renal injury) in preterm neonates during the first month of life. Preterm and term infants were recruited from Monash Newborn (neonatal intensive care unit at Monash Medical Centre) and Jesse McPherson Private Hospital, respectively. Infants were grouped according to gestational age at birth: ≤28 wk (n = 33), 29-31 wk (n = 44), 32-36 wk (n = 32), and term (≥37 wk (n = 22)). Measures of glomerular and tubular function were assessed on postnatal days 3-7, 14, 21, and 28. Glomerular and tubular function was significantly affected by gestational age at birth, as well as by postnatal age. By postnatal day 28, creatinine clearance remained significantly lower among preterm neonates compared with term infants; however, sodium excretion was not significantly different. Pathological proteinuria and high urinary NGAL levels were observed in a number of neonates, which may be indicative of renal injury; however, there was no correlation between the two markers. Findings suggest that neonatal renal function is predominantly influenced by renal maturity, and there was high capacity for postnatal tubular maturation among preterm neonates. There is insufficient evidence to suggest that urinary NGAL is a useful marker of renal injury in the preterm neonate. Copyright © 2014 the American Physiological Society.

  17. 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.

  18. 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…

  19. 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.

  20. Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

    DEFF Research Database (Denmark)

    Siggers, Richard H.; Siggers, Jayda; Thymann, Thomas

    2011-01-01

    The gastrointestinal inflammatory disorder, necrotizing enterocolitis (NEC), is among the most serious diseases for preterm neonates. Nutritional, microbiological and immunological dysfunctions all play a role in disease progression but the relationship among these determinants is not understood...... (particularly colostrum) protects against disease. Hence, the transition from parenteral to enteral nutrition shortly after birth plays a pivotal role to secure gut growth, digestive maturation and an appropriate response to bacterial colonization in the sensitive gut of preterm neonates....

  1. Prenatal determinants of neonatal lung function in high-risk newborns

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Loland, Lotte; Holst, Klaus Kähler

    2009-01-01

    responsiveness to methacholine by transcutaneous oxygen measurements. Risk factor analyses included anthropometrics; demographics; socioeconomic factors; parental atopic history; previous deliveries; exposures during the third trimester to the mother's smoking, alcohol, and medicines; third trimester pregnancy...... complications including mother's asthma status; and mode of delivery. RESULTS: Lung function was determined in 404 neonates, age 6 weeks. Neonates with body mass index in the upper quartile had 14% lower baseline forced expiratory volume at 0.5 second, and neonates of mothers smoking during the third trimester...

  2. A novel model to study neonatal Escherichia coli sepsis and the effect of treatment on the human immune system using humanized mice.

    Science.gov (United States)

    Schlieckau, Florian; Schulz, Daniela; Fill Malfertheiner, Sara; Entleutner, Kathrin; Seelbach-Goebel, Birgit; Ernst, Wolfgang

    2018-04-19

    Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth. Humanized mice were infected with Escherichia coli (E. coli). Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed. The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes. The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal E. coli sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long-term effects for the immune system of the child. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

    Science.gov (United States)

    Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Nehlsen-Cannarella, Sandra; Morukov, Boris; Pierson, Duane; Sams, Clarence

    2007-01-01

    There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation

  4. 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...

  5. Neonatal irradiation nephropathy in the growing dog. I. Renal morphological and functional adaptations following neonatal, sublethal, whole-body irradiation

    International Nuclear Information System (INIS)

    Wilke, W.L.; Phemister, R.D.; Jaenke, R.S.

    1979-01-01

    Sixty beagles were used to study the effects of exposure to 330 R 60 Co γ radiation (bilateral, whole-body) at 2 days of age on renal functional and morphological development in the growing dog. A significant deficit in grams kidney per kilogram body weight was found in irradiated dogs at 50 days of age (P < 0.05), but not at 125 or 200 days of age. Glomerular filtration rate (GFR) per kilogram body weight and GFR per gram kidney were not significantly different between irradiated and nonirradiated dogs at 50, 125, or 200 days of age, but blood urea nitrogen (BUN) was significantly elevated in irradiated dogs throughout this period (P < 0.05). The fractional distribution of intracortical renal blood flow, as determined by radiolabeled microspheres, to the outermost cortex was found to be reduced in irradiated animals at all ages evaluated (P < 0.05). The fractional blood flow to the outermost renal cortex was negatively correlated with BUN in both irradiated (P < 0.05) and nonirradiated (P < 0.05) animals. Based on prior demonstrations of reductions in nephron numbers following similar irradiation, these data indicate increases in mean single nephron GFR and nephronal hypertrophy in the kidneys of the neonatally irradiated dog. The renal functional and morphological adaptations are sufficient to maintain adequate renal function in growing, neonatally irradiated dogs. The BUN elevations in irradiated dogs are believed to be related to changes in intracortical renal blood flow, rather than indicating renal insufficiency. The possible importance of the functional and morphological adaptations to the subsequent development of chronic renal failure in neonatally irradiated animals is discussed

  6. 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

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

    DEFF Research Database (Denmark)

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

    studies have documented existence of a classical innate immune response, there is mainly indirect evidence of functional adaptive immunity. To address this aspect, groups of zebrafish were vaccinated with DNA-vaccines against the rhabdoviruses VHSV, IHNV and SVCV. Seven weeks later, the fish were...... challenged with SVCV by immersion. Despite some variability between replicate aquaria, there was a protective effect of the homologous vaccine and no effect of the heterologous vaccines. The results therefore confirm the existence of not only a well developed but also a fully functional adaptive immune...

  8. Rubella immune status of neonates - a window towards seroprevalence among childbearing women.

    Science.gov (United States)

    Pejcic, Iris; Rankovic Janevski, Milica; Knezevic, Aleksandra; Jevtovic, Djordje; Stanojevic, Maja

    2016-08-19

    When contracted in pregnancy, rubella may cause serious chronic infection of the fetus and development of Congenital Rubella Syndrome. Despite widespread application of rubella vaccination, periodical outbreaks are still being reported worldwide. The aim of this study was to determine rubella seroprevalence and antibody levels in neonates in Serbia as a proxy of maternal serostatus. ELISA based serological testing for rubella was done in 599 neonates treated at the Institute of Neonatology in Belgrade, from January 2010 to December 2011. All individuals with rubella IgG concentration ≥10 IU/ml were considered seropositive for rubella. The mean age of enrolled neonates was 18 ± 6 days. The overall seroprevalence of rubella IgG antibodies among the tested neonates was 540/599(90.2 %, 95 % CI: 87.5-92.3). Seropositivity rate among sera of the neonates enrolled in 2010 was significantly higher than those collected in 2011 (p 30 as compared to those from mothers aged rubella seroprevalence among newborns in Serbia, as a proxy of rubella serostatus of childbearing aged women. Notably, declining trend of rubella antibodies toward diminishing titers suggest the importance of sustained rubella serosurvey and antenatal screening at the national level.

  9. Fibroblast growth factor 21 in breast milk controls neonatal intestine function.

    Science.gov (United States)

    Gavaldà-Navarro, Aleix; Hondares, Elayne; Giralt, Marta; Mampel, Teresa; Iglesias, Roser; Villarroya, Francesc

    2015-09-02

    FGF21 is a hormonal factor with important functions in the control of metabolism. FGF21 is found in rodent and human milk. Radiolabeled FGF21 administered to lactating dams accumulates in milk and is transferred to neonatal gut. The small intestine of neonatal (but not adult) mice highly expresses β-Klotho in the luminal area. FGF21-KO pups fed by FGF21-KO dams showed decreased expression and circulating levels of incretins (GIP and GLP-1), reduced gene expression of intestinal lactase and maltase-glucoamylase, and low levels of galactose in plasma, all associated with a mild decrease in body weight. When FGF21-KO pups were nursed by wild-type dams (expressing FGF21 in milk), intestinal peptides and digestive enzymes were up-regulated, lactase enzymatic activity was induced, and galactose levels and body weight were normalized. Neonatal intestine explants were sensitive to FGF21, as evidenced by enhanced ERK1/2 phosphorylation. Oral infusion of FGF21 into neonatal pups induced expression of intestinal hormone factors and digestive enzymes, lactase activity and lactose absorption. These findings reveal a novel role of FGF21 as a hormonal factor contributing to neonatal intestinal function via its presence in maternal milk. Appropriate signaling of FGF21 to neonate is necessary to ensure optimal digestive and endocrine function in developing intestine.

  10. Postnatal nutritional restriction affects growth and immune function of piglets with intra-uterine growth restriction.

    Science.gov (United States)

    Hu, Liang; Liu, Yan; Yan, Chuan; Peng, Xie; Xu, Qin; Xuan, Yue; Han, Fei; Tian, Gang; Fang, Zhengfeng; Lin, Yan; Xu, Shengyu; Zhang, Keying; Chen, Daiwen; Wu, De; Che, Lianqiang

    2015-07-14

    Postnatal rapid growth by excess intake of nutrients has been associated with an increased susceptibility to diseases in neonates with intra-uterine growth restricted (IUGR). The aim of the present study was to determine whether postnatal nutritional restriction could improve intestinal development and immune function of neonates with IUGR using piglets as model. A total of twelve pairs of normal-birth weight (NBW) and IUGR piglets (7 d old) were randomly assigned to receive adequate nutrient intake or restricted nutrient intake (RNI) by artificially liquid feeding for a period of 21 d. Blood samples and intestinal tissues were collected at necropsy and were analysed for morphology, digestive enzyme activities, immune cells and expression of innate immunity-related genes. The results indicated that both IUGR and postnatal nutritional restriction delayed the growth rate during the sucking period. Irrespective of nutrient intake, piglets with IUGR had a significantly lower villous height and crypt depth in the ileum than the NBW piglets. Moreover, IUGR decreased alkaline phosphatase activity while enhanced lactase activity in the jejunum and mRNA expressions of Toll-like receptor 9 (TLR-9) and DNA methyltransferase 1 (DNMT1) in the ileum of piglets. Irrespective of body weight, RNI significantly decreased the number and/or percentage of peripheral leucocytes, lymphocytes and monocytes of piglets, whereas the percentage of neutrophils and the ratio of CD4+ to CD8+ were increased. Furthermore, RNI markedly enhanced the mRNA expression of TLR-9 and DNMT1, but decreased the expression of NOD2 and TRAF-6 in the ileum of piglets. In summary, postnatal nutritional restriction led to abnormal cellular and innate immune response, as well as delayed the growth and intestinal development of IUGR piglets.

  11. Commonly Employed African Neonatal Skin Care Products Compromise Epidermal Function in Mice.

    Science.gov (United States)

    Man, Mao-Qiang; Sun, Richard; Man, George; Lee, Dale; Hill, Zelee; Elias, Peter M

    2016-09-01

    Neonatal mortality is much higher in the developing world than in developed countries. Infections are a major cause of neonatal death, particularly in preterm infants, in whom defective epidermal permeability barrier function facilitates transcutaneous pathogen invasion. The objective was to determine whether neonatal skin care products commonly used in Africa benefit or compromise epidermal functions in murine skin. After twice-daily treatment of 6- to 8-week-old hairless mice with each skin care product for 3 days, epidermal permeability barrier function, skin surface pH, stratum corneum hydration, and barrier recovery were measured using a multiprobe adapter system physiology monitor. For products showing some benefits in these initial tests, the epidermal permeability barrier homeostasis was assessed 1 and 5 hours after a single application to acutely disrupted skin. All of the skin care products compromised basal permeability barrier function and barrier repair kinetics. Moreover, after 3 days of treatment, most of the products also reduced stratum corneum hydration while elevating skin surface pH to abnormal levels. Some neonatal skin care products that are widely used in Africa perturb important epidermal functions, including permeability barrier homeostasis in mice. Should these products have similar effects on newborn human skin, they could cause a defective epidermal permeability barrier, which can increase body fluid loss, impair thermoregulation, and contribute to the high rates of neonatal morbidity and mortality seen in Africa. Accordingly, alternative products that enhance permeability barrier function should be identified, particularly for use in preterm infants. © 2016 Wiley Periodicals, Inc.

  12. 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.

  13. Vitamin D and immune function in chronic kidney disease.

    Science.gov (United States)

    Liu, Wen-Chih; Zheng, Cai-Mei; Lu, Chien-Lin; Lin, Yuh-Feng; Shyu, Jia-Fwu; Wu, Chia-Chao; Lu, Kuo-Cheng

    2015-10-23

    The common causes of death in chronic kidney disease (CKD) patients are cardiovascular events and infectious disease. These patients are also predisposed to the development of vitamin D deficiency, which leads to an increased risk of immune dysfunction. Many extra-renal cells possess the capability to produce local active 1,25(OH)2D in an intracrine or paracrine fashion, even without kidney function. Vitamin D affects both the innate and adaptive immune systems. In innate immunity, vitamin D promotes production of cathelicidin and β-defensin 2 and enhances the capacity for autophagy via toll-like receptor activation as well as affects complement concentrations. In adaptive immunity, vitamin D suppresses the maturation of dendritic cells and weakens antigen presentation. Vitamin D also increases T helper (Th) 2 cytokine production and the efficiency of Treg lymphocytes but suppresses the secretion of Th1 and Th17 cytokines. In addition, vitamin D can decrease autoimmune disease activity. Vitamin D has been shown to play an important role in maintaining normal immune function and crosstalk between the innate and adaptive immune systems. Vitamin D deficiency may also contribute to deterioration of immune function and infectious disorders in CKD patients. However, it needs more evidence to support the requirements for vitamin D supplementation. Copyright © 2015. Published by Elsevier B.V.

  14. 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.

  15. 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.

  16. Mediation of host immune responses after immunization of neonatal calves with a heat-killed Mycobacterium avium subsp. paratuberculosis vaccine

    Science.gov (United States)

    A major drawback of current whole-cell vaccines for Mycobacterium avium subsp. paratuberculosis(MAP) is the interference with diagnostic tests for bovine tuberculosis and paratuberculosis. The current study was designed to explore effects of immunization with a heat-killed whole cell vaccine (Mycop...

  17. 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.

  18. Rubella immune status of neonates – a window towards seroprevalence among childbearing women

    Directory of Open Access Journals (Sweden)

    Iris Pejcic

    2016-08-01

    Full Text Available Abstract Background When contracted in pregnancy, rubella may cause serious chronic infection of the fetus and development of Congenital Rubella Syndrome. Despite widespread application of rubella vaccination, periodical outbreaks are still being reported worldwide. The aim of this study was to determine rubella seroprevalence and antibody levels in neonates in Serbia as a proxy of maternal serostatus. Methods ELISA based serological testing for rubella was done in 599 neonates treated at the Institute of Neonatology in Belgrade, from January 2010 to December 2011. All individuals with rubella IgG concentration ≥10 IU/ml were considered seropositive for rubella. Results The mean age of enrolled neonates was 18 ± 6 days. The overall seroprevalence of rubella IgG antibodies among the tested neonates was 540/599(90.2 %, 95 % CI: 87.5–92.3. Seropositivity rate among sera of the neonates enrolled in 2010 was significantly higher than those collected in 2011 (p 30 as compared to those from mothers aged <20 years (p = 0.02. Significant difference was also found between average IgG titers in the two study years (79 IU/mL in 2010 vs. 46 IU/mL in 2011, p < 0.0001. Conclusion We report on high rubella seroprevalence among newborns in Serbia, as a proxy of rubella serostatus of childbearing aged women. Notably, declining trend of rubella antibodies toward diminishing titers suggest the importance of sustained rubella serosurvey and antenatal screening at the national level.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes....... It is widely accepted that acute and chronic exercise alter the number and function of circulating cells of the innate immune system (e.g. neutrophils, monocytes and natural killer (NK) cells). A limited number of animal studies has helped us determine the extent to which these changes alter susceptibility...... in acquired immunity with acute exercise and training remains unknown. The production of secretory immunoglobulin A (SIgA) is the major effector function of the mucosal immune system providing the 'first line of defence' against pathogens. To date, the majority of exercise studies have assessed saliva SIg...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    from exercise studies. In this position statement, a panel of world-leading experts provides a consensus of current knowledge, briefly covering the background, explaining what we think we know with some degree of certainty, exploring continued controversies, and pointing to likely directions for future...... research. Part one of this position statement focuses on 'immune function and exercise' and part two on 'maintaining immune health'. Part one provides a brief introduction and history (Roy Shephard) followed by sections on: respiratory infections and exercise (Maree Gleeson); cellular innate immune...

  1. 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...

  2. The Design of New Adjuvants for Mucosal Immunity to Neisseria meningitidis B in Nasally Primed Neonatal Mice for Adult Immune Response

    Directory of Open Access Journals (Sweden)

    Tatiane Ferreira

    2012-01-01

    Full Text Available The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization.

  3. 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 ...

  4. Ibuprofen exposure in early neonatal life does not affect renal function in young adolescence.

    Science.gov (United States)

    Raaijmakers, Anke; Zhang, Zhen-Yu; Levtchenko, Elena; Simons, Sinno Hp; Cauwenberghs, Nicholas; Heuvel, Lambertus P van den; Jacobs, Lotte; Staessen, Jan A; Allegaert, Karel

    2018-03-01

    Ibuprofen exposure results in acute transient renal dysfunction in preterm neonates, but we are unaware of data on long-term renal safety. In a previously studied cohort of extreme low birth weight (ELBW, ibuprofen. In this post hoc analysis, we linked markers of renal function in young adolescence in ELBW cases with their perinatal (prenatal maternal, setting at birth, treatment modalities including drug prescription during neonatal stay, neonatal creatinine values, postdischarge growth) characteristics, including but not limited to ibuprofen exposure during neonatal stay. Ibuprofen exposure was not associated with significant differences in renal length or eGFR cysC . Moreover, we were unable to identify any other risk factor (perinatal characteristics, postnatal creatinine trends, postdischarge growth) on renal outcome in this cohort. Neonatal exposure to ibuprofen did not affect renal function. Larger studies are needed to explore the confounders of variability in renal function in former ELBW cases. This matters since ELBW relates to risk for hypertension, cardiovascular events and renal disease in later life and identification of risk factors holds the promise of secondary prevention. NCT02147457. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Modulation of immune development and function by intestinal microbiota.

    Science.gov (United States)

    Kabat, Agnieszka M; Srinivasan, Naren; Maloy, Kevin J

    2014-11-01

    The immune system must constantly monitor the gastrointestinal tract for the presence of pathogens while tolerating trillions of commensal microbiota. It is clear that intestinal microbiota actively modulate the immune system to maintain a mutually beneficial relation, but the mechanisms that maintain homeostasis are not fully understood. Recent advances have begun to shed light on the cellular and molecular factors involved, revealing that a range of microbiota derivatives can influence host immune functions by targeting various cell types, including intestinal epithelial cells, mononuclear phagocytes, innate lymphoid cells, and B and T lymphocytes. Here, we review these findings, highlighting open questions and important challenges to overcome in translating this knowledge into new therapies for intestinal and systemic immune disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. A DNC function that computes no effectively bi-immune set

    OpenAIRE

    Beros, Achilles A.

    2013-01-01

    In Diagonally Non-Computable Functions and Bi-Immunity, Carl Jockusch and Andrew Lewis proved that every DNC function computes a bi-immune set. They asked whether every DNC function computes an effectively bi-immune set. We construct a DNC function that computes no effectively bi-immune set, thereby answering their question in the negative.

  7. Potential role of the intestinal microbiota of the mother in neonatal immune education

    OpenAIRE

    Donnet-Hughes, Anne; Perez, Pablo F.; Doré, Joël; Leclerc, Marion; Levenez, Florence; Benyacoub, Jalil; Serrant, Patrick; Segura-Roggero, Iris; Schiffrin, Eduardo J.

    2017-01-01

    Mucosal dendritic cells are at the heart of decision-making processes that dictate immune reactivity to intestinal microbes. They ensure tolerance to commensal bacteria and a vigorous immune response to pathogens. It has recently been demonstrated that the former involves a limited migration of bacterially loaded dendritic cells from the Peyer's patches to the mesenteric lymph nodes. During lactation, cells from gut-associated lymphoid tissue travel to the breast via the lymphatics and periph...

  8. Sexual selection and immune function in Drosophila melanogaster.

    Science.gov (United States)

    McKean, Kurt A; Nunney, Leonard

    2008-02-01

    The evolution of immune function depends not only on variation in genes contributing directly to the immune response, but also on genetic variation in other traits indirectly affecting immunocompetence. In particular, sexual selection is predicted to trade-off with immunocompetence because the extra investment of resources needed to increase sexual competitiveness reduces investment in immune function. Additional possible immunological consequences of intensifying sexual selection include an exaggeration of immunological sexual dimorphism, and the reduction of condition-dependent immunological costs due to selection of 'good genes' (the immunocompetence handicap hypothesis, ICHH). We tested for these evolutionary possibilities by increasing sexual selection in laboratory populations of Drosophila melanogaster for 58 generations by reestablishing a male-biased sex ratio at the start of each generation. Sexually selected flies were larger, took longer to develop, and the males were more sexually competitive than males from control (equal sex ratio) lines. We found support for the trade-off hypothesis: sexually selected males were found to have reduced immune function compared to control males. However, we found no evidence that sexual selection promoted immunological sexual dimorphism because females showed a similar reduction in immune function. We found no evidence of evolutionary changes in the condition-dependent expression of immunocompetence contrary to the expectations of the ICHH. Lastly, we compared males from the unselected base population that were either successful (IS) or unsuccessful (IU) in a competitive mating experiment. IS males showed reduced immune function relative to IU males, suggesting that patterns of phenotypic correlation largely mirror patterns of genetic correlation revealed by the selection experiment. Our results suggest increased disease susceptibility could be an important cost limiting increases in sexual competitiveness in

  9. Effect of neonatal sublingual vaccination with native or denatured ovalbumin and adjuvant CpG or cholera toxin on systemic and mucosal immunity in mice.

    Science.gov (United States)

    Huang, C-F; Wu, T-C; Chu, Y-H; Hwang, K-S; Wang, C-C; Peng, H-J

    2008-11-01

    Sublingual immunotherapy has been applied for allergic diseases, but whether sublingual immunization in neonates can prevent sensitization has not been studied. In this study, we evaluate the effect of neonatal sublingual vaccination with native or denatured allergens alone or plus adjuvant on allergy prevention. Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with native or denatured ovalbumin (OVA) only, or combined adjuvant CpG or cholera toxin (CT). They were sensitized with OVA adsorbed onto alum 7 weeks after the last vaccination. Specific secretory IgA antibody responses were readily induced by neonatal vaccination with antigen plus CpG or CT, but not with antigen alone. Whereas vaccination with denatured OVA plus CpG markedly enhanced T helper 1 (Th1) responses and inhibited IgE production, vaccination with denatured OVA plus CT increased cervical lymph node cell production of interleukin-4 (IL-4), IL-5, IL-6, and serum IgG1 responses. These data demonstrate that neonatal sublingual vaccination with denatured OVA and CpG not only preferentially induces systemic Th1 responses and mucosal immunity, but also simultaneously abrogates IgE production. Neonatal sublingual vaccines may play a role for the strategy of allergy prevention.

  10. Effects of Parathyroid Hormone on Immune Function

    Directory of Open Access Journals (Sweden)

    Abdallah Sassine Geara

    2010-01-01

    Full Text Available Parathyroid hormone (PTH function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells. The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human, at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.

  11. Functional and immunohistochemical evaluation of porcine neonatal islet-like cell clusters

    DEFF Research Database (Denmark)

    Nielsen, T B; Yderstraede, K B; Schrøder, H D

    2003-01-01

    Porcine neonatal islet-like cell clusters (NICCs) may be an attractive source of insulin-producing tissue for xenotransplantation in type I diabetic patients. We examined the functional and immunohistochemical outcome of the islet grafts in vitro during long-term culture and in vivo after transpl...

  12. Effects of Antiparasite Chemotherapeutic Agents on Immune Functions.

    Science.gov (United States)

    1984-05-01

    suppression or augmentation of one or more of the functional moieties of the defense system. Examples of such immunomodulations are numerous. Most... helminthic infections and m .alig.ant diseases often modify the immune functicn of the host. For example, tetrac!clines irnibit chemotaxis and przgocytosis

  13. Cesarean section and disease associated with immune function

    DEFF Research Database (Denmark)

    Kristensen, Kim; Henriksen, Lonny

    2016-01-01

    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...

  14. 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

  15. [Iodinated contrast in pregnant women and neonatal thyroid function].

    Science.gov (United States)

    Chauvet, P; Terral, D; Colombier, M; Mulliez, A; Suarez, C; Brunhes, A; Gallot, D

    2016-12-01

    There is a theoretical risk for neonatal hypothyroidism after prenatal exposure to iodinated contrast media. Current recommendations are in favour of neonatal thyroid function assessment. Our aim was to check if recommendations were observed, and if neonatal evaluation demonstrated anomalies. Over the period from 01/01/2010 to 01/08/2015, maternal and newborn records were retrospectively reviewed. All pregnant women who underwent a computed tomography and their newborns were included. We collected thyroid-stimulating hormone (TSH), thyroxine (T4) and tri-iodothyronine (T3) levels. A total of 101 maternal and newborn records were reviewed. Mean gestational age at CT scan was 29.3±7.2 weeks. The mean dose of total iodine administered was 82.6±19.1mL. Only 21 newborns had a biological analysis (20.8%). All newborns had normal TSH and T4 levels at birth. Only 7 newborns had a T3 level above the upper threshold value, but according to expert opinion none have been considered pathological. Our study revealed that recommendations for neonatal thyroid function assessment after prenatal exposure to iodinated contrast media were not observed. This exposure seemed unlikely to have an important effect on thyroid function at birth. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Nutritional Status and Immune Functions in Maintenance Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Epidemiological studies suggest various kinds of immune dysregulation in hemodialysis (HD patients. The aim of this study was to investigate the relationship between immune functions and nutritional status of HD patients. We studied 54 patients with ESRD on chronic HD, included 34 females and 20 males with mean age 46.6 ± 16.3 (18–77 years. We measured the height and dry weight of all patients. The BMI was calculated by dividing weight (kg by height squared ( m 2 . In all patients serum urea, creatinine, albumin, iron, cholesterol, triglyceride, CRP, IgG, IgM, IgA, CD4, CD8, CD19, CD16-56 lymphocytes were measured. Kt/V values were calculated according to DOQI guideline. In this study, a positive correlation between albumin, cholesterol, and triglyceride levels as nutritional parameters and immune functions in terms of total and subtype lymphocyte counts was observed. Further prospective studies are needed to determine the clinical importance of this finding and the appropriate means of measurement and effects of nutrition on immune function in hemodialysis patients.

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    ") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term "physical activity" and the specific category of "exercise", which implies activity for a specific...... purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes...... function and exercise (Jeffrey Woods); acquired immunity and exercise (Nicolette Bishop); mucosal immunity and exercise (Michael Gleeson and Nicolette Bishop); immunological methods in exercise immunology (Monika Fleshner); anti-inflammatory effects of physical activity (Charlotte Green and Bente Pedersen...

  19. 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

    (n-3) PUFA influence immune function in adults and may also affect immune maturation during development. This randomized trial is, to our knowledge, the first to investigate whether fish oil supplementation in late infancy modifies immune responses. The study was a 2 x 2 intervention in 64 healthy...... 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

  20. Neonatal and Maternal 25-OH Vitamin D Serum Levels in Neonates with Early-Onset Sepsis.

    Science.gov (United States)

    Gamal, Taha Soliman; Madiha, Abd-Allah Sayed; Hanan, Mostafa Kamel; Abdel-Azeem, Mohamed El-Mazary; Marian, Gamil S

    2017-05-09

    Vitamin D is a fat-soluble vitamin that is important for calcium metabolism and plays an important role in the immune functions. The aim of this study was to measure neonatal and maternal 25-OH vitamin D serum levels in neonates with early onset sepsis. The study included fifty neonates with early onset sepsis (25 full-term and 25 preterm infants) and thirty age and sex matched healthy neonates as controls. After history taking and clinical examination, complete blood count, C-reactive protein and 25-OH vitamin D serum levels (neonatal and maternal) were measured for all neonates. The mean gestational age for neonates with sepsis was (37.5 ± 0.98 for full term and 34.1 ± 1.26 for preterm neonates). Neonatal and maternal 25-OH vitamin D serum levels were significantly lower in patients (6.4 ± 1.8 and 24.6 ± 2.2 nmol/L) than controls (42.5 ± 20.7 and 50.4 ± 21.4 nmol/L). Significant negative correlations between neonatal and maternal 25-OH vitamin D serum levels and all sepsis markers and significant positive correlations between neonatal and maternal 25-OH vitamin D levels were present. At cut-off values <20 nmol/L for neonatal and <42 nmol/L for maternal 25-OH vitamin D for detection of neonatal sepsis, the sensitivity, specificity, positive predicted value (PPV) and negative predicted value (NPV) were 84%, 79%, 94.7% and 82.3% for neonatal and 82%, 77%, 91.4% and 80.6% for maternal 25-OH vitamin D, respectively. Positive correlations between neonatal and maternal 25-OH Vitamin D serum levels are present and they are negatively correlated with all sepsis markers. They can be sensitive early predictors for early onset sepsis in neonates.

  1. The Association of Thyroid Function With Maternal and Neonatal Homocysteine Concentrations.

    Science.gov (United States)

    Barjaktarovic, Mirjana; Steegers, Eric A P; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Korevaar, Tim I M; Peeters, Robin P

    2017-12-01

    High homocysteine concentrations are associated with maternal pregnancy complications and low birth weight, jaundice, and cerebrovascular accidents in neonates. Thyroid hormone may interfere with homocysteine metabolism via stimulation of vitamin B12- and folate-dependent processes and via effects on enzymes of the remethylation pathway. Investigating the associations of maternal and neonatal thyroid function with homocysteine during pregnancy and after delivery, respectively. Within Generation R study, a population-based prospective cohort, we studied the associations of maternal and neonatal thyroid stimulating hormone (TSH) and free thyroxine (FT4) with homocysteine, folate, and vitamin B12 concentrations using multiple linear regression analyses. TSH, FT4, homocysteine, folate, and vitamin B12 concentrations were determined in early pregnancy (homocysteine and an inverse association of TSH with homocysteine. The associations attenuated after adjustment for folate and vitamin B12 concentration (β change: for FT4, 0.00559 ± 0.001, P homocysteine (P = 0.026) but no association of FT4 with folate or vitamin B12 (P ≥ 0.08). Higher thyroid function is associated with higher homocysteine concentrations in pregnant women and in neonates. These data provide new insights into the effects of thyroid hormone on folate- and vitamin B12-dependent processes during early growth and development. Copyright © 2017 Endocrine Society

  2. Long-Lasting Impact of Neonatal Exposure to Total Body Gamma Radiation on Secondary Lymphoid Organ Structure and Function.

    Science.gov (United States)

    Rangel-Moreno, Javier; de la Luz Garcia-Hernandez, Maria; Ramos-Payan, Rosalio; Biear, Jamie; Hernady, Eric; Sangster, Mark Y; Randall, Troy D; Johnston, Carl J; Finkelstein, Jacob N; Williams, Jacqueline P

    2015-10-01

    The acute period after total body irradiation (TBI) is associated with an increased risk of infection, principally resulting from the loss of hematopoietic stem cells, as well as disruption of mucosal epithelial barriers. Although there is a return to baseline infection control coinciding with the apparent progressive recovery of hematopoietic cell populations, late susceptibility to infection in radiation-sensitive organs such as lung and kidney is known to occur. Indeed, pulmonary infections are particularly prevalent in hematopoietic cell transplant (HCT) survivors, in both adult and pediatric patient populations. Preclinical studies investigating late outcomes from localized thoracic irradiation have indicated that the mechanisms underlying pulmonary delayed effects are multifactorial, including exacerbated and persistent production of pro-inflammatory molecules and abnormal cross-talk among parenchymal and infiltrating immune and inflammatory cell populations. However, in the context of low-dose TBI, it is not clear whether the observed exacerbated response to infection remains contingent on these same mechanisms. It is possible instead, that after systemic radiation-induced injury, the susceptibility to infection may be independently related to defects in alternative organs that are revealed only through the challenge itself; indeed, we have hypothesized that this defect may be due to radiation-induced chronic effects in the structure and function of secondary lymphoid organs (SLO). In this study, we investigated the molecular and cellular alterations in SLO (i.e., spleen, mediastinal, inguinal and mesenteric lymph nodes) after TBI, and the time points when there appears to be immune competence. Furthermore, due to the high incidence of pulmonary infections in the late post-transplantation period of bone marrow transplant survivors, particularly in children, we focused on outcomes in mice irradiated as neonates, which served as a model for a pediatric

  3. Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

    Directory of Open Access Journals (Sweden)

    Gold Diane R

    2006-03-01

    Full Text Available Abstract Background Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2, may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy. Methods We analyzed immune responses of cord blood mononuclear cells (CBMC from 50 healthy neonates (31 non-atopic and 19 atopic mothers. Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg or the allergen house dust mite Dermatophagoides farinae (Derf1, and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR, and the cytotoxic lymphocyte antigen 4 (CTLA4. Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR. Results Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07. Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049. IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001, GITR (r = 0.47, p = 0.004 and CTLA4 (r = 0.49, p = 0.003, independent of maternal atopy. Conclusion TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to

  4. Activation of the Innate Immune Receptors: Guardians of the Micro Galaxy : Activation and Functions of the Innate Immune Receptors.

    Science.gov (United States)

    De Nardo, Dominic

    2017-01-01

    The families of innate immune receptors are the frontline responders to danger. These superheroes of the host immune systems populate innate immune cells, surveying the extracellular environment and the intracellular endolysosomal compartments and cytosol for exogenous and endogenous danger signals. As a collective the innate immune receptors recognise a wide array of stimuli, and in response they initiate specific signalling pathways leading to activation of transcriptional or proteolytic pathways and the production of inflammatory molecules to destroy foreign pathogens and/or resolve tissue injury. In this review, I will give an overview of the innate immune system and the activation and effector functions of the families of receptors it comprises. Current key concepts will be described throughout, including innate immune memory, formation of innate immune receptor signalosomes, inflammasome formation and pyroptosis, methods of extrinsic cell communication and examples of receptor cooperation. Finally, several open questions and future directions in the field of innate immunity will be presented and discussed.

  5. Airway Mucosal Immune-suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During Pregnancy

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Bischoff, Anne L.; Folsgaard, Nilofar V.

    2015-01-01

    N1) pnd09 vaccination during pregnancy. Methods: One hundred and fifty-six women from the unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC 2010) received Influenza A(H1N1) pnd09-vaccination during the 2009 pandemic. Fifty-one mothers received the vaccine during pregnancy......Background: It is recommended to vaccinate pregnant women against influenza. A possible impact on the immune expression of the fetus has never been studied. We aim to study the immune signature in the upper airways and the incidence of infections in neonates born to mothers receiving Influenza A(H1......, IL-5, IL-13, eotaxin-1, eotaxin-3, TARC, MDC, IL-17, IL-1 beta, IL-8, transforming growth factor beta (TGF)-beta 1, IL-10 and IL-2. Infections were monitored the first year of life by daily diary cards and clinical controls. Results: Neonates of mothers vaccinated during pregnancy had significant up...

  6. Functional connectivity disruption in neonates with prenatal marijuana exposure

    OpenAIRE

    Karen eGrewen; Andrew eSalzwedel; Andrew eSalzwedel; Wei eGao; Wei eGao

    2015-01-01

    Prenatal marijuana exposure (PME) is linked to neurobehavioral and cognitive impairments, however findings in childhood and adolescence are inconsistent. Type-1 cannabinoid receptors (CB1R) modulate fetal neurodevelopment, mediating PME effects on growth of functional circuitry sub-serving behaviors critical for academic and social success. The purpose of this study was to investigate the effects of prenatal marijuana on development of early brain functional circuitry prior to prolonged post...

  7. Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms.

    Science.gov (United States)

    Rogers, Cynthia E; Sylvester, Chad M; Mintz, Carrie; Kenley, Jeanette K; Shimony, Joshua S; Barch, Deanna M; Smyser, Christopher D

    2017-02-01

    Alterations in the normal developmental trajectory of amygdala resting state functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants, and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years. Resting state fMRI data were obtained shortly after birth from 65 FT infants (gestational age [GA] ≥36 weeks) and 57 VPT infants (GA amygdala regions of interest. Total internalizing symptoms and the behavioral inhibition, depression/withdrawal, general anxiety, and separation distress subdomains were assessed in a subset (n = 44) at age 2 years using the Infant Toddler Social Emotional Assessment. In FT and VPT infants, the amygdala demonstrated positive correlations with subcortical and limbic structures and negative correlations with cortical regions, although magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years with regional specificity consistent with known pathophysiology in older populations: connectivity with the anterior insula related to depressive symptoms, with the dorsal anterior cingulate related to generalized anxiety, and with the medial prefrontal cortex related to behavioral inhibition. Amygdala rs-FC is well established in neonates. Variability in regional neonatal amygdala rs-FC predicted internalizing symptoms at 2 years, suggesting that risk for internalizing symptoms may be established in neonatal amygdala functional connectivity patterns. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. [Immunization against a new, infrequent alloantigen (Iy) on the platelet glycoprotein Ib/IX as a cause of a serious case of neonatal alloimmune thrombocytopenia].

    Science.gov (United States)

    Kiefel, V; Vicariot, M; Breitfeld, C; Giptner, A; Schlüter, C; Böhringer, M; Santoso, S; Kroll, H; Mueller-Eckhardt, C

    1994-01-01

    Neonatal alloimmune thrombocytopenia is the consequence of maternal alloimmunization against platelet-specific alloantigens, usually PIA1 or Br(a). The clinical picture is characterized by signs of haemorrhagic diathesis as a result of marked thrombocytopenia. In the last years, rare cases of immunization against 'low-frequency' or 'private' platelet alloantigens on the platelet glycoprotein (GP) complex IIb/IIIa have been found. This is the first report on NAIT due to maternal immunization against a low-frequency platelet alloantigen ('Iy') localized on platelet GP Ib/IX.

  9. Effect of Clostridium butyricum supplementation on the development of intestinal flora and the immune system of neonatal mice.

    Science.gov (United States)

    Miao, Rui-Xue; Zhu, Xin-Xin; Wan, Chao-Min; Wang, Zhi-Ling; Wen, Yang; Li, Yi-Yuan

    2018-01-01

    The objective of the present study was to examine whether Clostridium butyricum supplementation has a role in the regulation of the intestinal flora and the development of the immune system of neonatal mice. A total of 30 pregnant BALB/c mice, including their offspring, were randomly divided into three groups: In the maternal intervention group (Ba), maternal mice were treated with Clostridium butyricum from birth until weaning at postnatal day 21 (PD21) followed by administration of saline to the offspring at PD21-28; in the offspring intervention group (Ab), breast-feeding maternal mice were supplemented with saline and offspring were directly supplemented with Clostridium butyricum from PD21-28; in the both maternal and offspring intervention group (Bb), both maternal mice and offspring were supplemented with Clostridium butyricum at PD 0-21 and at PD21-28. While mice in the control group were given the same volume of normal saline. Stool samples from the offspring were collected at PD14, -21 and -28 to observe the intestinal flora by colony counts of Enterococcus spp., Enterobacter spp., Bifidobacterium spp. and Lactobacillus spp. Detection of intestinal secreted immunoglobulin A (sIgA) levels and serum cytokine (interferon-γ, and interleukin-12, -4 and -10) levels in offspring was performed to evaluate the effect on their immune system. The results revealed that compared with the control group, offspring in the Ba group displayed significantly decreased stool colony counts of Enterococcus spp. (t=3.123, Pflora balance in their offspring. However, due to insignificant effects on sIgA level and the associated cytokines, Clostridium butyricum had a limited influence on the balance of type 1 vs. type 2 T-helper cells. However, using Clostridium butyricum as an invention may be a safe method for improving the balance of intestinal flora and associated processes in offspring.

  10. Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood-brain barrier function.

    Science.gov (United States)

    Gudiño-Cabrera, Graciela; Ureña-Guerrero, Monica E; Rivera-Cervantes, Martha C; Feria-Velasco, Alfredo I; Beas-Zárate, Carlos

    2014-11-01

    It is likely that monosodium glutamate (MSG) is the excitotoxin that has been most commonly employed to characterize the process of excitotoxicity and to improve understanding of the ways that this process is related to several pathological conditions of the central nervous system. Excitotoxicity triggered by neonatal MSG treatment produces a significant pathophysiological impact on adulthood, which could be due to modifications in the blood-brain barrier (BBB) permeability and vice versa. This mini-review analyzes this topic through brief descriptions about excitotoxicity, BBB structure and function, role of the BBB in the regulation of Glu extracellular levels, conditions that promote breakdown of the BBB, and modifications induced by neonatal MSG treatment that could alter the behavior of the BBB. In conclusion, additional studies to better characterize the effects of neonatal MSG treatment on excitatory amino acids transporters, ionic exchangers, and efflux transporters, as well as the role of the signaling pathways mediated by erythropoietin and vascular endothelial growth factor in the cellular elements of the BBB, should be performed to identify the mechanisms underlying the increase in neurovascular permeability associated with excitotoxicity observed in several diseases and studied using neonatal MSG treatment. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  11. A microarray analysis of gnotobiotic mice indicating that microbial exposure during the neonatal period plays an essential role in immune system development

    Directory of Open Access Journals (Sweden)

    Yamamoto Masahiro

    2012-07-01

    Full Text Available Abstract Background Epidemiological studies have suggested that the encounter with commensal microorganisms during the neonatal period is essential for normal development of the host immune system. Basic research involving gnotobiotic mice has demonstrated that colonization at the age of 5 weeks is too late to reconstitute normal immune function. In this study, we examined the transcriptome profiles of the large intestine (LI, small intestine (SI, liver (LIV, and spleen (SPL of 3 bacterial colonization models—specific pathogen-free mice (SPF, ex-germ-free mice with bacterial reconstitution at the time of delivery (0WexGF, and ex-germ-free mice with bacterial reconstitution at 5 weeks of age (5WexGF—and compared them with those of germ-free (GF mice. Results Hundreds of genes were affected in all tissues in each of the colonized models; however, a gene set enrichment analysis method, MetaGene Profiler (MGP, demonstrated that the specific changes of Gene Ontology (GO categories occurred predominantly in 0WexGF LI, SPF SI, and 5WexGF SPL, respectively. MGP analysis on signal pathways revealed prominent changes in toll-like receptor (TLR- and type 1 interferon (IFN-signaling in LI of 0WexGF and SPF mice, but not 5WexGF mice, while 5WexGF mice showed specific changes in chemokine signaling. RT-PCR analysis of TLR-related genes showed that the expression of interferon regulatory factor 3 (Irf3, a crucial rate-limiting transcription factor in the induction of type 1 IFN, prominently decreased in 0WexGF and SPF mice but not in 5WexGF and GF mice. Conclusion The present study provides important new information regarding the molecular mechanisms of the so-called "hygiene hypothesis".

  12. Jungle Honey Enhances Immune Function and Antitumor Activity

    Science.gov (United States)

    Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C.; Sawai, Masaharu; Pinkerton, Kent E.; Takeuchi, Minoru

    2011-01-01

    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. PMID:19141489

  13. 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.

  14. The prevalence of and attitudes toward neonatal functional echocardiography use and training in the United States: a survey of neonatal intensive care unit medical directors.

    Science.gov (United States)

    Schachinger, S; Stansfield, R B; Ensing, G; Schumacher, R

    2014-01-01

    Internationally, neonatologists are increasingly performing functional echocardiography to evaluate the hemodynamic status and cardiac function in neonates. The purpose of this study was to describe the current prevalence of and attitudes toward the use and training of neonatologists in functional echocardiography in the United States. An anonymous survey was sent to United States neonatal intensive care unit medical directors. Neonatologists scored availability of echocardiography and attitudes toward the use and training of neonatologists in functional echocardiography. Response rate was 43.7% (247 of 565 surveys sent) and captured 95% of the neonatal-perinatal training programs. Nine percent of units had a functional echocardiography trained neonatologist; eight percent of the neonatal-perinatal training programs offered functional echocardiography training. There was no difference in the timely ability to obtain hemodynamic status with echocardiography in units compared by the presence of functional echocardiography trained neonatologists (mean = 3.13 vs. 2.67, p = 0.08) and fellowships (mean = 2.69 vs. 2.72, p = 0.85). Overall positive attitudes (mean = 14.6 ± 3.46) towards the training of neonatologists in functional echocardiography did not correlate with the perceived timely availability of echocardiography support (mean = 2.72 ± 1.43, r = -0.11, p = 0.1). Functional echocardiography use and training is not prevalent in the United States. There are positive attitudes toward the training of neonatologists in functional echocardiography that are independent of the presence of fellowships, neonatologists with echocardiography training, and the perceived availability of echocardiography support.

  15. Functional and morphologic damage in the neonatally irradiated canine kidney

    International Nuclear Information System (INIS)

    Peneyra, R.S.; Jaenke, R.S.

    1985-01-01

    Perinatal irradiation of the developing kidney results in progressive glomerulosclerosis (PGS) and renal failure. This syndrome may result from direct radiation damage to mature deep cortical nephrons and/or nephron functional adaptations resulting from outer cortical nephron ablation. Beagle dogs received single, whole-body exposures (330 R) to 60 Co gamma radiation at 4 days of age (IR4) to study the combined effects of direct radiation damage and nephron loss, or at 30 days of age (IR30) to study the effects of renal irradiation alone. To study the effects of nephron loss alone, dogs underwent unilateral nephrectomy (UN4) or superficial hyperthermic renal ablation (HY4) at 4 days of age. Nephron loss due to irradiation (IR4) and partial renal ablation (UN4 and HY4) was associated with compensatory nephron hypertrophy and increased single nephron glomerular filtration rate (SNGFR), while irradiation at 30 days resulted in transitory decreased SNGFR. Similar degrees of PGS occurred in IR4 dogs which experienced both irradiation and loss of nephrons and UN4 and HY4 dogs which experienced only loss of nephrons. PGS of lesser severity also occurred in IR30 dogs. These findings indicate that PGS associated with perinatal renal irradiation results from direct radiation damage to deep cortical nephrons and compensatory functional changes occurring in response to loss of renal mass

  16. Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction

    DEFF Research Database (Denmark)

    Eskild-Jensen, Anni; Thomsen, Karsten; Rungø, Christine

    2007-01-01

    Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal functio...... is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function....

  17. 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.

  18. Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin.

    Directory of Open Access Journals (Sweden)

    Andrea Baccarelli

    2008-07-01

    Full Text Available Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy.Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination, and 1,772 age-matched women from the surrounding noncontaminated area (reference; (ii a biomarker study on 51 mother-child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 microU/ml (95% confidence interval [CI] 0.90-1.08 in the reference area (n = 533, 1.35 microU/ml (95% CI 1.22-1.49 in zone B (n = 425, and 1.66 microU/ml (95% CI 1.19-2.31 in zone A (n = 56 (p 5 microU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001. Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, beta = 0.47, p < 0.001 and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, beta = 0.45, p = 0.005.Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.

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

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    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

  20. Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

    Science.gov (United States)

    Wheeler, Daniel W.; Thompson, Andrew J.; Corletto, Federico; Reckless, Jill; Loke, Justin C. T.; Lapaque, Nicolas; Grant, Andrew J.; Mastroeni, Pietro; Grainger, David J.; Padgett, Claire L.; O'Brien, John A.; Miller, Nigel G. A.; Trowsdale, John

    2011-01-01

    Background GABAA receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs [1]. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear [2]. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die [3]–[6]. As many anaesthetics act via GABAA receptors [7], the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. Principal Findings We demonstrate, using RT-PCR, that monocytes express GABAA receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABAA receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABAA receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. Significance Our results show that functional GABAA receptors are present on monocytes with properties similar to CNS GABAA receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABAA receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABAA receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be

  1. [Pulmonary function in children after neonatal meconium aspiration syndrome].

    Science.gov (United States)

    Djemal, N; Ben Ammar, H; Masmoudi, K; Rguaieg, R; Trigui, L; Ben Hmad, A; Kannou, M; Hmida, N; Gargouri, A; Zouari, N; Rekik, A

    2008-02-01

    Meconium aspiration syndrome is a disease of the newborn mature or post mature. The acute pulmonary consequences can be extremely severe. In the few studies of the long-term pulmonary sequelae, it seems that certain children surviving meconium aspiration syndrome keep an obstructive syndrome. The aim of our study was to assess long term respiratory residual damage from meconium aspiration syndrome. During a seven-year period going from 1994 to 2000, we reviewed the files of children hospitalized in neonatology department of Sfax for meconium aspiration syndrome. The children who were convoked (group M: n=27), underwent spirometry, followed by an exercise stress. An age matched control group (group C: n=23) of healthy children was investigated in the same way. The group M comprised 15 boys and 12 girls aged four to 11, an average of 7+/-1.9 years. With the study of the respiratory function, we did not find an obstructive syndrome. Spirometry revealed a total pulmonary capacity in an average of 133+/-55.65% of theoretical (group M) versus 105.5+/-27.96% of theoretical (group C) (Pmeconium aspiration syndrome tend to develop alveolar hyperinflation and airway hyperreactivity to exercise.

  2. 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.

  3. 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

  4. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses

    OpenAIRE

    Maggini, Silvia; Wintergerst, Eva S.; Beveridge, Stephen; Hornig, Dietrich H.

    2017-01-01

    Adequate intakes of micronutrients are required for the immune system to function efficiently. Micronutrient deficiency suppresses immunity by affecting innate, T cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. This situation increases susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilizatio...

  5. Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves

    International Nuclear Information System (INIS)

    Besser, T.E.

    1986-01-01

    High passive blood immunoglobulin concentrations are associated with decreased infectious enteric disease mortality in neonatal calves. Passive immunoglobulin transferred from the blood to the gastrointestinal tract may explain this protection. To measure the rate at which immunoglobulin G 1 (IgG 1 ) is transferred to the gastrointestinal tract, 125 I-labelled bovine IgG 1 anti-DNP antibody was administered to calves by intravenous injection. The clearance rate of 125 I-IgG 1 from the blood was measured and compared to the rate of 125 I-IgG 1 appearance in the gastrointestinal tract, as measured (1) by the rate of fecal 125 I-IgG 1 excretion, and (2) by the amount of 125 I-IgG 1 in the gastrointestinal tract of calves at necropsy. Rotavirus antibody titers in the gastrointestinal contents of 5- and 10-days-old calves correlated with the calves' serum passive rotavirus antibody titers, and were increased in proportion to the amount of colostral antibody fed on the first day of life. In contrast, when colostral rotavirus antibody was fed to 48-hour-old calves, when absorption of passive immunoglobulin does not occur, there was no measurable increase in antibody in the intestine 5 days later. Intestinal antibody in the 5- and 10-day-old calves therefore resulted from blood antibody transferred to the gastrointestinal tract. Rotavirus antibody administered to calves by parenteral injection protected them from infection and diarrhea after rotavirus challenge. These results indicate that passive blood IgG enters the calf gastrointestinal tract, where it contributes to intestinal immunity

  6. Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves

    Energy Technology Data Exchange (ETDEWEB)

    Besser, T.E.

    1986-01-01

    High passive blood immunoglobulin concentrations are associated with decreased infectious enteric disease mortality in neonatal calves. Passive immunoglobulin transferred from the blood to the gastrointestinal tract may explain this protection. To measure the rate at which immunoglobulin G/sub 1/ (IgG/sub 1/) is transferred to the gastrointestinal tract, /sup 125/I-labelled bovine IgG/sub 1/ anti-DNP antibody was administered to calves by intravenous injection. The clearance rate of /sup 125/I-IgG/sub 1/ from the blood was measured and compared to the rate of /sup 125/I-IgG/sub 1/ appearance in the gastrointestinal tract, as measured (1) by the rate of fecal /sup 125/I-IgG/sub 1/ excretion, and (2) by the amount of /sup 125/I-IgG/sub 1/ in the gastrointestinal tract of calves at necropsy. Rotavirus antibody titers in the gastrointestinal contents of 5- and 10-days-old calves correlated with the calves' serum passive rotavirus antibody titers, and were increased in proportion to the amount of colostral antibody fed on the first day of life. In contrast, when colostral rotavirus antibody was fed to 48-hour-old calves, when absorption of passive immunoglobulin does not occur, there was no measurable increase in antibody in the intestine 5 days later. Intestinal antibody in the 5- and 10-day-old calves therefore resulted from blood antibody transferred to the gastrointestinal tract. Rotavirus antibody administered to calves by parenteral injection protected them from infection and diarrhea after rotavirus challenge. These results indicate that passive blood IgG enters the calf gastrointestinal tract, where it contributes to intestinal immunity.

  7. Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

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    Fang Xu

    2017-11-01

    Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

  8. Controlled hypothermia may improve surfactant function in asphyxiated neonates with or without meconium aspiration syndrome.

    Science.gov (United States)

    Autilio, Chiara; Echaide, Mercedes; De Luca, Daniele; Pérez-Gil, Jesús

    2018-01-01

    Whole-body hypothermia (WBH) is used to improve neurological outcomes in perinatal asphyxia. Recent studies suggested a beneficial effect of hypothermia for some types of acute respiratory failure. However, no data are available about the biophysical function of human surfactant during WBH. We investigated whether WBH improves surfactant biophysical properties in asphyxiated neonates with or without meconium aspiration syndrome (MAS). Non-bronchoscopic bronchoalveolar lavage (BAL) has been collected from 10 asphyxiated neonates (2 with MAS, 8 with no lung disease (NLD)) at different time-points (pre-WBH, 24h, 48h, 72h of WBH and post-WBH). Surfactant was extracted and tested by captive bubble surfactometry (CBS) in triplicate, at 37°C and 33.5°C, through initial adsorption and dynamic compression-expansion cycling. Phosphatidylcholine and cholesterol were assayed using enzymatic methods. Clinical data were recorded in real-time. Minimum surface tension under dynamic testing was significantly improved as assessed at 33.5°C compared with its behavior at 37°C in NLD neonates: the difference was evident after at least 72h of WBH and remained significant at 6h after rewarming (72h: p = 0.009; rewarming: p = 0.040). Similar results were obtained in MAS patients whose surfactant activity improved already at 48h of hypothermia. Total cholesterol showed a trend to increase at the first 24-48h of hypothermia in NLD patients. Conversely, hypothermia seemed to reduce the excess of exogenous cholesterol in MAS surfactant. Surfactant biophysical properties may improve after 48-72h of WBH in asphyxiated neonates and the improvement is maintained shortly after rewarming. Due to study limitations, further studies are warranted to better clarify the effects of hypothermia on surfactant activity.

  9. Controlled hypothermia may improve surfactant function in asphyxiated neonates with or without meconium aspiration syndrome.

    Directory of Open Access Journals (Sweden)

    Chiara Autilio

    Full Text Available Whole-body hypothermia (WBH is used to improve neurological outcomes in perinatal asphyxia. Recent studies suggested a beneficial effect of hypothermia for some types of acute respiratory failure. However, no data are available about the biophysical function of human surfactant during WBH. We investigated whether WBH improves surfactant biophysical properties in asphyxiated neonates with or without meconium aspiration syndrome (MAS.Non-bronchoscopic bronchoalveolar lavage (BAL has been collected from 10 asphyxiated neonates (2 with MAS, 8 with no lung disease (NLD at different time-points (pre-WBH, 24h, 48h, 72h of WBH and post-WBH. Surfactant was extracted and tested by captive bubble surfactometry (CBS in triplicate, at 37°C and 33.5°C, through initial adsorption and dynamic compression-expansion cycling. Phosphatidylcholine and cholesterol were assayed using enzymatic methods. Clinical data were recorded in real-time.Minimum surface tension under dynamic testing was significantly improved as assessed at 33.5°C compared with its behavior at 37°C in NLD neonates: the difference was evident after at least 72h of WBH and remained significant at 6h after rewarming (72h: p = 0.009; rewarming: p = 0.040. Similar results were obtained in MAS patients whose surfactant activity improved already at 48h of hypothermia. Total cholesterol showed a trend to increase at the first 24-48h of hypothermia in NLD patients. Conversely, hypothermia seemed to reduce the excess of exogenous cholesterol in MAS surfactant.Surfactant biophysical properties may improve after 48-72h of WBH in asphyxiated neonates and the improvement is maintained shortly after rewarming. Due to study limitations, further studies are warranted to better clarify the effects of hypothermia on surfactant activity.

  10. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses.

    Science.gov (United States)

    Dowling, David J; Scott, Evan A; Scheid, Annette; Bergelson, Ilana; Joshi, Sweta; Pietrasanta, Carlo; Brightman, Spencer; Sanchez-Schmitz, Guzman; Van Haren, Simon D; Ninković, Jana; Kats, Dina; Guiducci, Cristiana; de Titta, Alexandre; Bonner, Daniel K; Hirosue, Sachiko; Swartz, Melody A; Hubbell, Jeffrey A; Levy, Ofer

    2017-11-01

    Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form. We used rational engineering and age- and species-specific modeling to construct and characterize polymer nanocarriers encapsulating a TLR8 agonist, allowing direct intracellular release after selective uptake by DCs. Chemically similar but morphologically distinct nanocarriers comprised of amphiphilic block copolymers were engineered for targeted uptake by murine DCs in vivo, and a range of TLR8 agonist-encapsulating polymersome formulations were then synthesized. Novel 96-well in vitro assays using neonatal human monocyte-derived DCs and humanized TLR8 mouse bone marrow-derived DCs enabled benchmarking of the TLR8 agonist-encapsulating polymersome formulations against conventional adjuvants and licensed vaccines, including live attenuated BCG vaccine. Immunogenicity of the TLR8 agonist adjuvanted antigen 85B (Ag85B)/peptide 25-loaded BCG-mimicking nanoparticle formulation was evaluated in vivo by using humanized TLR8 neonatal mice. Although alum-adjuvanted vaccines induced modest costimulatory molecule expression, limited T H -polarizing cytokine production, and significant cell death, BCG induced a robust adult-like maturation profile of neonatal DCs. Remarkably, TLR8 agonist polymersomes induced not only newborn DC maturation profiles similar to those induced by BCG but also stronger IL-12p70 production. On subcutaneous injection to neonatal mice, the TLR8 agonist-adjuvanted Ag85B peptide 25 formulation was comparable with BCG in inducing Ag85B-specific CD4 + T-cell numbers. TLR8 agonist

  11. Effects of selenium on mallard duck reproduction and immune function

    Energy Technology Data Exchange (ETDEWEB)

    Whiteley, P.L.; Yuill, T.M.; Fairbrother, A.

    1989-11-01

    Selenium from irrigation drain water and coal-fired power stations is a significant environmental contaminant in some regions of the USA. The objectives were to examine whether selenium-exposed waterfowl had altered immune function, disease resistance, or reproduction. Pairs of adult mallards were exposed for 95-99 days on streams with sodium selenite-treated water at 10 and 30 ppb, or on untreated streams. Selenium biomagnified through the food chain to the ducks. Disease resistance was decreased in ducklings hatched on the streams and challenged with duck hepatitis virus 1 (DHV1) when 15-days old. Liver selenium concentrations for these ducklings on the 10 and 30 ppb streams was 3.6 and 7.6 ppm dry weight, respectively. Mortality of ducklings purchased when 7-days old, exposed to selenium for 14 days, and challenged when 22-days old was not affected. However, their selenium exposure was lower (liver selenium 4.1 ppm dry weight for the 30 ppb stream). Five parameters of immune function were measured in adult ducks. Phagocytosis of killed Pasteurella multocida by blood heterophils and monocytes, and blood monocyte concentrations were higher in adult males following 84 days exposure to 30 ppb selenium. Their liver selenium concentrations were 11.1 ppm dry weight after 95-99 days exposure.

  12. [Infection of Mice with Normal Immune Function by Taenia asiatica].

    Science.gov (United States)

    Liu, Xiao-yan; Guo, Guang-wu; Chen, Li-hong; Mo, Xing-ze; Yu, Yue-sheng

    2015-08-01

    The Taenia asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min, 6 min and 8 mins were subcutaneously injected into mice with normal immune function(groups Al-A3 respectively, n=20 in each) and mice with immunosuppression (groups B1-B3, n=20 in each). All groups of mice began to show body discomfort on day 5 after infection and develop lumps on the back about on day 15. In groups Al-A3, animal death occurred during days 7-15, with a same survival rate of 95.0%(19/20) and infection rate of 89.4%(17/19), 73.6%(14/19) and 47.3%(9/19) respectively. In groups B1-B3, animal death occurred during days 7-50, with survival rate of 60%(13/20), 55%(11/20)and 55%(11/20) and infection rate of 76.9% (10/13), 54.5% (6/11) and 45.4% (5/11) respectively. After the scolex of cysticercus was evaginated with 15% pig bile, four suckers, an apparent rostellum and two distinct hook-like puncta structures were seen. These results indicate that mice with normal immune function can be used as a replacement of immunosuppressive mice to establish a T. asiatica oncosphere infection model. In addition, the T. asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min have the strongest infection ability.

  13. The vitamin D connection to pediatric infections and immune function.

    Science.gov (United States)

    Walker, Valencia P; Modlin, Robert L

    2009-05-01

    Over the past 20 y, a resurgence in vitamin D deficiency and nutritional rickets has been reported throughout the world, including the United States. Inadequate serum vitamin D concentrations have also been associated with complications from other health problems, including tuberculosis, cancer (prostate, breast, and colon), multiple sclerosis, and diabetes. These findings support the concept of vitamin D possessing important pleiotropic actions outside of calcium homeostasis and bone metabolism. In children, an association of nutritional rickets with respiratory compromise has long been recognized. Recent epidemiologic studies clearly demonstrate the link between vitamin D deficiency and the increased incidence of respiratory infections. Further research has also elucidated the contribution of vitamin D in the host defense response to infection. However, the mechanism(s) by which vitamin D levels contribute to pediatric infections and immune function has yet to be determined. This knowledge is particularly relevant and timely, because infants and children seem more susceptible to viral rather than bacterial infections in the face of vitamin D deficiency. The connection among vitamin D, infections, and immune function in the pediatric population indicates a possible role for vitamin D supplementation in potential interventions and adjuvant therapies.

  14. TLR2 and TLR4 co-activation utilizes distinct signaling pathways for the production of Th1/Th2/Th17 cytokines in neonatal immune cells.

    Science.gov (United States)

    Sugitharini, V; Shahana, P; Prema, A; Berla Thangam, E

    2016-09-01

    Co-activation of TLR2 and TLR4 by gram negative and gram positive bacterial ligands induces a robust pro-inflammatory response in inflammatory cells. In order to understand the signaling mechanism, we aimed to delineate the signaling molecules involved in TLR2 and TLR4 co-activation in neonatal immune cells for the production of Th1/Th2/Th17 inflammatory cytokines. For this, we pretreated cord blood and peripheral blood mononuclear and human mast cells with specific signaling molecule inhibitors such as BAY117082, PD98059 and LY294002 and then stimulated with LPS and PGN and assayed for cytokines IL-6, IL-12/IL-23p40 (Th1), IL-13 (Th2), IL-23 (Th17) and RANTES secretion. We found that upon co-stimulation the phosphorylation of NFκBp65, ERK1/2 and Akt was found to be higher than when stimulated with individual ligands in CBMCs. Also, when compared to adult cells, neonatal cells were more potent in the activation of ERK and Akt through TLR2 and TLR4 co-activation. In addition, neonatal cells possess similar capacity to activate NFκB as that of adult cells for IL-6 secretion. Furthermore, all three signaling molecules were found to be involved in the production of Th17 cytokines which is detrimental during inflammation induced by infection in neonates whereas NFκB is mainly involved in the induction of pro-inflammatory response and Th2 cytokines production. In conclusion, different signaling molecules were utilized for the production of different cytokines in immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Immunization

    Science.gov (United States)

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

  17. Cryptic impacts of temperature variability on amphibian immune function.

    Science.gov (United States)

    Terrell, Kimberly A; Quintero, Richard P; Murray, Suzan; Kleopfer, John D; Murphy, James B; Evans, Matthew J; Nissen, Bradley D; Gratwicke, Brian

    2013-11-15

    Ectothermic species living in temperate regions can experience rapid and potentially stressful changes in body temperature driven by abrupt weather changes. Yet, among amphibians, the physiological impacts of short-term temperature variation are largely unknown. Using an ex situ population of Cryptobranchus alleganiensis, an aquatic North American salamander, we tested the hypothesis that naturally occurring periods of temperature variation negatively impact amphibian health, either through direct effects on immune function or by increasing physiological stress. We exposed captive salamanders to repeated cycles of temperature fluctuations recorded in the population's natal stream and evaluated behavioral and physiological responses, including plasma complement activity (i.e. bacteria killing) against Pseudomonas aeruginosa, Escherichia coli and Aeromonas hydrophila. The best-fit model (ΔAICc=0, wi=0.9992) revealed 70% greater P. aeruginosa killing after exposure to variable temperatures and no evidence of thermal acclimation. The same model predicted 50% increased E. coli killing, but had weaker support (ΔAICc=1.8, wi=0.2882). In contrast, plasma defenses were ineffective against A. hydrophila, and other health indicators (leukocyte ratios, growth rates and behavioral patterns) were maintained at baseline values. Our data suggest that amphibians can tolerate, and even benefit from, natural patterns of rapid warming/cooling. Specifically, temperature variation can elicit increased activity of the innate immune system. This immune response may be adaptive in an unpredictable environment, and is undetectable by conventional health indicators (and hence considered cryptic). Our findings highlight the need to consider naturalistic patterns of temperature variation when predicting species' susceptibility to climate change.

  18. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses.

    Science.gov (United States)

    Maggini, Silvia; Wintergerst, Eva S; Beveridge, Stephen; Hornig, Dietrich H

    2007-10-01

    Adequate intakes of micronutrients are required for the immune system to function efficiently. Micronutrient deficiency suppresses immunity by affecting innate, T cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. This situation increases susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (active and passive), in individuals with chronic alcohol abuse, in certain diseases, during pregnancy and lactation, and in the elderly. This paper summarises the roles of selected vitamins and trace elements in immune function. Micronutrients contribute to the body's natural defences on three levels by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. Vitamins A, C, E and the trace element zinc assist in enhancing the skin barrier function. The vitamins A, B6, B12, C, D, E and folic acid and the trace elements iron, zinc, copper and selenium work in synergy to support the protective activities of the immune cells. Finally, all these micronutrients, with the exception of vitamin C and iron, are essential for antibody production. Overall, inadequate intake and status of these vitamins and trace elements may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition. Therefore, supplementation with these selected micronutrients can support the body's natural defence system by enhancing all three levels of immunity.

  19. The quality of clinical maternal and neonatal healthcare - a strategy for identifying 'routine care signal functions'.

    Directory of Open Access Journals (Sweden)

    Stephan Brenner

    Full Text Available A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs, a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC, the 'EmOC signal functions', a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example.We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi.Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants' adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks.The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining

  20. Impact of fetal and neonatal environment on beta cell function and development of diabetes

    DEFF Research Database (Denmark)

    Nielsen, Jens H; Haase, Tobias N; Jaksch, Caroline

    2014-01-01

    nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most...

  1. 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,

  2. 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

  3. Ventricular function and high-sensitivity cardiac troponin T in preterm infants with neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Nusarintowati Ramadhina

    2015-07-01

    Results Subjects had a mean gestational age of 31.5 (SD 2.18 weeks and mean birth weight of 1,525 (SD 437.5 g. The mean LV function measured by MPI was 0.281 (SD 0.075; mean EF was 72.5 (SD 5.09%; and mean FS was 38.3 (SD 4.29%. The RV function measured by TAPSE was mean 6.85 (SD 0.94 and that measured by MPI was median 0.255 (range 0.17-0.59. Serum hs-cTnT level was significantly higher in non-survivors than in survivors [282.08 (SD 77.81 pg/mL vs. 97.75 (24.2-142.2 pg/mL, respectively P =0.023]. There were moderate correlations between LV-MPI and hs-cTnT concentration (r=0.577; P=0.001, as well as between RV-MPI and hs-cTnT concentration (r=0.502; P=0.005. The positive correlation between LV and RV-MPI in neonatal sepsis was strong (r=0.77; P <0.001.Conclusion Left and right ventricular MPI show positive correlations with hs-cTnT levels. Serum hs-cTnT is significantly higher in non survivors. As such, this marker may have prognostic value for neonatal sepsis patients.

  4. Long-term cognitive functions in neonatal short bowel syndrome patients.

    Science.gov (United States)

    Huang, J; Cai, W; Tang, Q; Feng, Y; Tao, Y; Wang, Y; Wu, J

    2008-04-01

    The aim of the study was to evaluate the long-term effects of neonatal short bowel syndrome on cognitive functions during development. Nine patients diagnosed with short bowel syndrome during the neonatal period were enrolled in this study. Their medical records were reviewed; anthropometric measurements and blood tests were assayed; IQ tests (the Chinese versions of WAIS-R, WPPSI-R and WISC-R) were performed depending on their age, and a BSID assessment was carried out in those patients less than 4 years old. Eight of 9 patients were followed up except for one patient who died in a car accident at the age of three. All patients had been weaned off parenteral nutrition for more than 2 years. The average residual small bowel length was 58.1 cm (range 35-70 cm), and the mean parenteral nutrition (PN) duration was 73.1 days (43-147 days). The mean duration of the period without PN was 7.4 years (range 2.1-17.1 years). Weight, height and BMI for age were normal in 7 children except for 1 child, who was overweight. Hemoglobin and albumin concentrations were normal in all 8 patients. Evaluation of cognitive development showed normal results for all 8 patients while a verbal/performance discrepancy was found in 2. Patients with neonatal SBS who were weaned off PN for more than 2 years were found to have normal growth and cognitive development during this long-term follow-up. There was no evidence for a strong correlation between SBS and nutritional/cognition disorder. Longer term and controlled studies with a larger sample size are warranted.

  5. Evaluation of renal glomerular and tubular functional and structural integrity in neonates.

    Science.gov (United States)

    Awad, Hesham; el-Safty, Ibrahim; el-Barbary, Mohamed; Imam, Safaa

    2002-11-01

    Renal cells are not fully differentiated at birth, representing a major risk in preterm infants. We evaluated glomerular and tubular functional integrity as well as structural integrity of renal tubules among healthy full-term and preterm infants as well as diseased preterm infants. A total of 50 newborns (10 healthy full-term, 10 healthy preterm, and 30 diseased preterm, at 38.9 +/- 1.10, 34.2 +/- 0.92, and 32 +/- 2.47 weeks gestational age, respectively) were included in the present study. Glomerular function was assessed by measuring urinary levels of both microalbumin and immunoglobulin G as well as serum creatinine levels, whereas the proximal tubular function was investigated by measuring the urinary levels of both alpha1-microglobulin and beta2-microglobulin as well as retinol-binding protein. Also, distal tubular reabsorption capacity was investigated by assessing fractional excretion of sodium. Moreover, the structural integrity of renal proximal tubules was studied by measuring the urinary activities of both the brush-border membrane enzyme leucine-aminopeptidase (LAP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase. The preceding investigations were done on both the first and third days of life of all 50 newborns. Glomerular and tubular function and structure was relatively impaired at birth among both healthy and diseased preterm as well as healthy full-term neonates and improved rapidly thereafter. The diseased preterm neonates showed worse renal function and structure with minimal improvement regardless of the underlying sickness. Renal insufficiency and renal immaturity could be evaluated using enzymuria and low- and high-molecular-weight proteinuria as noninvasive methods.

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

    OpenAIRE

    Hua-Jia Dai; Ke-Zhu Hou; Zu-Jin Cai; Qi Zhou; Song Zhu; Jian-Wei Bi

    2016-01-01

    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 en...

  7. Diethylstilbestrol Exposure in Neonatal Mice Induces Changes in the Adulthood in the Immune Response to Taenia crassiceps without Modifications of Parasite Loads

    Directory of Open Access Journals (Sweden)

    Karen E. Nava-Castro

    2014-01-01

    Full Text Available Industrial growth has increased the exposition to endocrine disruptor compounds (EDC’s, which are exogenous agents with agonist or antagonist action of endogenous steroid hormones that may affect the course of parasite infections. We wanted to determine if the exposure to diethylstilbestrol (DES, an estrogen agonist, to both male and female mice affected the immune response and their susceptibility to T. crassiceps cysticercosis. In all infected groups, females showed higher parasite loads than males, and neonatal DES administration did not modify this pattern. In the spleen, noninfected mice showed sex-related differences in the percentage of the CD8+ subpopulation, but DES decreased the percentage of CD3+, CD19+, and CD8+ subpopulations in infected mice. In the mesenteric lymphatic node (MNL, DES showed a dimorphic effect in the percentage of CD19+ cells. Regarding estrogen receptor alpha (ER-α expression, DES treatment induced a reduction in the expression of this receptor in both noninfected female and male mice in the spleen, which was decreased only in males in CD3+ and CD8+ lymphocytes in MNL cell subpopulations. Our study is the first one to demonstrate that DES neonatal treatment in male and female mice affects the immune cell percentage, without effect on the susceptibility to T. crassiceps cysticercosis.

  8. 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...

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

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Pedersen, Bente K

    2007-01-01

    Marathoners are at an increased risk of developing upper respiratory tract infections (URTIs) following races and periods of hard training, which are associated with temporary changes in the immune system. The majority of the reported changes are decreases in function or concentration of certain...... 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...

  10. Identification and Immune Functional Characterization of Pigeon TLR7

    Science.gov (United States)

    Xiong, Dan; Song, Li; Pan, Zhiming; Chen, Xiang; Geng, Shizhong; Jiao, Xinan

    2015-01-01

    Toll-like receptor 7 (TLR7) is activated by single-stranded RNA and synthetic imidazoquinoline components, and induces interferon production. In this study, we cloned the TLR7 gene from King pigeon (Columba livia). The TLR7 open reading frame is 3144 bp and encodes a 1047-amino acid protein, consisting of a canonical TLR composition with 15 leucine-rich repeats (LRRs). Amino acid-inserting modifications were found at position 15 of LRR2, LRR11, LRR13, and LRR14 and position 10 of LRR10. The tissue distribution of pigeon TLR7 suggests that immune-associated tissues, especially the spleen and liver, have high TLR7 expression. HEK293T cells transfected with pigeon TLR7 plasmid responded to the agonist R848, indicating a functional TLR7 homolog. Following R848 stimulation of pigeon peripheral blood mononuclear cells, the levels of IFN-γ, IL-6, IL-8, CCL5, and IL-10 mRNA, assessed using quantitative real-time PCR, were significantly up-regulated. After Newcastle disease virus vaccine strain LaSota inoculation and agonist R848 injection, the level of TLR7 mRNA in the spleen of pigeons increased significantly in the R848-injected group, but decreased in the LaSota-inoculated group at three day post-infection (d.p.i.). The mRNA levels of inflammatory cytokines and chemokines were significantly upregulated in both LaSota-inoculated and R848-injected groups. Triggering pigeon TLR7 leads to robust up-regulation of inflammatory cytokines and chemokines, suggesting an important role in the innate immune response. PMID:25874762

  11. 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

    .... Although several factors contribute to inhalational anthrax, we hypothesized that unimpeded infection of Bacillus anthracis is directly linked to disabling the innate immune functions contributed by AM...

  12. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals.

    Directory of Open Access Journals (Sweden)

    Noah D Cohen

    Full Text Available Neutrophils play an important role in protecting against infection. Foals have age-dependent deficiencies in neutrophil function that may contribute to their predisposition to infection. Thus, we investigated the ability of a CpG-ODN formulated with Emulsigen to modulate functional responses of neutrophils in neonatal foals. Eighteen foals were randomly assigned to receive either a CpG-ODN with Emulsigen (N = 9 or saline intramuscularly at ages 1 and 7 days. At ages 1, 3, 9, 14, and 28, blood was collected and neutrophils were isolated from each foal. Neutrophils were assessed for basal and Rhodococcus equi-stimulated mRNA expression of the cytokines interferon-γ (IFN-γ, interleukin (IL-4, IL-6, and IL-8 using real-time PCR, degranulation by quantifying the amount of β-D glucuronidase activity, and reactive oxygen species (ROS generation using flow cytometry. In vivo administration of the CpG-ODN formulation on days 1 and 7 resulted in significantly (P<0.05 increased IFN-γ mRNA expression by foal neutrophils on days 3, 9, and 14. Degranulation was significantly (P<0.05 lower for foals in the CpG-ODN-treated group than the control group at days 3 and 14, but not at other days. No effect of treatment on ROS generation was detected. These results indicate that CpG-ODN administration to foals might improve innate and adaptive immune responses that could protect foals against infectious diseases and possibly improve responses to vaccination.

  13. Probiotic Lactobacillus rhamnosus GG enhanced Th1 cellular immunity but did not affect antibody responses in a human gut microbiota transplanted neonatal gnotobiotic pig model.

    Directory of Open Access Journals (Sweden)

    Ke Wen

    Full Text Available This study aims to establish a human gut microbiota (HGM transplanted gnotobiotic (Gn pig model of human rotavirus (HRV infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG feeding (14 doses, up to 109 colony-forming-unit [CFU]/dose effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 106 CFU/dose was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota.

  14. Life-history strategy determines constraints on immune function.

    Science.gov (United States)

    Parker, Benjamin J; Barribeau, Seth M; Laughton, Alice M; Griffin, Lynn H; Gerardo, Nicole M

    2017-05-01

    Determining the factors governing investment in immunity is critical to understanding host-pathogen ecological and evolutionary dynamics. Studies often consider disease resistance in the context of life-history theory, with the expectation that investment in immunity will be optimized in anticipation of disease risk. Immunity, however, is constrained by context-dependent fitness costs. How the costs of immunity vary across life-history strategies has yet to be considered. Pea aphids are typically unwinged but produce winged offspring in response to high population densities and deteriorating conditions. This is an example of polyphenism, a strategy used by many organisms to adjust to environmental cues. The goal of this study was to examine the relationship between the fitness costs of immunity, pathogen resistance and the strength of an immune response across aphid morphs that differ in life-history strategy but are genetically identical. We measured fecundity of winged and unwinged aphids challenged with a heat-inactivated fungal pathogen, and found that immune costs are limited to winged aphids. We hypothesized that these costs reflect stronger investment in immunity in anticipation of higher disease risk, and that winged aphids would be more resistant due to a stronger immune response. However, producing wings is energetically expensive. This guided an alternative hypothesis - that investing resources into wings could lead to a reduced capacity to resist infection. We measured survival and pathogen load after live fungal infection, and we characterized the aphid immune response to fungi by measuring immune cell concentration and gene expression. We found that winged aphids are less resistant and mount a weaker immune response than unwinged aphids, demonstrating that winged aphids pay higher costs for a less effective immune response. Our results show that polyphenism is an understudied factor influencing the expression of immune costs. More generally, our work

  15. Structure-informed insights for NLR functioning in plant immunity

    NARCIS (Netherlands)

    Sukarta, Octavina Citra Ayudhany; Slootweg, Erik J.; Goverse, Aska

    2016-01-01

    To respond to foreign invaders, plants have evolved a cell autonomous multilayered immune system consisting of extra- and intracellular immune receptors. Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) mediate recognition of pathogen effectors inside the cell and trigger a

  16. A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

    Science.gov (United States)

    St Pierre, Cristina; Guo, Jane; Shin, John D; Engstrom, Laura W; Lee, Hyun-Hee; Herbert, Alan; Surdi, Laura; Baker, James; Salmon, Michael; Shah, Sanjiv; Ellis, J Michael; Houshyar, Hani; Crackower, Michael A; Kleinschek, Melanie A; Jones, Dallas C; Hicks, Alexandra; Zaller, Dennis M; Alves, Stephen E; Ramadas, Ravisankar A

    2017-01-01

    While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.

  17. A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system

    Science.gov (United States)

    Engstrom, Laura W.; Lee, Hyun-Hee; Herbert, Alan; Surdi, Laura; Baker, James; Salmon, Michael; Shah, Sanjiv; Ellis, J. Michael; Houshyar, Hani; Crackower, Michael A.; Kleinschek, Melanie A.; Jones, Dallas C.; Hicks, Alexandra; Zaller, Dennis M.; Alves, Stephen E.

    2017-01-01

    While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the ‘immune fingerprint’ of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders. PMID:28719615

  18. Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis.

    Science.gov (United States)

    Sampaio-Pinto, Vasco; Rodrigues, Sílvia C; Laundos, Tiago L; Silva, Elsa D; Vasques-Nóvoa, Francisco; Silva, Ana C; Cerqueira, Rui J; Resende, Tatiana P; Pianca, Nicola; Leite-Moreira, Adelino; D'Uva, Gabriele; Thorsteinsdóttir, Sólveig; Pinto-do-Ó, Perpétua; Nascimento, Diana S

    2018-02-26

    So far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  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

    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.

  1. 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......Marathoners are at an increased risk of developing upper respiratory tract infections (URTIs) following races and periods of hard training, which are associated with temporary changes in the immune system. The majority of the reported changes are decreases in function or concentration of certain...... function and reduce the risk of URTIs have been sought. This paper focuses on the effect of glutamine, vitamin C, bovine colostrum and glucose. Although, some of these supplements can affect the physiological and immune changes associated with marathon racing, none of the supplements discussed have...

  2. DNA vaccination of neonate piglets in the face of maternal immunity induces humoral memory and protection against a virulent pseudorabies virus challenge.

    Science.gov (United States)

    Fischer, Laurent; Barzu, Simona; Andreoni, Christine; Buisson, Nathalie; Brun, André; Audonnet, Jean Christophe

    2003-04-02

    DNA vaccination represents a unique opportunity to overcome the limitations of conventional vaccine strategy in early life in the face of maternal-derived immunity. We used the model of pseudorabies virus (PRV) infection in pigs to further explore the potential of DNA vaccination in piglets born to sows repeatedly vaccinated with a PRV inactivated vaccine. A single immunisation of 8-week-old piglets with a DNA vaccine expressing secreted forms of PRV gB, gC, and gD, triggered an active serological response, confirming that DNA vaccination can over-ride significant residual maternal-derived immunity. A clear anamnestic response was evidenced when a secondary DNA vaccination was performed at 11 weeks of age, suggesting that DNA vaccination, performed in the face of passive immunity, elicited a strong humoral memory. We subsequently explored the potential of DNA vaccination in neonate piglets (5-6 days of age) in the face of very high titres of maternal antibodies and demonstrated that very high titres of passive antibodies selectively inhibited serological responses but not the establishment of potent memory responses. Finally, we demonstrated that DNA vaccination provided protection against an infectious PRV challenge at the end of the fattening period (i.e. at approximately 5 months of age). Collectively, our results pave the way for a new flexible vaccination program, which could ensure uninterrupted protection of fattening pigs over their entire economical life under field conditions.

  3. Proposed method to construct Boolean functions with maximum possible annihilator immunity

    Science.gov (United States)

    Goyal, Rajni; Panigrahi, Anupama; Bansal, Rohit

    2017-07-01

    Nonlinearity and Algebraic(annihilator) immunity are two core properties of a Boolean function because optimum values of Annihilator Immunity and nonlinearity are required to resist fast algebraic attack and differential cryptanalysis respectively. For a secure cypher system, Boolean function(S-Boxes) should resist maximum number of attacks. It is possible if a Boolean function has optimal trade-off among its properties. Before constructing Boolean functions, we fixed the criteria of our constructions based on its properties. In present work, our construction is based on annihilator immunity and nonlinearity. While keeping above facts in mind,, we have developed a multi-objective evolutionary approach based on NSGA-II and got the optimum value of annihilator immunity with good bound of nonlinearity. We have constructed balanced Boolean functions having the best trade-off among balancedness, Annihilator immunity and nonlinearity for 5, 6 and 7 variables by the proposed method.

  4. Functional and phenotypic profiling of innate immunity during Salmonella infection

    DEFF Research Database (Denmark)

    Sørensen, Rikke Brandt; Pedersen, Susanne Brix

    . The results presented in this thesis add to the current knowledge about innate immunity to Salmonella, suggest new host immune cell subsets important for bacterial containment and provide a basic understanding of bacteria-induced DC inflammatory programs. The two latter could prove important in regard......Salmonellae are food borne pathogens, typically acquired by the oral ingestion of contaminated food or water, causing disease in both healthy and immunocompromised individuals. To gain insight into early immune regulation events caused by Salmonella as well as inflammatory signatures induced......DC) in bacterial infections, whereas the other major dendritic cell subset, plasmacytoid DC (pDC), plays an important part in antiviral responses, and is less well characterised in regard to antibacterial immunity. Using multi-parametric flow cytometry, we were able to show for the first time that pDC accumulated...

  5. 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.

  6. Investment in constitutive immune function by North American elk experimentally maintained at two different population densities.

    Directory of Open Access Journals (Sweden)

    Cynthia J Downs

    Full Text Available 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 resources that are available for investment in immune function. Our objective was to understand the relationship between immune function and density dependence mediated by trade-offs between immune function, nutritional condition, and reproduction. To determine how immune function relates to density-dependent processes, we quantified bacteria killing ability, hemolytic-complement activity, and nutritional condition of North American elk (Cervus elaphus from populations maintained at experimentally high- and low-population densities. When compared with elk from the low-density population, those from the high-density population had higher bacteria killing ability and hemolytic-complement activity despite their lower nutritional condition. Similarly, when compared with adults, yearlings had higher bacteria killing ability, higher hemolytic-complement activity, and lower nutritional condition. Pregnancy status and lactational status did not change either measure of constitutive immunity. Density-dependent processes affected both nutritional condition and investment in constitutive immune function. Although the mechanism for how density affects immunity is ambiguous, we hypothesize two possibilities: (i individuals in higher population densities and in poorer nutritional condition invested more into constitutive immune defenses, or (ii had higher parasite loads causing higher induced immune responses. Those explanations are not mutually exclusive, and might be synergistic, but overall our results provide stronger support for the hypothesis that animals in poorer nutritional condition invest

  7. A test of energetic trade-offs between growth and immune function in watersnakes.

    Science.gov (United States)

    Korfel, Chelsea A; Chamberlain, Jeremy D; Gifford, Matthew E

    2015-10-01

    Energy budgets explain how organisms allocate energetic intake to accomplish essential processes. A likely life history trade-off occurs between growth and immune response in juvenile organisms, where growth is important to avoid predation or obtain larger prey and immune response is essential to survival in the presence of environmental pathogens. We examined the innate (wound healing) and adaptive (lymphoid tissue, thymus and spleen) components of immune response along with growth in two populations of the diamond-backed watersnake Nerodia rhombifer raised in a common environment. We found that neonate snakes born to females from populations characterized by different predator and prey environments did not differ in energetic intake, but snakes from the population containing large prey grew significantly faster than those from a population containing small prey. Thymus mass, when corrected for body mass, was larger in snakes from the small prey population than in snakes from the large prey population. Additionally, the snakes from the population containing small prey healed significantly faster than those from the population containing large prey. Thus, we detected a negative correlation between growth (over a 4-month period) and wound healing across populations that is suggestive of an energetic trade-off between growth and immune response. The differences observed in growth and immune response among these two populations appear to suggest different energy allocation strategies to maximize fitness in response to differing conditions experienced by snakes in the two populations.

  8. Neonatal sublingual vaccination with Salmonella proteins and adjuvant cholera toxin or CpG oligodeoxynucleotides induces mucosal and systemic immunity in mice.

    Science.gov (United States)

    Huang, Ching-Feng; Wang, Chih-Chien; Wu, Tzee-Chung; Wu, Keh-Gong; Lee, Chin-Cheng; Peng, Ho-Jen

    2008-03-01

    Salmonella enteritidis is one of the most common enteric pathogens that cause acute gastroenteritis. A vaccine that can induce systemic and mucosal immune responses by a simple, noninvasive pathway and provide protection against this mucosal pathogen is needed. Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with sonicated Salmonella proteins (SSP) only, or SSP combined with adjuvant CpG or cholera toxin (CT). A booster vaccination was given 7 weeks after the last treatment. Serum and saliva antibody responses, cytokine profiles of spleen cells, survival rate, and intestinal morphology after live S enteritidis challenge were investigated. Saliva-specific secretory IgA (SIgA) antibody responses were markedly enhanced by neonatal sublingual vaccination with SSP together with adjuvant CpG or CT. Whereas vaccination with SSP and CpG enhanced spleen cell interferon-gamma production and serum-specific IgG2a antibody responses, vaccination with SSP and CT increased spleen cell interleukin (IL)-4, IL-5, IL-6, and interferon-gamma production and serum-specific IgG1 and IgG2a antibody responses. Vaccination with SSP and CpG or CT protected against intestinal necrosis and was associated with a higher survival rate after oral challenge with live S enteritidis. The vaccinated mice with higher specific IgG and saliva-specific secretory IgA antibody levels had a better survival rate. Neonatal sublingual vaccination with adjuvant CpG or CT can induce both mucosal and systemic immunity and may play a crucial role in protection against enteric pathogens.

  9. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

    Science.gov (United States)

    Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-01-01

    ABSTRACT Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). Conclusions: The level of IgA in colostrum or breast milk and level of placental Ig

  10. 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.

  11. The Effect of Ethnicity on Wideband Absorbance of Neonates with Healthy Middle Ear Functions in Malaysia: A Preliminary Study.

    Science.gov (United States)

    Wali, Hamzah A; Mazlan, Rafidah

    2018-01-01

    Although ethnicity effect on wideband absorbance (WBA) findings was evident for adults, its effect on neonates has not been established yet. This study aimed to investigate the influence of ethnicity on WBA measured at 0 daPa from neonates with healthy middle ear functions. Participants were 99 normal, healthy, full-term newborn babies with chronological age between 11 and 128 hours of age (mean=46.73, standard deviation=26.36). A cross-sectional study design was used to measure WBA at 16 one-third octave frequency points from 99 neonates comprising of three ethnic groups: Malays (n=58), Chinese (n=13) and Indians (n=28). A total of 165 ears (83.3%) that passed a battery of tests involving distortion product otoacoustic emissions, 1 kHz tympanometry and acoustic stapedial reflex were further tested using WBA. Moreover, body size measurements were recorded from each participant. The Malays and Indians neonates showed almost identical WBA response across the frequency range while the Chinese babies showed lower absorbance values between 1.25 kHz and 5 kHz. However, the differences observed in WBA between the three ethnic groups were not statistically significant ( p =0.23). Additionally, there were no statistically significant difference in birth weight, height and head circumference among the three ethnic groups. This study showed that Malays, Chinese and Indians neonates were not significantly different in their WBA responses. In conclusion, to apply for the ethnic-specific norms is not warranted when testing neonates from population constitute of these three ethnicities.

  12. Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

    Science.gov (United States)

    Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri

    2018-01-01

    Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

  13. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

    Directory of Open Access Journals (Sweden)

    Signorá Peres Konrad

    2012-10-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10 and monosodium glutamate (monosodium glutamate, n = 13 groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%, an increased area under the curve of total insulin secretion during glucose overload (39.3%, and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times, bradycardic responses (>4 times, and vagal (~38% and sympathetic effects (~36% were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  14. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents.

    Science.gov (United States)

    Konrad, Signorá Peres; Farah, Vera; Rodrigues, Bruno; Wichi, Rogério Brandão; Machado, Ubiratan Fabres; Lopes, Heno Ferreira; D'Agord Schaan, Beatriz; De Angelis, Kátia; Irigoyen, Maria Cláudia

    2012-10-01

    The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (~38%) and sympathetic effects (~36%) were reduced as compared to the control group. Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  15. The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury.

    Science.gov (United States)

    Weekley, Holly; Nikolaou, Sia; Hu, Liangjun; Eismann, Emily; Wylie, Christopher; Cornwall, Roger

    2012-08-01

    The pathophysiology of paradoxical elbow flexion contractures following neonatal brachial plexus injury (NBPI) is incompletely understood. The current study tests the hypothesis that this contracture occurs by denervation-induced impairment of elbow flexor muscle growth. Unilateral forelimb paralysis was created in mice in four neonatal (5-day-old) BPI groups (C5-6 excision, C5-6 neurotomy, C5-6 neurotomy/repair, and C5-T1 global excision), one non-neonatal BPI group (28-day-old C5-6 excision), and two neonatal muscle imbalance groups (triceps tenotomy ± C5-6 excision). Four weeks post-operatively, motor function, elbow range of motion, and biceps/brachialis functional lengths were assessed. Musculocutaneous nerve (MCN) denervation and reinnervation were assessed immunohistochemically. Elbow flexion motor recovery and elbow flexion contractures varied inversely among the neonatal BPI groups. Contracture severity correlated with biceps/brachialis shortening and MCN denervation (relative axon loss), with no contractures occurring in mice with MCN reinnervation (presence of growth cones). No contractures or biceps/brachialis shortening occurred following non-neonatal BPI, regardless of denervation or reinnervation. Neonatal triceps tenotomy did not cause contractures or biceps/brachialis shortening, nor did it worsen those following neonatal C5-6 excision. Denervation-induced functional shortening of elbow flexor muscles leads to variable elbow flexion contractures depending on the degree, permanence, and timing of denervation, independent of muscle imbalance. Copyright © 2012 Orthopaedic Research Society.

  16. Increased litter survival rates, reduced clinical illness and better lactogenic immunity against TGEV in gilts that were primed as neonates with porcine respiratory coronavirus (PRCV).

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2003-09-01

    Establishing immunological memory in female piglets at a young age with PRCV was effective in inducing a secondary immune response to a limiting dose of virulent TGEV given orally 13-18 days prior to farrowing. Subsequently, because of passive antibody transfer, the offspring of these primed gilts were more efficient in surviving a lethal TGEV challenge. An average survival rate of 89% occurred in 6 litters of piglets from primed gilts that were boosted with 2.8 x 10(6) plaque forming units (PFU) of TGEV whereas 76% of the piglets survived in three litters that suckled primed gilts boosted with 3.0 x 10(5)PFU of TGEV. Non-primed gilts given identical pre-farrowing doses of TGEV had litter survival rates of 63 and 55%, respectively. Moreover, both groups of litters from primed gilts suffered less clinical illness (as measured by the extent of weight loss post-challenge) than control litters. Priming of the piglets as neonates and boosting the pregnant gilts produced an anamnestic systemic immune response and correspondingly higher milk titers in the primed gilts compared to control animals. Thus, priming piglets with PRCV was beneficial in providing resistance to TGEV and could be incorporated into a vaccine strategy that yields better protection against TGEV.

  17. Sexual dimorphism in immune function changes during the annual cycle in house sparrows

    Science.gov (United States)

    Pap, Péter László; Czirják, Gábor Árpád; Vágási, Csongor István; Barta, Zoltán; Hasselquist, Dennis

    2010-10-01

    Difference between sexes in parasitism is a common phenomenon among birds, which may be related to differences between males and females in their investment into immune functions or as a consequence of differential exposure to parasites. Because life-history strategies change sex specifically during the annual cycle, immunological responses of the host aiming to reduce the impact of parasites may be sexually dimorphic. Despite the great complexity of the immune system, studies on immunoecology generally characterise the immune status through a few variables, often overlooking potentially important seasonal and gender effects. However, because of the differences in physiological and defence mechanisms among different arms of the immune system, we expect divergent responses of immune components to environmental seasonality. In male and female house sparrows ( Passer domesticus), we measured the major components of the immune system (innate, acquired, cellular and humoral) during four important life-history stages across the year: (1) mating, (2) breeding, (3) moulting and (4) during the winter capture and also following introduction to captivity in aviary. Different individuals were sampled from the same population during the four life cycle stages. We found that three out of eight immune variables showed a significant life cycle stage × sex interaction. The difference in immune response between the sexes was significant in five immune variables during the mating stage, when females had consistently stronger immune function than males, while variables varied generally non-significantly with sex during the remaining three life cycle stages. Our results show that the immune system is highly variable between life cycle stages and sexes, highlighting the potential fine tuning of the immune system to specific physiological states and environmental conditions.

  18. 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.

  19. Modulating the function of the immune system by thyroid hormones and thyrotropin.

    Science.gov (United States)

    Jara, Evelyn L; Muñoz-Durango, Natalia; Llanos, Carolina; Fardella, Carlos; González, Pablo A; Bueno, Susan M; Kalergis, Alexis M; Riedel, Claudia A

    2017-04-01

    Accumulating evidence suggests a close bidirectional communication and regulation between the neuroendocrine and immune systems. Thyroid hormones (THs) can exert responses in various immune cells, e.g., monocytes, macrophages, natural killer cells, and lymphocytes, affecting several inflammation-related processes (such as, chemotaxis, phagocytosis, reactive oxygen species generation, and cytokines production). The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions, including sepsis, inflammation, autoimmune diseases and viral infections. Under these conditions, TH therapy could contribute to restoring normal physiological functions. Here we discuss the effects of THs and thyroid stimulating hormone (TSH) on the immune system and the contribution to inflammation and pathogen clearance, as well as the consequences of thyroid pathologies over the function of the immune system. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  20. 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 cells...... in peripheral blood of healthy volunteers and cancer patients. These immune responses were directed against a HLA-A2-restricted peptide epitope derived from Foxp3. Foxp3-reactive T cells were characterized as cytotoxic CD8+ T cells. These cells recognized dendritic cells incubated with recombinant Foxp3 protein...... indicating that this protein was indeed internalized, processed and cross-presented in the context of HLA-A2. More importantly, however, Foxp3-specific T cells were able to specifically recognize Tregs. Similarly, Foxp3+ malignant T cells established from a Cutaneous T-cell lymphomas (CTCL) patient were...

  1. Military Strategies for Sustainment of Nutrition and Immune Function in the Field

    National Research Council Canada - National Science Library

    1999-01-01

    This publication, Military Strategies for Sustainment of Nutrition and Immune Function in the Field, is the latest in a series of reports based on workshops sponsored by the Committee on Military Nutrition Research (CMNR...

  2. Constitutive immune function responds more slowly to handling stress than corticosterone in a shorebird

    NARCIS (Netherlands)

    Buehler, Deborah M.; Bhola, Nina; Barjaktarov, Daliborka; Goymann, Wolfgang; Schwabl, Ingrid; Tieleman, B. Irene; Piersma, Theunis

    2008-01-01

    Ecological immunologists are interested in how immune function changes during different seasons and under different environmental conditions. However, an obstacle to answering such questions is discerning the effects of biological factors of interest and investigation artifacts such as handling

  3. Differing activation status and immune effector molecule expression profiles of neonatal and maternal lymphocytes in an African population.

    NARCIS (Netherlands)

    Engelmann, I.; Moeller, U.; Santamaria, A.; Kremsner, P.G.; Luty, A.J.F.

    2006-01-01

    Higher susceptibility of newborns to infections has been attributed to the hypo-responsiveness of their cellular immune system. Here we compared the activation status and expression of cytokines and cytotoxic molecules of cord versus maternal peripheral blood mononuclear cells in an African

  4. The Role of Interpersonal Problems in the Relationship Between Early Abuse Experiences and Adult Immune Functioning

    OpenAIRE

    Waldron, Jonathan Cook

    2012-01-01

    The current study aimed to test the long-term impact of abuse on immune functioning and to test the mediating role of interpersonal problems in the relationship between early child abuse experiences and immune functioning. A sample of 89 undergraduate adult women (M age = 19.24) completed reports of child abuse histories, interpersonal problems, and negative life events, and provided saliva samples to measure Secretory Immunoglobulin A (sIgA) and antibody level for Herpes Simplex Virus Type 1...

  5. 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...... 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...

  6. Soybean and green tea polyphenols improve immune function and redox status in very old ovariectomized mice.

    Science.gov (United States)

    Baeza, Isabel; De Castro, Nuria M; Arranz, Lorena; De la Fuente, Mónica

    2010-12-01

    In previous work we have observed that ovariectomy in rodents, a good model of mimicking human ovarian hormone loss, causes premature aging of the immune system. The prooxidative and inflammatory state that underlies the aging process is the base of that premature immunosenescence. It has been found that nutritional interventions with polyphenolic antioxidants constitute a good alternative to rejuvenate age-affected immune functions. In this study, we administered a diet supplemented with polyphenols (coming from soybean isoflavones and green tea) to sham-operated and ovariectomized mature mice for 15 weeks, until they reached a very old age. We have studied the effect of this supplementation on a broad range of parameters of immune function (in macrophages and lymphocytes) and oxidative stress (enzymatic and nonenzymatic antioxidant defences, oxidant compounds, and lipid peroxidation damage) in peritoneal leukocytes. The results showed that ovariectomy accelerates the age-related impairment of immune functions in very old mice as well as the oxidative and proinflammatory imbalance, and that the administration of soybean isoflavones and green tea improve the immune and redox state in these animals. Because the immune system is a good marker of health and a predictor of longevity, we suggest that an adequate nutritional treatment with polyphenols could be a highly recommended tool to fight against the detrimental effects of the lack of female sex hormones, through an improvement of the immune cell functions and redox state.

  7. Effect of intrauterine resuscitation on umbilical cord blood parameters of full-term fetal distress and evaluation of neonatal nerve function

    Directory of Open Access Journals (Sweden)

    Mei-Hao Luo

    2016-04-01

    Full Text Available Objective: To study the effect of intrauterine resuscitation on umbilical cord blood parameters of fullterm fetal distress and neonatal nerve function. Methods: A total of 74 cases of women who gave birth in Gynecology and Obstetrics Department of our hospital and had fetal distress during labor from February 2008 to October 2010 were selected for study and randomly divided into two groups, observation group received intrauterine resuscitation, control group received conventional treatment, and then contents of umbilical arterial blood gas parameters and cytokines of two groups of patients, contents of serum nerve injury molecules of neonates as well as neonatal asphyxia condition and nerve function were compared. Results: pH value, PO2 and HCO3- in umbilical cord blood of observation group were higher than those of control group, and PCO2 and BE absolute value were lower than those of control group; IL-6, IL-8 and IFN-γ contents in umbilical arterial blood and umbilical venous blood of observation group of patients were significantly lower than those of control group; 1 d, 3 d, 5 d and 7 d after birth, serum NSE and S-100 protein contents of observation group of neonates were significantly lower than those of control group; neonatal asphyxia condition and nerve function were better than those of control group. Conclusion: Intrauterine resuscitation can improve intrauterine fetal anoxia and reduce acidosis while reduce neonatal nerve function injury and prevent neonatal asphyxia, and it is an ideal method to treat full-term fetal distress.

  8. Effects of birth asphyxia on neonatal hippocampal structure and function in the spiny mouse.

    Science.gov (United States)

    Fleiss, B; Coleman, H A; Castillo-Melendez, M; Ireland, Z; Walker, D W; Parkington, H C

    2011-11-01

    Studies of human neonates, and in animal experiments, suggest that birth asphyxia results in functional compromise of the hippocampus, even when structural damage is not observable or resolves in early postnatal life. The aim of this study was to determine if changes in hippocampal function occur in a model of birth asphyxia in the precocial spiny mouse where it is reported there is no major lesion or infarct. Further, to assess if, as in human infants, this functional deficit has a sex-dependent component. At 37 days gestation (term=39 days) spiny mice fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5min of in utero asphyxia causing systemic acidosis and hypoxia. At 5 days of age hippocampal function was assessed ex vivo in brain slices, or brains were collected for examination of structure or protein expression. This model of birth asphyxia did not cause infarct or cystic lesion in the postnatal day 5 (P5) hippocampus, and the number of proliferating or pyknotic cells in the hippocampus was unchanged, although neuronal density in the CA1 and CA3 was increased. Protein expression of synaptophysin, brain-derived neurotrophic factor (BDNF), and the inositol trisphosphate receptor 1 (IP(3)R1) were all significantly increased after birth asphyxia, while long-term potentiation (LTP), paired pulse facilitation (PPF), and post-tetanic potentiation (PTP) were all reduced at P5 by birth asphyxia. In control P5 pups, PPF and synaptic fatigue were greater in female compared to male pups, and after birth asphyxia PPF and synaptic fatigue were reduced to a greater extent in female vs. male pups. In contrast, the asphyxia-induced increase in synaptophysin expression and neuronal density were greater in male pups. Thus, birth asphyxia in this precocial species causes functional deficits without major structural damage, and there is a sex-dependent effect on the hippocampus. This may be a clinically relevant model for assessing

  9. The insulin receptor substrate Chico regulates antibacterial immune function in Drosophila.

    Science.gov (United States)

    McCormack, Sarah; Yadav, Shruti; Shokal, Upasana; Kenney, Eric; Cooper, Dustin; Eleftherianos, Ioannis

    2016-01-01

    Molecular and genetic studies in model organisms have recently revealed a dynamic interplay between immunity and ageing mechanisms. In the fruit fly Drosophila melanogaster, inhibition of the insulin/insulin-like growth factor signaling pathway prolongs lifespan, and mutations in the insulin receptor substrate Chico extend the survival of mutant flies against certain bacterial pathogens. Here we investigated the immune phenotypes, immune signaling activation and immune function of chico mutant adult flies against the virulent insect pathogen Photorhabdus luminescens as well as to non-pathogenic Escherichia coli bacteria. We found that D. melanogaster chico loss-of-function mutant flies were equally able to survive infection by P. luminescens or E. coli compared to their background controls, but they contained fewer numbers of bacterial cells at most time-points after the infection. Analysis of immune signaling pathway activation in flies infected with the pathogenic or the non-pathogenic bacteria showed reduced transcript levels of antimicrobial peptide genes in the chico mutants than in controls. Evaluation of immune function in infected flies revealed increased phenoloxidase activity and melanization response to P. luminescens and E. coli together with reduced phagocytosis of bacteria in the chico mutants. Changes in the antibacterial immune function in the chico mutants was not due to altered metabolic activity. Our results indicate a novel role for chico in the regulation of the antibacterial immune function in D. melanogaster. Similar studies will further contribute to a better understanding of the interconnection between ageing and immunity and lead to the identification and characterization of the molecular host components that modulate both important biological processes.

  10. 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

  11. 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.

  12. 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

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

    Science.gov (United States)

    Hargadon, Kristian M

    2013-01-01

    Dendritic cells (DC) 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 programing 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-tumor immunity.

  14. Neonatal functional intestinal obstruction and the presence of severely immature ganglion cells on rectal biopsy: 6 year experience.

    Science.gov (United States)

    Burki, Tariq; Kiho, Liina; Scheimberg, Irene; Phelps, Simon; Misra, Devesh; Ward, Harry; Colmenero, Isabel

    2011-05-01

    We report our experience of managing eight babies who presented with neonatal intestinal obstruction and whose rectal biopsies showed severely immature ganglion cells. Neonatal unit records were reviewed to detect patients with suspected Hirschsprung's disease or functional intestinal obstruction. Those with intestinal atresia, anorectal malformation, malrotation, cystic fibrosis and prematurity were excluded. We identified 73 patients born at term. Twenty-seven did not need a rectal biopsy. Twenty-one had biopsy proven Hirschsprung's disease, while 17 had a normal rectal biopsy. Eight patients, all of whom presented with severe abdominal distension, showed immature ganglion cells. Seven had failed to pass meconium after birth. X-rays in all patients showed distended loops of bowel. Two neonates underwent an emergency laparotomy and a stoma. A repeat biopsy at 3 months showed maturation of ganglion cells and the stoma was reversed. Rectal biopsy was repeated in two other patients 2-9 months after the first biopsy and showed mature ganglion cells. At follow-up, one patient still suffers from severe constipation. Seven are asymptomatic now, including the two patients who needed a stoma. Immature ganglion cells on rectal biopsy may be an indicator of transient functional immaturity of the intestine.

  15. Early life ozone exposure results in dysregulated innate immune function and altered microRNA expression in airway epithelium.

    Directory of Open Access Journals (Sweden)

    Candice C Clay

    Full Text Available Exposure to ozone has been associated with increased incidence of respiratory morbidity in humans; however the mechanism(s behind the enhancement of susceptibility are unclear. We have previously reported that exposure to episodic ozone during postnatal development results in an attenuated peripheral blood cytokine response to lipopolysaccharide (LPS that persists with maturity. As the lung is closely interfaced with the external environment, we hypothesized that the conducting airway epithelium of neonates may also be a target of immunomodulation by ozone. To test this hypothesis, we evaluated primary airway epithelial cell cultures derived from juvenile rhesus macaque monkeys with a prior history of episodic postnatal ozone exposure. Innate immune function was measured by expression of the proinflammatory cytokines IL-6 and IL-8 in primary cultures established following in vivo LPS challenge or, in response to in vitro LPS treatment. Postnatal ozone exposure resulted in significantly attenuated IL-6 mRNA and protein expression in primary cultures from juvenile animals; IL-8 mRNA was also significantly reduced. The effect of antecedent ozone exposure was modulated by in vivo LPS challenge, as primary cultures exhibited enhanced cytokine expression upon secondary in vitro LPS treatment. Assessment of potential IL-6-targeting microRNAs miR-149, miR-202, and miR-410 showed differential expression in primary cultures based upon animal exposure history. Functional assays revealed that miR-149 is capable of binding to the IL-6 3' UTR and decreasing IL-6 protein synthesis in airway epithelial cell lines. Cumulatively, our findings suggest that episodic ozone during early life contributes to the molecular programming of airway epithelium, such that memory from prior exposures is retained in the form of a dysregulated IL-6 and IL-8 response to LPS; differentially expressed microRNAs such as miR-149 may play a role in the persistent modulation of the

  16. Understanding immune function as a pace of life trait requires environmental context.

    Science.gov (United States)

    Tieleman, B Irene

    2018-01-01

    This article provides a brief historical perspective on the integration of physiology into the concept of the pace of life of birds, evaluates the fit of immune function into this framework, and asks what it will take to fruitfully understand immune functioning of birds in pace of life studies in the future. In the late 1970s, physiology started to seriously enter avian life history ecology, with energy as the main currency of interest, inspired by David Lack's work in the preceding decades emphasizing how food availability explained life history variation. In an effort to understand the trade-off between survival and reproduction, and specifically the mortality costs associated with hard work, in the 1980s and 1990s, other physiological phenomena entered the realm of animal ecologists, including endocrinology, oxidative stress, and immunology. Reviewing studies thus far to evaluate the role of immune function in a life history context and particularly to address the questions whether immune function (1) consistently varies with life history variation among free-living bird species and (2) mediates life history trade-offs in experiments with free-living bird species; I conclude that, unlike energy metabolism, the immune system does not closely covary with life history among species nor mediates the classical trade-offs within individuals. Instead, I propose that understanding the tremendous immunological variation uncovered among free-living birds over the past 25 years requires a paradigm shift. The paradigm should shift from viewing immune function as a costly trait involved in life history trade-offs to explicitly including the benefits of the immune system and placing it firmly in an environmental and ecological context. A first step forward will be to quantify the immunobiotic pressures presented by diverse environmental circumstances that both shape and challenge the immune system of free-living animals. Current developments in the fields of infectious

  17. Nutrigenomics and immune function in fish: new insights from omics technologies.

    Science.gov (United States)

    Martin, Samuel A M; Król, Elżbieta

    2017-10-01

    The interplay between nutrition and immune system is well recognised, however the true integration of research between nutrition, animal energy status and immune function is still far from clear. In fish nutrition, especially for species maintained in aquaculture, formulated feeds are significantly different from the natural diet with recent changes in nutrient sources, especially with protein and oil sources now being predominated by terrestrial derived ingredients. Additionally, many feeds are now incorporated to health management and termed functional feeds, which are believed to improve fish health, reduce disease outbreaks and/or improve post-infection recovery. Using new omics technologies, including transcriptomics (microarray and RNA-seq) and proteomics, the impacts of nutrition on the immune system is becoming clearer. By using molecular pathway enrichment analysis, modules of genes can indicate how both local (intestinal) and systemic immune function are being altered. Although great progress has been made to define the changes in host immune function, understanding the interplay between fish nutrition, intestinal microbiome and immune system is only just beginning to emerge. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Impact of vitamin D on immune function: lessons learned from genome-wide analysis

    Science.gov (United States)

    Chun, Rene F.; Liu, Philip T.; Modlin, Robert L.; Adams, John S.; Hewison, Martin

    2014-01-01

    Immunomodulatory responses to the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25D) have been recognized for many years, but it is only in the last 5 years that the potential role of this in normal human immune function has been recognized. Genome-wide analyses have played a pivotal role in redefining our perspective on vitamin D and immunity. The description of increased vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1) expression in macrophages following a pathogen challenge, has underlined the importance of intracrine vitamin D as key mediator of innate immune function. It is now clear that both macrophages and dendritic cells (DCs) are able to respond to 25-hydroxyvitamin D (25D), the major circulating vitamin D metabolite, thereby providing a link between the function of these cells and the variations in vitamin D status common to many humans. The identification of hundreds of primary 1,25D target genes in immune cells has also provided new insight into the role of vitamin D in the adaptive immune system, such as the modulation of antigen-presentation and T cells proliferation and phenotype, with the over-arching effects being to suppress inflammation and promote immune tolerance. In macrophages 1,25D promotes antimicrobial responses through the induction of antibacterial proteins, and stimulation of autophagy and autophagosome activity. In this way variations in 25D levels have the potential to influence both innate and adaptive immune responses. More recent genome-wide analyses have highlighted how cytokine signaling pathways can influence the intracrine vitamin D system and either enhance or abrogate responses to 25D. The current review will discuss the impact of intracrine vitamin D metabolism on both innate and adaptive immunity, whilst introducing the concept of disease-specific corruption of vitamin D metabolism and how this may alter the requirements for vitamin D in maintaining a healthy immune system in humans. PMID:24795646

  19. Impact of vitamin D on immune function: lessons learned from genome-wide analysis.

    Science.gov (United States)

    Chun, Rene F; Liu, Philip T; Modlin, Robert L; Adams, John S; Hewison, Martin

    2014-01-01

    Immunomodulatory responses to the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25D) have been recognized for many years, but it is only in the last 5 years that the potential role of this in normal human immune function has been recognized. Genome-wide analyses have played a pivotal role in redefining our perspective on vitamin D and immunity. The description of increased vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1) expression in macrophages following a pathogen challenge, has underlined the importance of intracrine vitamin D as key mediator of innate immune function. It is now clear that both macrophages and dendritic cells (DCs) are able to respond to 25-hydroxyvitamin D (25D), the major circulating vitamin D metabolite, thereby providing a link between the function of these cells and the variations in vitamin D status common to many humans. The identification of hundreds of primary 1,25D target genes in immune cells has also provided new insight into the role of vitamin D in the adaptive immune system, such as the modulation of antigen-presentation and T cells proliferation and phenotype, with the over-arching effects being to suppress inflammation and promote immune tolerance. In macrophages 1,25D promotes antimicrobial responses through the induction of antibacterial proteins, and stimulation of autophagy and autophagosome activity. In this way variations in 25D levels have the potential to influence both innate and adaptive immune responses. More recent genome-wide analyses have highlighted how cytokine signaling pathways can influence the intracrine vitamin D system and either enhance or abrogate responses to 25D. The current review will discuss the impact of intracrine vitamin D metabolism on both innate and adaptive immunity, whilst introducing the concept of disease-specific corruption of vitamin D metabolism and how this may alter the requirements for vitamin D in maintaining a healthy immune system in humans.

  20. Impact of vitamin D on immune function: lessons learned from genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Rene F Chun

    2014-04-01

    Full Text Available Immunomodulatory responses to the active form of vitamin D (1,25-dihydroxyvitamin D, 1,25D have been recognized for many years, but it is only in the last five years that the potential role of this in normal human immune function has been recognized. Genome-wide analyses have played a pivotal role in redefining our perspective on vitamin D and immunity. The description of increased vitamin D receptor (VDR and 1α-hydroxylase (CYP27B1 expression in macrophages following a pathogen challenge, has underlined the importance of intracrine vitamin D as key mediator of innate immune function. It is now clear that both macrophages and DCs are able to respond to 25-hydroxyvitamin D (25D, the major circulating vitamin D metabolite, thereby providing a link between the function of these cells and the variations in vitamin D status common to many humans. The identification of hundreds of primary 1,25D target genes in immune cells has also provided new insight into the role of vitamin D in the adaptive immune system, such as the modulation of antigen-presentation and T cells proliferation and phenotype, with the over-arching effects being to suppress inflammation and promote immune tolerance. In macrophages 1,25D promotes antimicrobial responses through the induction of antibacterial proteins, and stimulation of autophagy and autophagosome activity. In this way variations in 25D levels have the potential to influence both innate and adaptive immune responses. More recent genome-wide analyses have highlighted how cytokine signaling pathways can influence the intracrine vitamin D system and either enhance or abrogate responses to 25D. The current review will discuss the impact of intracrine vitamin D metabolism on both innate and adaptive immunity, whilst introducing the concept of disease-specific corruption of vitamin D metabolism and how this may alter the requirements for vitamin D in maintaining a healthy immune system in humans.

  1. Effect of Nutritional Supplements on Immune Function and Body Weight in Malnourished Adults

    OpenAIRE

    Lawrence J. Cheskin; Joseph Margolick; Scott Kahan; Andrea H. Mitola; Kavita H. Poddar; Tricia Nilles; Sanjivani Kolge; Frederick Menendez; Michelande Ridoré; Shing-Jung Wang; Jacob Chou; Eve Carlson

    2010-01-01

    In the United States, approximately 5% of the population is malnourished or has low body weight, which can adversely affect immune function. Malnutrition is more prevalent in older adults and is often a result of energy imbalance from various causes. Dietary supplementation to promote positive energy balance can reverse malnutrition, but has not been assessed for its effect on immune parameters. This 8-week clinical feeding trial evaluated the effect of a commercially available, high-protein,...

  2. Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Mokra D

    2016-12-01

    Full Text Available Severe meconium aspiration syndrome (MAS in the neonates often requires a ventilatory support. As a method of choice, a conventional mechanical ventilation with small tidal volumes (VT<6 ml/kg and appropriate ventilatory pressures is used. The purpose of this study was to assess the short-term effects of the small-volume CMV performed by two neonatal ventilators: Aura V (Chirana Stara Tura a.s., Slovakia and SLE5000 (SLE Ltd., UK on the lung functions of rabbits with experimentally-induced MAS and to estimate whether the newly developed neonatal version of the ventilator Aura V is suitable for ventilation of the animals with MAS.

  3. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery.

    Science.gov (United States)

    Heidegger, Simon; Gössl, Dorothée; Schmidt, Alexandra; Niedermayer, Stefan; Argyo, Christian; Endres, Stefan; Bein, Thomas; Bourquin, Carole

    2016-01-14

    Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.

  4. Constitutive immune function responds more slowly to handling stress than corticosterone in a shorebird.

    Science.gov (United States)

    Buehler, Deborah M; Bhola, Nina; Barjaktarov, Daliborka; Goymann, Wolfgang; Schwabl, Ingrid; Tieleman, B Irene; Piersma, Theunis

    2008-01-01

    Ecological immunologists are interested in how immune function changes during different seasons and under different environmental conditions. However, an obstacle to answering such questions is discerning the effects of biological factors of interest and investigation artifacts such as handling stress. Here we examined handling stress and its effects on constitutive (noninduced) immune function via two protocols on captive red knots (Calidris canutus). We investigated how constitutive immunity responds to handling stress, how quickly these changes take place, and the practical implications for researchers interested in sampling baseline immune levels. We found that Staphylococcus aureus and Candida albicans killing increased with handling stress while total leukocyte and lymphocyte concentrations decreased. However, although corticosterone increased significantly and rapidly in response to handling stress, none of the 10 measures of constitutive immunity that we tested differed significantly from baseline within 20 or 30 min of capture. Thus, researchers interested in baseline immune function should sample animals as soon as possible after capture, but studies in species not easily sampled in less than 3 min (such as red knots) could still yield useful results.

  5. Identification and functionality of proteomes secreted by rat cardiac stem cells and neonatal cardiomyocytes

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Chimenti, I.; Marban, E.; Van Eyk, J.E.

    2010-01-01

    Roč. 10, č. 2 (2010), s. 245-253 ISSN 1615-9853 Institutional research plan: CEZ:AV0Z40310501 Keywords : animal proteomics * cardiac stem cells * neonatal cardiomyocytes Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.815, year: 2010

  6. 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.

  7. 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.

  8. 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

  9. Effects of Al on the splenic immune function and NE in rats.

    Science.gov (United States)

    Hu, Chongwei; Li, Jing; Zhu, Yanzhu; Bai, Chongsheng; Zhang, Jihong; Xia, Shiliang; Li, Yanfei

    2013-12-01

    Norepinephrine (NE) regulates the splenic immune function and it may be related to the effects of Aluminum (Al) on the splenic immune function. Here, the aim of this study was to further explore the effects of aluminum trichloride (AlCl3) on the splenic immune function and its relationship with NE. Forty male Wistar rats were orally exposed to AlCl3 (0, 64.18, 128.36 and 256.72 mg/kg BW) through drinking water for 120 days. The CD3(+), CD4(+), CD8(+) T lymphocytes, the T and B lymphocytes proliferation rates and serum NE concentration were examined. The correlation analysis between splenic immune function and NE were done. The results showed that the CD3(+), CD4(+), CD8(+) T lymphocytes and the T and B lymphocytes proliferation rates decreased and NE concentration increased in AlCl3-treated rats. NE was negatively correlated with proportions of CD3(+), CD4(+) T lymphocytes and T and B lymphocytes proliferation rates, but not correlated with CD8(+) T lymphocytes. The results suggest that AlCl3 suppresses the splenic immune function and NE plays important role in this process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Neonatal Tetanus: A Continuing Menace

    African Journals Online (AJOL)

    Alasia Datonye

    WHO/EPI/GEN/86/7 REVE 1 (ENGLISH). 27. UNICEF. Neonatal tetanus: protecting mothers and children. The State of World's Children 1994: 10. 28. WHO. EPI: Disease incidence and immunization coverage (Saudi Arabia). Weekly Epidem. Record. 1986;. 61(7): 45-46. 29. WHO. EPI. Neonatal tetanus mortality surveys.

  12. 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.

  13. 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.

  14. Subversion of plant cellular functions by bacterial type-III effectors: beyond suppression of immunity.

    Science.gov (United States)

    Macho, Alberto P

    2016-04-01

    Most bacterial plant pathogens employ a type-III secretion system to inject type-III effector (T3E) proteins directly inside plant cells. These T3Es manipulate host cellular processes in order to create a permissive niche for bacterial proliferation, allowing development of the disease. An important role of T3Es in plant pathogenic bacteria is the suppression of plant immune responses. However, in recent years, research has uncovered T3E functions different from direct immune suppression, including the modulation of plant hormone signaling, metabolism or organelle function. This insight article discusses T3E functions other than suppression of immunity, which may contribute to the modulation of plant cells in order to promote bacterial survival, nutrient release, and bacterial replication and dissemination. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. The highly buffered Arabidopsis immune signaling network conceals the functions of its components.

    Directory of Open Access Journals (Sweden)

    Rachel A Hillmer

    2017-05-01

    Full Text Available Plant immunity protects plants from numerous potentially pathogenic microbes. The biological network that controls plant inducible immunity must function effectively even when network components are targeted and disabled by pathogen effectors. Network buffering could confer this resilience by allowing different parts of the network to compensate for loss of one another's functions. Networks rich in buffering rely on interactions within the network, but these mechanisms are difficult to study by simple genetic means. Through a network reconstitution strategy, in which we disassemble and stepwise reassemble the plant immune network that mediates Pattern-Triggered-Immunity, we have resolved systems-level regulatory mechanisms underlying the Arabidopsis transcriptome response to the immune stimulant flagellin-22 (flg22. These mechanisms show widespread evidence of interactions among major sub-networks-we call these sectors-in the flg22-responsive transcriptome. Many of these interactions result in network buffering. Resolved regulatory mechanisms show unexpected patterns for how the jasmonate (JA, ethylene (ET, phytoalexin-deficient 4 (PAD4, and salicylate (SA signaling sectors control the transcriptional response to flg22. We demonstrate that many of the regulatory mechanisms we resolved are not detectable by the traditional genetic approach of single-gene null-mutant analysis. Similar to potential pathogenic perturbations, null-mutant effects on immune signaling can be buffered by the network.

  17. Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke.

    Science.gov (United States)

    Ceprián, Maria; Jiménez-Sánchez, Laura; Vargas, Carlos; Barata, Lorena; Hind, Will; Martínez-Orgado, Jose

    2017-04-01

    and purpose: Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS). Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke. The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS. Middle Cerebral Artery Occlusion (MCAO) was achieved in neonatal Wistar rats by introducing a nylon filament to the left MCA for 3 h; 15 min after removing the occluder vehicle (MCAO-V) or CBD single dose 5 mg/kg (MCAO-C) were administered i. p. Similarly manipulated but non-occluded rats served as controls (SHM). A set of behavioral tests was then conducted one week (P15) or one month (P38) after MCAO. Brain damage was then assessed by magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (H + -MRS) and histologic (TUNEL for cell death, immunohistochemistry for neuron, astrocyte and microglia identification) studies. CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H + -MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation. CBD administration after MCAO led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 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.

  19. [Age-related decline of immune function and age-related diseases].

    Science.gov (United States)

    Isobe, Ken-ichi; Nishio, Naomi; Ito, Sachiko

    2009-07-01

    Effects of aging on immune system are widespread. The development of T and B cells declines with age. The functions of matured T and B cell also decline with age. Consequently, infections present major clinical problems for elderly patients. Many of age-related diseases are related to innate immunity. For example, the pathogenesis of atherosclerosis and Alzheimer disease are related to macrophages (microglia). The Ox-LDL or A-beta induces macrophages or microglia to produce inflammatory cytokines, chemokines and matrix metalloproteinases. Recently neutrophils have been shown to be an important immune cells in atherosclerosis. Neutrophils secrete inflammatory cytokines. In wound healing neutrophils also work as first important immune cells, which affect age-related decline of wound repair.

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

    DEFF Research Database (Denmark)

    Hojman, Pernille

    2017-01-01

    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...... cancer through mobilization and activation of cytotoxic immune cells, restriction of inflammatory signaling pathways in myeloid immune cells, and regulation of acute and chronic systemic inflammatory responses. In conclusion, I propose that exercise has the potential to target tumor growth through...... 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....

  1. Seasonal redistribution of immune function in a migrant shorebird: annual-cycle effects override adjustments to thermal regime.

    Science.gov (United States)

    Buehler, Deborah M; Piersma, Theunis; Matson, Kevin; Tieleman, B Irene

    2008-12-01

    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 most wild animals. We measured constitutive immune indices once a month for a year on captive red knots (Calidris canutus). We also examined temperature as an environmental contributor to immune variation by manipulating ambient temperature to vary energy expenditure. To identify relationships among immune indices, we performed principal-component analysis. We found significant repeatability in immune indices over the annual cycle and covariation of immune indices within and among individuals. This covariation suggests immune strategies as individual traits among individuals and the use of different immune strategies during different annual-cycle stages within individuals. Over the annual cycle, both higher-cost phagocyte-based immunity and lower-cost lymphocyte-based immunity were high during mass change, but there was a clear shift toward lower-cost lymphocyte-based immunity during peak molt. Experimental manipulation of temperature had little effect on annual variation in immune function. This suggests that other environmental factors, such as food availability and disease, should also be examined in the future.

  2. Immune activation is associated with decreased thymic function in asymptomatic, untreated HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    Thandiwe Manjati

    2016-07-01

    Full Text Available 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 HIV positive treatment-naive individuals has thus far not been investigated. Aims and objectives: To optimise a five-colour flow cytometric assay for measurement of thymic function by measuring recent thymic emigrants (RTEs in treatment-naive HIV-infected patients and healthy controls and correlate results with levels of immune activation, CD4 counts and viral load. Methods: Blood obtained from 53 consenting HIV-positive individuals and 32 controls recruited from HIV prevention and testing clinic in Cape Town, South Africa. RTEs were measured (CD3+/CD4+/CD45RA+/CD31+/CD62L+ and levels were correlated with CD4 counts of HIV-infected individuals, log viral load and levels of immune activation (CD8+/CD38+ T-cells. Results: HIV-infected individuals had reduced frequencies of RTEs when compared to controls (p = 0.0035. Levels of immune activation were inversely correlated with thymic function(p = 0.0403, and the thymic function in HIV-infected individuals showed no significant correlation with CD4 counts (p = 0.31559 and viral load (p = 0.20628. Conclusions: There was impaired thymic function in HIV-infected individuals, which was associated with increased levels of immune activation. The thymic dysfunction was not associated with CD4 counts and viral load. Immune activation may result in inflammatory damage to the thymus and subsequent thymic dysfunction, and CD4 counts and viral load may not necessarily reflect thymic dysfunction in HIV.

  3. The contribution of maternal psychological functioning to infant length of stay in the Neonatal Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Cherry AS

    2016-06-01

    Full Text Available Amanda S Cherry,1 Melissa R Mignogna,1 Angela Roddenberry Vaz,1 Carla Hetherington,2 Mary Anne McCaffree,2 Michael P Anderson,3 Stephen R Gillaspy1 1Section of General and Community Pediatrics, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma, College of Medicine, Oklahoma City, OK, 3Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City, OK, USA Objective: Assess maternal psychological functioning within the Neonatal Intensive Care Unit (NICU and its contribution to neonate length of stay (LOS in the NICU.Study design: Mothers of infants admitted to the NICU (n=111 were assessed regarding postpartum depression, postpartum social support, postpartum NICU stress, and maternal anxiety at 2 weeks postpartum. Illness severity was assessed with the Clinical Risk Index for Babies (CRIB.Results: Postpartum depression was not significantly correlated with LOS, but was significantly correlated with trait anxiety (r=0.620, which was significantly correlated with LOS (r=0.227. Among mothers with previous mental health history, substance abuse history and CRIB score were the best predictors of LOS. For mothers without a prior mental health issues, delivery type, stress associated with infant appearance, and CRIB scores were the best predictors of LOS. In this group, LOS was found to increase on average by 7.06 days per one unit increase in stress associated with infant appearance among mothers with the same delivery type and CRIB score.Conclusion: Significant correlations of trait anxiety, stress associated with infant appearance, and parental role with LOS support the tenet that postpartum psychological functioning can be associated with NICU LOS. Keywords: NICU, postpartum depression, postpartum anxiety, parental stress, CRIB

  4. 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

    populations, including myeloid-derived suppressor cells (MDSCs), which serve to suppress immune system function. We have identified immune-suppressive MDSCs in the brains of GBM patients and found that they were in close proximity to self-renewing cancer stem cells (CSCs). MDSCs were selectively depleted...... that MIF is primarily an indirect promoter of GBM progression, working to suppress immune rejection by activating and protecting immune suppressive MDSCs within the GBM tumor microenvironment. Stem Cells 2016;34:2026-2039....

  5. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection

    International Nuclear Information System (INIS)

    Hansen, Spencer J.; Rushton, John; Dekonenko, Alexander; Chand, Hitendra S.; Olson, Gwyneth K.; Hutt, Julie A.; Pickup, David; Lyons, C. Rick; Lipscomb, Mary F.

    2011-01-01

    Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and monocyte-derived DCs (MDDCs). A CPXV infection of DCs at a multiplicity of infection of 10 was nonproductive, altered cellular morphology, and failed to reduce cell viability. A CPXV infection of DCs did not stimulate cytokine or chemokine secretion directly, but suppressed toll-like receptor (TLR) agonist-induced cytokine secretion and a DC-stimulated mixed leukocyte reaction (MLR). LPS-stimulated NF-κB nuclear translocation and host cytokine gene transcription were suppressed in CPXV-infected MDDCs. Early viral immunomodulatory genes were upregulated in MDDCs, consistent with early DC immunosuppression via synthesis of intracellular viral proteins. We conclude that a nonproductive CPXV infection suppressed DC immune function by synthesizing early intracellular viral proteins that suppressed DC signaling pathways.

  8. 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.

  9. Immunization of dogs with recombinant GnRH-1 suppresses the development of reproductive function.

    Science.gov (United States)

    Liu, Ya; Tian, Yuan; Zhao, Xijie; Jiang, Shudong; Li, Fubao; Zhang, Yunhai; Zhang, Xiaorong; Li, Yunsheng; Zhou, Jie; Fang, Fugui

    2015-02-01

    This study was designed to evaluate the effect of active immunization using recombinant GnRH-I protein on reproductive function in dogs. Six male and six female dogs were randomly assigned to either a control group or an immunization group (n = 3 males or 3 females/group). Dogs (aged 16 weeks) were immunized against GnRH-I with a maltose-binding protein-gonadotropin-releasing hormone I hexamer generated by recombinant DNA technology. Blood samples were taken at 4-week intervals after immunization. The serum concentrations of testosterone and estradiol and anti-GnRH-I antibodies were determined by RIA and ELISA, respectively. The results showed that active immunization with recombinant GnRH-I increased the serum levels of anti-GnRH antibodies (P dogs and a significant reduction (P dogs. Microscopically, spermatogonia were visible, but no spermatids and spermatozoa were detected in the seminiferous tubules. Neither early antral nor antral follicles were found in the immunized group. These results demonstrate that recombinant GnRH-I is an effective immunogen in dogs. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. 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.

  11. 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)

  12. Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

    Science.gov (United States)

    Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

    2018-02-06

    Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. 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.

  14. Sex versus parthenogenesis; immune function in a facultatively parthenogenetic phasmatid (Extatosoma tiaratum).

    Science.gov (United States)

    Alavi, Yasaman; Elgar, Mark Adrian; Jones, Therésa Melanie

    2017-07-01

    Facultative parthenogenetic species, in which females can alternate between sex and parthenogenesis, are useful models to investigate the costs and benefits of sex and parthenogenesis, an ongoing issue in biology. The necessary empirical studies comparing the outcomes of alternative reproductive modes on life history traits are rare and focus mainly on traits directly associated with reproductive fitness. Immune function determines the ability of individuals to defend themselves against injury and disease and is therefore likely to have a significant impact on fitness. Here, we used the facultatively parthenogenetic Australian phasmatid, Extatosoma tiaratum, to investigate the effect of both maternal and offspring mode of conception (sexual or parthenogenetic) on offspring immune function (haemocyte concentration, lytic activity and phenoloxidase activity). We show that when parthenogenesis persists beyond one generation, it has negative effects on immune response in terms of haemocyte concentration and lytic activity. Phenoloxidase activity positively correlates with the level of microsatellite heterozygosity. Moreover, immune response decreases across consecutive sampling weeks, suggesting there are physiological constraints with respect to mounting immune responses in close time intervals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells

    Directory of Open Access Journals (Sweden)

    Mahmood Y. Bilal

    2017-11-01

    Full Text Available Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN and thyroid-related proteins [thyroglobulin (TG and thyroid peroxidase (TPO]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes. Treatment of leukocytes with sodium iodide (NaI resulted in significant changes in immunity-related transcriptome with an emphasis on increased chemokine expression as probed with targeted RNASeq. Similarly, treatment of leukocytes with NaI or Lugol’s iodine induced increased protein production of both pro- and anti-inflammatory cytokines. These alterations were not attributed to iodide-induced de novo thyroid hormone synthesis. However, upon incubation with thyroid-derived TG, primary human leukocytes but not Jurkat T cells released thyroxine and triiodothyronine indicating that immune cells could potentially influence thyroid hormone balance. Overall, our studies reveal the novel network between human immune cells and thyroid-related molecules and highlight the importance of iodine in regulating the function of human immune cells.

  16. 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...

  17. Age and environment affect constitutive immune function in Red Knots (Calidris canutus)

    NARCIS (Netherlands)

    Buehler, Deborah M.; Tieleman, B. Irene; Piersma, Theunis; Guglielmo, C.G.

    2009-01-01

    We studied subspecies, age and environmental effects on constitutive immune function (natural antibody and complement titres, haptoglobin activity and leukocyte concentrations) in Red Knots (Calidris canutus). We compared C. c. islandica and C. c. canutus in the Wadden Sea and found no difference in

  18. Dual function of C-type lectin-like receptors in the immune system.

    NARCIS (Netherlands)

    Cambi, A.; Figdor, C.G.

    2003-01-01

    Carbohydrate-binding C-type lectin and lectin-like receptors play an important role in the immune system. The large family can be subdivided into subtypes according to their structural similarities and functional differences. The selectins are of major importance in mediating cell adhesion and

  19. 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.

  20. Herbal supplements and athlete immune function--what's proven, disproven, and unproven?

    Science.gov (United States)

    Senchina, David S; Shah, Nisarg B; Doty, Danielle M; Sanderson, Cole R; Hallam, Justus E

    2009-01-01

    The purpose of this paper is to critically evaluate current immunological and clinical literature regarding the effects of herbal preparations on athlete immune function. First, we review rates of herbal supplement use by athletes. Second, we use ginseng (Panax ginseng) and coneflower (Echinacea spp.) as models for examining how herbal supplements may influence immune function within the contexts of exercise and sport, while briefly considering several other popular herbal products. Third, we proffer several evidence-based hypotheses to explain apparent discrepancies among the cumulative data, concomitantly advancing a novel conceptual framework which may be useful to understanding herbal supplements and athlete immune function using Echinacea supplements as a model. Fourth, we apply the proposed framework to some prospective data regarding the effects of Echinacea pallida and Echinacea simulata on in vitro cytokine production and cell proliferation in peripheral blood mononuclear cells collected from male collegiate wrestlers and soccer players during training. Fifth and finally, we evaluate the current knowledge on herbal supplements and athlete immune function, identify gaps and limitations in knowledge, and advance several possible options for future research.

  1. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

    Science.gov (United States)

    Heidegger, Simon; Gößl, Dorothée; Schmidt, Alexandra; Niedermayer, Stefan; Argyo, Christian; Endres, Stefan; Bein, Thomas; Bourquin, Carole

    2015-12-01

    Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized

  2. WIP Remodeling Actin behind the Scenes: How WIP Reshapes Immune and Other Functions

    Directory of Open Access Journals (Sweden)

    Mira Barda-Saad

    2012-06-01

    Full Text Available Actin polymerization is a fundamental cellular process regulating immune cell functions and the immune response. The Wiskott-Aldrich syndrome protein (WASp is an actin nucleation promoting factor, which is exclusively expressed in hematopoietic cells, where it plays a key regulatory role in cytoskeletal dynamics. WASp interacting protein (WIP was first discovered as the binding partner of WASp, through the use of the yeast two hybrid system. WIP was later identified as a chaperone of WASp, necessary for its stability. Mutations occurring at the WASp homology 1 domain (WH1, which serves as the WIP binding site, were found to cause the Wiskott-Aldrich syndrome (WAS and X-linked thrombocytopenia (XLT. WAS manifests as an immune deficiency characterized by eczema, thrombocytopenia, recurrent infections, and hematopoietic malignancies, demonstrating the importance of WIP for WASp complex formation and for a proper immune response. WIP deficiency was found to lead to different abnormalities in the activity of various lymphocytes, suggesting differential cell-dependent roles for WIP. Additionally, WIP deficiency causes cellular abnormalities not found in WASp-deficient cells, indicating that WIP fulfills roles beyond stabilizing WASp. Indeed, WIP was shown to interact with various binding partners, including the signaling proteins Nck, CrkL and cortactin. Recent studies have demonstrated that WIP also takes part in non immune cellular processes such as cancer invasion and metastasis, in addition to cell subversion by intracellular pathogens. Understanding of numerous functions of WIP can enhance our current understanding of activation and function of immune and other cell types.

  3. 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

  4. Functional Laterality of Task-Evoked Activation in Sensorimotor Cortex of Preterm Infants: An Optimized 3 T fMRI Study Employing a Customized Neonatal Head Coil.

    Science.gov (United States)

    Scheef, Lukas; Nordmeyer-Massner, Jurek A; Smith-Collins, Adam Pr; Müller, Nicole; Stegmann-Woessner, Gaby; Jankowski, Jacob; Gieseke, Jürgen; Born, Mark; Seitz, Hermann; Bartmann, Peter; Schild, Hans H; Pruessmann, Klaas P; Heep, Axel; Boecker, Henning

    2017-01-01

    Functional magnetic resonance imaging (fMRI) in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD) responses in sensorimotor cortex (SMC). Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level. Here, we employed a custom-designed neonatal MR-coil adapted and optimized to the head size of a newborn in order to improve robustness, reliability and validity of neonatal sensorimotor fMRI. Thirteen preterm infants with a median gestational age of 26 weeks were scanned at term-corrected age using a prototype 8-channel neonatal head coil at 3T (Achieva, Philips, Best, NL). Sensorimotor stimulation was elicited by passive extension/flexion of the elbow at 1 Hz in a block design. Analysis of temporal signal to noise ratio (tSNR) was performed on the whole brain and the SMC, and was compared to data acquired with an 'adult' 8 channel head coil published previously. Task-evoked activation was determined by single-subject SPM8 analyses, thresholded at p lateralization of SMC activation, as found in children and adults, is already present in the newborn period.

  5. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians' skin.

    Science.gov (United States)

    Fan, Wenqiao; Jiang, Yusong; Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Sun, Hanchang; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians.

  6. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians’ skin

    Science.gov (United States)

    Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians. PMID:29267366

  7. Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.

    Science.gov (United States)

    Senchina, David S; Hallam, Justus E; Kohut, Marian L; Nguyen, Norah A; Perera, M Ann d N

    2014-01-01

    Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.

  8. Cerebrospinal Fluid Cytokines Correlate With Aseptic Meningitis and Blood-Brain Barrier Function in Neonatal-Onset Multisystem Inflammatory Disease: Central Nervous System Biomarkers in Neonatal-Onset Multisystem Inflammatory Disease Correlate With Central Nervous System Inflammation.

    Science.gov (United States)

    Rodriguez-Smith, Jackeline; Lin, Yen-Chih; Tsai, Wanxia Li; Kim, Hanna; Montealegre-Sanchez, Gina; Chapelle, Dawn; Huang, Yan; Sibley, Cailin H; Gadina, Massimo; Wesley, Robert; Bielekova, Bibiana; Goldbach-Mansky, Raphaela

    2017-06-01

    To evaluate proinflammatory cytokines and leukocyte subpopulations in the cerebrospinal fluid (CSF) and blood of patients with neonatal-onset multisystem inflammatory disease (NOMID) after treatment, and to compare inflammatory cytokines in the CSF and blood in 6 patients treated with 2 interleukin-1 (IL-1) blockers-anakinra and canakinumab. During routine follow-up visits between December 2011 and October 2013, we immunophenotyped the CSF of 17 pediatric NOMID patients who were treated with anakinra, and analyzed CSF cytokine levels in samples obtained at baseline and at 3-5-year follow-up visits and compared them to samples from healthy controls. CSF levels of IL-6, interferon-γ-inducible 10-kd protein (IP-10/CXCL10), and IL-18 and monocyte and granulocyte counts significantly decreased with anakinra treatment but did not normalize to levels in the controls, even in patients fulfilling criteria for clinical remission. CSF IL-6 and IL-18 levels significantly correlated with measures of blood-brain barrier function, specifically CSF protein (r = 0.75 and r = 0.81, respectively) and albumin quotient (r = 0.79 and r = 0.68, respectively). When patients were treated with canakinumab versus anakinra, median CSF white blood cell counts and IL-6 levels were significantly higher with canakinumab treatment (10.2 cells/mm 3 versus 3.7 cells/mm 3 and 150.7 pg/ml versus 28.5 pg/ml, respectively) despite similar serum cytokine levels. CSF leukocyte subpopulations and cytokine levels significantly improve with optimized IL-1 blocking treatment, but do not normalize. The correlation of CSF IL-6, IP-10/CXCL10, and IL-18 levels with clinical laboratory measures of inflammation and blood-brain barrier function suggests that they may have a role as biomarkers in central nervous system (CNS) inflammation. The difference in inhibition of CSF biomarkers between 2 IL-1 blocking agents, anakinra and canakinumab, suggests differences in efficacy in the intrathecal

  9. PTEN functions as a melanoma tumor suppressor by promoting host immune response.

    Science.gov (United States)

    Dong, Y; Richards, J-Ae; Gupta, R; Aung, P P; Emley, A; Kluger, Y; Dogra, S K; Mahalingam, M; Wajapeyee, N

    2014-09-18

    Cancer cells acquire several traits that allow for their survival and progression, including the ability to evade the host immune response. However, the mechanisms by which cancer cells evade host immune responses remain largely elusive. Here we study the phenomena of immune evasion in malignant melanoma cells. We find that the tumor suppressor phosphatase and tensin homolog (PTEN) is an important regulator of the host immune response against melanoma cells. Mechanistically, PTEN represses the expression of immunosuppressive cytokines by blocking the phosphatidylinositide 3-kinase (PI3K) pathway. In melanoma cells lacking PTEN, signal transducer and activator of transcription 3 activates the transcription of immunosuppressive cytokines in a PI3K-dependent manner. Furthermore, conditioned media from PTEN-deficient, patient-derived short-term melanoma cultures and established melanoma cell lines blocked the production of the interleukin-12 (IL-12) in human monocyte-derived dendritic cells. Inhibition of IL-12 production was rescued by restoring PTEN or using neutralizing antibodies against the immunosuppressive cytokines. Furthermore, we report that PTEN, as an alternative mechanism to promote the host immune response against cancer cells, represses the expression of programmed cell death 1 ligand, a known repressor of the host immune response. Finally, to establish the clinical significance of our results, we analyzed malignant melanoma patient samples with or without brisk host responses. These analyses confirmed that PTEN loss is associated with a higher percentage of malignant melanoma samples with non-brisk host responses compared with samples with brisk host responses. Collectively, these results establish that PTEN functions as a melanoma tumor suppressor in part by regulating the host immune response against melanoma cells and highlight the importance of assessing PTEN status before recruiting melanoma patients for immunotherapies.

  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. Social competitiveness and plasticity of neuroendocrine function in old age: influence of neonatal novelty exposure and maternal care reliability.

    Directory of Open Access Journals (Sweden)

    Katherine G Akers

    Full Text Available Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care.

  12. Social competitiveness and plasticity of neuroendocrine function in old age: influence of neonatal novelty exposure and maternal care reliability.

    Science.gov (United States)

    Akers, Katherine G; Yang, Zhen; DelVecchio, Dominic P; Reeb, Bethany C; Romeo, Russell D; McEwen, Bruce S; Tang, Akaysha C

    2008-06-30

    Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care.

  13. A new Caucasian case of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD): a clinical, molecular, and functional study.

    Science.gov (United States)

    Fiermonte, Giuseppe; Parisi, Giovanni; Martinelli, Diego; De Leonardis, Francesco; Torre, Giuliano; Pierri, Ciro Leonardo; Saccari, Alessia; Lasorsa, Francesco Massimo; Vozza, Angelo; Palmieri, Ferdinando; Dionisi-Vici, Carlo

    2011-12-01

    Citrin is the liver-specific isoform of the mitochondrial aspartate/glutamate carrier (AGC2). AGC2 deficiency is an autosomal recessive disorder with two age related phenotypes: neonatal intrahepatic cholestasis (NICCD, OMIM#605814) and adult-onset type II citrullinemia (CTLN2, OMIM#603471). NICCD arises within the first few weeks of life resulting in prolonged cholestasis and metabolic abnormalities including aminoacidemia and galactosuria. Usually symptoms disappear within the first year of life, thus making a diagnosis difficult after this time. In this study we report a new Caucasian case of NICCD, a seven week old Romanian boy with prolonged jaundice. Sequencing of the AGC2 gene showed a novel homozygous missense double-nucleotide (doublet) mutation, which produces the change of the glycine at position 437 into glutamate. Functional studies, carried out on the recombinant mutant protein, for the first time demonstrated, that NICCD is caused by a reduced transport activity of AGC2. The presence of AGC2 deficiency in other ethnic groups besides Asian population suggests further consideration for NICCD diagnosis of any neonate with an unexplained cholestasis; a prompt diagnosis is crucial to resolve the metabolic decompensation with an appropriate dietary treatment. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Neonatal nonepileptic myoclonus is a prominent clinical feature of KCNQ2 gain-of-function variants R201C and R201H

    DEFF Research Database (Denmark)

    Mulkey, Sarah B; Ben-Zeev, Bruria; Nicolai, Joost

    2017-01-01

    patients had encephalopathy from birth and presented with prominent startle-like myoclonus, which could be triggered by sound or touch. In seven patients, electroencephalography (EEG) was performed in the neonatal period and showed a burst-suppression pattern. However, myoclonus did not have an EEG......-of-function variants, supporting the value of in vitro functional screening. These findings suggest that gain-of-function and loss-of-function variants need different targeted therapeutic approaches....

  15. Functional Laterality of Task-Evoked Activation in Sensorimotor Cortex of Preterm Infants: An Optimized 3 T fMRI Study Employing a Customized Neonatal Head Coil.

    Directory of Open Access Journals (Sweden)

    Lukas Scheef

    Full Text Available Functional magnetic resonance imaging (fMRI in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD responses in sensorimotor cortex (SMC. Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level.Here, we employed a custom-designed neonatal MR-coil adapted and optimized to the head size of a newborn in order to improve robustness, reliability and validity of neonatal sensorimotor fMRI. Thirteen preterm infants with a median gestational age of 26 weeks were scanned at term-corrected age using a prototype 8-channel neonatal head coil at 3T (Achieva, Philips, Best, NL. Sensorimotor stimulation was elicited by passive extension/flexion of the elbow at 1 Hz in a block design. Analysis of temporal signal to noise ratio (tSNR was performed on the whole brain and the SMC, and was compared to data acquired with an 'adult' 8 channel head coil published previously. Task-evoked activation was determined by single-subject SPM8 analyses, thresholded at p < 0.05, whole-brain FWE-corrected.Using a custom-designed neonatal MR-coil, we found significant positive BOLD responses in contralateral SMC after unilateral passive sensorimotor stimulation in all neonates (analyses restricted to artifact-free data sets = 8/13. Improved imaging characteristics of the neonatal MR-coil were evidenced by additional phantom and in vivo tSNR measurements: phantom studies revealed a 240% global increase in tSNR; in vivo studies revealed a 73% global and a 55% local (SMC increase in tSNR, as compared to the 'adult' MR-coil.Our findings strengthen the

  16. 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.

  17. 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.

  18. Effect of Nutritional Supplements on Immune Function and Body Weight in Malnourished Adults

    Directory of Open Access Journals (Sweden)

    Lawrence J. cheskin

    2010-01-01

    Full Text Available In the United States, approximately 5% of the population is malnourished or has low body weight, which can adversely affect immune function. Malnutrition is more prevalent in older adults and is often a result of energy imbalance from various causes. Dietary supplementation to promote positive energy balance can reverse malnutrition, but has not been assessed for its effect on immune parameters. This 8-week clinical feeding trial evaluated the effect of a commercially available, high-protein, high-energy formula on body weight and immune parameters in 30 adult volunteers with body-mass indices (BMI <21 kg/m 2 . After the intervention, participants gained a mean of 3.74 lbs and increased BMI by 0.58 kg/m 2 . The intervention improved lean body mass and limited body fat accumulation. However, no clinically significant improvements in immune measures were observed. These results support the use of high-protein, high-energy supplements in the treatment of underweight/malnutrition. Further investigation utilizing feeding studies of longer duration, and/or studying severely malnourished individuals may be needed to detect an effect on immune parameters of weight gain promoted by nutritional supplements.

  19. Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations.

    Science.gov (United States)

    Kozora, E; Filley, C M; Zhang, L; Brown, M S; Miller, D E; Arciniegas, D B; Pelzman, J L; West, S G

    2012-04-01

    This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

  20. 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.

  1. Immunization against lysozyme-like proteins affect sperm function and fertility in the rat.

    Science.gov (United States)

    Narmadha, Ganapathy; Yenugu, Suresh

    2016-11-01

    Proteins of the epididymal and testicular mileu contribute to sperm maturation and a vast majority of them remain uncharacterised. In this study, the role of three Lysozyme-like (LYZL) proteins, namely LYZL1, LYZL4 and LYZL6 in sperm function was assessed using in vitro neutralization and auto antibodies generation model. Rats immunized with LYZL1, LYZL4 and LYZL6 proteins had a litter size of 5.93, 8.47 and 2.10 respectively compared to 9.96 in the control rats. The litter size was further reduced to 4.53, 7.67 and 1.23 for the corresponding proteins in the second mating conducted 14 weeks after immunization. Epididymal and testicular fluids obtained from the immunized rats displayed a very high antibody titre against all the three proteins. Sperm count was significantly reduced in rats immunized with LYZL1 or LYZL6 and to a lower extent in LYZL4 group. Acrosome reaction associated calcium release was inhibited in spermatozoa obtained from LYZL1 or LYZL4 or LYZL6 immunized rats as well as in spermatozoa incubated with antiserum against the three proteins. Impairment in path velocity, progressive velocity and track speed were observed in spermatozoa obtained from LYZL6 immunized rats. Treatment of spermatozoa with LYZL6 recombinant protein did not potentiate calcium release and acrosome reaction. Results of this study indicate a role for LYZL proteins in sperm function and further studies are warranted to explore them as potential contraceptive agents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. Regulation of immune cell function and differentiation by the NKG2D receptor.

    Science.gov (United States)

    Zafirova, Biljana; Wensveen, Felix M; Gulin, Maja; Polić, Bojan

    2011-11-01

    NKG2D is one of the most intensively studied immune receptors of the past decade. Its unique binding and signaling properties, expression pattern, and functions have been attracting much interest within the field due to its potent antiviral and anti-tumor properties. As an activating receptor, NKG2D is expressed on cells of the innate and adaptive immune system. It recognizes stress-induced MHC class I-like ligands and acts as a molecular sensor for cells jeopardized by viral infections or DNA damage. Although the activating functions of NKG2D have been well documented, recent analysis of NKG2D-deficient mice suggests that this receptor may have a regulatory role during NK cell development. In this review, we will revisit known aspects of NKG2D functions and present new insights in the proposed influence of this molecule on hematopoietic differentiation.

  5. Neonatal Caffeine Treatment and Respiratory Function at 11 Years in Children under 1,251 g at Birth.

    Science.gov (United States)

    Doyle, Lex W; Ranganathan, Sarath; Cheong, Jeanie L Y

    2017-11-15

    Caffeine in the newborn period shortens the duration of assisted ventilation and reduces the incidence of bronchopulmonary dysplasia, but its effects on respiratory function in later childhood are unknown. To determine if children born with birth weight less than 1,251 g who were treated with neonatal caffeine had improved respiratory function at 11 years of age compared with children treated with placebo. Children enrolled in the CAP (Caffeine for Apnea of Prematurity) randomized controlled trial and assessed at the Royal Women's Hospital in Melbourne at 11 years of age had expiratory flow rates measured according to the standards of the American Thoracic Society. Values were converted to z-scores predicted for age, height, ethnicity, and sex. Parents completed questionnaires related to their child's respiratory health. A total of 142 children had expiratory flows measured. Expiratory flows were better in the caffeine group, by approximately 0.5 SD for most variables (e.g., FEV 1 ; mean z-score, -1.00 vs. -1.53; mean difference, 0.54; 95% confidence interval, 0.14-0.94; P = 0.008). Fewer children in the caffeine group had values for FVC below the fifth centile (11% vs. 28%; odds ratio, 0.31; 95% confidence interval, 0.12-0.77; P = 0.012). When adjusted for bronchopulmonary dysplasia, the difference in flow rates between groups diminished. Caffeine treatment in the newborn period improves expiratory flow rates in midchildhood, which seems to be achieved by improving respiratory health in the newborn period. Follow-up lung function testing in adulthood is vital for these individuals. Future placebo-controlled randomized trials of neonatal caffeine are unlikely. Clinical trial registered with www.clinicaltrials.gov (NCT00182312).

  6. The effects of electroshock on immune function and disease progression in juvenile spring chinook salmon

    Science.gov (United States)

    VanderKooi, S.P.; Maule, A.G.; Schreck, C.B.

    2001-01-01

    Although much is known about the effects of electroshock on fish physiology, consequences to the immune system and disease progression have not received attention. Our objectives were to determine the effects of electroshock on selected immune function in juvenile spring chinook salmon Oncorhynchus tshawytscha, the mechanism of any observed alteration, and the effects of electroshock on disease progression. We found that the ability of anterior kidney leukocytes to generate antibody-producing cells (APC) was suppressed 3 h after a pulsed-DC electroshock (300 V, 50 Hz, 8 ms pulse width) but recovered within 24 h. This response was similar in timing and magnitude to that of fish subjected to an acute handling stress. The mechanism of suppression is hypothesized to be via an elevation of plasma cortisol concentrations in response to stress. Other monitored immune functions, skin mucous lysozyme levels, and respiratory burst activity were not affected by exposure to electroshock. The progression of a Renibacterium salmoninarum (RS) infection may have been altered after exposure to an electroshock. The electroshock did not affect infection severity or the number of mortalities, but may have accelerated the time to death. The limited duration of APC suppression and lack of effects on lysozyme and respiratory burst, as well as infection severity and mortality levels in RS-infected fish, led us to conclude that electrofishing under the conditions we tested is a safe procedure in regards to immunity and disease.

  7. Effects of small increases in corticosterone levels on morphology, immune function, and feather development.

    Science.gov (United States)

    Butler, Michael W; Leppert, Lynda L; Dufty, Alfred M

    2010-01-01

    Stressors encountered during avian development may affect an individual's phenotype, including immunocompetence, growth, and feather quality. We examined effects of simulated chronic low-level stress on American kestrel (Falco sparverius) nestlings. Continuous release of corticosterone, a hormone involved in the stress response, can model chronic stress in birds. We implanted 13-d-old males with either corticosterone-filled implants or shams and measured their growth, immune function, and feather coloration. We found no significant differences between groups at the end of the weeklong exposure period in morphometrics (mass, tarsus, wing length, and asymmetry), immunocompetence (cutaneous immunity, heterophil/lymphocyte ratio, and humoral immunity), or feather coloration. One week subsequent to implant removal, however, differences were detected. Sham-implanted birds had significantly longer wings and a reduced level of cutaneous immune function compared with those of birds given corticosterone-filled implants. Therefore, increases of only 2 ng/mL in basal corticosterone titer can have small but measurable effects on subsequent avian development.

  8. 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.

  9. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

    Science.gov (United States)

    Zhen, Anjie; Rezek, Valerie; Youn, Cindy; Lam, Brianna; Chang, Nelson; Rick, Jonathan; Carrillo, Mayra; Martin, Heather; Kasparian, Saro; Syed, Philip; Rice, Nicholas; Brooks, David G; Kitchen, Scott G

    2017-01-03

    Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.

  10. 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.

  11. 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.

  12. Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

    Science.gov (United States)

    Sood, Siddharth; Yu, Lijia; Visvanathan, Kumar; Angus, Peter William; Gow, Paul John; Testro, Adam Gareth

    2016-01-01

    AIM To investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODS Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTS Cirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1 (P = 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated (P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSION QFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection. PMID:28050238

  13. Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins

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    Povelones Michael

    2010-09-01

    Full Text Available Abstract Background The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, Anopheles gambiae, has uncovered an array of components and mechanisms involved in defence against pathogen infections. Two of these immune factors are LRIM1 and APL1C, which are leucine-rich repeat (LRR containing proteins that activate complement-like defence responses against malaria parasites. In addition to their LRR domains, these leucine-rich repeat immune (LRIM proteins share several structural features including signal peptides, patterns of cysteine residues, and coiled-coil domains. Results The identification and characterisation of genes related to LRIM1 and APL1C revealed putatively novel innate immune factors and furthered the understanding of their likely molecular functions. Genomic scans using the shared features of LRIM1 and APL1C identified more than 20 LRIM-like genes exhibiting all or most of their sequence features in each of three disease-vector mosquitoes with sequenced genomes: An. gambiae, Aedes aegypti, and Culex quinquefasciatus. Comparative sequence analyses revealed that this family of mosquito LRIM-like genes is characterised by a variable number of 6 to 14 LRRs of different lengths. The "Long" LRIM subfamily, with 10 or more LRRs, and the "Short" LRIMs, with 6 or 7 LRRs, also share the signal peptide, cysteine residue patterning, and coiled-coil sequence features of LRIM1 and APL1C. The "TM" LRIMs have a predicted C-terminal transmembrane region, and the "Coil-less" LRIMs exhibit the characteristic LRIM sequence signatures but lack the C-terminal coiled-coil domains. Conclusions The evolutionary plasticity of the LRIM LRR domains may provide templates for diverse recognition properties, while their coiled-coil domains could be involved in the formation

  14. 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

  15. 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

  16. Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers.

    Science.gov (United States)

    Li, X; Andres, A; Shankar, K; Pivik, R T; Glasier, C M; Ramakrishnaiah, R H; Zhang, Y; Badger, T M; Ou, X

    2016-12-01

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lobe network is different in newborns from normal-weight or obese mothers. Thirty-four full-term healthy infants from uncomplicated pregnancies were included, with 18 born to normal-weight and 16 born to obese mothers. Two weeks after delivery, the infants underwent an magnetic resonance imaging (MRI) examination during natural sleep, which included structural imaging and resting-state functional MRI (fMRI) scans. Independent component analysis was used to identify the prefrontal lobe network, and dual regression was used to compare functional connectivity between groups. Infants born to normal-weight mothers had higher recruiting (Pmaternal intelligence quotient, gestational weight gain and infant postmenstrual age, gender, birth weight/length, head circumference and neonatal diet. The functional connectivity strength in dorsal anterior cingulate cortex negatively correlated (Pmaternal fat mass percentage measured at early pregnancy. This preliminary study indicates that exposure to maternal obesity in utero may be associated with changes in resting-state functional connectivity in the newborn offspring's brain.

  17. 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

  18. 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

  19. Neonatal sepsis

    Science.gov (United States)

    ... 1 week and before 3 months of age. Causes Neonatal sepsis can be caused by bacteria such as Escherichia ... and Tests Lab tests can help diagnose neonatal sepsis and identify the cause of the infection. Blood tests may include: Blood ...

  20. Associations between male testosterone and immune function in a pathogenically stressed forager-horticultural population.

    Science.gov (United States)

    Trumble, Benjamin C; Blackwell, Aaron D; Stieglitz, Jonathan; Thompson, Melissa Emery; Suarez, Ivan Maldonado; Kaplan, Hillard; Gurven, Michael

    2016-11-01

    Despite well-known fitness advantages to males who produce and maintain high endogenous testosterone levels, such phenotypes may be costly if testosterone-mediated investment in reproductive effort trade-off against investment in somatic maintenance. Previous studies of androgen-mediated trade-offs in human immune function find mixed results, in part because most studies either focus on a few indicators of immunity, are confounded by phenotypic correlation, or are observational. Here the association between male endogenous testosterone and 13 circulating cytokines are examined before and after ex vivo antigen stimulation with phytohemagglutinin (PHA) and lipopolysaccharides (LPS) in a high pathogen population of Bolivian forager-horticulturalists. A Milliplex 13-plex cytokine panel measured cytokine concentration in whole blood samples from 109 Tsimane men aged 40-89 (median = 50 years) before and after antigen stimulation with PHA and LPS. Urinary testosterone was measured via enzyme immunoassay, demographic, and anthropometric data were collected as part of the Tsimane Health and Life History Project. Higher endogenous testosterone was associated with down-regulated responses in all cytokines after PHA stimulation (but significantly in only 2/13 cytokines), controlling for age and body mass index. In contrast, testosterone was not significantly associated with down-regulation of cytokines after LPS stimulation. MANOVAs indicate that men with higher testosterone showed reduced cytokine responses to PHA compared with LPS (p = 0.0098). Endogenous testosterone appears to be immunomodulatory rather than immunosuppressive. Potentially costlier forms of immune activation like those induced by PHA (largely T-cell biased immune activation) are down-regulated in men with higher testosterone, but testosterone has less impact on potentially less costly immune activation following LPS stimulation (largely B-cell mediated immunity). © 2016 Wiley Periodicals, Inc.

  1. 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.

  2. 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

  3. 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)

  4. 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.

  5. The innate immune function of airway epithelial cells in inflammatory lung disease.

    Science.gov (United States)

    Hiemstra, Pieter S; McCray, Paul B; Bals, Robert

    2015-04-01

    The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed. Copyright ©ERS 2015.

  6. The Functions of Bursal Hexapeptide (BHP) on Immune Response and the Molecular Mechanism on Immature B Cell.

    Science.gov (United States)

    Zong, Man Man; Zhou, Guang Fang; Zheng, Yang; Yu, Yuan Nan; Zhou, Chuan Jie; Feng, Xiu Li; Cao, Rui Bing; Chen, Pu Yan; Yang, Mei

    2018-02-08

    The bursa of Fabricius (BF) is an acknowledged central immune organ, and is important to B cell differentiation. Bursal hexapeptide (BHP) is the recently reported bursalderived peptide, while its inducing function on immune response is uncertain. The main objective of this study was to analyze the immune responses to JEV vaccine in mice induced by BHP plus JEV vaccine, and to detect the signal and biological functions of BHP on immature B cells. Mice were immunized with Japanese encephalitis virus (JEV) vaccine and BHP from 0.01 mg/mL to 0.25 mg/mL to detect antibody response and cellular immune response, respectively. The production of IgG, IgG1 and IgG2a specific to JEV in serum from immunized mice were measured by ELISA, and T cell subpopulation from immunized mice were detected with using fluorochrome conjugated mAbs of the corresponding PE-Cys/FITC/PE by flow cytometry. Spleen cells from all immunized mice were harvested after one week of second immunization for lymphocyte proliferation assay. Mouse immature B cell WEHI-231 cell was treated with 0.01μg/mL BHP for 4h, and analyzed the involved biological function and pathway of differentially expressed genes with gene microarray. BHP co-immunization with JEV vaccine generated significant increased antibody levels, neutralizing antibody titers and spleen lymphocyte viability, compared to that of vaccine control. The subpopulations of T cells in spleen lymphocytes were significantly modified in the mice coimmunized with JEV vaccine and BHP. The analysis results of gene expression profiles of WEHI- 231 mouse immature B cells with BHP treatment showed that the regulated genes with BHP treatment were involved various immune related biological functions, including proliferation and activation of lymphocyte and T cell, T cell mediated immunity and regulation of adaptive immune response. Furthermore, BHP stimulated three significant enriched pathways, including amphetamine addiction, long-term potentiation, and RIG

  7. Reduction of intestinal mucosal immune function in heat-stressed rats and bacterial translocation.

    Science.gov (United States)

    Liu, Xiaoxi; Li, Huanrong; Lu, An; Zhong, Yougang; Hou, Xiaolin; Wang, Ning; Jia, Dan; Zan, Junlan; Zhao, Hong; Xu, Jianqin; Liu, Fenghua

    2012-01-01

    The aim of this study was to further understand the effects and mechanism of heat stress on the intestinal mucosal immune system of the rat, including changes in the intestinal mucosal barrier and immune function and their effects on bacterial translocation. Sprague Dawley (SD) rats were randomly divided into control and heat-stress groups. Both groups were housed in a 25°C environment of 60% relative humidity. The heat-stress group was subjected to 40°C for 2 h daily over 3 days. Compared with the control group villi length in the small intestines of the heat-stress group was shortened. Jejunal mucosa were seriously damaged and the number of goblet cells in the epithelia of the duodenum and jejunum was significantly reduced. Electron microscopy revealed intestinal mucosal disorder, a large number of exudates of inflammatory fibrous material, fuzzy tight junction structure between epithelial cells, and cell gap increases in the heat-stress group. Transcription of IFN-γ, IL-2, IL-4, and IL-10, was significantly reduced, as was that of the intestinal mucosal immune-related proteins TLR2, TLR4, and IgA. The number of CD3(+) T cells and CD3(+)CD4(+)CD8(-) T cells in the mesenteric lymph nodes (MLNs) was significantly lower, while the number of CD3(+)CD4(-)CD8(+) T cells was significantly increased. The bacteria isolated from the MLNs were Escherichia coli. Heat stress damages rat intestinal mechanical and mucosal immune barriers, and reduces immune function of the intestinal mucosa and mesenteric lymphoid tissues, leading to bacterial translocation.

  8. 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...

  9. 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...

  10. 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.

  11. Functional Role of Transient Receptor Potential Channels in Immune Cells and Epithelia

    Directory of Open Access Journals (Sweden)

    Mohammad Khalil

    2018-02-01

    Full Text Available Transient receptor potential (TRP ion channels are widely expressed in several tissues throughout the mammalian organism. Originally, TRP channel physiology was focusing on its fundamental meaning in sensory neuronal function. Today, it is known that activation of several TRP ion channels in peptidergic neurons does not only result in neuropeptide release and consecutive neurogenic inflammation. Growing evidence demonstrates functional extra-neuronal TRP channel expression in immune and epithelial cells with important implications for mucosal immunology. TRP channels maintain intracellular calcium homeostasis to regulate various functions in the respective cells such as nociception, production and release of inflammatory mediators, phagocytosis, and cell migration. In this review, we provide an overview about TRP-mediated effects in immune and epithelial cells with an emphasis on mucosal immunology of the gut. Crosstalk between neurons, epithelial cells, and immune cells induced by activation of TRP channels orchestrates the immunologic response. Understanding of its molecular mechanisms paves the way to novel clinical approaches for the treatment of various inflammatory disorders including IBD.

  12. [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.

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

    Science.gov (United States)

    Hojman, Pernille

    2017-08-15

    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 cancer through mobilization and activation of cytotoxic immune cells, restriction of inflammatory signaling pathways in myeloid immune cells, and regulation of acute and chronic systemic inflammatory responses. In conclusion, I propose that exercise has the potential to target tumor growth through 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. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  14. 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.

  15. Distinct mechanisms of the newborn innate immunity.

    Science.gov (United States)

    Kumar, S Kingsley Manoj; Bhat, B Vishnu

    2016-05-01

    The ontogeny of immunity during early life is of high importance as it shapes the immune system for the entire course of life. The microbiome and the environment contribute to the development of immunity in newborns. As immune responses in newborns are predominantly less experienced they are increasingly susceptible to infections. Though the immune cells in newborns are in 'naïve' state, they have been shown to mount adult-like responses in several circumstances. The innate immunity plays a vital role in providing protection during the neonatal period. Various stimulants have been shown to enhance the potential and functioning of the innate immune cells in newborns. They are biased against the production of pro-inflammatory cytokines and this makes them susceptible to wide variety of intracellular pathogens. The adaptive immunity requires prior antigenic experience which is very limited in newborns. This review discusses in detail the characteristics of innate immunity in newborns and the underlying developmental and functional mechanisms involved in the immune response. A better understanding of the immunological milieu in newborns could help the medical fraternity to find novel methods for prevention and treatment of infection in newborns. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. 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

  17. 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.

  18. 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...

  19. 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.

  20. [Ginkgo biloba extract enhances the immune function of spleen and thymus in SD rats].

    Science.gov (United States)

    Wang, Yong; Si, Lifang; Li, Xiangneng; Li, Zhansheng

    2015-06-01

    To study the effect of Ginkgo biloba extract (GBE) on the immune function of spleen and thymus in SD rats. Forty SD rats were randomly divided into four groups (10 rats each group). Three experimental groups were given GBE daily by gavage in doses of 40, 120, 360 mg/(kg.d), respectively. Animals in the control group were fed the same amount of PBS. After 28 days, the rats were sacrificed by chloral hydrate anesthesia. The spleen and thymus were harvested to determine the organ index first. MTT assay was used to detect the concanavalin A (ConA)-induced splenic lymphocyte proliferation and transformation. Neutral red assay was performed to measure the rat peritoneal macrophage phagocytosis. The ultrastructural changes of spleen and thymus were observed under scanning electron microscope. Administration of GBE in the rats increased the mass indexes of rat thymus and spleen, dose-dependently elevated the lymphocyte proliferative responses and enhanced the peritoneal macrophage phagocytosis. In experimental groups, the numbers of mature spleen and thymus lymphocytes were significantly raised in comparison with the control rats. GBE plays a regulatory role in immune function of the rat by increasing the mass of immune organs, increasing the number of mature T lymphocytes as well as their proliferative responses, and enhancing the phagocytic capacity of peritoneal macrophages.

  1. Effects of subchronic aluminum exposure on the immune function of erythrocytes in rats.

    Science.gov (United States)

    Zhu, Yanzhu; Zhao, Hansong; Li, Xinwei; Zhang, Lichao; Hu, Chongwei; Shao, Bing; Sun, Hao; Bah, Alphajoh A; Li, Yanfei; Zhang, Zhigang

    2011-12-01

    This study assessed effects of aluminum (Al) exposure on the immune function of erythrocytes in rats. Forty male Wistar rats (5 weeks old) weighed 110-120 g were randomly allocated equally into four groups according to their weights and were orally exposed to 0, 64.18, 128.36, and 256.72 mg/kg body weight aluminum trichloride in drinking water for 120 days. Levels of erythrocytes C(3b) receptor rate (RBC-C(3b)RR), erythrocytes C(3b) immune complex rosette rate (RBC-ICR), erythrocytes rosette forming enhancing rate (ERER) and erythrocytes rosette forming inhibitory rate (ERIR) were determined by the end of experiment. The three Al-treated groups had lower values of RBC-C(3b)RR and ERER, and higher values of RBC-ICR and ERIR than those in control group. The levels of RBC-C(3b)RR and ERER decreased, while the levels of RBC-ICR and ERIR increased with the increases of Al content in drinking water. The results suggest that the immune function of erythrocytes in rats is suppressed by Al exposure.

  2. 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.

  3. The impact of leukapheresis on immune-cell number and function in patients with advanced cancer.

    Science.gov (United States)

    Gulley, James L; Marté, Jennifer; Heery, Christopher R; Madan, Ravi A; Steinberg, Seth M; Leitman, Susan F; Tsang, Kwong Y; Schlom, Jeffrey

    2015-11-01

    Leukapheresis is often performed in cancer patients to harvest stem cells, manufacture therapeutic vaccines, or follow immunologic response to therapy. We have recently described the minimal impact of leukapheresis on normal donors. Here we provide additional immunologic data from patients with advanced cancer who underwent leukapheresis. Using data from cancer patients on clinical trials who had leukapheresis (n = 64) or peripheral blood draws only (n = 90) as controls for immune analysis, we evaluated the impact of leukapheresis on number and function of lymphocytes. In the leukapheresis group, median age was 63.5 (range 38-82); 87.5 % were male. Comparing pre- and post-leukapheresis values within the groups, with each patient as its own control, there was no significant difference in enzyme-linked immunosorbent spot (ELISPOT), antivector humoral response, absolute lymphocyte count (ALC), or T cell number. Twelve patients completed three leukaphereses with subsequent ELISPOT analysis; seven had increased responses to flu (1.1- to 2.3-fold) with an even distribution around no change. Nineteen patients had matched ALC values after completing three leukaphereses with no significant change from baseline. These data provide evidence that leukapheresis has no detectable effects on a cancer patient's immune system in terms of number or function. These results contribute to a growing body of evidence refuting the hypothesis that a patient's immune competence is meaningfully affected by the procedure. Limitations include a restriction to 2-L leukapheresis procedure and small sample size.

  4. 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

  5. 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.

  6. 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

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

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    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

  8. Trans-epithelial immune cell transfer during suckling modulates delayed-type hypersensitivity in recipients as a function of gender.

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    Lisa J Ma

    Full Text Available INTRODUCTION: Breast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult. METHODS: Non-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls. RESULTS: Despite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3-4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3-4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam amplified a subsequent DTH response in females and yet suppressed one in males. DISCUSSION: These results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted.

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

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    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.

  10. Anaesthetic impairment of immune function is mediated via GABA(A receptors.

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    Daniel W Wheeler

    2011-02-01

    Full Text Available GABA(A receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A receptors are present on monocytes with properties similar to CNS GABA(A receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life

  11. Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

    Science.gov (United States)

    Wheeler, Daniel W; Thompson, Andrew J; Corletto, Federico; Reckless, Jill; Loke, Justin C T; Lapaque, Nicolas; Grant, Andrew J; Mastroeni, Pietro; Grainger, David J; Padgett, Claire L; O'Brien, John A; Miller, Nigel G A; Trowsdale, John; Lummis, Sarah C R; Menon, David K; Beech, John S

    2011-02-24

    GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life

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

    Science.gov (United States)

    Gustafson, Claire E; Qi, Qian; Hutter-Saunders, Jessica; Gupta, Sheena; Jadhav, Rohit; Newell, Evan; Maecker, Holden; Weyand, Cornelia M; Goronzy, Jörg J

    2017-01-01

    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.

  13. Identification of surrogates and correlates of protection in protective immunity against Mycobacterium bovis infection induced in neonatal calves by vaccination with M. bovis BCG Pasteur and M. bovis BCG Danish.

    Science.gov (United States)

    Hope, J C; Thom, M L; McAulay, M; Mead, E; Vordermeier, H M; Clifford, D; Hewinson, R G; Villarreal-Ramos, B

    2011-03-01

    Vaccination of neonatal calves with Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces a significant degree of protection against infection with virulent M. bovis, the causative agent of bovine tuberculosis (bTB). We compared two strains of BCG, Pasteur and Danish, in order to confirm that the current European human vaccine strain (BCG Danish) induced protective immunity in calves, and we assessed immune responses to determine correlates of protection that could assist future vaccine evaluation in cattle. Both vaccine strains induced antigen (purified protein derivate [PPD])-specific gamma interferon (IFN-γ) in whole-blood cultures. These responses were not significantly different for BCG Pasteur and BCG Danish and peaked at week 2 to 4 postvaccination. Vaccination with either BCG Danish or BCG Pasteur induced significant protection against bTB, with reductions in both lesion score and bacteriological burden evident in both groups of vaccinated calves compared with nonvaccinated control calves. Measurement of IFN-γ-expressing T lymphocytes postvaccination and postchallenge revealed both correlates and surrogates of protective efficacy. The frequency of central memory T lymphocytes present at 12 weeks postvaccination (at the time of M. bovis challenge) correlated significantly with protection. Conversely, the number of IFN-γ-expressing effector T cells present after M. bovis challenge was correlated with disease. These results demonstrate that vaccination of neonatal calves with either BCG Pasteur or BCG Danish induces protective immune responses against TB. In addition, we show that measurement of antigen-specific T lymphocyte populations may provide a reliable means for identifying protective vaccine candidates.

  14. Extracellular vesicles regulate immune responses and cellular function in intestinal inflammation and repair.

    Science.gov (United States)

    Bui, Triet M; Mascarenhas, Lorraine A; Sumagin, Ronen

    2018-02-02

    Tightly controlled communication among the various resident and recruited cells in the intestinal tissue is critical for maintaining tissue homeostasis, re-establishment of the barrier function and healing responses following injury. Emerging evidence convincingly implicates extracellular vesicles (EVs) in facilitating this important cell-to-cell crosstalk by transporting bioactive effectors and genetic information in healthy tissue and disease. While many aspects of EV biology, including release mechanisms, cargo packaging, and uptake by target cells are still not completely understood, EVs contribution to cellular signaling and function is apparent. Moreover, EV research has already sparked a clinical interest, as a potential diagnostic, prognostic and therapeutic tool. The current review will discuss the function of EVs originating from innate immune cells, namely, neutrophils, monocytes and macrophages, as well as intestinal epithelial cells in healthy tissue and inflammatory disorders of the intestinal tract. Our discussion will specifically emphasize the contribution of EVs to the regulation of vascular and epithelial barrier function in inflamed intestines, wound healing, as well as trafficking and activity of resident and recruited immune cells.

  15. Ionizing radiation selectively reduces skin regulatory T cells and alters immune function.

    Directory of Open Access Journals (Sweden)

    Yu Zhou

    Full Text Available The skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth's magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel.

  16. 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

  17. Immune function parameters as markers of biological age and predictors of longevity

    Science.gov (United States)

    de Toda, Irene Martínez; Maté, Ianire; Vida, Carmen; Cruces, Julia; De la Fuente, Mónica

    2016-01-01

    Chronological age is not a good indicator of how each individual ages and thus how to maintain good health. Due to the long lifespan in humans and the consequent difficulty of carrying out longitudinal studies, finding valid biomarkers of the biological age has been a challenge both for research and clinical studies. The aim was to identify and validate several immune cell function parameters as markers of biological age. Adult, mature, elderly and long-lived human volunteers were used. The chemotaxis, phagocytosis, natural killer activity and lymphoproliferation in neutrophils and lymphocytes of peripheral blood were analyzed. The same functions were measured in peritoneal immune cells from mice, at the corresponding ages (adult, mature, old and long lived) in a longitudinal study. The results showed that the evolution of these functions was similar in humans and mice, with a decrease in old subjects. However, the long-lived individuals maintained values similar to those in adults. In addition, the values of these functions in adult prematurely aging mice were similar to those in chronologically old animals, and they died before their non-prematurely aging mice counterparts. Thus, the parameters studied are good markers of the rate of aging, allowing the determination of biological age. PMID:27899767

  18. A trade-off between embryonic development rate and immune function of avian offspring is concealed by embryonic temperature

    Science.gov (United States)

    Martin, Thomas E.; Arriero, Elena; Majewska, Ania

    2011-01-01

    Long embryonic periods are assumed to reflect slower intrinsic development that are thought to trade off to allow enhanced physiological systems, such as immune function. Yet, the relatively rare studies of this trade-off in avian offspring have not found the expected trade-off. Theory and tests have not taken into account the strong extrinsic effects of temperature on embryonic periods of birds. Here, we show that length of the embryonic period did not explain variation in two measures of immune function when temperature was ignored, based on studies of 34 Passerine species in tropical Venezuela (23 species) and north temperate Arizona (11 species). Variation in immune function was explained when embryonic periods were corrected for average embryonic temperature, in order to better estimate intrinsic rates of development. Immune function of offspring trades off with intrinsic rates of embryonic development once the extrinsic effects of embryonic temperatures are taken into account.

  19. Assessing the impacts of total liquid ventilation on left ventricular diastolic function in a model of neonatal respiratory distress syndrome.

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    Michaël Sage

    Full Text Available Filling the lung with dense liquid perfluorocarbons during total liquid ventilation (TLV might compress the myocardium, a plausible explanation for the instability occasionally reported with this technique. Our objective is to assess the impacts of TLV on the cardiovascular system, particularly left ventricular diastolic function, in an ovine model of neonatal respiratory distress syndrome.Eight newborns lambs, 3.0 ± 0.4 days (3.2 ± 0.3kg were used in this crossover experimental study. Animals were intubated, anesthetized and paralyzed. Catheters were inserted in the femoral and pulmonary arteries. A high-fidelity pressure catheter was inserted into the left ventricle. Surfactant deficiency was induced by repeated lung lavages with normal saline. TLV was then conducted for 2 hours using a liquid ventilator prototype. Thoracic echocardiography and cardiac output assessment by thermodilution were performed before and during TLV.Left ventricular end diastolic pressure (LVEDP (9.3 ± 2.1 vs. 9.2 ± 2.4mmHg, p = 0.89 and dimension (1.90 ± 0.09 vs. 1.86 ± 0.12cm, p = 0.72, negative dP/dt (-2589 ± 691 vs. -3115 ± 866mmHg/s, p = 0.50 and cardiac output (436 ± 28 vs. 481 ± 59ml/kg/min, p = 0.26 were not affected by TLV initiation. Left ventricular relaxation time constant (tau slightly increased from 21.5 ± 3.3 to 24.9 ± 3.7ms (p = 0.03. Mean arterial systemic (48 ± 6 vs. 53 ± 7mmHg, p = 0.38 and pulmonary pressures (31.3 ± 2.5 vs. 30.4 ± 2.3mmHg, p = 0.61 were stable. As expected, the inspiratory phase of liquid cycling exhibited a small but significant effect on most variables (i.e. central venous pressure +2.6 ± 0.5mmHg, p = 0.001; LVEDP +1.18 ± 0.12mmHg, p<0.001.TLV was well tolerated in our neonatal lamb model of severe respiratory distress syndrome and had limited impact on left ventricle diastolic function when compared to conventional mechanical ventilation.

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

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    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

  1. Effect of oral supplementation of bamboo grass leaves extract on cellular immune function in dairy cows

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    Hiromichi Ohtsuka

    2014-01-01

    Full Text Available Beta glucans extracted from bamboo (Sasa sensanensis grass leaves are known to have an immune-modulatory effect in animals. These glucans have been used for the treatment of diseases such as viral infections, inflammation, and cancer. The aim of this study was to evaluate the immuno-modulatory effect of SanSTAGETM (pure compounds obtained from the bamboo grass leaves; 25% of bamboo grass extract and 75% of dextrin on peripheral blood leukocyte population and mRNA expression of immune related molecules of 20 dairy cows. Ten cows were orally administered 30 mg/kg/day of SanSTAGETM for first two weeks; the other 10 cows were control without supplementation. The blood samples were collected in tubes containing dipotassium-EDTA for analysis of leukocyte population, and in tubes containing heparin for analysis of cytokine production. Cows supplemented with SanSTAGETM showed an increased number of CD8+ T cells and expression of perforin (cytotoxicity factor to virally infected cells and MX-2 (anti-virus factor. The study describes for the first time that oral administration of supplement extracted from Kumaizasa bamboo grass leaves affects cellar immune function of dairy cows, and can be recommended as part of diet for prevention of infectious diseases.

  2. Long-term Follow-up of Neonatal Brachial Plexopathy: Psychological and Physical Function in Adolescents and Young Adults.

    Science.gov (United States)

    Butler, Lesley; Mills, Janith; Richard, Heather M; Riddle, Russell; Ezaki, Marybeth; Oishi, Scott

    2017-09-01

    The prevalence of neonatal brachial plexus palsy (NBPP) has been increasing since the early 1980s. No known studies have examined long-term psychological health and quality of life (QOL) in young adults. The purpose of this study was to investigate the psychosocial and intellectual aspects of NBPP during adolescence into young adulthood. A total of 31 patients were enrolled in the adolescent group (16 to 18 y) and 25 in the young adult group (23 to 28 y). Clinical assessment included functional ability, range of motion and strength, weight and body mass index, and education level. Patients were administered measures of psychiatric symptomatology, self-concept, QOL, and cognitive function. Narakas injury level for the adolescent group included 11 level I, 6 level II, 8 level III, and 6 level IV. The young adult group had 10 level I, 2 level II, 9 level III, and 4 level IV. The degree of physical impairment determined by the Modified Mallet Classification showed persistent impairment in both groups. The average DASH scores were higher than the normal range for the adolescent and young adult groups. Forty-five percent of the adolescents and 68% of the young adults were either overweight or obese. All received high school diplomas with 20 of the young adults pursuing higher education.Scores on measures of psychiatric symptomatology and self-concept showed that both groups fell within the normal range. QOL for both groups was also within the normal range. All participants scored average to above average on the cognitive assessment. All measurements were patient reported. Patients with NBPP can adapt and participate in most activities. This patient sample demonstrated persistent functional limitations and a higher rate of comorbid obesity. However, these patients function psychologically and cognitively within the normal range and many have pursued higher education. Level IV.

  3. 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

  4. 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

  5. Differential functional genomic effects of anti-inflammatory phytocompounds on immune signaling

    Directory of Open Access Journals (Sweden)

    Vanisree Staniforth

    2010-09-01

    Full Text Available Abstract Background Functional comparative genomic analysis of the cellular immunological effects of different anti-inflammatory phytocompounds is considered as a helpful approach to distinguish the complex and specific bioactivities of candidate phytomedicines. Using LPS-stimulated THP-1 monocytes, we characterize here the immunomodulatory activities of three single phytocompounds (emodin, shikonin, and cytopiloyne and a defined phytocompound mixture extracted from Echinacea plant (BF/S+L/Ep by focused DNA microarray analysis of selected immune-related genes. Results Shikonin and emodin significantly inhibited the early expression (within 0.5 h of approximately 50 genes, notably cytokines TNF-α, IL-1β and IL-4, chemokines CCL4 and CCL8, and inflammatory modulators NFATC3 and PTGS2. In contrast, neither cytopiloyne nor BF/S+L/Ep inhibited the early expression of these 50 genes, but rather inhibited most late-stage expression (~12 h of another immune gene subset. TRANSPATH database key node analysis identified the extracellular signal-regulated kinase (ERK 1/2 activation pathway as the putative target of BF/S+L/Ep and cytopiloyne. Western blot confirmed that delayed inactivation of the ERK pathway was indeed demonstrable for these two preparations during the mid-stage (1 to 4 h of LPS stimulation. We further identified ubiquitin pathway regulators, E6-AP and Rad23A, as possible key regulators for emodin and shikonin, respectively. Conclusion The current focused DNA microarray approach rapidly identified important subgenomic differences in the pattern of immune cell-related gene expression in response to specific anti-inflammatory phytocompounds. These molecular targets and deduced networks may be employed as a guide for classifying, monitoring and manipulating the molecular and immunological specificities of different anti-inflammatory phytocompounds in key immune cell systems and for potential pharmacological application.

  6. 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

  7. Enhancement of innate and adaptive immune functions by multiple Echinacea species.

    Science.gov (United States)

    Zhai, Zili; Liu, Yi; Wu, Lankun; Senchina, David S; Wurtele, Eve S; Murphy, Patricia A; Kohut, Marian L; Cunnick, Joan E

    2007-09-01

    Echinacea preparations are commonly used as nonspecific immunomodulatory agents. Alcohol extracts from three widely used Echinacea species, Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea, were investigated for immunomodulating properties. The three Echinacea species demonstrated a broad difference in concentrations of individual lipophilic amides and hydrophilic caffeic acid derivatives. Mice were gavaged once a day (for 7 days) with one of the Echinacea extracts (130 mg/kg) or vehicle and immunized with sheep red blood cells (sRBC) 4 days prior to collection of immune cells for multiple immunological assays. The three herb extracts induced similar, but differential, changes in the percentage of immune cell populations and their biological functions, including increased percentages of CD49+ and CD19+ lymphocytes in spleen and natural killer cell cytotoxicity. Antibody response to sRBC was significantly increased equally by extracts of all three Echinacea species. Concanavalin A-stimulated splenocytes from E. angustifolia- and E. pallida-treated mice demonstrated significantly higher T cell proliferation. In addition, the Echinacea treatment significantly altered the cytokine production by mitogen-stimulated splenic cells. The three herbal extracts significantly increased interferon-alpha production, but inhibited the release of tumor necrosis factor-gamma and interleukin (IL)-1beta. Only E. angustifolia- and E. pallida-treated mice demonstrated significantly higher production of IL-4 and increased IL-10 production. Taken together, these findings demonstrated that Echinacea is a wide-spectrum immunomodulator that modulates both innate and adaptive immune responses. In particular, E. angustifolia or E. pallida may have more anti-inflammatory potential.

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

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    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.

  9. 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

  10. 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.

  11. A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair

    Science.gov (United States)

    Babu, Mohan; Beloglazova, Natalia; Flick, Robert; Graham, Chris; Skarina, Tatiana; Nocek, Boguslaw; Gagarinova, Alla; Pogoutse, Oxana; Brown, Greg; Binkowski, Andrew; Phanse, Sadhna; Joachimiak, Andrzej; Koonin, Eugene V.; Savchenko, Alexei; Emili, Andrew; Greenblatt, Jack; Edwards, Aled M.; Yakunin, Alexander F.

    2011-01-01

    Summary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks, and 5′-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair. PMID:21219465

  12. Immune function and phenotype before and after highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Søndergaard, S R; Aladdin, H; Ullum, H

    1999-01-01

    Immune functions represented by equal CD4 counts before and after highly active antiretroviral therapy (i.e., pre- and post-HAART) in the same HIV-infected patients, were examined. Twelve HIV-infected patients were included. Patients had equal CD4 counts pre- and post-HAART and were studied...... expression of CD38 on T cells, indicates that following long-term HAART, repopulation occurs with less activated cells with increased proliferative capacity. This finding may be of clinical importance in considering risk and vulnerability for progression of opportunistic infections post-HAART....

  13. 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

    ,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......(+)) and CD3(+)/CD4(+) T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism...

  14. Determinants of DHA status and functional effects on metabolic markers and immune modulation in early life

    DEFF Research Database (Denmark)

    Harsløf, Laurine Bente Schram

    LCPUFA on metabolic markers such as glucose homeostasis, lipid profile and blood pressure in young children is limited. No studies have explored whether polymorphisms of genes encoding proteins involved in the mechanisms behind the effect (such as PPARG2 and COX2) can support the findings of diet studies...... by identifying the involved pathways and genes. The second part of the PhD thesis explores whether functional effects of n-3 LCPUFA on metabolic markers and immune maturation in young children can be supported by polymorphisms in genes involved in the mechanisms (PPARG2, COX2 and NFKB1). Results can be found...

  15. 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.

  16. Opposite variations in maternal and neonatal thyroid function induced by iodine supplementation during pregnancy

    DEFF Research Database (Denmark)

    Nøhr, S B; Laurberg, P

    2000-01-01

    pregnancy, and 95 took no artificial iodine supplementation. Iodine supplementation (+I) induced opposite variations in thyroid function in the mother and the fetus. In +I mothers, TSH was 7.6% lower than in mothers with no supplementation (P

  17. Effect of Infant Formula Containing a Low Dose of the Probiotic CNCM I-3446 on Immune and Gut Functions in C-Section Delivered Babies: A Pilot Study

    Directory of Open Access Journals (Sweden)

    L. Baglatzi

    2016-01-01

    Full Text Available Background In the absence of breast-feeding and its immunomodulatory factors, supplementation of starter infant formula (IF with probiotics is currently used to support immune functions and gut development. Aim To assess whether immune-related beneficial effects of regular dose (10 7 CFU/g of powder of the probiotic Bifidobacterium lactis CNCM I-3446 (hereafter named B. lactis in starter IF supplementation can be maintained with starter IF containing a low dose (10 4 CFU/g of powder of B. lactis. Method This trial was designed as a pilot, prospective, double-blind, randomized, single-center clinical trial of two parallel groups ( n = 77 infants/group of C-section delivered infants receiving a starter IF containing either low dose or regular dose of the probiotic B. lactis from birth to six months of age. In addition, a reference group of infants breast-fed for a minimum of four months ( n = 44 infants, also born by C-section, were included. All groups were then provided follow-up formula without B. lactis up to 12 months of age. Occurrence of diarrhea, immune and gut maturation, responses to vaccinations, and growth were assessed from birth to 12 months. The effect of low-dose B. lactis formula was compared to regular-dose B. lactis formula, considered as reference for IF with probiotics, and both were further compared to breast-feeding as a physiological reference. Results Data showed that feeding low-dose B. lactis IF provides similar effects as feeding regular-dose B. lactis IF or breast milk. No consistent statistical differences regarding early life protection against gastrointestinal infections, immune and gut maturation, microbiota establishment, and growth were observed between randomized formula-fed groups as well as with the breast-fed reference group. Conclusion This pilot study suggests that supplementing C-section born neonates with low-dose B. lactis -containing starter formula may impact immune as well as gut maturation similarly

  18. 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

  19. Primary immunodeficiency in the neonate: Early diagnosis and management.

    Science.gov (United States)

    Walkovich, Kelly; Connelly, James A

    2016-02-01

    Many primary immunodeficiencies (PIDs) manifest in the neonatal period but can be challenging to diagnose and manage optimally. In part, the difficulty stems from the natural immaturity of the neonatal immune system that may mask immune deficits and/or complicate interpretation of clinical findings and laboratory assays. The great diversity of PIDs--from innate immune system defects to those that impact the humoral and/or cellular components of the adaptive immune system--and the rapid rate at which new PIDs are being discovered makes it challenging for practitioners to stay current. Moreover, recent appreciation for immune deficiencies that lead to autoinflammation and autoimmunity have broadened the spectrum of neonatal PID, adding additional complexity to an already intricate field. This article serves to highlight the deficiencies in the neonatal immune system, while providing a review of the more common PIDs that present in the neonate and guidelines for diagnosis and supportive care. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Neonatal milk supplementation in lambs has persistent effects on growth and metabolic function that differ by sex and gestational age.

    Science.gov (United States)

    Berry, Mary J; Jaquiery, Anne L; Oliver, Mark H; Harding, Jane E; Bloomfield, Frank H

    2016-12-01

    The perinatal environment has a major influence on long-term health and disease risk. Preterm birth alters early-life environment and is associated with altered metabolic function in adulthood. Whether preterm birth per se or the early nutritional interventions used to support growth in preterm infants underpins this association is unknown. Lambs born preterm, following dexamethasone induction of labour, or spontaneously at term were randomised to receive nutrient supplementation, analogous to the milk fortifier used clinically or water as a control for the first 2 weeks after birth. Thereafter, nutrition was not different between groups. Growth was monitored, and the glucose-insulin axis function was assessed in juvenile (4 months) and adult life (14 months). Early nutrition influenced adult metabolic function and body composition to a greater extent than preterm birth. In supplemented females, arginine-stimulated insulin secretion was increased in preterm but reduced in term-born juveniles compared with controls (repeated-measures ANOVA Psupplemented preterm males, adult weight, ponderal index (PI) and fasting insulin concentrations were elevated compared with preterm controls (weight, 75 (sem 3) v. 69 (sem 2) kg; PI, 48·0 (sem 2·1) v. 43·7 (sem 1·7) kg/m3; fasting insulin, 0·19 (sem 0·02) v. 0·10 (sem 0·02) ng/ml). Conversely, supplemented term-born males had reduced adult weight, PI and fasting insulin concentrations compared with term-born controls (weight, 64 (sem 2) v. 70 (sem 2) kg; PI, 44·4 (sem 1·8) v. 48·2 (sem 1·7) kg/m3; fasting insulin, 0·09 (sem 0·02) v. 0·14 (sem 0·02) ng/ml; all group×supplement interactions Pbirth and early nutrition. Human studies are urgently needed to investigate the adult sex-specific health implications of neonatal nutritional strategies.

  1. Executive function assessment in New Zealand 2-year olds born at risk of neonatal hypoglycemia.

    Directory of Open Access Journals (Sweden)

    Judith M Ansell

    Full Text Available A growing number of babies are born with perinatal risk factors that may impair later development. These children are often assessed at 2 years to help predict outcome and direct support services. Executive function is an important predictor of academic achievement and behavior, but there are limited assessments of executive function in 2-year-olds and few have been tested in at-risk populations. Therefore, we developed a battery of four age-appropriate tasks to assess executive function in 2-year-olds. At 24 months' corrected age 368 children completed tasks assessing attention, inhibition, working memory and cognitive flexibility. Scores on different tasks were weakly correlated, suggesting that they measured separate aspects of executive function, with combined scores for this cohort approximating a normal distribution. Significantly more boys (67% than girls (57% were unable to inhibit their behavior on the Snack Delay Task and girls (M = 3.24, SD = 2.4 had higher mean scores than boys (M = 2.7, SD = 2.7 on the Ducks and Buckets Reverse Categorization Task of working memory. Performance was significantly affected by family socioeconomic status. Mean scores were lower on all four individual tasks and on the global score of overall performance in children from a low household income ($70,001. Maternal education was only associated with scores on the working memory task and the global score; and a measure of neighborhood deprivation was only associated with scores on the two inhibitory tasks and the global score. Our findings confirm the feasibility of assessing executive function in 2-year-olds, and its ability to discriminate effects of socioeconomic status, a common confounder in child development research. Further development and standardization of this test battery comparing at-risk children with a normative population would provide a much-needed measure of executive function in early childhood.

  2. Acceleration of Functional Maturation and Differentiation of Neonatal Porcine Islet Cell Monolayers Shortly In Vitro Cocultured with Microencapsulated Sertoli Cells

    Directory of Open Access Journals (Sweden)

    Francesca Mancuso

    2010-01-01

    Full Text Available The limited availability of cadaveric human donor pancreata as well as the incomplete success of the Edmonton protocol for human islet allografts fasten search for new sources of insulin the producing cells for substitution cell therapy of insulin-dependent diabetes mellitus (T1DM. Starting from isolated neonatal porcine pancreatic islets (NPIs, we have obtained cell monolayers that were exposed to microencapsulated monolayered Sertoli cells (ESCs for different time periods (7, 14, 21 days. To assess the development of the cocultured cell monolayers, we have studied either endocrine cell phenotype differentiation markers or c-kit, a hematopoietic stem cell marker, has recently been involved with growth and differentiation of β-cell subpopulations in human as well as rodent animal models. ESC which were found to either accelerate maturation and differentiation of the NPIs β-cell phenotype or identify an islet cell subpopulation that was marked positively for c-kit. The insulin/c-kit positive cells might represent a new, still unknown functionally immature β-cell like element in the porcine pancreas. Acceleration of maturation and differentiation of our NPI cell monolayers might generate a potential new opportunity to develop insulin-producing cells that may suite experimental trials for cell therapy of T1DM.

  3. Effects of micro-encapsulation on morphology and endocrine function of cryopreserved neonatal porcine islet-like cell clusters.

    Science.gov (United States)

    Murakami, M; Satou, H; Kimura, T; Kobayashi, T; Yamaguchi, A; Nakagawara, G; Iwata, H

    2000-10-27

    For the success of clinical islets transplantation, the development of a long-term storage method is necessary. However, the structure of digested islets is scanty for culture and cryopreservation. In this study, the effect of micro-encapsulation to cryopreserved porcine islet-like cell clusters (ICCs) was investigated. The ICCs prepared from neonatal pigs by collagenase digestion and culture technique were cryopreserved and micro-encapsulated in 5% agarose membranes. After cryopreservation, ICC cultured without encapsulation (group A) and cultured with encapsulation (group B) were assessed by comparison with no cryopreserved ICC (control) both in vitro by static incubation test and in vivo in a xenotransplantation study. Micro-encapsulation was able to maintain the fine morphology and the number of ICCs of group B after 7 days of culture. There were not significant differences in insulin secretion of group B and control on day 1 and 7 of culture (1 day:11+/-0.99, 7 days: 5.30+/-1.08 microU/ICC/hr NS versus control). On day 7 of culture, the retrieval rate of group B (105.2+/-9.8%) is obviously higher compared with group A (63.0+/-6.3%). In the xenotransplatation model, the ICCs of group B showed long survival time (7.9+/-0.4 weeks) and good transplantation effect. Our study suggests that micro-encapsulation is one of the useful method for cryopreserved ICC to maintain the fine morphology and effectively recover the endocrine function.

  4. 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.

  5. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

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    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal

  6. Maternal iodine status and the thyroid function of pregnant mothers and their neonates in Jaffna District of Sri Lanka

    Directory of Open Access Journals (Sweden)

    Thirunavukkarasu Yoganathan

    2015-01-01

    Full Text Available Introduction: Iodine status of pregnant women and their newborns have not been studied in Jaffna District, Sri Lanka. This study was planned to assess the maternal iodine status and thyroid function at the third trimester of gestation and the thyrotrophin level of their neonate. Methods: Four hundred and seventy-seven pregnant women and their newborns were randomly selected among six Medical Officers of Health Divisions out of 12 in Jaffna District, Sri Lanka. Maternal thyroid stimulating hormone (TSH, free thyroxine (fT4, thyroglobulin (Tg, urinary iodine levels, and the neonatal thyrotrophin (nTSH level were assessed. Results: In this study, mean age, weight, height, and gestational age of the mothers were 28.95 (±5.46 years, 63.02 (±11.56 kg, 154.39 (±6.00 cm, and 39.33 (±1.37 weeks, respectively. Maternal median urinary iodine concentration (UIC was 140.0 μg/L (inter-quartile range 126.0–268.0 μg/L. Median values of the maternal serum TSH, fT4,and Tg were 1.9 mIU/L, 12.6 pmol/L, and 21.4 IU/L, respectively. Among the 477 newborns, 50.5% (n = 239 were males. Mean birth weight of newborn was 3.03 (±0.43 kg, while the mean length was 51.1 (±2.1 cm. Among the newborns, 18% (n = 86 had nTSH level > mIU/L and 37.7% (n = 180 within TSH level > mIU/L. nTSH level had positive but very weak correlations with maternal thyroid parameters, that is, UIC (r = 0.06, P = 0.13, fT4 (r = 0.01, P = 0.05, TSH (r = 0.09, P = 0.05, and Tg (r = 0.12, P = 0.03. Conclusion: On the basis of the World Health Organization criteria, the iodine status of pregnant women was inadequate in this region and also nTSH levels indicate moderate iodine deficiency during pregnancy. Therefore, the continuous education on adequate iodine intake during pregnancy and monitoring of iodine status are useful.

  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. Early exposure to ultraviolet-B radiation decreases immune function later in life.

    Science.gov (United States)

    Ceccato, Emma; Cramp, Rebecca L; Seebacher, Frank; Franklin, Craig E

    2016-01-01

    Amphibians have declined dramatically worldwide. Many of these declines are occurring in areas where no obvious anthropogenic stressors are present. It is proposed that in these areas, environmental factors such as elevated solar ultraviolet-B (UV-B) radiation could be responsible. Ultraviolet-B levels have increased in many parts of the world as a consequence of the anthropogenic destruction of the ozone layer. Amphibian tadpoles are particularly sensitive to the damaging effects of UV-B radiation, with exposure disrupting growth and fitness in many species. Given that UV-B can disrupt immune function in other animals, we tested the hypothesis that early UV-B exposure suppresses the immune responses of amphibian tadpoles and subsequent juvenile frogs. We exposed Limnodynastes peronii tadpoles to sublethal levels of UV-B radiation for 6 weeks after hatching, then examined indices of immune function in both the tadpoles and the subsequent metamorphs. There was no significant effect of UV-B on tadpole leucocyte counts or on their response to an acute antigen (phytohaemagglutinin) challenge. However, early UV-B exposure resulted in a significant reduction in both metamorph leucocyte abundance and their response to an acute phytohaemagglutinin challenge. These data demonstrate that early UV-B exposure can have carry-over effects on later life-history traits even if the applied stressor has no immediately discernible effect. These findings have important implications for our understanding of the effects of UV-B exposure on amphibian health and susceptibility to diseases such as chytridiomycosis.

  9. Quantitative, Phenotypical, and Functional Characterization of Cellular Immunity in Children and Adolescents With Down Syndrome.

    Science.gov (United States)

    Schoch, Justine; Rohrer, Tilman R; Kaestner, Michael; Abdul-Khaliq, Hashim; Gortner, Ludwig; Sester, Urban; Sester, Martina; Schmidt, Tina

    2017-05-15

    Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, knowledge regarding T cells is limited. Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus [VZV] and cytomegalovirus [CMV]). Results were correlated with immunoglobulin (Ig) G responses. Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4+ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG-positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome. Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  10. Effects of vitamin C supplementation on performance, iron status and immune function of weaned piglets.

    Science.gov (United States)

    Zhao, Junmei; Li, Defa; Piao, Xiangshu; Yang, Wenjun; Wang, Fenglai

    2002-02-01

    Two experiments were conducted to evaluate the effects of vitamin C supplementation on performance, iron status and immune function of pigs during the 21-day post-weaning period. In experiment one, 48 crossbred pigs (Chester White x Large White x Yorkshire), weaned at 30 days of age and weighing 7.7 +/- 0.9 kg, were allotted to diets containing either 0 or 300 mg/kg vitamin C. In experiment two, 96 crossbred pigs (Chester White x Large White x Yorkshire), weaned at 20 +/- 2 days and weighing 7.1 +/- 0.5 kg, were allotted to diets containing 0.75 or 300 mg/kg vitamin C. Six replicate pens were assigned to each treatment in experiment one while experiment two had eight replicates. All pens housed two barrows and two gilts. In both experiments, no improvement (P > 0.05) in growth rate, feed intake or feed conversion was observed as a result of vitamin C supplementation. Plasma iron concentration increased (P immunity (P > 0.05). In trial 2, the plasma levels of the immunoglobulin IgG showed a linear (P = 0.07) increase with increasing levels of vitamin C and the same trend was noted in trial 1. Antibody titers to bovine serum albumin also tended to increase in both trials but the increases were not statistically significant. In conclusion, the overall results of these experiments indicate that weanling pig performance is not improved as a result of vitamin C supplementation. Whether or not vitamin C plays a role in stimulating humoral immune function in pigs requires further study since the results of our experiments do not completely rule out the possibility that such a role exists.

  11. Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1.

    Science.gov (United States)

    Procario, Megan C; McCarthy, Mary K; Levine, Rachael E; Molloy, Caitlyn T; Weinberg, Jason B

    2016-03-02

    Neonatal mice are more susceptible than adults to mouse adenovirus type 1 (MAV1) respiratory infection. In adult mice, MAV-1 respiratory infection induces production of prostaglandin E2 (PGE2), a lipid mediator that exerts suppressive effects on a variety of host immune functions. We tested the hypothesis that exaggerated PGE2 production in neonatal mice contributes to increased susceptibility to MAV-1. PGE2 concentrations were lower in lungs of uninfected neonatal mice than in adults. PGE2 production was induced by both MAV-1 and a nonspecific stimulus to a greater degree in neonatal mice than in adults, but only in adults was PGE2 induced in a virus-specific manner. Lung viral loads were equivalent in PGE2-deficient neonatal mice and wild type controls, as was virus-induced expression of IFN-γ, IL-17A, and CCL5 in the lungs. PGE2 deficiency had minimal effect on production of virus-specific IgG or establishment of protective immunity in neonatal mice. Collectively, our data indicate that lung PGE2 production is exaggerated early in life, but this effect does not mediate increased susceptibility to MAV-1 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. 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

  13. Effects of bacteria-produced human alpha, beta, and gamma interferons on in vitro immune functions.

    Science.gov (United States)

    Shalaby, M R; Weck, P K; Rinderknecht, E; Harkins, R N; Frane, J W; Ross, M J

    1984-04-01

    The effects of bacteria-produced human interferons (HuIFN) alpha, beta, and gamma on in vitro immune functions of human peripheral blood mononuclear cells (PBMC) were studied. Proliferative response to phytohemagglutinin was significantly inhibited by the addition of HuIFN-alpha 2 or HuIFN-beta at 10, 100, or 1000 U/ml. In contrast, HuIFN-gamma showed suppressive activities only when added at 1000 U/ml. HuIFN-alpha 2 or HuIFN-beta caused significant inhibition of human mixed-lymphocyte reaction (MLR) as measured by [3H]thymidine incorporation. Similar inhibition was caused by HuIFN-gamma when it was added only at very low concentrations (1 U/ml); 10, 100, or 1000 U/ml resulted in no or only a modest increase in MLR. All three interferons exhibited dose-related effects on PWM-induced immunoglobulin synthesis in cultures of PBMC. These data demonstrate that purified interferons produced by recombinant DNA technology can significantly alter in vitro immune functions and that HuIFN-gamma has properties which are different from those of HuIFN-alpha 2 or HuIFN-beta.

  14. 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.

  15. 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

  16. 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.

  17. Effects of aluminum on immune functions of cultured splenic T and B lymphocytes in rats.

    Science.gov (United States)

    She, Yue; Wang, Nan; Chen, Chongxiao; Zhu, Yanzhu; Xia, Shiliang; Hu, Chongwei; Li, Yanfei

    2012-06-01

    The effects of Aluminum (Al) exposure on immune functions of cultured splenic T and B lymphocytes of rats were studied. The lymphocytes were isolated from spleen of healthy male Wistar rats weighing 110-120 g. The cultured cells in RPMI-1640 medium were exposed to 0 (control group), 0.035 (low-dose group), 0.07 (medial-dose group), and 0.14 (high-dose group) mg/mL Al(3+) as aluminum trichloride (AlCl(3)) in an incubator under 5% CO(2) at 37°C for 24 h. The T and B lymphocyte proliferation was measured with a tetrazolium dye colorimetric assay. The levels of interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α were determined by iodine [(125)I] IL-2, IL-6, and TNF-α radioimmunoassay kits, respectively. The proportions of CD3(+), CD4(+), and CD8(+) T lymphocytes were measured with a flow cytometer. The results showed that the T and B lymphocyte proliferation, the levels of IL-2, IL-6, TNF-α, the proportions of CD3(+) and CD4(+) T lymphocytes, and the ratio of CD4(+)/CD8(+) T lymphocytes were lowered by Al treatments, while the proportion of CD8(+) T lymphocytes was increased. These findings indicate that Al exposure can inhibit the immune functions of splenic T and B lymphocytes of rats in vitro.

  18. Effects of aluminum exposure on the allergic responses and humoral immune function in rats.

    Science.gov (United States)

    Zhu, Yanzhu; Xu, Jinfeng; Sun, Hao; Hu, Chongwei; Zhao, Hansong; Shao, Bing; Bah, Alphajoh A; Li, Yanfei

    2011-10-01

    This study was conducted to assess effects of aluminum (Al) exposure on allergic responsive reactions and humoral immune function in rats. Forty male Wistar rats (5 weeks old) weighed 110-120 g were randomly allocated into four groups and were orally exposed to 0, 64.18, 128.36, and 256.72 mg/kg body weight aluminum trichloride in drinking water for 120 days. The levels of immunoglobulin (Ig) G, IgA, IgM, IgE, Complement factor (C)3, and C4 in serum were determined by ELISA and nephelometric assays at the end of experiment. The results showed that the levels of IgM, C3, and C4 were lowered, and the levels of IgG, IgA, and IgE were increased in an Al-dose dependent manner. The increased in IgE level and the decreased in C3 and C4 levels indicate that Al induces allergic responses in rats; while the increased levels in IgG and IgA and the decreased level in IgM suggest that Al disorders the humoral immune function in rats.

  19. Suppressive effects of aluminum trichloride on the T lymphocyte immune function of rats.

    Science.gov (United States)

    Zhu, Yanzhu; Hu, Chongwei; Li, Xinwei; Shao, Bing; Sun, Hao; Zhao, Hansong; Li, Yanfei

    2012-03-01

    Aluminum (Al) has increasingly been used in the daily life, and could cause the change of human health because it can accumulate in the organs. A rat model was thus used to examine potential effect of Al on the immune function. Forty male Wistar rats (5 weeks old) weighed 110-120 g were randomly allocated into four groups and were orally exposed to 0, 64.18, 128.36, and 256.72 mg/kg body weight aluminum trichloride (AlCl3) in drinking water for 120 days. The levels of CD3+, CD4+, CD8+ T lymphocyte, acid non-specific activity esterase (ANAE+) in blood, and interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) in serum were determined at the end of experiment. The results showed that the proportions of CD3+, CD4+ T lymphocyte, the ratio of CD4+/CD8+, and the levels of ANAE+, IL-2, and TNF-α were significantly reduced in AlCl3-treated rats, while the proportion of CD8+ T lymphocyte was increased in an AlCl3-dose dependent manner. Our findings indicate that a long term exposure of AlCl3 could suppress the T lymphocyte immune function of rats. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. [Effect of perioperative intestinal probiotics on intestinal flora and immune function in patients with colorectal cancer].

    Science.gov (United States)

    Zhu, Dajian; Chen, Xiaowu; Wu, Jinhao; Ju, Yongle; Feng, Jing; Lu, Guangsheng; Ouyang, Manzhao; Ren, Baojun; Li, Yong

    2012-08-01

    To investigate the effect of perioperative application of intestinal probiotics to substitute oral intestinal antimicrobial agents on intestinal flora and immune function in surgical patients with colorectal cancer. Sixty patients with colorectal cancer undergoing elective laparoscopic radical surgery were randomized to receive preoperative bowel preparation using oral intestinal antimicrobial agents (n=20) or using oral intestinal probiotics (Jinshuangqi Tablets, 2.0 g, 3 times daily) since the fifth day before the operation and at 24 h after the operation for 7 consecutive days. Upon admission and 7 days after the operation, fecal samples and fasting peripheral venous blood were collected from the patients to examine the intestinal flora and serum levels of interleukin-2 (IL-2), IgA, IgG, and IgM, NK cell activity, T lymphocytes subsets CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) ratio. At 7 days after the operation, the patients receiving probiotics showed significantly increased counts of intestinal Bifidobacterium, Lactobacillus, and Enterococcus (Pprobiotics group compared with those in patients with conventional intestinal preparation (Pprobiotics to replace preoperative oral intestinal antimicrobial agents can effectively correct intestinal flora imbalance and improve the immune function of surgical patients with colorectal cancer.

  1. Effects of sheltering on physiology, immune function, behavior, and the welfare of dogs.

    Science.gov (United States)

    Protopopova, Alexandra

    2016-05-15

    Approximately 4 million dogs live in animal shelters each year. However, understanding and measuring the welfare of these kenneled dogs presents a challenge. One way to determine welfare is by assessing how stay at the shelter influences physiology, immune function, and behavior of the dogs. Prior research, from all of these domains, has not resulted in clear conclusions on how the animal shelter influences the well-being of dogs. One robust finding is that, when placed into a kennel environment, dogs experience a spike in cortisol levels followed by a decrease to original at-home levels. Current evidence cannot differentiate between several proposed hypotheses that may be responsible for this pattern. In addition, very few studies have assessed the effects of kenneling on immune function of dogs, and of these, no consistent findings have emerged. However, this line of inquiry can have a large impact as infectious diseases are rampant in animal shelters. The ability of behavioral measures to inform us about the welfare of dogs is discussed by reviewing published and new data on the effects of kenneling on dog behavior. Prior research has suffered from a lack of consistent operational definitions when defining abnormal behavior in dogs, resulting in difficult to interpret results. Research on the well-being of individual dogs, rather than on group averages, may be a fruitful next step in determining and improving the welfare of dogs housed in shelters. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.

    Science.gov (United States)

    Diaz, Miguel F; Vaidya, Abishek B; Evans, Siobahn M; Lee, Hyun J; Aertker, Benjamin M; Alexander, Alexander J; Price, Katherine M; Ozuna, Joyce A; Liao, George P; Aroom, Kevin R; Xue, Hasen; Gu, Liang; Omichi, Rui; Bedi, Supinder; Olson, Scott D; Cox, Charles S; Wenzel, Pamela L

    2017-05-01

    Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E 2 (PGE 2 ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement. Stem Cells 2017;35:1259-1272. © 2017 AlphaMed Press.

  3. Effects of selenizing angelica polysaccharide and selenizing garlic polysaccharide on immune function of murine peritoneal macrophage.

    Science.gov (United States)

    Gao, Zhenzhen; Liu, Kuanhui; Tian, Weijun; Wang, Hongchao; Liu, Zhenguang; Li, Youying; Li, Entao; Liu, Cui; Li, Xiuping; Hou, Ranran; Yue, Chanjuan; Wang, Deyun; Hu, Yuanliang

    2015-07-01

    The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune function of murine peritoneal macrophages taking two non-selenizing polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3 on murine macrophages function were evaluated by phagocytosis and nitric oxide (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2, 0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 μg or normal saline 0.4 mL. The peritoneal macrophages were collected and cultured to determine the contents of TNF-α, IL-6 and IL-10 in supernatants by enzyme-linked immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly promote the phagocytosis and secretion of NO and three cytokines of macrophages in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This indicates that selenylation modification can further improve the immune-enhancing activity of polysaccharide, and sCAP2 could be as a new immunopotentiator. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Viral immune evasion due to persistence of activated T cells without effector function.

    Science.gov (United States)

    Zajac, A J; Blattman, J N; Murali-Krishna, K; Sourdive, D J; Suresh, M; Altman, J D; Ahmed, R

    1998-12-21

    We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69(hi), CD44(hi), CD62Llo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8- CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.

  5. Neonatal arrhythmias.

    Science.gov (United States)

    Poddar, Banani; Basu, Srikanta; Parmar, Veena R

    2006-02-01

    Neonatal arrhythmias are not uncommon; however, they rarely cause hemodynamic compromise. This paper aims to study the etiology, spectrum and outcome of neonates with arrhythmias who presented to a pediatric department. All neonates, either inborn or brought to the pediatric emergency with rhythm disorders, between August 1999 to August 2002, were included prospectively. Evaluation including a search for secondary causes of rhythm disorder and a chest X-ray, standard 12-lead electrocardiography and echocardiography in all. The management required in each and the outcomes were noted. Nine neonates were identified, of which 4 were inborn. Tachycardia was seen in 8 neonates and bradycardia in only one. Three neonates had an antenatal onset of arrhythmias; in the rest it was postnatal in onset. Five neonates had a secondary rhythm disorder, secondary to metabolic derangements in 4 and a cardiac mass in 1. Five had ventricular arrhythmias and 5 had hemodynamic compromise due to the arrhythmia. The outcome was poor in 4 and was related to the underlying illness. Tachyarrhythmia is more common than bradyarrhythmia in the neonate. Arrhythmias secondary to various metabolic causes are more common than primary rhythm disorders.

  6. Tuberculosis neonatal

    OpenAIRE

    Pastor Durán, Xavier

    1986-01-01

    PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..

  7. 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.

  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. 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

  10. A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome

    Science.gov (United States)

    Joyeux, Luc; Pranpanus, Savitree; Van der Merwe, Johannes; Verbeken, Eric; De Vleeschauwer, Stephanie; Gayan-Ramirez, Ghislaine; Deprest, Jan

    2017-01-01

    Objectives We aimed to develop a more representative model for neonatal congenital diaphragmatic hernia repair in a large animal model, by creating a large defect in a fast-growing pup, using functional pulmonary and diaphragmatic read outs. Background Grafts are increasingly used to repair congenital diaphragmatic hernia with the risk of local complications. Growing animal models have been used to test novel materials. Methods 6-week-old rabbits underwent fiberoptic intubation, left subcostal laparotomy and hemi-diaphragmatic excision (either nearly complete (n = 13) or 3*3cm (n = 9)) and primary closure (Gore-Tex patch). Survival was further increased by moving to laryngeal mask airway ventilation (n = 15). Sham operated animals were used as controls (n = 6). Survivors (90 days) underwent chest X-Ray (scoliosis), measurements of maximum transdiaphragmatic pressure and breathing pattern (tidal volume, Pdi). Rates of herniation, lung histology and right hemi-diaphragmatic fiber cross-sectional area was measured. Results Rabbits surviving 90 days doubled their weight. Only one (8%) with a complete defect survived to 90 days. In the 3*3cm defect group all survived to 48 hours, however seven (78%) died later (16–49 days) from respiratory failure secondary to tracheal stricture formation. Use of a laryngeal mask airway doubled 90-day survival, one pup displaying herniation (17%). Cobb angel measurements, breathing pattern, and lung histology were comparable to sham. Under exertion, sham animals increased their maximum transdiaphragmatic pressure 134% compared to a 71% increase in patched animals (p<0.05). Patched animals had a compensatory increase in their right hemi-diaphragmatic fiber cross-sectional area (p<0.0001). Conclusions A primarily patched 3*3cm defect in growing rabbits, under laryngeal mask airway ventilation, enables adequate survival with normal lung function and reduced maximum transdiaphragmatic pressure compared to controls. PMID:28358826

  11. A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome.

    Directory of Open Access Journals (Sweden)

    Mary Patrice Eastwood

    Full Text Available We aimed to develop a more representative model for neonatal congenital diaphragmatic hernia repair in a large animal model, by creating a large defect in a fast-growing pup, using functional pulmonary and diaphragmatic read outs.Grafts are increasingly used to repair congenital diaphragmatic hernia with the risk of local complications. Growing animal models have been used to test novel materials.6-week-old rabbits underwent fiberoptic intubation, left subcostal laparotomy and hemi-diaphragmatic excision (either nearly complete (n = 13 or 3*3cm (n = 9 and primary closure (Gore-Tex patch. Survival was further increased by moving to laryngeal mask airway ventilation (n = 15. Sham operated animals were used as controls (n = 6. Survivors (90 days underwent chest X-Ray (scoliosis, measurements of maximum transdiaphragmatic pressure and breathing pattern (tidal volume, Pdi. Rates of herniation, lung histology and right hemi-diaphragmatic fiber cross-sectional area was measured.Rabbits surviving 90 days doubled their weight. Only one (8% with a complete defect survived to 90 days. In the 3*3cm defect group all survived to 48 hours, however seven (78% died later (16-49 days from respiratory failure secondary to tracheal stricture formation. Use of a laryngeal mask airway doubled 90-day survival, one pup displaying herniation (17%. Cobb angel measurements, breathing pattern, and lung histology were comparable to sham. Under exertion, sham animals increased their maximum transdiaphragmatic pressure 134% compared to a 71% increase in patched animals (p<0.05. Patched animals had a compensatory increase in their right hemi-diaphragmatic fiber cross-sectional area (p<0.0001.A primarily patched 3*3cm defect in growing rabbits, under laryngeal mask airway ventilation, enables adequate survival with normal lung function and reduced maximum transdiaphragmatic pressure compared to controls.

  12. Renal function in neonates with twin-twin transfusion syndrome treated with or without fetoscopic laser surgery.

    Science.gov (United States)

    Verbeek, Lianne; Joemmanbaks, Faiez A; Quak, Jacoba M E; Sukhai, Ram N; Middeldorp, Johanna M; Oepkes, Dick; Lopriore, Enrico

    2017-09-01

    The aim of this study is to investigate the short-term renal function in neonates with twin-twin transfusion syndrome (TTTS), treated with fetoscopic laser surgery (laser group) or conservatively (non-laser group). Creatinine and urea levels and urine output were recorded in the first week after birth. Primary outcome was short-term renal dysfunction, defined as a creatinine level of >100 μmol/L during the first week postpartum. We evaluated 312 twins (laser group, n = 274; non-laser group, n = 38). Median creatinine and urea levels were lower in the laser group than in the non-laser group (71 versus 82 μmol/L, p = 0.002). Short-term renal dysfunction was lower in the laser group compared to the non-laser group (7.2 versus 34.4%, p < 0.001). Within the laser group, creatinine levels were significantly higher in the subgroup with incomplete laser surgery compared to twins with successful laser surgery (76 versus 69 μmol/L, p = 0.018). No differences were found between donors and recipients except for a higher incidence of oliguria in donors in the non-laser group on day 1. Short-term renal dysfunction occurs less frequently in TTTS twins treated with fetoscopic laser coagulation, particularly after complete surgery, suggesting that laser surgery may have a protective effect on renal function. What is Known: • Antenatally, donor twins in TTTS have severe oliguria due to chronic hypovolemia and impaired renal perfusion • Postnatally, donor twins may suffer from severe renal complications, particularly in TTTS twins treated conservatively. What is New: • The incidence of short-term renal failure in TTTS twins treated with complete laser surgery is low. • After incomplete laser surgery, the incidence of short-term renal dysfunction is increased.

  13. Effect of maternal administration of allopregnanolone before birth asphyxia on neonatal hippocampal function in the spiny mouse.

    Science.gov (United States)

    Fleiss, Bobbi; Parkington, Helena C; Coleman, Harold A; Dickinson, Hayley; Yawno, Tamara; Castillo-Melendez, Margie; Hirst, Jon J; Walker, David W

    2012-01-18

    Clinically, treatment options where fetal distress is anticipated or identified are limited. Allopregnanolone is an endogenous steroid, that positively modulates the GABA(A) receptor, and that has anti-apoptotic and anti-excitotoxic actions, reducing brain damage in adult animal models of brain injury. We sought to determine if prophylactic treatment of the pregnant female with a single dose of this steroid could reduce birth asphyxia-induced losses in hippocampal function at 5 days of age (P5) in spiny mouse neonates (Acomys cahirinus). At 37 days gestation (term=39 days) and 1h before inducing birth asphyxia, spiny mice dams were injected subcutaneously (0.2 ml) with either 3mg/kg allopregnanolone or 20% w/v β-cyclodextrin vehicle. One hour later, fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5 min of in utero asphyxia, causing acidosis and hypoxia. At P5, ex vivo hippocampal plasticity was assessed, or brains collected to determine cell proliferation (proliferating cell nuclear antigen; PCNA) or calcium channel expression (inositol trisphosphate receptor type 1; IP(3)R1) using immunohistochemistry. Allopregnanolone partially prevented the decrease in long term potentiation at P5, and the asphyxia-induced increase in IP(3)R1 expression in CA1 pyramidal neurons. There was no effect of allopregnanolone on the asphyxia induced impairment of the input/output (I/O) curve and paired-pulse facilitation (PPF). In control birth pups, maternal allopregnanolone treatment caused significant changes in short term post-synaptic plasticity and also reduced hippocampal proliferation at P5. These findings show that allopregnanolone can modulate hippocampal development and synaptic function in a normoxic or hypoxic environment, possibly by modifying calcium metabolism. Best practice for treatment dose and timing of treatment will need to be carefully considered. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. 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.

  15. Physical activity, immune function and inflammation in kidney patients (the PINK study): a feasibility trial protocol.

    Science.gov (United States)

    Highton, Patrick James; Neale, Jill; Wilkinson, Thomas J; Bishop, Nicolette C; Smith, Alice C

    2017-05-29

    Patients with chronic kidney disease (CKD) display increased infection-related mortality and elevated cardiovascular risk only partly attributed to traditional risk factors. Patients with CKD also exhibit a pro-inflammatory environment and impaired immune function. Aerobic exercise has the potential to positively impact these detriments, but is under-researched in this patient population. This feasibility study will investigate the effects of acute aerobic exercise on inflammation and immune function in patients with CKD to inform the design of larger studies intended to ultimately influence current exercise recommendations. Patients with CKD, including renal transplant recipients, will visit the laboratory on two occasions, both preceded by appropriate exercise, alcohol and caffeine restrictions. On visit 1, baseline assessments will be completed, comprising anthropometrics, body composition, cardiovascular function and fatigue and leisure time exercise questionnaires. Participants will then undertake an incremental shuttle walk test to estimate predicted peak O 2 consumption (VO 2 peak). On visit 2, participants will complete a 20 min shuttle walk at a constant speed to achieve 85% estimated VO 2 peak. Blood and saliva samples will be taken before, immediately after and 1 hour after this exercise bout. Muscle O 2 saturation will be monitored throughout exercise and recovery. Age and sex-matched non-CKD 'healthy control' participants will complete an identical protocol. Blood and saliva samples will be analysed for markers of inflammation and immune function, using cytometric bead array and flow cytometry techniques. Appropriate statistical tests will be used to analyse the data. A favourable opinion was granted by the East Midlands-Derby Research Ethics Committee on 18 September 2015 (ref 15/EM/0391), and the study was approved and sponsored by University Hospitals of Leicester Research and Innovation (ref 11444). The study was registered with ISRCTN (ref

  16. 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.

  17. A strategy for bacterial production of a soluble functional human neonatal Fc receptor

    DEFF Research Database (Denmark)

    Andersen, Jan Terje; Justesen, Sune; Berntzen, Gøril

    2008-01-01

    (human) or newborn (rodents), and may translocate IgG over mucosal surfaces. FcRn interacts with the Fc-region of IgG and domain III of albumin with binding at pH 6.0 and release at pH 7.4. Knowledge of these interactions has facilitated design of recombinant proteins with altered serum half-lives and....../or altered biodistribution. To generate further research in this field, there is a great need for large amounts of soluble human FcRn (shFcRn) for in vitro interaction studies. In this report, we describe a novel laboratory scale production of functional shFcRn in Escherichia coli (E. coli) at milligram...... correctly formed as demonstrated by circular dichroism (CD). Furthermore, functional and stringent pH dependent binding to IgG and human serum albumin were demonstrated by ELISA and surface plasmon resonance (SPR). This method may be easily adapted for the expression of large amounts of other FcRn species...

  18. Thyroid function in mothers who gave birth to neonates with transient congenital hypothyroidism

    International Nuclear Information System (INIS)

    Karam, G.A.; Hakimi, H.; Rezaeian, M.; Gafarzadeh, A.; Rashidinejad, H.; Khaksari, M.

    2009-01-01

    Objective: To determine the thyroid status of mother's of newborns with primary congenital hypothyroidism. Methodology: Thyroid function tests were carried out on 80 mothers of hypothyroid newborns and 80 mothers of non-hypothyroid newborns as control. Results: The mean difference of the tests revealed that mothers of congenitally hypothyroid infants had a lower triiodothyronine resin uptake (T3RU) concentrations compared with the control population. The higher value of free thyroxin index (FTI) in case group showed a tendency to significance. The proportional frequency distribution showed; T3RU and triiodothyronine (T3) had a significant difference, and FTI showed a tendency to significance. There were no significant differences between; thyroid-stimulating hormone (TSH), thyroxine (T4) and anti-thyroid peroxidase antibodies (anti-TPO) in two groups. Conclusions: These results indicated that at least some cases of primary congenital hypothyroidism were attributable to the maternal thyroid disease. Therefore, we recommend that each pregnant woman should be assessed for thyroid function in region with a high prevalence of thyroid disease. (author)

  19. Neonatal Platelet Transfusions and Future Areas of Research.

    Science.gov (United States)

    Sola-Visner, Martha; Bercovitz, Rachel S

    2016-10-01

    Thrombocytopenia affects approximately one fourth of neonates admitted to neonatal intensive care units, and prophylactic platelet transfusions are commonly administered to reduce bleeding risk. However, there are few evidence-based guidelines to inform clinicians' decision-making process. Developmental differences in hemostasis and differences in underlying disease processes make it difficult to apply platelet transfusion practices from other patient populations to neonates. Thrombocytopenia is a risk factor for common preterm complications such as intraventricular hemorrhage; however, a causal link has not been established, and platelet transfusions have not been shown to reduce risk of developing intraventricular hemorrhage. Platelet count frequently drives the decision of whether to transfuse platelets, although there is little evidence to demonstrate what a safe platelet nadir is in preterm neonates. Current clinical assays of platelet function often require large sample volumes and are not valid in the setting of thrombocytopenia; however, evaluation of platelet function and/or global hemostasis may aid in the identification of neonates who are at the highest risk of bleeding. Although platelets' primary role is in establishing hemostasis, platelets also carry pro- and antiangiogenic factors in their granules. Aberrant angiogenesis underpins common complications of prematurity including intraventricular hemorrhage and retinopathy of prematurity. In addition, platelets play an important role in host immune defenses. Infectious and inflammatory conditions such as sepsis and necrotizing enterocolitis are commonly associated with late-onset thrombocytopenia in neonates. Severity of thrombocytopenia is correlated with mortality risk. The nature of this association is unclear, but preclinical data suggest that thrombocytopenia contributes to mortality rather than simply being a proxy for disease severity. Neonates are a distinct patient population in whom

  20. Functional T lymphocyte immune deficiency in a population of homosexual men who do not exhibit symptoms of acquired immune deficiency syndrome.

    OpenAIRE

    Shearer, G M; Payne, S M; Joseph, L J; Biddison, W E

    1984-01-01

    To determine whether healthy homosexual men are immunologically impaired, peripheral blood leukocytes (PBL) from 20 male homosexuals were compared prospectively with PBL from 14 age-matched male heterosexual donors with respect to: (a) the capacity of their PBL to generate functional T cell immune responses in vitro; and (b) the content of total T cells and T cell subsets in their peripheral blood. The homosexual donors studied indicated moderate sexual life styles in that all but one of the ...

  1. 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

  2. Intraoperative fluid therapy in neonates

    African Journals Online (AJOL)

    The evidence base for the administration of intraoperative fluids in neonates is poor and extrapolated from adults and children. Differences from adults and children in physiology and anatomy of neonates inform our practice. Keywords: fluid ..... compromise lung function and wound healing. The EGL develops early in ...

  3. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

    Directory of Open Access Journals (Sweden)

    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  4. Neonatal hypertension.

    Science.gov (United States)

    Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

    2017-03-01

    Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.

  5. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts

    Science.gov (United States)

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-01-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine. PMID:25903472

  6. 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.

  7. Effects of Corticosterone on Immune Functions of Cultured Rat Splenic Lymphocytes Exposed to Aluminum Trichloride.

    Science.gov (United States)

    Yang, Xu; Xu, Feibo; Zhuang, Cuicui; Bai, Chongsheng; Huang, Wanyue; Song, Miao; Han, Yanfei; Li, Yanfei

    2016-10-01

    Aluminum (Al) exposure is toxic to immune system. Studies have implicated that glucocorticoids (GCs) exert the dual regulation effect on the immune function depending on the concentration. However, it is unknown whether a dual effect of GCs exists in the AlCl3-treated lymphocytes. Corticosterone (Cort) is one kind of GCs. To investigate the effect of different concentration Cort on AlCl3-treated lymphocytes, rat splenic lymphocyte was isolated and cultured with 0.55 mmol/L AlCl3, simultaneously administrated Cort at final concentration of 0 (control group, CG), 10(-8) (low-level group, LG), and 10(-6) (high-level group, HG) mol/L, respectively. Another group without AlCl3 and Cort served as the blank group (BG). We found that low concentration Cort increased the T and B lymphocyte proliferation rate, proportions of CD4(+) T lymphocyte subset, IgG, IL-2, and TNF-α contents, whereas high concentration Cort decreased those in AlCl3-treated lymphocytes. In conclusion, the results of this study indicated that low concentration Cort relieves the immunotoxicity of AlCl3 on the splenic lymphocytes, whereas high concentration Cort aggravates it.

  8. Effects of yogurt containing Lactobacillus plantarum HOKKAIDO on immune function and stress markers.

    Science.gov (United States)

    Nishimura, Mie; Ohkawara, Tatsuya; Tetsuka, Kyohei; Kawasaki, Yo; Nakagawa, Ryoji; Satoh, Hiroki; Sato, Yuji; Nishihira, Jun

    2016-07-01

    Lactobacillus plantarum HOKKAIDO (HOKKAIDO strain) was isolated from well-pickled vegetables in Hokkaido, Japan. We report a randomized, double-blind, placebo-controlled study evaluating the effects of L. plantarum HOKKAIDO on immune function and stress markers in 171 adult subjects. Subjects were divided into three groups: the L. plantarum HOKKAIDO yogurt group, the placebo-1 group who ingested yogurt without the HOKKAIDO strain, and the placebo-2 group who ingested a yogurt-like dessert without the HOKKAIDO strain. Hematological tests and body composition measurements were performed before and after 4 and 8 weeks of blinded ingestion. Although no significant differences in natural killer cell activity were observed, it was found that neutrophil ratio significantly decreased and lymphocytes tended to increase in the HOKKAIDO strain yogurt group compared with the yogurt-like dessert group. In addition, the neutrophil-to-lymphocyte ratio, a stress marker, tended to improve in the HOKKAIDO strain yogurt group compared with the yogurt-like dessert group. These results suggest that the ingestion of HOKKAIDO strain yogurt tends to improve immune activity and decrease stress markers.

  9. 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.

  10. 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

  11. A Perspective on the Structural and Functional Constraints for Immune Evasion: Insights from Influenza Virus.

    Science.gov (United States)

    Wu, Nicholas C; Wilson, Ian A

    2017-08-18

    Influenza virus evolves rapidly to constantly escape from natural immunity. Most humoral immune responses to influenza virus target the hemagglutinin (HA) glycoprotein, which is the major antigen on the surface of the virus. The HA is composed of a globular head domain for receptor binding and a stem domain for membrane fusion. The major antigenic sites of HA are located in the globular head subdomain, which is highly tolerant of amino acid substitutions and continual addition of glycosylation sites. Nonetheless, the evolution of the receptor-binding site and the stem region on HA is severely constrained by their functional roles in engaging the host receptor and in mediating membrane fusion, respectively. Here, we review how broadly neutralizing antibodies (bnAbs) exploit these evolutionary constraints to protect against diverse influenza strains. We also discuss the emerging role of other epitopes that are conserved only in subsets of viruses. This rapidly increasing knowledge of the evolutionary biology, immunology, structural biology, and virology of influenza virus is invaluable for development and design of more universal influenza vaccines and novel therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effects of immunization against LHRH and treatment with trenbolone acetate on reproductive function of beef bulls and steers

    Science.gov (United States)

    The objectives of this study were (1) to evaluate the ability of trenbolone acetate (TBA) administered in tandem with LHRH immunization to suppress reproductive function in beef bulls and (2) to examine the effects of LHRH and androgen (TBA) signaling on pituitary function. In order to address thes...

  13. Tirosinemia neonatal Neonatal tyrosinemia

    Directory of Open Access Journals (Sweden)

    Rafael J. Manotas Cabarcas

    1995-04-01

    Full Text Available Mediante la técnica de Udenfriend y Cooper, se midieron los niveles de tirosina en la sangre del cordón de 26 prematuros y 31 niños de término, con el fin de comparar las concentraciones según la edad gestacional y detectar la presencia de la tirosinemia neonatal. Se encontró un caso de esta entidad en un niño de 31 semanas de edad gestacional, lo cual correspondió al 3.8% de los prematuros y al 1.8% del grupo total. La concentración de tirosina en el paciente fue de 53 JJ.M. El promedio de las concentraciones en los prematuros menores de 32 semanas fue de 16.8 :t 6.3 JJ.M; el de los niños entre 33 y 36 semanas fue de 19.3 :t 7.6 JJ.M y el de los niños de término, de 17.2 :t 9.4 JJ.M. Las pruebas estadísticas no mostraron tendencias ni diferencias significativas entre estas concentraciones. El promedio ponderado para el grupo total fue 17.7 :t 7.3 JJ.M. Se recomienda establecer programas de tamizaje para detectar este problema porque puede presentar repercusiones neurológicas posteriores.

    By means of the Udenfriend-Cooper technique, levels of tyrosine were measured in the cord blood of 26 preterm and 31 term Infants; the objective was to compare tyrosine concentrations according to gestational age and to detect the presence of neonatal tyrosinemia. A case of this disease was found In an Infant with 31 weeks of gestational age; this case represented 3.8% of preterm Infants and 1.8% of the total group. Average tyrosine concentration according to age was as follows: 16.8: ± 6.3  µM in Infants under 32 weeks of gestational age; 19.3: ±: 7.6 µM In those between 33 and 36 weeks and 17.2 : ±: 9.4 µM In the term Infants

  14. Echinoderm immunity.

    Science.gov (United States)

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats.

  15. Neonatal retinoblastoma

    Directory of Open Access Journals (Sweden)

    Tero T Kivelä

    2017-01-01

    Full Text Available From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support

  16. Neonatal Retinoblastoma

    Science.gov (United States)

    Kivelä, Tero T.; Hadjistilianou, Theodora

    2017-01-01

    From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree) Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support for parents when

  17. 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

  18. 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...

  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. 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.

  1. The Effect of Krill Oil Supplementation on Exercise Performance and Markers of Immune Function.

    Directory of Open Access Journals (Sweden)

    Mariasole Da Boit

    Full Text Available Krill oil is a rich source of the long-chain n-3 polyunsaturated fatty acids (PUFAs, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, which may alter immune function after exercise. The aim of the study was to determine the effects of krill oil supplementation on post exercise immune function and performance.Nineteen males and 18 females (age: 25.8 ± 5.3 years; mean ± S.D. were randomly assigned to 2 g/day of krill oil (n = 18 or placebo (n = 19 supplementation for 6 weeks. A maximal incremental exercise test and cycling time trial (time to complete set amount of work were performed pre-supplementation with the time trial repeated post-supplementation. Blood samples collected pre- and post- supplementation at rest, and immediately, 1 and 3h post-exercise. Plasma IL-6 and thiobarbituric acid reactive substances (TBARS concentrations and, erythrocyte fatty acid composition were measured. Natural killer (NK cell cytotoxic activity and peripheral blood mononuclear cell (PBMC IL-2, IL-4, IL-10, IL-17 and IFNγ production were also measured.No effects of gender were noted for any variable. PBMC IL-2 and NK cell cytotoxic activity were greater (P < 0.05 3h post exercise in the krill oil compared to the control group. Plasma IL-6 and TBARS, PBMC IL-4, IL-10, IL-17 and IFNγ production, along with performance and physiological measures during exercise, were not different between groups.Six weeks of krill oil supplementation can increase PBMC IL-2 production and NK cell cytotoxic activity 3h post-exercise in both healthy young males and females. Krill oil does not modify exercise performance.

  2. Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function.

    Science.gov (United States)

    Cabral, Guy A; Rogers, Thomas J; Lichtman, Aron H

    2015-06-01

    Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆(9)-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been identified in immune cells such as monocytes, macrophages, basophils, lymphocytes, and dendritic cells and are believed to be enzymatically produced and released "on demand" in a similar fashion as the eicosanoids. It is now recognized that other phytocannabinoids such as cannabidiol (CBD) and cannabinol (CBN) can alter the functional activities of the immune system. This special edition of the Journal of Neuroimmune Pharmacology (JNIP) presents a collection of cutting edge original research and review articles on the medical implications of phytocannabinoids and the endocannabinoid system. The goal of this special edition is to provide an unbiased assessment of the state of research related to this topic from leading researchers in the field. The potential untoward effects as well as beneficial uses of marijuana, its phytocannabinoid composition, and synthesized cannabinoid analogs are discussed. In addition, the role of the endocannabinoid system and approaches to its manipulation to treat select human disease processes are addressed.

  3. 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.

  4. 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.

  5. The Diversity, Structure, and Function of Heritable Adaptive Immunity Sequences in the Aedes aegypti Genome.

    Science.gov (United States)

    Whitfield, Zachary J; Dolan, Patrick T; Kunitomi, Mark; Tassetto, Michel; Seetin, Matthew G; Oh, Steve; Heiner, Cheryl; Paxinos, Ellen; Andino, Raul

    2017-11-20

    The Aedes aegypti mosquito transmits arboviruses, including dengue, chikungunya, and Zika virus. Understanding the mechanisms underlying mosquito immunity could provide new tools to control arbovirus spread. Insects exploit two different RNAi pathways to combat viral and transposon infection: short interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs) [1, 2]. Endogenous viral elements (EVEs) are sequences from non-retroviral viruses that are inserted into the mosquito genome and can act as templates for the production of piRNAs [3, 4]. EVEs therefore represent a record of past infections and a reservoir of potential immune memory [5]. The large-scale organization of EVEs has been difficult to resolve with short-read sequencing because they tend to integrate into repetitive regions of the genome. To define the diversity, organization, and function of EVEs, we took advantage of the contiguity associated with long-read sequencing to generate a high-quality assembly of the Ae. aegypti-derived Aag2 cell line genome, an important and widely used model system. We show EVEs are acquired through recombination with specific classes of long terminal repeat (LTR) retrotransposons and organize into large loci (>50 kbp) characterized by high LTR density. These EVE-containing loci have increased density of piRNAs compared to similar regions without EVEs. Furthermore, we detected EVE-derived piRNAs consistent with a targeted processing of persistently infecting virus genomes. We propose that comparisons of EVEs across mosquito populations may explain differences in vector competence, and further study of the structure and function of these elements in the genome of mosquitoes may lead to epidemiological interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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.

  8. 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.

  9. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection

    Directory of Open Access Journals (Sweden)

    Stig Bengmark

    2011-12-01

    formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system.

  10. Neonatal Nursing

    OpenAIRE

    Crawford, Doreen; Morris, Maryke

    1994-01-01

    "Neonatal Nursing" offers a systematic approach to the nursing care of the sick newborn baby. Nursing actions and responsibilities are the focus of the text with relevant research findings, clinical applications, anatomy, physiology and pathology provided where necessary. This comprehensive text covers all areas of neonatal nursing including ethics, continuing care in the community, intranatal care, statistics and pharmokinetics so that holistic care of the infant is described. This book shou...

  11. Passive transfer of maternal Mycoplasma hyopneumoniae-specific cellular immunity to piglets.

    Science.gov (United States)

    Bandrick, Meggan; Pieters, Maria; Pijoan, Carlos; Molitor, Thomas W

    2008-03-01

    Immunity in the neonatal animal is primarily maternally derived, either by lymphocytes that pass into the newborn across the placenta or following colostrum ingestion. However, the effect of this passively transferred cellular maternal immunity on the newborn's immune repertoire is not clearly understood. Various studies have shown that colostral lymphocytes are activated and possess functional abilities; however, no studies have shown the transfer of colostral antigen-specific T-cell-specific responses in a newborn. In this study we examined the transfer of vaccine-induced Mycoplasma hyopneumoniae cellular immunity from immune dams to newborn piglets. Newborn piglets from vaccinated and nonvaccinated dams were assessed in two ways for cellular immune responses specific to M. hyopneumoniae: (i) delayed-type hypersensitivity (DTH) testing and (ii) in vitro lymphocyte proliferation, assayed on piglet blood lymphocytes and sow colostral lymphocytes. DTH responses to M. hyopneumoniae were detected only for offspring of vaccinated sows, whereas DTH responses to the nonspecific mitogen phytohemagglutinin were seen for all piglets. M. hyopneumoniae-specific proliferation was seen for colostral lymphocytes from vaccinated sows and for blood lymphocytes from neonatal piglets of vaccinated dams but not for blood lymphocytes from piglets of nonvaccinated sows. Functional antigen-specific T cells were transferred to offspring from vaccinated sows and participated in the neonatal immune response upon stimulation. These data have implications for defining disease intervention strategies.

  12. Passive Transfer of Maternal Mycoplasma hyopneumoniae-Specific Cellular Immunity to Piglets▿

    Science.gov (United States)

    Bandrick, Meggan; Pieters, Maria; Pijoan, Carlos; Molitor, Thomas W.

    2008-01-01

    Immunity in the neonatal animal is primarily maternally derived, either by lymphocytes that pass into the newborn across the placenta or following colostrum ingestion. However, the effect of this passively transferred cellular maternal immunity on the newborn's immune repertoire is not clearly understood. Various studies have shown that colostral lymphocytes are activated and possess functional abilities; however, no studies have shown the transfer of colostral antigen-specific T-cell-specific responses in a newborn. In this study we examined the transfer of vaccine-induced Mycoplasma hyopneumoniae cellular immunity from immune dams to newborn piglets. Newborn piglets from vaccinated and nonvaccinated dams were assessed in two ways for cellular immune responses specific to M. hyopneumoniae: (i) delayed-type hypersensitivity (DTH) testing and (ii) in vitro lymphocyte proliferation, assayed on piglet blood lymphocytes and sow colostral lymphocytes. DTH responses to M. hyopneumoniae were detected only for offspring of vaccinated sows, whereas DTH responses to the nonspecific mitogen phytohemagglutinin were seen for all piglets. M. hyopneumoniae-specific proliferation was seen for colostral lymphocytes from vaccinated sows and for blood lymphocytes from neonatal piglets of vaccinated dams but not for blood lymphocytes from piglets of nonvaccinated sows. Functional antigen-specific T cells were transferred to offspring from vaccinated sows and participated in the neonatal immune response upon stimulation. These data have implications for defining disease intervention strategies. PMID:18184823

  13. Immune cells in term and preterm labor

    Science.gov (United States)

    Gomez-Lopez, Nardhy; StLouis, Derek; Lehr, Marcus A; Sanchez-Rodriguez, Elly N; Arenas-Hernandez, Marcia

    2014-01-01

    Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm. PMID:24954221

  14. Evaluation of a System-specific Function to Describe the Pharmacokinetics of Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia

    NARCIS (Netherlands)

    Bijleveld, Yuma A.; de Haan, Timo R.; van der Lee, Johanna H.; Groenendaal, Floris; Dijk, Peter H.; van Heijst, Arno; de Jonge, Rogier C. J.; Dijkman, Koen P.; van Straaten, Henrica L. M.; Rijken, Monique; Zonnenberg, Inge A.; Cools, Filip; Zecic, Alexandra; Nuytemans, Debbie H. G. M.; van Kaam, Anton H.; Mathôt, Ron A. A.

    2018-01-01

    The pharmacokinetic (PK) properties of i.v. benzylpenicillin in term neonates undergoing moderate hypothermia after perinatal asphyxia were evaluated, as to date these are unknown. To do so, a system-specific modeling approach was applied, in which our recently developed covariate model describing

  15. Effect of immunization against prostate- and testis-expressed (PATE) proteins on sperm function and fecundity in the rat.

    Science.gov (United States)

    Rajesh, Angireddy; Yenugu, Suresh

    2015-08-01

    Evaluating the immunocontraceptive potential of sperm-bound proteins is an active area of investigation. In this study, we analyzed the role of prostate- and testes-expressed (PATE) and PATE-F proteins in sperm function. Capacitation was measured as a function of tyrosine phosphorylation of sperm membrane proteins. Ionophore-induced acrosome reaction was assessed by measuring the fluorescence intensity of calcium-bound Fluo 3-AM and sperm-bound PNA-FITC in a flow cytometer. Rat spermatozoa subjected to capacitation and acrosome reaction in vitro displayed changes in the PATE and PATE-F protein localization on their surface, indicating the role of these proteins in sperm function. Capacitation and ionophore-induced acrosome reaction in vitro were inhibited in spermatozoa pre-incubated with antiserum raised in rabbit against PATE or PATE-F. Male rats were immunized with PATE proteins to assess their role in sperm function and fecundity. Antibody titer in the serum, testicular, and epididymal fluid was measured by ELISA. The motility parameters were recorded using CASA. High antibody titer was observed in serum, epididymal, and testicular fluid in rats immunized with PATE or PATE-F protein. Immunization did not cause any structural damage and inflammation in the testis and epididymis. PATE and PATE-F antisera obtained from the immunized rats inhibited acrosome reaction. Motility parameters, capacitation, acrosome reaction, and fecundity were compromised in PATE-F-immunized rats, whereas the same were not affected in rats immunized with PATE. These results suggest that PATE-F might play an important role in sperm function and fecundity and can be explored further to determine its immunocontraceptive potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Constitutive immune function in European starlings, Sturnus vulgaris, is decreased immediately after an endurance flight in a wind tunnel.

    Science.gov (United States)

    Nebel, Silke; Bauchinger, Ulf; Buehler, Deborah M; Langlois, Lillie A; Boyles, Michelle; Gerson, Alexander R; Price, Edwin R; McWilliams, Scott R; Guglielmo, Christopher G

    2012-01-15

    Life-history theory predicts that animals face a trade-off in energy allocation between performing strenuous exercise, such as migratory flight, and mounting an immune response. We experimentally tested this prediction by studying immune function in European starlings, Sturnus vulgaris, flown in a wind tunnel. Specifically, we predicted that constitutive immune function decreases in response to training and, additionally, in response to immediate exercise. We compared constitutive immune function among three groups: (1) 'untrained' birds that were kept in cages and were not flown; (2) 'trained' birds that received flight training over a 15 day period and performed a 1-4 h continuous flight, after which they rested for 48 h before being sampled; and (3) 'post-flight' birds that differed from the 'trained' group only in being sampled immediately after the final flight. A bird in our trained group represents an individual during migration that has been resting between migratory flights for at least 2 days. A bird in our post-flight group represents an individual that has just completed a migratory flight and has not yet had time to recover. Three of our four indicators (haptoglobin, agglutination and lysis) showed the predicted decrease in immune function in the post-flight group, and two indicators (haptoglobin, agglutination) showed the predicted decreasing trend from the untrained to trained to post-flight group. Haptoglobin levels were negatively correlated with flight duration. No effect of training or flight was detected on leukocyte profiles. Our results suggest that in European starlings, constitutive immune function is decreased more as a result of immediate exercise than of exercise training. Because of the recent emergence of avian-borne diseases, u