Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves.

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Liang, Guanxiang; Malmuthuge, Nilusha; Bao, Hua; Stothard, Paul; Griebel, Philip J; Guan, Le Luo

2016-08-11

Postnatal development of the mammalian mucosal immune system is crucial for responding to the rapid colonization by commensal bacteria and possible exposure to pathogens. This study analyzed expression patterns for mRNAs and their relationship with microRNAs (miRNAs) in the bovine small intestine during the critical neonatal period (0 to 42 days). This analysis revealed molecular mechanisms regulating the postnatal development of the intestinal mucosal immune system. Small intestine samples (jejunum and ileum) were collected from newborn male, Holstein calves immediately post-partum (n = 3) and at 7 (n = 5), 21 (n = 5), and 42 (n = 5) days of age and the transcriptomes were profiled using RNA-Seq. When analyzing all time points collectively, greater expression of genes encoding the complement functional pathway, as well as lower expression of genes encoding Toll-like receptors and NOD-like receptors were observed in the jejunum when compared to the ileum. In addition, significant changes in the expression of immune-related genes were detected within the first week post-partum in both jejunum and ileum. For example, increased expression of genes encoding tight junction proteins (claudin 1, claudin 4 and occludin), an antimicrobial peptide (Regenerating Islet-Derived 3-γ), NOD-like receptors (NACHT, LRR and PYD domain-containing protein 3), regulatory T cell marker (forkhead box P3), and both anti-inflammatory (interleukin 10) and pro-inflammatory (interleukin 8) cytokines was observed throughout the small intestine of 7-day-old calves when compared to newborn calves. Moreover, the expression of mucosal immune-related genes were either positively or negatively correlated with total bacterial population depending on both intestinal region and age. The integrated analysis of miRNAs and mRNAs supported the conclusion that miRNAs may regulate temporal changes in the expression of genes encoding tight junction proteins (miR-335), cytokines (miR-335) and

Immunity peculiarities of neonates in case of perinatal pathology

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О. S. Godovanets

2018-02-01

of the evidences of immune system components participation in perinatal pathology pathogenesis is detected correlation between immune disorders severity and clinical manifestation of diseases, as well as immune indices normalization in a long-term organism adaptation formation. Conclusions. Based on the data obtained it has been concluded that immune system status determination is reasonable for diagnostics of disadaptation syndrome severity in early neonatal period.

Immunizations, neonatal hyperbilirubinemia and animal-induced injuries.

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Bennett, Sean R; Brennan, Beth; Bernstein, Henry H

2007-08-01

To report recent research findings and new recommendations on immunizations, neonatal hyperbilirubinemia, and animal-induced injuries. Vaccines against rotavirus and human papilloma virus have entered clinical use. Varicella outbreaks among previously vaccinated children have prompted the recommendation for a two-dose varicella vaccine series. Broader coverage for influenza vaccination is now recommended in the US and Canada. Diagnosis and treatment of neonatal hyperbilirubinemia uses population and hour-based norms for total serum bilirubin and assessment of risk factors. Delayed cord clamping is not apparently a risk factor for jaundice but warrants more study. Universal predischarge screening shows promise but is not yet officially recommended. New treatments for hyperbilirubinemia are being evaluated. Dogs are the chief cause of animal bites in children and the largest reservoir for rabies worldwide. In North America and Europe, cats and wild animals cause most human rabies. Postexposure prophylaxis should follow region-appropriate guidelines. New vaccines are available against rotavirus and human papilloma virus. Changes have been made to official immunization recommendations. Appropriate vaccine use can reduce the pediatric disease burden further. Hyperbilirubinemia is the subject of ongoing study, which may lead to improved diagnosis and treatment protocols and reduce the incidence of acute bilirubin encephalopathy. The best tool for rabies prevention after an animal bite is prompt postexposure prophylaxis.

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...... 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...

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury

OpenAIRE

Winerdal, Max; Winerdal, Malin E.; Wang, Ying-Qing; Fredholm, Bertil B.; Winqvist, Ola; Ådén, Ulrika

2015-01-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R−/−) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction siz...

Efficacy of screening immune system function in at-risk newborns

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Pavlovski, Christopher J

2014-01-01

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

New strategies to prevent fetal and neonatal complications in Rhesus D immunization

OpenAIRE

Tiblad, Eleonor

2012-01-01

The general purpose of this thesis was to investigate if fetal and neonatal complications due to RhD immunization in the mother could be prevented by 1) reducing procedurerelated complications in intrauterine blood transfusions and by 2) reducing the incidence of RhD immunization by providing routine antenatal anti-D prophylaxis during pregnancy selectively to non-immunized RhD negative women with RhD positive fetuses. Paper I was a retrospective study including 284 intra...

Immune responses to rAAV6: The influence of canine parvovirus vaccination and neonatal administration of viral vector

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Andrea L H Arnett

2011-11-01

Full Text Available Recombinant adeno-associated viral (rAAV vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV. rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, one month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice.

Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses.

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Dantoft, Widad; Martínez-Vicente, Pablo; Jafali, James; Pérez-Martínez, Lara; Martin, Kim; Kotzamanis, Konstantinos; Craigon, Marie; Auer, Manfred; Young, Neil T; Walsh, Paul; Marchant, Arnaud; Angulo, Ana; Forster, Thorsten; Ghazal, Peter

2017-01-01

Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1) and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1) roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity differences. These

Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses

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Widad Dantoft

2017-09-01

Full Text Available Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV is the most common cause of congenital infection. By using unbiased systems analyses of transcriptomic resources for HCMV neonatal infection, we find the systemic response of a preterm congenital HCMV infection, involves a focused IFN regulatory response associated with dendritic cells. Further analysis of transcriptional-programming of neonatal dendritic cells in response to HCMV infection in culture revealed an early dominant IFN-chemokine regulatory subnetworks, and at later times the plasticity of pathways implicated in cell-cycle control and lipid metabolism. Further, we identify previously unknown suppressed networks associated with infection, including a select group of GPCRs. Functional siRNA viral growth screen targeting 516-GPCRs and subsequent validation identified novel GPCR-dependent antiviral (ADORA1 and proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, and SORT1 roles. By contrast a gene family cluster of protocadherins is significantly differentially induced in neonatal cells, suggestive of possible immunomodulatory roles. Unexpectedly, programming responses of adult and neonatal dendritic cells, upon HCMV infection, demonstrated comparable quantitative and qualitative responses showing that functionally, neonatal dendritic cell are not overly compromised. However, a delay in responses of neonatal cells for IFN subnetworks in comparison with adult-derived cells are notable, suggestive of subtle plasticity

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.

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

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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.

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

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

2017-10-01

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

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

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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.

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice.

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Russell, Ryan F; McDonald, Jacqueline U; Lambert, Laura; Tregoning, John S

2016-05-01

Neonates are at a high risk of infection, but vaccines are less effective in this age group; tailored adjuvants could potentially improve vaccine efficacy. Increased understanding about danger sensing by the innate immune system has led to the rational design of novel adjuvants. But differences in the neonatal innate immune response, for example, to Toll-like receptor (TLR) agonists, can reduce the efficacy of these adjuvants in early life. We therefore targeted alternative danger-sensing pathways, focusing on a range of compounds described as inflammasome agonists, including nanoscale silicon dioxide (NanoSiO2), calcium pyrophosphate dihydrate (CPPD) crystals, and muramyl tripeptide (M-Tri-DAP), for their ability to act as adjuvants.In vitro, these compounds induced an interleukin 1-beta (IL-1β) response in the macrophage-like cell line THP1.In vivo, adult CB6F1 female mice were immunized intramuscularly with H1N1 influenza vaccine antigens in combination with NanoSiO2, CPPD, or M-Tri-DAP and subsequently challenged with H1N1 influenza virus (A/England/195/2009). The adjuvants boosted anti-hemagglutinin IgG and IgA antibody levels. Both adult and neonatal animals that received NanoSiO2-adjuvanted vaccines lost significantly less weight and recovered earlier after infection than control animals treated with antigen alone. Administration of the adjuvants led to an influx of activated inflammatory cells into the muscle but to little systemic inflammation measured by serum cytokine levels. Blocking IL-1β or caspase 1 in vivo had little effect on NanoSiO2 adjuvant function, suggesting that it may work through pathways other than the inflammasome. Here we demonstrate that NanoSiO2 can act as an adjuvant and is effective in early life. Vaccines can fail to protect the most at-risk populations, including the very young, the elderly, and the immunocompromised. There is a gap in neonatal immunity between the waning of maternal protection and routine infant immunization

Delayed development of systemic immunity in preterm pigs as a model for preterm infants

DEFF Research Database (Denmark)

Nguyen, Duc Ninh; Jiang, Pingping; Frøkiær, Hanne

2016-01-01

-mediated IL-6 and TNF-α production. These immune parameters remained different between preterm and near-term pigs at 2-3 weeks, even when adjusted for post-conceptional age. Our data suggest that systemic immunity follows a distinct developmental trajectory following preterm birth that may be influenced......Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life......, relative to those born at near-term or term. Using pigs as a model, we characterized blood leukocyte subsets, antimicrobial activities and TLR-mediated cytokine production during the first weeks after preterm birth. Relative to near-term and term pigs, newborn preterm pigs had low blood leukocyte counts...

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

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

2016-01-01

-related mediators. This was supported by the PCA showing a highly significant difference between children with vs. without siblings: p...BACKGROUND: Siblings have been shown to reduce the risk of later asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates. We hypothesized that siblings exert immune modulatory......-cohort (COPSAC2010). The association between airway mediator levels and presence of siblings was investigated using conventional statistics and principle component analyses (PCA). RESULTS: Neonates with siblings had an up-regulated level of airway immune-mediators, with predominance of Type 1- and Type 17...

Early Microbes Modify Immune System Development and Metabolic Homeostasis-The "Restaurant" Hypothesis Revisited.

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Nash, Michael J; Frank, Daniel N; Friedman, Jacob E

2017-01-01

The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the "Restaurant" hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate's gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

Immune cell subsets, cytokine and cortisol levels during the first week of life in neonates born to pre-eclamptic mothers.

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Sava, Florentina; Toldi, Gergely; Treszl, András; Hajdú, Júlia; Harmath, Ágnes; Rigó, János; Tulassay, Tivadar; Vásárhelyi, Barna

2017-06-01

To address the hypothesis that pre-eclampsia (PE) impacts the fetal immune system, we investigated the prevalence of distinct immune cell subsets along with plasma cortisol and cytokine levels in pre-term newborns of PE mothers. Cord blood and peripheral blood samples on the 1st, 3rd and 7th postnatal days of life were collected from 14 pre-term infants affected by PE and 14 non-PE pregnancies. We measured plasma cortisol and cytokine levels with immunoassays and assessed the prevalence of T, NK and DC subsets using flow cytometry. The prevalence of CD4+ cells was lower in PE infants, while that of memory T cells was higher. Myeloid DCs had a lower prevalence in PE neonates. Cytokine and cortisol levels were lower in PE neonates. Our observations show that PE pregnancies are associated with altered newborn immune status during the first week of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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.

Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

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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.

Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

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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

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

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Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Acosta, Luz P; Obcena, Anamae; Brion, Job D; Capeding, Rosario Z

2014-01-01

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.

Unusual loss of chymosin in mammalian lineages parallels neo-natal immune transfer strategies.

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Lopes-Marques, Mónica; Ruivo, Raquel; Fonseca, Elza; Teixeira, Ana; Castro, L Filipe C

2017-11-01

Gene duplication and loss are powerful drivers of evolutionary change. The role of loss in phenotypic diversification is notably illustrated by the variable enzymatic repertoire involved in vertebrate protein digestion. Among these we find the pepsin family of aspartic proteinases, including chymosin (Cmy). Previous studies demonstrated that Cmy, a neo-natal digestive pepsin, is inactivated in some primates, including humans. This pseudogenization event was hypothesized to result from the acquisition of maternal immune immunoglobulin G (IgG) transfer. By investigating 94 mammalian subgenomes we reveal an unprecedented level of Cmy erosion in placental mammals, with numerous independent events of gene loss taking place in Primates, Dermoptera, Rodentia, Cetacea and Perissodactyla. Our findings strongly suggest that the recurrent inactivation of Cmy correlates with the evolution of the passive transfer of IgG and uncovers a noteworthy case of evolutionary cross-talk between the digestive and the immune system, modulated by gene loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Infections in Neonatal Intensive Care: Prevalence, Prevention and Antibiotic use

NARCIS (Netherlands)

van den Hoogen, A.

2009-01-01

Neonatal infections are an important cause of morbidity in neonatal intensive care units (NICUs). Prematurity or very low birth weight is an important predisposing factor for neonatal infection. In addition, preterm infants have a compromized immune system and they often require invasive procedures

Rearing environment affects development of the immune system in neonates

NARCIS (Netherlands)

Inman, C.F.; Haverson, K.; Konstantinov, S.R.; Jones, P.H.; Harris, C.; Smidt, H.; Miller, B.; Bailey, M.; Stokes, C.

2010-01-01

P>Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect

Three cases of neonatal tetanus in Papua New Guinea lead to development of national action plan for maternal and neonatal tetanus elimination.

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Datta, Siddharta Sankar; Barnabas, Roland; Sitther, Adeline; Guarenti, Laura; Toikilik, Steven; Kariwiga, Grace; Sui, Gerard Pai

2013-01-01

Maternal or neonatal tetanus causes deaths primarily in Asia and Africa and is usually the result of poor hygiene during delivery. In 2011, three neonatal tetanus cases were investigated in Papua New Guinea, and all three cases were delivered at home by untrained assistants. The babies were normal at birth but subsequently developed spasms. A neonatal tetanus case must be viewed as a sentinel event indicating a failure of public health services including immunization, antenatal care and delivery care. The confirmation of these cases led to the drafting of the Papua New Guinea National Action Plan for Maternal and Neonatal Tetanus Elimination. This included three rounds of a tetanus toxoid supplementary immunization campaign targeting women of childbearing age (WBCA) and strengthening of other clean delivery practices. The first immunization round was conducted in April and May 2012, targeting 1.6 million WBCA and achieved coverage of 77%. The government of Papua New Guinea should ensure detailed investigation of all neonatal tetanus cases reported in the health information system and perform subprovincial analysis of tetanus toxoid coverage following completion of all three immunization rounds. Efforts also should be made to strengthen clean delivery practices to help eliminate maternal and neonatal tetanus in Papua New Guinea.

Three cases of neonatal tetanus in Papua New Guinea lead to development of national action plan for maternal and neonatal tetanus elimination

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Grace Kariwiga

2013-06-01

Full Text Available Maternal or neonatal tetanus causes deaths primarily in Asia and Africa and is usually the result of poor hygiene during delivery. In 2011, three neonatal tetanus cases were investigated in Papua New Guinea, and all three cases were delivered at home by untrained assistants. The babies were normal at birth but subsequently developed spasms. A neonatal tetanus case must be viewed as a sentinel event indicating a failure of public health services including immunization, antenatal care and delivery care. The confirmation of these cases led to the drafting of the Papua New Guinea National Action Plan for Maternal and Neonatal Tetanus Elimination. This included three rounds of a tetanus toxoid supplementary immunization campaign targeting women of childbearing age (WBCA and strengthening of other clean delivery practices. The first immunization round was conducted in April and May 2012, targeting 1.6 million WBCA and achieved coverage of 77%. The government of Papua New Guinea should ensure detailed investigation of all neonatal tetanus cases reported in the health information system and perform sub-provincial analysis of tetanus toxoid coverage following completion of all three immunization rounds. Efforts also should be made to strengthen clean delivery practices to help eliminate maternal and neonatal tetanus in Papua New Guinea.

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

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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.

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

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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.

Neonatal Vaccination: Challenges and Intervention Strategies.

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Morris, Matthew C; Surendran, Naveen

2016-01-01

While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.

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

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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.

Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1 at Weanling Age.

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Bettina Wagner

Full Text Available Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4 producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC. Neonatal vaccination was performed by oral biotinylated IgE (IgE-bio treatment at birth followed by intramuscular injection of a single dose of streptavidin-conjugated gC/IL-4 fusion protein (Sav-gC/IL-4 for crosslinking of receptor-bound IgE-bio (group 1. Neonates in group 2 received the intramuscular Sav-gC/IL-4 vaccine only. Group 3 remained non-vaccinated at birth. After vaccination, gC antibody production was not detectable. The ability of the vaccine to induce protection was evaluated by an EHV-1 challenge infection after weaning at 7 months of age. Groups 1 and 2 responded to EHV-1 infection with an earlier onset and overall significantly increased anti-gC serum antibody responses compared to control group 3. In addition, group 1 weanlings had a decreased initial fever peak after infection indicating partial protection from EHV-1 infection. This suggested that the neonatal vaccination induced a memory B-cell response at birth that was recalled at weanling age after EHV-1 challenge. In conclusion, early stimulation of neonatal immunity via the innate arm of the immune system can induce partial protection and increased antibody responses against EHV-1.

Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

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Jafar Majidi-Zolbanin

2014-06-01

Full Text Available Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic double-stranded ribonucleic acid (Poly I: C during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice. Methods: Male C57BL/6 mice were treated with either saline or Poly I:C (1 mg/kg and 4 mg/kg on postnatal days (PND 3-5 (early neonatal phase or PND 14-16 (late neonatal phase, and then subjected to behavioral tests, including tail suspension test and forced swimming test, during adolescence (PND 35 or 40 and adulthood (PND 85 or 90. Results: The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice, but late neonatal immune activation only increases depression in adult mice. In other words, these findings indicated that the nature of the offspring's neuropathology can depend on the severity of the insult, the pup's age at the time of the insult, and offspring age at the time of behavioral testing. Conclusion: These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.

Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans.

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Newburg, D S

2009-04-01

This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans constitute an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a greater incidence of severe diarrhea and respiratory diseases than those who are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are composed of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These

Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

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Nash, Michael J.; Frank, Daniel N.; Friedman, Jacob E.

2017-01-01

The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research. PMID:29326657

Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

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Michael J. Nash

2017-12-01

Full Text Available The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD. This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

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Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

2016-03-01

Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

Neonatal mucosal immunology.

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Torow, N; Marsland, B J; Hornef, M W; Gollwitzer, E S

2017-01-01

Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies. In this review, we discuss immune maturation in the gut and lung and how microbes have a central role in this process.

Porcine neonatal blood dendritic cells, but not monocytes, are more responsive to TLRs stimulation than their adult counterparts.

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Gael Auray

Full Text Available The neonatal immune system is often considered as immature or impaired compared to the adult immune system. This higher susceptibility to infections is partly due to the skewing of the neonatal immune response towards a Th2 response. Activation and maturation of dendritic cells (DCs play an important role in shaping the immune response, therefore, DCs are a target of choice for the development of efficient and protective vaccine formulations able to redirect the neonatal immune response to a protective Th1 response. As pigs are becoming more important for vaccine development studies due to their similarity to the human immune system, we decided to compare the activation and maturation of a subpopulation of porcine DCs in adult and neonatal pigs following stimulation with different TLR ligands, which are promising candidates for adjuvants in vaccine formulations. Porcine blood derived DCs (BDCs were directly isolated from blood and consisted of a mix of conventional and plasmacytoid DCs. Following CpG ODN (TLR9 ligand and imiquimod (TLR7 ligand stimulation, neonatal BDCs showed higher levels of expression of costimulatory molecules and similar (CpG ODN or higher (imiquimod levels of IL-12 compared to adult BDCs. Another interesting feature was that only neonatal BDCs produced IFN-α after TLR7 or TLR9 ligand stimulation. Stimulation with CpG ODN and imiquimod also induced enhanced expression of several chemokines. Moreover, in a mixed leukocyte reaction assay, neonatal BDCs displayed a greater ability to induce lymphoproliferation. These findings suggest that when stimulated via TLR7 or TLR9 porcine DCs display similar if not better response than adult porcine DCs.

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

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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.

Swine as a model for the study of maternal neonatal immunoregulation

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Butler, J.E.; Cambier, J.C.; Klobasa, F.; Werhahn, E.

1986-01-01

Swine provide a useful model for evaluating maternal antibody influences on the immune system of developing neonates. Unlike rodents and humans, no antibodies are transferred passively in utero so that newborn piglets, unlike mice pups and babies, enter the world having had no previous exposure to antibodies of their mothers. If maternal antibodies transmitted in utero are immunoregulatory and are in part the basis for neonatal unresponsiveness in neonatal mice and infants, swine offer a model with which to study this regulation. Neonatal piglets can be obtained at birth before suckling and reared in ''artificial sows'' without maternal antibodies which may be administered to neonates in metered amounts with regard to specificity, isotype and idiotype. Fetal piglets can be manipulated surgically in utero; their blood vascular system can be cannulated permitting in utero immunization and continuous sampling. Maternal immunoglobulins play an immunoregulatory role in both conventional and artificial feeding experiments. Data are presented which illustrate the magnitude of this phenomenon and which show that such an effect occurs naturally when piglets suckling first gestation and multilitter sows are compared. Finally, data are reviewed on the characterization of an idiotype anti-idiotype system developed to probe the mechanism of maternal neonatal immunoregulation

Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.

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Askenasy, Nadir

2016-04-01

The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.

Neonatal corticosterone administration in rodents as a tool to investigate the maternal programming of emotional and immune domains

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Simone Macrì

2017-02-01

Full Text Available Neonatal experiences exert persistent influences on individual development. These influences encompass numerous domains including emotion, cognition, reactivity to external stressors and immunity. The comprehensive nature of the neonatal programming of individual phenotype is reverberated in the large amount of experimental data collected by many authors in several scientific fields: biomedicine, evolutionary and molecular biology. These data support the view that variations in precocious environmental conditions may calibrate the individual phenotype at many different levels. Environmental influences have been traditionally addressed through experimental paradigms entailing the modification of the neonatal environment and the multifactorial (e.g. behaviour, endocrinology, cellular and molecular biology analysis of the developing individual's phenotype. These protocols suggested that the role of the mother in mediating the offspring's phenotype is often associated with the short-term effects of environmental manipulations on dam's physiology. Specifically, environmental manipulations may induce fluctuations in maternal corticosteroids (corticosterone in rodents which, in turn, are translated to the offspring through lactation. Herein, I propose that this mother-offspring transfer mechanism can be leveraged to devise experimental protocols based on the exogenous administration of corticosterone during lactation. To support this proposition, I refer to a series of studies in which these protocols have been adopted to investigate the neonatal programming of individual phenotype at the level of emotional and immune regulations. While these paradigms cannot replace traditional studies, I suggest that they can be considered a valid complement.

Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

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Ilan, Yaron

2016-01-01

Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

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Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

2017-01-01

Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis.

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Jain, Nitya; Walker, W Allan

2015-01-01

Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility.

Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

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Conglei Li

2012-01-01

Full Text Available Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc., which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs, such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1. Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.

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

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

2015-01-01

Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced...... lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation.  Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children.......  Results: The neonatal forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP (β-coefficient, −0.12; 95% CI, −0.21 to −0.04; P approach, including hs-CRP, IL-6...

Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.

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Navar-Boggan, A M; Halsey, N A; Golden, W C; Escobar, G J; Massolo, M; Klein, N P

2010-09-01

Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, Pimmunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (Pimmunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.

Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit.

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Aydemir, Cumhur; Onay, Huseyin; Oguz, Serife Suna; Ozdemir, Taha Resid; Erdeve, Omer; Ozkinay, Ferda; Dilmen, Ugur

2011-09-01

Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%). In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

Our Immune System

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Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

Immune System Quiz

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... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

Inmunización intranasal con AFCo1 induce respuesta inmune de memoria, sistemica y mucosal en ratones neonatal

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Julio A. Balboa

2009-08-01

Full Text Available Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n. route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay PL1 (Proteoliposome from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1 by nasal route in neonatal mice. They were immunized i.n. 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL was significantly higher than AFPL1 (1107 U/mL. AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i.n. immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i.n. dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory.

Design of smart neonatal health monitoring system using SMCC.

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De, Debashis; Mukherjee, Anwesha; Sau, Arkaprabha; Bhakta, Ishita

2017-02-01

Automated health monitoring and alert system development is a demanding research area today. Most of the currently available monitoring and controlling medical devices are wired which limits freeness of working environment. Wireless sensor network (WSN) is a better alternative in such an environment. Neonatal intensive care unit is used to take care of sick and premature neonates. Hypothermia is an independent risk factor for neonatal mortality and morbidity. To prevent it an automated monitoring system is required. In this Letter, an automated neonatal health monitoring system is designed using sensor mobile cloud computing (SMCC). SMCC is based on WSN and MCC. In the authors' system temperature sensor, acceleration sensor and heart rate measurement sensor are used to monitor body temperature, acceleration due to body movement and heart rate of neonates. The sensor data are stored inside the cloud. The health person continuously monitors and accesses these data through the mobile device using an Android Application for neonatal monitoring. When an abnormal situation arises, an alert is generated in the mobile device of the health person. By alerting health professional using such an automated system, early care is provided to the affected babies and the probability of recovery is increased.

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

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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.

Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell-mediated immune responses in piglets.

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Bandrick, Meggan; Theis, Kara; Molitor, Thomas W

2014-06-05

Passively acquired maternal derived immunity (MDI) is a double-edged sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated immunity (CMI) are critical immediate defenses for the neonate; however, MDI may interfere with the induction of active immunity in the neonate, i.e. passive interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal piglets. To determine whether CMI and AMI responses could be induced in piglets with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M. hyopneumoniae-specific antibody, lymphoproliferation, and delayed type hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination. Piglets with M. hyopneumoniae-specific MDI failed to show vaccine-induced AMI responses; there was no rise in M. hyopneumoniae antibody levels following vaccination of piglets in the presence of M. hyopneumoniae-specific MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen-specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI responses following vaccination. In this study neonatal M. hyopneumoniae-specific CMI was not subject to passive interference by MDI. Further, it appears that both maternal derived and endogenous CMI contribute to M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI.

Food components and the Immune System: from tonic agents to allergens

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Ana Maria Caetano Faria

2013-05-01

Full Text Available The intestinal mucosa is the major site of contact with antigens, and it lodges the largest lymphoid tissue in the body. In physiological conditions, microbiota and dietary antigens are the natural sources of stimulation for the gut associated lymphoid tissues (GALT and for the immune system as a whole. Germ free models have provided some insights on the immunological role of gut antigens. However, most of the GALT is not located in the large intestine, where gut microbiota is prominent. It is concentrated in the small intestine where protein absorption takes place. In this review, we will address the involvement of food components in the development and the function of the immune system. Studies in mice have already shown that dietary proteins are critical elements for the developmental shift of the immature neonatal immune profile into a fully developed immune system. The immunological effects of other food components (such as vitamins and lipids will also be addressed. Most of the cells in the GALT are activated and local proinflammatory mediators are abundant. Regulatory elements are known to provide a delicate yet robust balance that keeps the gut homeostasis at check. Usually antigenic contact in the gut induces two major immune responses, oral tolerance and production of secretory IgA. However, under pathological conditions mucosal homeostasis is disturbed resulting in inflammatory reactions such as food hypersensitivity. Food allergy development depends on many factors such as genetic predisposition, biochemical features of allergens and a growing array of environmental elements. Neuroimmune interactions are also implicated in food allergy and they are examples of the high complexity of the phenomenon. Recent findings on the gut circuits triggered by food components will be reviewed to show that, far beyond their role as nutrients, they are critical players in the operation of immune system in health and disease.

Model systems to analyze the role of miRNAs and commensal microflora in bovine mucosal immune system development.

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Liang, Guanxiang; Malmuthuge, Nilusha; Guan, Le Luo; Griebel, Philip

2015-07-01

Information is rapidly accumulating regarding the role of miRNAs as key regulators of immune system development and function. It is also increasingly evident that miRNAs play an important role in host-pathogen interactions through regulation of both innate and acquired immune responses. Little is known, however, about the specific role of miRNAs in regulating normal development of the mucosal immune system, especially during the neonatal period. Furthermore, there is limited knowledge regarding the possible role the commensal microbiome may play in regulating mucosal miRNAs expression, although evidence is emerging that a variety of enteric pathogens influence miRNA expression. The current review focuses on recent information that miRNAs play an important role in regulating early development of the bovine mucosal immune system. A possible role for the commensal microbiome in regulating mucosal development by altering miRNA expression is also discussed. Finally, we explore the potential advantages of using the newborn calf as a model to determine how interactions between developmental programming, maternal factors in colostrum, and colonization of the gastrointestinal tract by commensal bacteria may alter mucosal miRNA expression and immune development. Identifying the key factors that regulate mucosal miRNA expression is critical for understanding how the balance between protective immunity and inflammation is maintained to ensure optimal gastrointestinal tract function and health of the whole organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

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Yike Jiang

2017-07-01

Full Text Available While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1, we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG, a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.

[Immune system and tumors].

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Terme, Magali; Tanchot, Corinne

2017-02-01

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples.

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Wilson, Randall M; Marshall, Nicole E; Jeske, Daniel R; Purnell, Jonathan Q; Thornburg, Kent; Messaoudi, Ilhem

2015-06-01

Maternal obesity is one of the several key factors thought to modulate neonatal immune system development. Data from murine studies demonstrate worse outcomes in models of infection, autoimmunity, and allergic sensitization in offspring of obese dams. In humans, children born to obese mothers are at increased risk for asthma. These findings suggest a dysregulation of immune function in the children of obese mothers; however, the underlying mechanisms remain poorly understood. The aim of this study was to examine the relationship between maternal body weight and the human neonatal immune system. Umbilical cord blood samples were collected from infants born to lean, overweight, and obese mothers. Frequency and function of major innate and adaptive immune cell populations were quantified using flow cytometry and multiplex analysis of circulating factors. Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood. These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neurological consequences of systemic inflammation in the premature neonate.

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Patra, Aparna; Huang, Hong; Bauer, John A; Giannone, Peter J

2017-06-01

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

Neurological consequences of systemic inflammation in the premature neonate

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Aparna Patra

2017-01-01

Full Text Available Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

On Modelling an Immune System

OpenAIRE

Monroy, Raúl; Saab, Rosa; Godínez, Fernando

2004-01-01

Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

Skin innate immune system

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Berna Aksoy

2013-06-01

Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

Neonatal immune activation during early and late postnatal brain development differently influences depression-related behaviors in adolescent and adult C57BL/6 mice

OpenAIRE

Jafar Majidi-Zolbanin; Mohammad-Hossein Doosti; Behzad Baradaran; Mohammad Amani; Maryam Azarfarin; Ali-Akbar Salari

2014-01-01

Aim: Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions, resulting in greater risk for the development of neuropsychiatric disorders, such as anxiety and depression, later in life. In addition, previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents. This study aimed to investigate for the first time whether immune challenge with a viral mimic, synthetic dou...

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...... 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...... for the synergistic coexistence between trillions of bacteria in the gastrointestinal tract and their mammalian hosts. The IEC actively communicate with the microbiota of the gut lumen and tolerance establishment in the intestine is induced as a result of a balanced and controlled communication between IEC...

Adaptation in the innate immune system and heterologous innate immunity.

Science.gov (United States)

Martin, Stefan F

2014-11-01

The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

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

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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.

Systemic fungal infections in neonates

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Rao S

2005-01-01

Full Text Available Advances in neonatal management have led to considerable improvement in newborn survival. However, early (72hours onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp -LRC-1 has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.

Immune System

Science.gov (United States)

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

Weakened Immune Systems

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... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

Science.gov (United States)

Azevedo, Raimunda S S; de Sousa, Jorge R; Araujo, Marialva T F; Martins Filho, Arnaldo J; de Alcantara, Bianca N; Araujo, Fernanda M C; Queiroz, Maria G L; Cruz, Ana C R; Vasconcelos, Beatriz H Baldez; Chiang, Jannifer O; Martins, Lívia C; Casseb, Livia M N; da Silva, Eliana V; Carvalho, Valéria L; Vasconcelos, Barbara C Baldez; Rodrigues, Sueli G; Oliveira, Consuelo S; Quaresma, Juarez A S; Vasconcelos, Pedro F C

2018-01-08

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

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Felix R Stahl

Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

Immune system simulation online

DEFF Research Database (Denmark)

Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

2011-01-01

MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

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

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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

Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection

NARCIS (Netherlands)

An, Dong Sung; Poon, Betty; Tsong Fang, Raphael Ho; Weijer, Kees; Blom, Bianca; Spits, Hergen; Chen, Irvin S. Y.; Uittenbogaart, Christel H.

2007-01-01

The goal of this study was to develop a small-animal model to study human immunodeficiency virus type 1 (HIV-1) pathogenesis in blood and primary and secondary lymphoid organs. Rag2(-/-)gamma(c)(-/-) mice that are neonatally injected with human CD34(+) cells develop a functional human immune system

Human perinatal immunity in physiological conditions and during infection.

Science.gov (United States)

van Well, Gijs T J; Daalderop, Leonie A; Wolfs, Tim; Kramer, Boris W

2017-12-01

The intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal exposure to microorganisms and related inflammatory stimuli. Both the innate and adaptive immune systems of the fetus and neonate are immature, which makes them highly susceptible to infections. There is good evidence that prenatal infections are a primary cause of preterm births. Additionally, the association between antenatal inflammation and adverse neonatal outcomes has been well established. The lung, gastrointestinal tract, and skin are exposed to amniotic fluid during pregnancy and are probable targets of infection and subsequent inflammation during pregnancy. We found a large number of studies focusing on prenatal infection and the host response. Intrauterine infection and fetal immune responses are well studied, and we describe clinical data on cellular, cytokine, and humoral responses to different microbial challenges. The link to postnatal immunological effects including immune paralysis and/or excessive immune activation, however, turned out to be much more complicated. We found studies relating prenatal infectious or inflammatory hits to well-known neonatal diseases such as respiratory distress syndrome, bronchopulmonary dysplasia, and necrotizing enterocolitis. Despite these data, a direct link between prenatal hits and postnatal immunological outcome could not be undisputedly established. We did however identify several unresolved topics and propose questions for further research.

Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

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Muscoplat, Miriam Halstead; Rajamani, Sripriya

2017-01-01

The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

Neonatal Outcomes of Rh-Negative Pregnancies in a Tertiary Level Neonatal Intensive Care Unit: A Prospective Study

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Chacham

2016-07-01

Full Text Available Background Rhesus incompatibility is a preventable cause for severe neonatal hyperbilirubinemia, hydrops fetalis and still births. The prevalence of the Rh-negative blood group among Indian woman varies from 2% - 10%. Despite declining the incidence of Rhesus incompatibility, due to availability of anti-D immunoglobulin, and improved antenatal care of the Rh-negative pregnant woman, it still accounts for a significant proportion of neonatal hyperbilirubinemia and neuro-morbidity. The prevalence of Rh-negative women having Rh-positive neonates is 60%. Objectives This study aimed to estimate the incidence of Rh iso-immunization and evaluate the outcomes of Rh iso-immunized neonates. Methods This prospective observational study was conducted in a tertiary level neonatal intensive care unit, Princess Esra hospital, Deccan college of medical sciences, Hyderabad, Telangana, India. Consecutive intramural and extramural neonates admitted to neonatal intensive care unit with the Rh-negative mother’s blood group and hyperbilirubinemia were enrolled. Neonates born to Rh+ve mothers were excluded. Neonatal gestational age, birth weight, age at admission, duration of phototherapy, duration of hospitalization, neonatal examination and investigations were recorded in a predesigned, pretested performa. Results A total of 90 neonates were born to Rh-negative mothers, of which 70% (63 had the Rh-positive blood group and 30% had the Rh-negative blood group. Of these 63 neonates, 48 (76.2% had hyperbilirubinemia and 43 neonates (68.3% had significant hyperbilirubinemia (total serum bilirubin > 15mg/dL. Among them, 2%, 75% and 23% were born to primi, multi and grandmutli, respectively. Also, 14.5% of the neonates were large for dates (LFD, 75% appropriate for dates (AFD and 10.5% were small for dates (SFD. Premature and SFD neonates had higher incidence of hyperbilirubinemia. Significantly higher incidence of jaundice occurred within 72 hours of life. The mean

Alternative Immune Systems

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Luis Fernando Cadavid Gutierrez

2011-09-01

Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

The twilight of immunity: emerging concepts in aging of the immune system.

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Nikolich-Žugich, Janko

2018-01-01

Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

Neonatal Feeding Behavior as a Complex Dynamical System.

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Goldfield, Eugene C; Perez, Jennifer; Engstler, Katherine

2017-04-01

The requirements of evidence-based practice in 2017 are motivating new theoretical foundations and methodological tools for characterizing neonatal feeding behavior. Toward that end, this article offers a complex dynamical systems perspective. A set of critical concepts from this perspective frames challenges faced by speech-language pathologists and allied professionals: when to initiate oral feeds, how to determine the robustness of neonatal breathing during feeding and appropriate levels of respiratory support, what instrumental assessments of swallow function to use with preterm neonates, and whether or not to introduce thickened liquids. In the near future, we can expect vast amounts of new data to guide evidence-based practice. But unless practitioners are able to frame these issues in a systems context larger than the individual child, the availability of "big data" will not be effectively translated to clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Immune System (For Parents)

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... of the Immune System Print en español El sistema inmunitario The immune system, which is made up ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

Immune System and Disorders

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Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

Immune System Dysfunction in the Elderly.

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Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

2017-01-01

Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

The impact of maternal obesity during pregnancy on offspring immunity.

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Wilson, Randall M; Messaoudi, Ilhem

2015-12-15

In the United States, approximately 64% of women of childbearing age are either overweight or obese. Maternal obesity during pregnancy is associated with a greater risk for adverse maternal-fetal outcomes. Adverse health outcomes for the offspring can persist into adulthood, increasing the incidence of several chronic conditions including cardiovascular disease, diabetes, and asthma. Since these diseases have a significant inflammatory component, these observations are indicative of perturbation of the normal development and maturation of the immune system of the offspring in utero. This hypothesis is strongly supported by data from several rodent studies. Although the mechanisms of these perturbations are not fully understood, it is thought that increased placental inflammation due to obesity may directly affect neonatal development through alterations in nutrient transport. In this review we examine the impact of maternal obesity on the neonatal immune system, and potential mechanisms for the changes observed. Published by Elsevier Ireland Ltd.

Conceptual Spaces of the Immune System.

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Fierz, Walter

2016-01-01

The immune system can be looked at as a cognitive system. This is often done in analogy to the neuro-psychological system. Here, it is demonstrated that the cognitive functions of the immune system can be properly described within a new theory of cognitive science. Gärdenfors' geometrical framework of conceptual spaces is applied to immune cognition. Basic notions, like quality dimensions, natural properties and concepts, similarities, prototypes, saliences, etc., are related to cognitive phenomena of the immune system. Constraints derived from treating the immune system within a cognitive theory, like Gärdenfors' conceptual spaces, might well prove to be instrumental for the design of vaccines, immunological diagnostic tests, and immunotherapy.

Immune System and Kidney Transplantation.

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Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

Imunidade passiva, morbidade neonatal e desempenho de cabritos em diferentes manejos de colostro Passive immunity, neonatal morbidity and performance of kids in different colostrum management

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Sara Vilar Dantas Simões

2005-12-01

Full Text Available Objetivando determinar o manejo de colostro que permitisse a melhor aquisição de imunidade passiva em cabritos e avaliar possíveis relações entre imunidade, morbidade e desempenho, amostras de sangue foram obtidas de 58 cabritos da raça Saanen antes e 30 horas após a primeira ingestão de colostro. Os cabritos foram distribuídos em cinco grupos experimentais. No Tratamento 1 (T1 o colostro foi ingerido ad libitum durante 24 horas. Nos demais tratamentos o colostro foi fornecido em mamadeira; os cabritos do T2 ingeriram 200mL de colostro após o parto; do T3, ingeriram 400mL de colostro sendo 200mL após o parto e 200mL após 8 horas; do T4, ingeriram também 400mL de colostro, sendo 200mL após o parto, 200mL após 14 horas; e os do T5 ingeriram 600mL de colostro, 200mL após o parto, 200mL as 12 e 200mL as 24 horas. Os valores séricos de gamaglobulinas foram avaliados por eletroforese. O ganho de peso diário foi utilizado para avaliação do desempenho no período de aleitamento. A ocorrência de doenças foi registrada do nascimento até 28 dias. A menor concentração de gamaglobulinas foi encontrada nos animais do Grupo 2 (1,65g/dL e a maior concentração foi observada no Grupo 3 (2,60g/dL. Foi observado no Grupo 3 mais animais com diarréia, porém não foram encontradas diferenças estatísticas significativas ao nível de 5%. Os diferentes manejos de colostro não estiveram associados com o desempenho dos cabritos até o final do período neonatal.The experiment was performed to determine the kid management that ensures the best passive immunity, and to evaluate the relationship between passive immunity, neonatal morbidity and performance. Blood samples were obtained from 58 Saanen kids before colostrum ingestion and 30h after. The kids were submitted to five treatments: (T1 kids were allowed to nurse the dam for 24 hours ingesting colostrum ad libitum; (T2 kids were bottle-fed with 200mL colostrum in the first hour of life; (T

Dynamics of immune system vulnerabilities

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Stromberg, Sean P.

The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding.

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Jost, Ted; Lacroix, Christophe; Braegger, Christian P; Rochat, Florence; Chassard, Christophe

2014-09-01

Breast milk has recently been recognized as source of commensal and potential probiotic bacteria. The present study investigated whether viable strains of gut-associated obligate anaerobes are shared between the maternal and neonatal gut ecosystem via breastfeeding. Maternal faeces, breast milk and corresponding neonatal faeces collected from seven mothers-neonate pairs at three neonatal sampling points were analyzed by culture-independent (pyrosequencing) and culture-dependent methods (16S rRNA gene sequencing, pulsed field gel electrophoresis, random amplified polymorphic DNA and repetitive extragenic palindromic polymerase chain reaction. Pyrosequencing allowed identifying gut-associated obligate anaerobic genera, like Bifidobacterium, Bacteroides, Parabacteroides and members of the Clostridia (Blautia, Clostridium, Collinsella and Veillonella) shared between maternal faeces, breast milk and neonatal faeces. Using culture, a viable strain of Bifidobacterium breve was shown to be shared between all three ecosystems within one mother-neonate pair. Furthermore, pyrosequencing revealed that several butyrate-producing members of the Clostridia (Coprococcus, Faecalibacterium, Roseburia and Subdoligranulum) were shared between maternal faeces and breast milk. This study shows that (viable) obligate gut-associated anaerobes may be vertically transferred from mother to neonate via breastfeeding. Thus, our data support the recently suggested hypothesis of a novel way of mother-neonate communication, in which maternal gut bacteria reach breast milk via an entero-mammary pathway to influence neonatal gut colonization and maturation of the immune system. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

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Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

2017-04-01

The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

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

on the nutritional, microbial and immunological interactions during the early feeding-induced mucosal dysfunction and later NEC development. We show that introduction of suboptimal enteral formula diets, coupled with parenteral nutrition, predispose to disease, while advancing amounts of mother's milk from birth...... (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.......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...

Neonatal colonisation expands a specific intestinal antigen-presenting cell subset prior to CD4 T-cell expansion, without altering T-cell repertoire.

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Charlotte F Inman

Full Text Available Interactions between the early-life colonising intestinal microbiota and the developing immune system are critical in determining the nature of immune responses in later life. Studies in neonatal animals in which this interaction can be examined are central to understanding the mechanisms by which the microbiota impacts on immune development and to developing therapies based on manipulation of the microbiome. The inbred piglet model represents a system that is comparable to human neonates and allows for control of the impact of maternal factors. Here we show that colonisation with a defined microbiota produces expansion of mucosal plasma cells and of T-lymphocytes without altering the repertoire of alpha beta T-cells in the intestine. Importantly, this is preceded by microbially-induced expansion of a signal regulatory protein α-positive (SIRPα(+ antigen-presenting cell subset, whilst SIRPα(-CD11R1(+ antigen-presenting cells (APCs are unaffected by colonisation. The central role of intestinal APCs in the induction and maintenance of mucosal immunity implicates SIRPα(+ antigen-presenting cells as orchestrators of early-life mucosal immune development.

Immunological unresponsiveness of the neonatal ruminant to gastrointestinal helminths

International Nuclear Information System (INIS)

Soulsby, E.J.L.

1981-01-01

Parasitic gastro-enteritis of domestic ruminants is a disease syndrome which is most usually seen in young animals in their first grazing season. Although this may be due, in part, to greater susceptibility of young animals to the pathogenic effects of parasitic infection, there is also good evidence that young animals are less able to mount a satisfactory protective immune response or a response which will reject an existing infection. This phenomenon is exemplified by Haemonchus contortus and Trichostrongylus spp. infection in sheep, but the phenomenon is recognized in other species including neonatal rodents (e.g. rats infected with Nippostrongylus brasiliensis) and has been demonstrated in neonatal cattle infected with Taenia saginata. The present consideration will deal mainly with the failure of lambs to mount an effective immune response to gastrointestinal nematodes during the neonatal period. (author)

Adverse consequences of neonatal antibiotic exposure.

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Cotten, Charles M

2016-04-01

Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

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

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Luba Sominsky

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

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.

The Immune System Game

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Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

2015-01-01

We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

Immune regulation in gut and cord : opportunities for directing the immune system

NARCIS (Netherlands)

de Roock, S.

2012-01-01

The gut is an important organ for the immune system. Microbes and immune cells interact directly or via epithelial cells. Both TH17 and Treg cells mature in this environment. The composition of the microbiota has an important influence on the immune homeostasis. Influencing the immune system via the

Local and systemic tumor immune dynamics

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Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

[Neonatal septicemia in the G-DRG system].

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Mohrmann, M; Hentschel, R; Böhler, T; Dirschedl, P

2006-12-01

The introduction of Diagnosis Related Groups in Germany (G-DRG) has brought forward the obligation for physicians to take into account an intricate system of medical, economical and legal implementations. Mistakes in the process of encoding the principal diagnosis or procedures may have financial consequences. Problems to determine the correct ICD-code will be most prominent for diseases with poorly defined or even inconsistent diagnostic criteria as is the case for neonatal septicemia. We decided to evaluate whether the introduction of G-DRG resulted in a change of frequency of the diagnosis "neonatal septicemia". We analysed data derived from the quality assurance program "Neonatalerhebung" in the state of Baden-Württemberg during the years of 2001 through 2004, i. e., 2 years before and 2 years during the introduction of G-DRG. During this period an annual number of 12,316 up to 13,172 newborns were admitted to the participating hospitals. The mean number of diagnoses per patient increased from 2.2 to 3.8. The frequency of the diagnosis of septicemia remained constant. The percentage of newborns receiving antibiotic therapy did not change. The ratio of cases with "septicemia yes" over "antibiotics yes" did not change. Although it is difficult to determine the diagnosis of neonatal septicemia and in spite of the economic implications of this diagnosis, no change in the frequency of this diagnosis occurred during the introduction of DRG. Assuming that the participating hospitals used an identical database for the quality assurance program "Neonatalerhebung" and for accounting, we conclude that the DRG system is stable with respect to neonatal septicemia.

Technique Selectively Represses Immune System

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... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

Play the Immune System Defender Game

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... Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic cells are immune cells ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

Immune Evasion, Immunopathology and the Regulation of the Immune System

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Bruno Faivre

2013-02-01

Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

Microbial-immune cross-talk and regulation of the immune system.

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Cahenzli, Julia; Balmer, Maria L; McCoy, Kathy D

2013-01-01

We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

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Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2017-11-01

Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

In immune defense: redefining the role of the immune system in chronic disease.

Science.gov (United States)

Rubinow, Katya B; Rubinow, David R

2017-03-01

The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

Relation Between Interleukin-1-β And Interleukin-8 Levels In Breast Milk (Colostrum) And Neonatal Physiological Jaundice

International Nuclear Information System (INIS)

Mohamed, A.A.; Moawad, A.T.; Marei, E.S.

2011-01-01

The immune system of neonates is influenced by maternal immunity during pregnancy and lactation. Breast-fed neonates have higher incidence of neonatal jaundice and higher level of total serum bilirubin than formula-fed infants. The aim of this study was to find a relationship between neonatal physiological jaundice and interleukin-1-beta (IL-1-β) and interleukin-8 (IL-8) in the colostrum of nursing mothers. Breast milk (colostrum) was collected from 45 nursing mothers of healthy full term neonates. The sharing mothers and their neonates were divided into two groups according to the presence of neonatal jaundice and the level of total serum bilirubin. All jaundiced neonates had total serum bilirubin level more than 12 mg/dl which appeared on the third postpartum day, all of them were breast-fed only. They were subjected to full history through clinical examination and laboratory investigations including determination of colostral levels of IL-1-β and IL-8, by ELISA, and determination of neonatal total serum bilirubin levels. This study revealed that mothers of neonates with physiological jaundice had higher concentrations of IL-1-β and IL-8 in their colostrums as compared with control group. Moreover, it displayed that total serum bilirubin level of jaundiced neonates was higher than its level in non-jaundiced neonates. There were significant correlations between IL- 1-β and IL-8 with mother's age in all groups, while there were inverse correlations between IL-1-β, IL-8 and gestational age of non- jaundiced neonates. Additionally, there was significant correlation between IL-1-β and IL-8 in the colostrum of all mothers enrolled in this study. On the other hand, no correlation was determined between cytokines IL-1-β, IL-8 and total serum bilirubin in all neonates sharing in this study. This study clearly demonstrated that the levels of immunomodulating agents such as cytokines IL-1-β and IL-8 were elevated in the colostrum of mothers with jaundiced neonates

A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Directory of Open Access Journals (Sweden)

Matthew E. Brown

2018-04-01

Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

Post-neonatal drop in alveolar SP-A expression

DEFF Research Database (Denmark)

Stray-Pedersen, Arne; Vege, Ashild; Stray-Pedersen, Asbjorg

2008-01-01

BACKGROUND: Surfactant protein A (SP-A) is synthesized in the lung and is a part of the innate immune system. The aim of this study was to evaluate the expression of SP-A in lung tissue from fetuses, infants, children and adults with special regard to sudden infant death syndrome (SIDS). METHODS......: A total of 160 cases were studied; 19 fetuses and neonates, 59 SIDS and 49 explained infant deaths below 1 year of age, 19 toddlers and 14 adults. Immunohistochemical detection of SP-A using monoclonal antibodies was performed by microscopy of lung tissue specimens collected at autopsy. A scoring system...

Time for a neonatal-specific consensus definition for sepsis.

Science.gov (United States)

Wynn, James L; Wong, Hector R; Shanley, Thomas P; Bizzarro, Matthew J; Saiman, Lisa; Polin, Richard A

2014-07-01

To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. The review focused primarily on pediatric literature relevant to the topic of interest. Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.

Evaluation of a low-dose neonatal chest radiographic system

International Nuclear Information System (INIS)

Burton, E.M.; Kirks, D.R.; Strife, J.L.; Henry, G.C.; Kereiakes, J.G.

1988-01-01

A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad [0.009 vs 0.029 mGy]) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad [0.009 vs 0.037 mGy]). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness

Immune System

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... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

An MRI system for imaging neonates in the NICU: initial feasibility study

Energy Technology Data Exchange (ETDEWEB)

Tkach, Jean A.; Loew, Wolfgang; Pratt, Ron G.; Daniels, Barret R.; Giaquinto, Randy O.; Winter, Patrick M.; Li, Yu; Dumoulin, Charles L. [Cincinnati Children' s Hospital Medical Center, Imaging Research Center, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Hillman, Noah H.; Jobe, Alan H.; Kallapur, Suhas G.; Merhar, Stephanie L.; Ikegami, Machiko; Whitsett, Jeffrey A. [Perinatal Institute, Cincinnati Children' s Hospital Medical Center, Division of Neonatology and Pulmonary Biology, Cincinnati, OH (United States); Kline-Fath, Beth M. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

2012-11-15

Transporting premature infants from a neonatal intensive care unit (NICU) to a radiology department for MRI has medical risks and logistical challenges. To develop a small 1.5-T MRI system for neonatal imaging that can be easily installed in the NICU and to evaluate its performance using a sheep model of human prematurity. A 1.5-T MRI system designed for orthopedic use was adapted for neonatal imaging. The system was used for MRI examinations of the brain, chest and abdomen in 12 premature lambs during the first hours of life. Spin-echo, fast spin-echo and gradient-echo MR images were evaluated by two pediatric radiologists. All animals remained physiologically stable throughout the imaging sessions. Animals were imaged at two or three time points. Seven brain MRI examinations were performed in seven different animals, 23 chest examinations in 12 animals and 19 abdominal examinations in 11 animals. At each anatomical location, high-quality images demonstrating good spatial resolution, signal-to-noise ratio and tissue contrast were routinely obtained within 30 min using standard clinical protocols. Our preliminary experience demonstrates the feasibility and potential of the neonatal MRI system to provide state-of-the-art MRI capabilities within the NICU. Advantages include overall reduced cost and site demands, lower acoustic noise, improved ease of access and reduced medical risk to the neonate. (orig.)

An MRI system for imaging neonates in the NICU: initial feasibility study

International Nuclear Information System (INIS)

Tkach, Jean A.; Loew, Wolfgang; Pratt, Ron G.; Daniels, Barret R.; Giaquinto, Randy O.; Winter, Patrick M.; Li, Yu; Dumoulin, Charles L.; Hillman, Noah H.; Jobe, Alan H.; Kallapur, Suhas G.; Merhar, Stephanie L.; Ikegami, Machiko; Whitsett, Jeffrey A.; Kline-Fath, Beth M.

2012-01-01

Transporting premature infants from a neonatal intensive care unit (NICU) to a radiology department for MRI has medical risks and logistical challenges. To develop a small 1.5-T MRI system for neonatal imaging that can be easily installed in the NICU and to evaluate its performance using a sheep model of human prematurity. A 1.5-T MRI system designed for orthopedic use was adapted for neonatal imaging. The system was used for MRI examinations of the brain, chest and abdomen in 12 premature lambs during the first hours of life. Spin-echo, fast spin-echo and gradient-echo MR images were evaluated by two pediatric radiologists. All animals remained physiologically stable throughout the imaging sessions. Animals were imaged at two or three time points. Seven brain MRI examinations were performed in seven different animals, 23 chest examinations in 12 animals and 19 abdominal examinations in 11 animals. At each anatomical location, high-quality images demonstrating good spatial resolution, signal-to-noise ratio and tissue contrast were routinely obtained within 30 min using standard clinical protocols. Our preliminary experience demonstrates the feasibility and potential of the neonatal MRI system to provide state-of-the-art MRI capabilities within the NICU. Advantages include overall reduced cost and site demands, lower acoustic noise, improved ease of access and reduced medical risk to the neonate. (orig.)

An MRI system for imaging neonates in the NICU: initial feasibility study.

Science.gov (United States)

Tkach, Jean A; Hillman, Noah H; Jobe, Alan H; Loew, Wolfgang; Pratt, Ron G; Daniels, Barret R; Kallapur, Suhas G; Kline-Fath, Beth M; Merhar, Stephanie L; Giaquinto, Randy O; Winter, Patrick M; Li, Yu; Ikegami, Machiko; Whitsett, Jeffrey A; Dumoulin, Charles L

2012-11-01

Transporting premature infants from a neonatal intensive care unit (NICU) to a radiology department for MRI has medical risks and logistical challenges. To develop a small 1.5-T MRI system for neonatal imaging that can be easily installed in the NICU and to evaluate its performance using a sheep model of human prematurity. A 1.5-T MRI system designed for orthopedic use was adapted for neonatal imaging. The system was used for MRI examinations of the brain, chest and abdomen in 12 premature lambs during the first hours of life. Spin-echo, fast spin-echo and gradient-echo MR images were evaluated by two pediatric radiologists. All animals remained physiologically stable throughout the imaging sessions. Animals were imaged at two or three time points. Seven brain MRI examinations were performed in seven different animals, 23 chest examinations in 12 animals and 19 abdominal examinations in 11 animals. At each anatomical location, high-quality images demonstrating good spatial resolution, signal-to-noise ratio and tissue contrast were routinely obtained within 30 min using standard clinical protocols. Our preliminary experience demonstrates the feasibility and potential of the neonatal MRI system to provide state-of-the-art MRI capabilities within the NICU. Advantages include overall reduced cost and site demands, lower acoustic noise, improved ease of access and reduced medical risk to the neonate.

Growth and recruitment in the immune network

NARCIS (Netherlands)

Boer, R.J. de; Hogeweg, P.; Perelson, A.S.

1992-01-01

The development of the immune repertoire during neonatal life involves a strong selection process among different clones. We investigate the hypothetis that repertoire selection is carried out during early life by the immune network. There are at least two processes in repertoire selection: clonal

Approaches Mediating Oxytocin Regulation of the Immune System.

Science.gov (United States)

Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

2016-01-01

The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

Upregulation of TGF-beta 1 in neonates of mothers receiving Influenza A (H1N1) vaccination during pregnancy

DEFF Research Database (Denmark)

Bischoff, Anne Louise; Folsgaard, N.; Bisgaard, H.

2012-01-01

Background: Influenza vaccination of pregnant women is generally considered safe,but the effects on the immune system of the unborn child are unknown.Objectives: Our primary objective was to explore differences in cytokine and chemokine levels in nasal mucosal lining fluid in neonates of mothers...... vaccinated during or after pregnancy. Method: IFN-c, IL-1b, IL-2, -4, -5, -10, - 12p70, -13, -17, TNF-a, IL-8, eotaxin-1,eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1b, TGF-b1 and TARC were quantified in nasal mucosal lining fluid in neonates of mothers receiving Influenza A (H1N1v) vaccine during (n = 52......) or after pregnancy (n = 118) in our unselected Copenhagen Prospective Study on Asthma in Childhood 2010 birth-cohort. Result: Neonates of mothers vaccinated during pregnancy showed a significant up-regulation of the immune-regulatory TGF-b1 (P = 0.0004), significant down regulation (P

Immune System Toxicity and Immunotoxicity Hazard Identification

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Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

Science.gov (United States)

Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

2017-12-01

Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

Elevated DMBT1 levels in neonatal gastrointestinal diseases

DEFF Research Database (Denmark)

Müller, Hanna; Renner, Marcus; Helmke, Burkhard M

2016-01-01

Deleted in malignant brain tumor 1 (DMBT1) is involved in innate immunity and epithelial differentiation. Previous studies in adults indicated a strong intestinal expression of DMBT1 and an important role in inflammatory bowel diseases. Here, we analyzed the DMBT1 expression in the fetal gastroin......, and herniation. DMBT1 may play a role in epithelial differentiation and local innate immunity during neonatal inflammatory bowel processes....

Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism.

Science.gov (United States)

Correia, Miguel Fragata; Maria, Ana Teresa; Prado, Sara; Limbert, Catarina

2015-03-06

Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis. 2015 BMJ Publishing Group Ltd.

Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

Science.gov (United States)

Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

2015-06-23

F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure.

Directory of Open Access Journals (Sweden)

Ihssane Zouikr

Full Text Available Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis during postnatal day (PND 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG as well as rostral and caudal axes of the ventrolateral PAG (VLPAG. Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb as compared to medial habenula (MHb, however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process.

Altered Formalin-Induced Pain and Fos Induction in the Periaqueductal Grey of Preadolescent Rats following Neonatal LPS Exposure

Science.gov (United States)

Zouikr, Ihssane; James, Morgan H.; Campbell, Erin J.; Clifton, Vicki L.; Beagley, Kenneth W.; Dayas, Christopher V.; Hodgson, Deborah M.

2014-01-01

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process. PMID:24878577

A review of neonatal tetanus in University of Maiduguri Teaching Hospital, North-eastern Nigeria

OpenAIRE

Alhaji, M. A.; Bello, M. A.; Elechi, H. A.; Akuhwa, R. T.; Bukar, F. L.; Ibrahim, H. A.

2013-01-01

Background: Neonatal tetanus is a vaccine preventable disease and is a leading cause of neonatal mortality in developing countries. The effectiveness of immunization and hygienic umbilical cord care practices in the prevention of the disease has been established. Objective: The objective of this study was to audit the scourge of neonatal tetanus in a tertiary health facility in a resource-limited setting. Materials and Methods: The study was a retrospective study. Case notes of neonates admit...

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

OpenAIRE

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for patholog...

Feeding Our Immune System: Impact on Metabolism

Directory of Open Access Journals (Sweden)

Isabelle Wolowczuk

2008-01-01

Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

Weakened Immune System and Adult Vaccination

Science.gov (United States)

... Basics Adult Vaccination Resources for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share ... people with health conditions such as a weakened immune system. If you have cancer or other immunocompromising conditions, ...

Recent Advances in Aptamers Targeting Immune System.

Science.gov (United States)

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

Differential oxidative stress induced by dengue virus in monocytes from human neonates, adult and elderly individuals.

Directory of Open Access Journals (Sweden)

Nereida Valero

Full Text Available Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group were infected with different dengue virus types (DENV- 1 to 4 and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

Transport modeling: An artificial immune system approach

Directory of Open Access Journals (Sweden)

Teodorović Dušan

2006-01-01

Full Text Available This paper describes an artificial immune system approach (AIS to modeling time-dependent (dynamic, real time transportation phenomenon characterized by uncertainty. The basic idea behind this research is to develop the Artificial Immune System, which generates a set of antibodies (decisions, control actions that altogether can successfully cover a wide range of potential situations. The proposed artificial immune system develops antibodies (the best control strategies for different antigens (different traffic "scenarios". This task is performed using some of the optimization or heuristics techniques. Then a set of antibodies is combined to create Artificial Immune System. The developed Artificial Immune transportation systems are able to generalize, adapt, and learn based on new knowledge and new information. Applications of the systems are considered for airline yield management, the stochastic vehicle routing, and real-time traffic control at the isolated intersection. The preliminary research results are very promising.

Colostrum protein uptake in neonatal lambs examined by descriptive and quantitative liquid chromatography-tandem mass spectrometry

DEFF Research Database (Denmark)

Hernandez Castellano, Lorenzo E; Argüello, Anastasio; Almeida, André M

2015-01-01

Colostrum intake is a key factor for newborn ruminant survival because the placenta does not allow the transfer of immune components. Therefore, newborn ruminants depend entirely on passive immunity transfer from the mother to the neonate, through the suckling of colostrum. Understanding...... the importance of specific colostrum proteins has gained significant attention in recent years. However, proteomics studies of sheep colostrum and their uptake in neonate lambs has not yet been presented. The aim of this study was to describe the proteomes of sheep colostrum and lamb blood plasma, using sodium...... relative quantification of how neonatal plasma protein concentrations change as an effect of colostrum intake. The results of this study describe the presence of 70 proteins in the ovine colostrum proteome. Furthermore, colostrum intake resulted in an increase of 8 proteins with important immune functions...

Hereditary and microbiological factors influencing the airway immunological profile of neonates

DEFF Research Database (Denmark)

Følsgaard, Nilofar

2012-01-01

is well-recognized, with estimated heritability as high as 60% in asthma. Atopic hereditary disease linkage in the offspring seems stronger for maternal than paternal atopic disease. But it is not known how parental atopic disease may affect early immunity in the target organ, the airways. COPSAC has...... mucosa. There was no paternal linkage to the mucosal immune response pattern, suggesting maternal programming of the fetus or neonate is causing an aberrant local airway immune profile in the newborn child. Furthermore our results suggest an association between maternal atopic disease and the expression...... recently reported an association between abnormal bacterial colonization with M. catarrhalis, S. pneumoniae, H. influenzae of the upper airways of neonates and later development of asthma. This led to the hypothesis that the interaction between genetics and this microbiome in very early life may cause...

Cesarean section changes neonatal gut colonization

DEFF Research Database (Denmark)

Stokholm, Jakob; Thorsen, Jonathan; Chawes, Bo L

2016-01-01

BACKGROUND: Delivery by means of cesarean section has been associated with increased risk of childhood immune-mediated diseases, suggesting a role of early bacterial colonization patterns for immune maturation. OBJECTIVE: We sought to describe the influence of delivery method on gut and airway......-driven partial least squares analyses. The initial airway microbiota was unaffected by birth method. CONCLUSION: Delivery by means of cesarean section was associated with early colonization patterns of the neonatal gut but not of the airways. The differences normalized within the first year of life. We speculate...

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

Neonatal Tetanus After Home Delivery: Report of One Case

Directory of Open Access Journals (Sweden)

Shou-Chih Chang

2010-06-01

Full Text Available Neonatal tetanus is a rare disease in developed countries, but remains common in developing countries. Pregnant women immigrating to Taiwan from developing countries may carry a risk of neonatal tetanus to the child, because of inadequate tetanus toxoid immunization and inappropriate postnatal cord care. Many young pediatricians in Taiwan are unfamiliar with this disease. Herein, we describe the clinical course of a newborn with neonatal tetanus, who was admitted with complaints of difficult feeding and muscle rigidity. After mechanical ventilation for 58 days and a prolonged hospital stay, the infant was discharged in good condition. It is important to maintain a high index of suspicion for neonatal sepsis when infants present with seizure-like symptoms, in order to allow its early diagnosis and appropriate treatment.

Melatonin: Buffering the Immune System

Directory of Open Access Journals (Sweden)

Juan M. Guerrero

2013-04-01

Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

Melatonin: Buffering the Immune System

Science.gov (United States)

Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

2013-01-01

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

The immune system, adaptation, and machine learning

Science.gov (United States)

Farmer, J. Doyne; Packard, Norman H.; Perelson, Alan S.

1986-10-01

The immune system is capable of learning, memory, and pattern recognition. By employing genetic operators on a time scale fast enough to observe experimentally, the immune system is able to recognize novel shapes without preprogramming. Here we describe a dynamical model for the immune system that is based on the network hypothesis of Jerne, and is simple enough to simulate on a computer. This model has a strong similarity to an approach to learning and artificial intelligence introduced by Holland, called the classifier system. We demonstrate that simple versions of the classifier system can be cast as a nonlinear dynamical system, and explore the analogy between the immune and classifier systems in detail. Through this comparison we hope to gain insight into the way they perform specific tasks, and to suggest new approaches that might be of value in learning systems.

The Immune System and Bodily Defence

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 2. The Immune System and Bodily Defence How Do Parasites and the Immune System Choose their Dances? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 2 February 1997 pp 17-24 ...

The Immune System and Bodily Defence

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 9. The Immune System and Bodily Defence How Does the Immune System Recognize Everything Under the Sun? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 9 September 1997 pp 6-10 ...

The S(c)ensory Immune System Theory.

Science.gov (United States)

Veiga-Fernandes, Henrique; Freitas, António A

2017-10-01

Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms. This context determined the emergence of the 'sensory immune system', which operates in a s(c)ensor mode to ensure systems physiology, organismic homeostasis, and perpetuation of its replicating molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune genes undergo more adaptive evolution than non-immune system genes in Daphnia pulex

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McTaggart Seanna J

2012-05-01

Full Text Available Abstract Background Understanding which parts of the genome have been most influenced by adaptive evolution remains an unsolved puzzle. Some evidence suggests that selection has the greatest impact on regions of the genome that interact with other evolving genomes, including loci that are involved in host-parasite co-evolutionary processes. In this study, we used a population genetic approach to test this hypothesis by comparing DNA sequences of 30 putative immune system genes in the crustacean Daphnia pulex with 24 non-immune system genes. Results In support of the hypothesis, results from a multilocus extension of the McDonald-Kreitman (MK test indicate that immune system genes as a class have experienced more adaptive evolution than non-immune system genes. However, not all immune system genes show evidence of adaptive evolution. Additionally, we apply single locus MK tests and calculate population genetic parameters at all loci in order to characterize the mode of selection (directional versus balancing in the genes that show the greatest deviation from neutral evolution. Conclusions Our data are consistent with the hypothesis that immune system genes undergo more adaptive evolution than non-immune system genes, possibly as a result of host-parasite arms races. The results of these analyses highlight several candidate loci undergoing adaptive evolution that could be targeted in future studies.

Unique aspects of the perinatal immune system.

Science.gov (United States)

Zhang, Xiaoming; Zhivaki, Dania; Lo-Man, Richard

2017-08-01

The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided. Advancement in our understanding of age-related remodelling of immune networks and the consequent tuning of immune responsiveness will open up new possibilities for immune intervention and vaccine strategies that are designed specifically for early life.

Maternal allergic disease does not affect the phenotype of T and B cells or the immune response to allergens in neonates.

Science.gov (United States)

Rindsjö, E; Joerink, M; Johansson, C; Bremme, K; Malmström, V; Scheynius, A

2010-07-01

It is hypothesized that the in utero environment in allergic mothers can affect the neonatal immune responses. The aim of this study was to analyse the effect of maternal allergic disease on cord blood mononuclear cell (CBMC) phenotype and proliferative responses upon allergen stimulation. Peripheral blood mononuclear cells (PBMC) from 12 allergic and 14 nonallergic mothers and CBMC from their children were analysed. In the mothers, we determined cell proliferation, production of IL-4 and expression of FOXP3 in response to allergen stimulation. In the children, we evaluated cell proliferation and FOXP3 expression following allergen stimulation. Furthermore, expression of different homing markers on T cells and regulatory T cells and maturity of the T cells and B cell subsets were evaluated directly ex vivo. The timothy- and birch-allergic mothers responded with increased proliferation and/or IL-4 production towards timothy and birch extract, respectively, when compared to nonallergic mothers. This could not be explained by impairment of FOXP3(+) regulatory T cells in the allergic mothers. CBMC proliferation and FOXP3 expression in response to allergens were not affected by the allergic status of the mother. Also, phenotype of T cells, FOXP3(+) regulatory T cells and B cells was not affected by the allergic status of the mother. Our results suggest that maternal allergic disease has no effect on the neonatal response to allergens or the phenotype of neonatal lymphocytes. The factors studied here could, however, still affect later development of allergy.

Prenatal Alcohol Exposure and the Developing Immune System.

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Gauthier, Theresa W

2015-01-01

Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

Review of the systems biology of the immune system using agent-based models.

Science.gov (United States)

Shinde, Snehal B; Kurhekar, Manish P

2018-06-01

The immune system is an inherent protection system in vertebrate animals including human beings that exhibit properties such as self-organisation, self-adaptation, learning, and recognition. It interacts with the other allied systems such as the gut and lymph nodes. There is a need for immune system modelling to know about its complex internal mechanism, to understand how it maintains the homoeostasis, and how it interacts with the other systems. There are two types of modelling techniques used for the simulation of features of the immune system: equation-based modelling (EBM) and agent-based modelling. Owing to certain shortcomings of the EBM, agent-based modelling techniques are being widely used. This technique provides various predictions for disease causes and treatments; it also helps in hypothesis verification. This study presents a review of agent-based modelling of the immune system and its interactions with the gut and lymph nodes. The authors also review the modelling of immune system interactions during tuberculosis and cancer. In addition, they also outline the future research directions for the immune system simulation through agent-based techniques such as the effects of stress on the immune system, evolution of the immune system, and identification of the parameters for a healthy immune system.

Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

Science.gov (United States)

Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

2014-05-01

Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ageing and the immune system: focus on macrophages.

Science.gov (United States)

Linehan, E; Fitzgerald, D C

2015-03-01

A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

The Immune System and Bodily Defence

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 6. The Immune System and Bodily Defence How Does the Immune System Organize Itself so as to Connect Target Recognition to Expected Functions? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 6 June 1997 pp 25-38 ...

Investigating immune system aging: system dynamics and agent-based modeling

OpenAIRE

Figueredo, Grazziela; Aickelin, Uwe

2010-01-01

System dynamics and agent based simulation models can\\ud both be used to model and understand interactions of entities within a population. Our modeling work presented here is concerned with understanding the suitability of the different types of simulation for the immune system aging problems and comparing their results. We are trying to answer questions such as: How fit is the immune system given a certain age? Would an immune boost be of therapeutic value, e.g. to improve the effectiveness...

The Equine Neonatal Cardiovascular System in Health and Disease.

Science.gov (United States)

Marr, Celia M

2015-12-01

The neonatal foal is in a transitional state from prenatal to postnatal circulation. Healthy newborn foals often have cardiac murmurs and dysrhythmias, which are usually transient and of little clinical significance. The neonatal foal is prone to infection and cardiac trauma. Echocardiography is the main tool used for valuation of the cardiovascular system. With prompt identification and appropriate action, dysrhythmias and other sequel to cardiac trauma can be corrected. With infection, the management and prognosis are driven by concurrent sepsis. Congenital disease represents an interesting diagnostic challenge for the neonatologist, but surgical correction is not appropriate for most equids. Copyright © 2015 Elsevier Inc. All rights reserved.

Prenatal Alcohol Exposure and the Developing Immune System

OpenAIRE

Gauthier, Theresa W.

2015-01-01

Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensiv...

Pathogenic bacteria colonizing the airways in asymptomatic neonates stimulates topical inflammatory mediator release

DEFF Research Database (Denmark)

Følsgaard, Nilofar Vahman; Schjørring, Susanne; Chawes, Bo Lund Krogsgaard

2013-01-01

Rationale: Bacterial colonization of neonatal airways with the pathogenic bacterial species, Moraxella catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, is associated with later development of childhood asthma. Objectives: To study a possible association between colonization...... with pathogenic bacterial strains and the immune signature of the upper airways in healthy neonates. Methods: A total of 20 cytokines and chemokines were quantified in vivo in the airway mucosal lining fluid of 662 neonates from the Copenhagen Prospective Study of Asthma in Childhood 2010 birth cohort...

Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

Science.gov (United States)

Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

2013-12-01

The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

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

, 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...... significant and positive association to up-regulation of TGF-beta 1 levels (P = 0.0003) and significant negative association to other mediators. The study was not powered to study differences in the incidence of infections in early infancy which did not differ between the study groups. Conclusion: Influenza A......(H1N1) pnd09 vaccination during pregnancy up-regulates TGF-beta 1 and down-regulates key mediators of the protective immunity....

A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy

Energy Technology Data Exchange (ETDEWEB)

Trivedi, Shamik B.; Vesoulis, Zachary A.; Rao, Rakesh; Liao, Steve M.; Mathur, Amit M. [Washington University School of Medicine, Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, St. Louis, MO (United States); Shimony, Joshua S.; McKinstry, Robert C. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States)

2017-10-15

Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24 months. MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24 months. Data were analyzed using univariate and multivariate linear and logistic regression. Fifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18-24 months in neonates with HIE. (orig.)

A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy

International Nuclear Information System (INIS)

Trivedi, Shamik B.; Vesoulis, Zachary A.; Rao, Rakesh; Liao, Steve M.; Mathur, Amit M.; Shimony, Joshua S.; McKinstry, Robert C.

2017-01-01

Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24 months. MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24 months. Data were analyzed using univariate and multivariate linear and logistic regression. Fifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18-24 months in neonates with HIE. (orig.)

Viral subversion of the immune system

International Nuclear Information System (INIS)

Gillet, L.; Vanderplasschen, A.

2005-01-01

The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines. (author)

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

Science.gov (United States)

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Innate Immunity and Human Milk MicroRNAs Content: A New Perspective for Premature Newborns

Directory of Open Access Journals (Sweden)

Erika Cione

2017-02-01

Full Text Available Context The premature newborns are prone to develop both early onset and late onset neonatal sepsis. The major causes of this phenomenon rely on the immaturity of the immune system, which has reduced capability to respond adequately to pathogens. Evidence Acquisition Titles and abstracts of previous papers were scanned before reading the full-text, in order to retrieve appropriate information. The databases used for searching were PubMed, Cochrane, and Embase for articles published before 1st of July, 2016. Secondary search for articles cited in reference lists were identified by the primary search. This review focused on neonatal sepsis incidence and the associated immune response with regards to microRNAs of human milk as a new microelement that enables regulation of innate immunity functions. Results Since human milk is a valuable source of microRNAs, a better understanding of its content will open a new therapeutic avenue for the clinical management of infectious diseases affecting premature newborns. The variation in miRNAs quantity in human milk needs to be considered. Mother’s milk can have different amounts of miRNAs and the identification of a microMilk batch richer of miRNAs can be a nutrition intervention method for modulating innate immunity in clinical management of premature newborns. Conclusions Routine translation of the microMilk concept for neonatal intensive care unit (NICU, in the management of premature newborns could be a way of defending premature newborns and Very Low Birth Weight (VLBW infants from both early and late sepsis.

Learning and Memory... and the Immune System

Science.gov (United States)

Marin, Ioana; Kipnis, Jonathan

2013-01-01

The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS),…

Physical Activities, Exercises, and Their Effects to the Immune System

OpenAIRE

Nurmasitoh, Titis

2015-01-01

Every systems in human body correlate to maintain homeostasis. One of those systems which contribute to maintain homeostasis is the immune system. The immune system defends physiological functions against foreign substances and cancer cells through a complex and multilayered mechanism. The ability to defend against foreign substances and abnormal cells is done by two types of immune system, which are Innate immune system and adaptive/acquired immune system. There are also certain factors that...

Early immune response patterns to pathogenic bacteria are associated to increased risk of lower respiratory infections in children

DEFF Research Database (Denmark)

Vissing, N. H.; Larsen, Jeppe Madura; Rasmussen, Mette Annelie

2014-01-01

Neonatal colonisation of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood (1). Therefore, we hypothesized that children developing LRI have an abnormal immune response to pathogenic bacteria in infancy. We aimed...... to characterise the systemic immune response to pathogenic bacteria at the age of 6 months and study the association with incidence of LRI during the first 3 years of life....

Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

Science.gov (United States)

Ameri, Pietro; Ferone, Diego

2012-01-01

During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment. Copyright © 2012 S. Karger AG, Basel.

Performance of the definitions of the systemic inflammatory response syndrome and sepsis in neonates.

Science.gov (United States)

Hofer, Nora; Zacharias, Eva; Müller, Wilhelm; Resch, Bernhard

2012-09-01

The aim of this study was to examine the applicability of the definitions of the systemic inflammatory response syndrome (SIRS) and sepsis to neonates during the first 3 days of life. This is a retrospective study of all term neonates hospitalized within the first 24 h of life from 2004 to 2010 at our neonatal intensive care unit. Of 476 neonates, 30 (6 %) had a diagnosis of culture-proven early-onset sepsis (EOS) and 81 (17 %) had culture-negative clinical EOS or suspected EOS. SIRS and sepsis criteria were applied to 116 (24 %) and 61 (13 %) neonates, respectively. Of 30 neonates with culture proven, EOS 14 (53 %) fulfilled SIRS and sepsis criteria. The single diagnostic criterion of SIRS applied to 20 % (hypothermia or fever), 43 % (white blood cell count/immature-to-total neutrophil ratio), 87 % (respiratory symptoms), and 33 % (cardiocirculatory symptoms) of all neonates with culture-proven EOS. The definitions of SIRS and sepsis did not apply to about half of all cases of culture-proven EOS. An evidence-based approach to find the appropriate criteria for defining EOS in the neonate is needed.

Promoting tissue regeneration by modulating the immune system.

Science.gov (United States)

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

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.

The Immune System in Irritable Bowel Syndrome

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Cremon, Cesare; Carini, Giovanni; Bellacosa, Lara; Zecchi, Lisa; De Giorgio, Roberto; Corinaldesi, Roberto; Stanghellini, Vincenzo

2011-01-01

The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches. PMID:22148103

Neonatal pain

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Walker, Suellen M

2014-01-01

Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

Natural evolution, disease, and localization in the immune system

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Deem, Michael

2004-03-01

Adaptive vertebrate immune system is a wonder of modern evolution. Under most circumstances, the dynamics of the immune system is well-matched to the dynamics of pathogen growth during a typical infection. Some pathogens, however, have evolved escape mechanisms that interact in subtle ways with the immune system dynamics. In addition, negative interactions the immune system, which has evolved over 400 000 000 years, and vaccination,which has been practiced for only 200 years, are possible. For example,vaccination against the flu can actually increase susceptibility to the flu in the next year. As another example, vaccination against one of the four strains of dengue fever typically increases susceptibility against the other three strains. Immunodominance also arises in the immune system control of nascent tumors--the immune system recognizes only a small subset of the tumor specific antigens, and the rest are free to grow and cause tumor growth. In this talk, I present a physical theory of original antigenic sin and immunodominance. How localization in the immune system leads to the observed phenomena is discussed. 1) M. W. Deem and H. Y. Lee, ``Sequence Space Localization in the Immune System Response to Vaccination and Disease,'' Phys. Rev. Lett. 91 (2003) 068101

Clinical case of using discrete plasmapheresis in infant with early neonatal sepsis and hemolytic disease

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S. V. Aborin

2017-01-01

Full Text Available Currently in the literature there are insufficient data on the use of efferent hemocorrection methods in neonatal practice. The basic principle of this method is the removal of plasma containing endotoxins and exotoxins and other pathological substances, replacing it with donor plasma, colloid and crystalloid solutions. The therapeutic effect of plasmapheresis includes detoxification, anti-inflammatory and immunomodulatory effects by removing toxins and removal of circulating immune complexes, inflammatory mediators, and activated structures of the complement system. Discrete plasmapheresis in neonatal practice may be used in any body mass of the patient. This article describes a clinical case of successful application of discrete plasmapheresis in full-term newborn baby is in critical condition. The severity was due to severe early neonatal sepsis, development of multiple organ failure and accompanying RH-conflict. After two sessions of plasmapheresis was observed a positive clinical effect in reducing intoxication, systemic inflammatory response syndrome. Reducing the level of bilirubin is allowed to avoid the operation replacement blood transfusion.

Immune response induction in the central nervous system

DEFF Research Database (Denmark)

Owens, Trevor; Babcock, Alicia

2002-01-01

The primary function of the immune response is protection of the host against infection with pathogens, including viruses. Since viruses can infect any tissue of the body, including the central nervous system (CNS), it is logical that cells of the immune system should equally have access to all...... tissues. Nevertheless, the brain and spinal cord are noted for their lack of immune presence. Relative to other organ systems, the CNS appears immunologically privileged. Furthermore, when immune responses do occur in the CNS, they are frequently associated with deleterious effects such as inflammatory...

The role of the immune system in kidney disease.

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Tecklenborg, J; Clayton, D; Siebert, S; Coley, S M

2018-05-01

The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. © 2018 British Society for Immunology.

3D ultrasound system to investigate intraventricular hemorrhage in preterm neonates

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Kishimoto, J.; de Ribaupierre, S.; Lee, D. S. C.; Mehta, R.; St. Lawrence, K.; Fenster, A.

2013-11-01

Intraventricular hemorrhage (IVH) is a common disorder among preterm neonates that is routinely diagnosed and monitored by 2D cranial ultrasound (US). The cerebral ventricles of patients with IVH often have a period of ventricular dilation (ventriculomegaly). This initial increase in ventricle size can either spontaneously resolve, which often shows clinically as a period of stabilization in ventricle size and eventual decline back towards a more normal size, or progressive ventricular dilation that does not stabilize and which may require interventional therapy to reduce symptoms relating to increased intracranial pressure. To improve the characterization of ventricle dilation, we developed a 3D US imaging system that can be used with a conventional clinical US scanner to image the ventricular system of preterm neonates at risk of ventriculomegaly. A motorized transducer housing was designed specifically for hand-held use inside an incubator using a transducer commonly used for cranial 2D US scans. This system was validated using geometric phantoms, US/MRI compatible ventricle volume phantoms, and patient images to determine 3D reconstruction accuracy and inter- and intra-observer volume estimation variability. 3D US geometric reconstruction was found to be accurate with an error of 0.05) for the measured ventricle volumes between observers. This 3D US system can reliably produce 3D US images of the neonatal ventricular system. There is the potential to use this system to monitor the progression of ventriculomegaly over time in patients with IVH.

Prenatal and neonatal radiation injury and lymphohematopoietic development in the dog

International Nuclear Information System (INIS)

Nold, J.B.

1985-01-01

Immunologic and hematopoietic responses were studied in beagle dogs following prenatal or neonatal irradiation to evaluate the effects of ionizing radiation on the developing lymphohematopoietic system. In prenatally-irradiated dogs thymic medullary volumes were significantly reduced at birth, but had returned to control levels by 12 weeks of age. Irradiated dogs exhibited a significant reduction in primary humoral antibody responses and showed a concurrent decrease in T helper lymphocytes in the peripheral blood. In neonatally-irradiated dogs lymphocyte blastogenic responses were sharply decreased at 8 weeks, but returned to control levels by 12 weeks of age. Contact sensitivity to dinitrochlorobenzene was decreased, indicating reduced cell-mediated immune responses. Alterations in peripheral blood lymphocyte subpopulations included decreases in B cells and increases in T cells, possibly due to increased numbers of T suppressor cells. There were significant reductions in body size and body tissue weights in all irradiated dogs, although these were more severe and persistent in the prenatally-irradiated dogs. These data show that prenatally or neonatally-irradiated dogs have significantly postnatal immunologic and hematopoietic defects. The effect on bone marrow function in prenatally-irradiated dogs was more severe and persistent than in neonatally-irradiated animals; however, the neonatally-irradiated dogs exhibited more severe alterations in lymphocyte subpopulations than did the prenatally-irradiated dogs. The observation of altered lymphocyte subpopulations suggests altered immunoregulation and raises some important questions relating to radiation-induced immunodeficiency and increased susceptibility to clinical disease, including neoplasia

Nutritional support for the infant's immune system

NARCIS (Netherlands)

Niers, L.; Stasse-Wolthuis, M.; Rombouts, F.M.; Rijkers, G.T.

2007-01-01

Newborn babies possess a functional but immature immune system as a defense against a world teeming with microorganisms. Breast milk contains a number of biological, active compounds that support the infant's immune system. These include secretory immunoglobulin A (IgA), which confers specific

Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

Directory of Open Access Journals (Sweden)

Heng Liu

Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

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Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2013-01-01

Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

Toll-like receptors in neonatal sepsis.

LENUS (Irish Health Repository)

O'Hare, Fiona M

2013-06-01

Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

Effects of engineered nanoparticles on the innate immune system.

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Liu, Yuanchang; Hardie, Joseph; Zhang, Xianzhi; Rotello, Vincent M

2017-12-01

Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

The mirror neuron system as revealed through neonatal imitation: presence from birth, predictive power and evidence of plasticity.

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Simpson, Elizabeth A; Murray, Lynne; Paukner, Annika; Ferrari, Pier F

2014-01-01

There is strong evidence that neonates imitate previously unseen behaviours. These behaviours are predominantly used in social interactions, demonstrating neonates' ability and motivation to engage with others. Research on neonatal imitation can provide a wealth of information about the early mirror neuron system (MNS), namely its functional characteristics, its plasticity from birth and its relation to skills later in development. Although numerous studies document the existence of neonatal imitation in the laboratory, little is known about its natural occurrence during parent-infant interactions and its plasticity as a consequence of experience. We review these critical aspects of imitation, which we argue are necessary for understanding the early action-perception system. We address common criticisms and misunderstandings about neonatal imitation and discuss methodological differences among studies. Recent work reveals that individual differences in neonatal imitation positively correlate with later social, cognitive and motor development. We propose that such variation in neonatal imitation could reflect important individual differences of the MNS. Although postnatal experience is not necessary for imitation, we present evidence that neonatal imitation is influenced by experience in the first week of life.

Parental satisfaction in the traditional system of neonatal intensive ...

African Journals Online (AJOL)

Background. Traditional systems of neonatal intensive care unit (NICU) care predispose parents to increased levels of stress and anxiety due to parental separation from their infant. Parental satisfaction, an indicator of the quality of care, is significantly compromised during prolonged NICU stay. The research is limited in ...

Trauma: the role of the innate immune system

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Rijkers GT

2006-05-01

Full Text Available Abstract Immune dysfunction can provoke (multiple organ failure in severely injured patients. This dysfunction manifests in two forms, which follow a biphasic pattern. During the first phase, in addition to the injury by trauma, organ damage is caused by the immune system during a systemic inflammatory response. During the second phase the patient is more susceptible for sepsis due to host defence failure (immune paralysis. The pathophysiological model outlined in this review encompasses etiological factors and the contribution of the innate immune system in the end organ damage. The etiological factors can be divided into intrinsic (genetic predisposition and physiological status and extrinsic components (type of injury or "traumaload" and surgery or "intervention load". Of all the factors, the intervention load is the only one which, can be altered by the attending emergency physician. Adjustment of the therapeutic approach and choice of the most appropriate treatment strategy can minimize the damage caused by the immune response and prevent the development of immunological paralysis. This review provides a pathophysiological basis for the damage control concept, in which a staged approach of surgery and post-traumatic immunomonitoring have become important aspects of the treatment protocol. The innate immune system is the main objective of immunomonitoring as it has the most prominent role in organ failure after trauma. Polymorphonuclear phagocytes and monocytes are the main effector-cells of the innate immune system in the processes that lead to organ failure. These cells are controlled by cytokines, chemokines, complement factors and specific tissue signals. The contribution of tissue barrier integrity and its interaction with the innate immune system is further evaluated.

Role of Osmolytes in Regulating Immune System.

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Kumar, Tarun; Yadav, Manisha; Singh, Laishram Rajendrakumar

2016-01-01

The immune system has evolved to protect the host organism from diverse range of pathogenic microbes that are themselves constantly evolving. It is a complex network of cells, humoral factors, chemokines and cytokines. Dysregulation of immune system results in various kinds of immunological disorders. There are several external agents which govern the regulation of immune system. Recent studies have indicated the role of osmolytes in regulation of various immunological processes such as Ag-Ab interaction, Ig assembly, Ag presentation etc. In this present review, we have systematically discussed the role of osmolytes involved in regulation of several key immunological processes. Osmolytes are involved in the regulation of several key immunological processes such as immunoglobulin assembly and folding, immune cells proliferation, regulation of immune cells function, Ag-Ab interaction, antigen presentation, inflammatory response and protection against photo-immunosuppression. Hence, osmolytes and their transporters might be used as potential drug and drug targets respectively. This review is therefore designed to help clinicians in development of osmolyte based therapeutic strategies in the treatment of various immunological disorders. Appropriate future perspectives have also been included.

Investigating Relationships between Reproduction, Immune Defenses, and Cortisol in Dall Sheep.

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Downs, Cynthia J; Boan, Brianne V; Lohuis, Thomas D; Stewart, Kelley M

2018-01-01

Life-history theory is fundamental to understanding how animals allocate resources among survival, development, and reproduction, and among traits within these categories. Immediate trade-offs occur within a short span of time and, therefore, are more easily detected. Trade-offs, however, can also manifest across stages of the life cycle, a phenomenon known as carryover effects. We investigated trade-offs on both time scales in two populations of Dall sheep ( Ovis dalli dalli ) in Southcentral Alaska. Specifically, we (i) tested for glucocorticoid-mediated carryover effects from the breeding season on reproductive success and immune defenses during parturition and (ii) tested for trade-offs between immune defenses and reproduction within a season. We observed no relationship between cortisol during mating and pregnancy success; however, we found marginal support for a negative relationship between maternal cortisol and neonate birth weights. Low birth weights, resulting from high maternal cortisol, may result in low survival or low fecundity for the neonate later in life, which could result in overall population decline. We observed a negative relationship between pregnancy and bacterial killing ability, although we observed no relationship between pregnancy and haptoglobin. Study site affected bactericidal capacity and the inflammatory response, indicating the influence of external factors on immune responses, although we could not test hypotheses about the cause of those differences. This study helps advance our understanding of the plasticity and complexity of the immune system and provides insights into the how individual differences in physiology may mediate differences in fitness.

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

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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.

Exploring the Homeostatic and Sensory Roles of the Immune System.

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Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

2016-01-01

Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.

Trauma equals danger—damage control by the immune system

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Stoecklein, Veit M.; Osuka, Akinori; Lederer, James A.

2012-01-01

Traumatic injuries induce a complex host response that disrupts immune system homeostasis and predisposes patients to opportunistic infections and inflammatory complications. The response to injuries varies considerably by type and severity, as well as by individual variables, such as age, sex, and genetics. These variables make studying the impact of trauma on the immune system challenging. Nevertheless, advances have been made in understanding how injuries influence immune system function as well as the immune cells and pathways involved in regulating the response to injuries. This review provides an overview of current knowledge about how traumatic injuries affect immune system phenotype and function. We discuss the current ideas that traumatic injuries induce a unique type of a response that may be triggered by a combination of endogenous danger signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally, we review and propose strategies for redirecting injury responses to help restore immune system homeostasis. PMID:22654121

Strengthening health system to improve immunization for migrants in China.

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Fang, Hai; Yang, Li; Zhang, Huyang; Li, Chenyang; Wen, Liankui; Sun, Li; Hanson, Kara; Meng, Qingyue

2017-07-01

Immunization is the most cost-effective method to prevent and control vaccine-preventable diseases. Migrant population in China has been rising rapidly, and their immunization status is poor. China has tried various strategies to strengthen its health system, which has significantly improved immunization for migrants. This study applied a qualitative retrospective review method aiming to collect, analyze and synthesize health system strengthening experiences and practices about improving immunizations for migrants in China. A conceptual framework of Theory of Change was used to extract the searched literatures. 11 searched literatures and 4 national laws and policies related to immunizations for migrant children were carefully studied. China mainly employed 3 health system strengthening strategies to significantly improve immunization for migrant population: stop charging immunization fees or immunization insurance, manage immunization certificates well, and pay extra attentions on immunization for special children including migrant children. These health system strengthening strategies were very effective, and searched literatures show that up-to-date and age-appropriate immunization rates were significantly improved for migrant children. Economic development led to higher migrant population in China, but immunization for migrants, particularly migrant children, were poor. Fortunately various health system strengthening strategies were employed to improve immunization for migrants in China and they were rather successful. The experiences and lessons of immunization for migrant population in China might be helpful for other developing countries with a large number of migrant population.

Effects of splenectomy on the humoral immune system

International Nuclear Information System (INIS)

Rozing, J.; Brons, N.H.C.; Benner, R.

1978-01-01

Experiments were performed to investigate the influence of neonatal and adult splenectomy on humoral immunity in mice. In the bone marrow and lymph nodes of both groups of splenectomized mice the number of immunoglobulin (Ig)-positive (B) lymphocytes was significantly higher than in sham-operated mice. These higher numbers of B cells probably reflect a compensation for the absence of the B cell population of the spleen. Hardly any quantitative differences in the serum immunoglobulins were found between splenectomized and sham-splenectomized mice. Only for the IgM class was a significantly lower concentration found in the serum of splenectomized animals. This low concentration of IgM in the blood of splenectomized mice was caused by a failure of the remaining organs to compensate completely for the removal of the quantitatively important population of IgM-producing plasma cells in the spleen. Nevertheless, the number of precursors of IgM-producing plasma cells in bone marrow and lymph nodes and their ability to differentiate into IgM-producing plasma cells was not diminished by splenectomy. Probably the spleen provides a highly efficient environment for the differentiation into IgM-producing plasma cells. By investigating the synergistic ability of bone marrow cells and thymus cells from neonatally splenectomized mice it was found that these cells were fully capable of co-operating in the adoptive plaque-forming cell response to sheep red blood cells (SFBC). (author)

Crosstalk between cancer and the neuro-immune system.

Science.gov (United States)

Kuol, Nyanbol; Stojanovska, Lily; Apostolopoulos, Vasso; Nurgali, Kulmira

2018-02-15

In the last decade, understanding of cancer initiation and progression has been given much attention with studies mainly focusing on genetic abnormalities. Importantly, cancer cells can influence their microenvironment and bi-directionally communicate with other systems such as the immune system. The nervous system plays a fundamental role in regulating immune responses to a range of disease states including cancer. Its dysfunction influences the progression of cancer. The role of the immune system in tumor progression is of relevance to the nervous system since they can bi-directionally communicate via neurotransmitters and neuropeptides, common receptors, and, cytokines. However, cross-talk between these cells is highly complex in nature, and numerous variations are possible according to the type of cancer involved. The neuro-immune interaction is essential in influencing cancer development and progression. Copyright © 2017 Elsevier B.V. All rights reserved.

Immune system alterations in amyotrophic lateral sclerosis

DEFF Research Database (Denmark)

Hovden, H; Frederiksen, J L; Pedersen, S W

2013-01-01

Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...... cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might...

Modeling evolution and immune system by cellular automata

International Nuclear Information System (INIS)

Bezzi, M.

2001-01-01

In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

Neonatal tetanus in Turkey; what has changed in the last decade?

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Kocamaz Halil

2008-08-01

Full Text Available Abstract Background Neonatal tetanus (NT is still considered as one of the major causes of neonatal death in many developing countries. The aim of the present study was to assess the characteristics of sixty-seven infants with the diagnosis of neonatal tetanus followed-up in the Pediatric Infectious Diseases Ward of Dicle University Hospital, Diyarbakir, between 1991 and 2006, and to draw attention to factors that may contribute (or may have contributed to the elimination of the disease in Diyarbakir. Methods The data of sixty-seven infants whose epidemiological and clinical findings were compatible with neonatal tetanus were reviewed. Patients were stratified into two groups according to whether they survived or not to assess the effect of certain factors in the prognosis. Factors having a contribution to the higher rate of tetanus among newborn infants were discussed. Results A total of 55 cases of NT had been hospitalized between 1991 and 1996 whereas only 12 patients admitted in the last decade. All of the infants had been delivered at home by untrained traditional birth attendants (TBA, and none of the mothers had been immunized with tetanus toxoid during her pregnancy. Twenty-eight (41.8% of the infants died during their follow-up. Lower birth weight, younger age at onset of symptoms and at the time admission, the presence of opisthotonus, risus sardonicus and were associated with a higher mortality rate. Conclusion Although the number of neonatal tetanus cases admitted to our clinic in recent years is lower than in the last decade efforts including appropriate health education of the masses, ensurement of access to antenatal sevices and increasing the rate of tetanus immunization among mothers still should be made in our region to achieve the goal of neonatal tetanus elimination.

Ureaplasma-associated prenatal, perinatal, and neonatal morbidities.

Science.gov (United States)

Silwedel, Christine; Speer, Christian P; Glaser, Kirsten

2017-11-01

Ureaplasma species (spp.) have been acknowledged as major causative pathogens in chorioamnionitis and prematurity, but may also contribute to key morbidities in preterm infants. Several epidemiological and experimental data indicate an association of neonatal Ureaplasma colonization and/or infection with bronchopulmonary dysplasia. Furthermore, a potential causal relation with other inflammation-induced morbidities, such as intraventricular hemorrhage, white matter injury, necrotizing enterocolitis, and retinopathy of prematurity, has been debated. Areas covered: This review will summarize current knowledge on the role of Ureaplasma spp. in prenatal, perinatal, and neonatal morbidities, while furthermore examining mutual underlying mechanisms. We try to elaborate who is at particular risk of Ureaplasma-induced inflammation and subsequent secondary morbidities. Expert commentary: Most likely by complex interactions with immunological processes, Ureaplasma spp. can induce pro-inflammation, but may also downregulate the immune system. Tissue damage, possibly causing the above mentioned complications, is likely to result from both ways: either directly cytokine-associated, or due to a higher host vulnerability to secondary impact factors. These events are very likely to begin in prenatal stages, with the most immature preterm infants being most susceptible and at highest risk.

Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model.

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Hinderer, Christian; Bell, Peter; Louboutin, Jean-Pierre; Katz, Nathan; Zhu, Yanqing; Lin, Gloria; Choa, Ruth; Bagel, Jessica; O'Donnell, Patricia; Fitzgerald, Caitlin A; Langan, Therese; Wang, Ping; Casal, Margret L; Haskins, Mark E; Wilson, James M

2016-09-01

High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme α-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I. These studies established the efficacy of the human vector in the canine model, and allowed for estimation of the minimum effective dose, providing key information for the design of first-in-human trials. This approach can facilitate evaluation of human therapeutics in relevant animal models, and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet

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Guohui eCai

2015-01-01

Full Text Available Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS. Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

The influence of pregnancy on systemic immunity.

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Pazos, Michael; Sperling, Rhoda S; Moran, Thomas M; Kraus, Thomas A

2012-12-01

Adaptations in maternal systemic immunity are presumed to be responsible for observed alterations in disease susceptibility and severity as pregnancy progresses. Epidemiological evidence as well as animal studies have shown that influenza infections are more severe during the second and third trimesters of pregnancy, resulting in greater morbidity and mortality, although the reason for this is still unclear. Our laboratory has taken advantage of 20 years of experience studying the murine immune response to respiratory viruses to address questions of altered immunity during pregnancy. With clinical studies and unique animal model systems, we are working to define the mechanisms responsible for altered immune responses to influenza infection during pregnancy and what roles hormones such as estrogen or progesterone play in these alterations.

State of immune system lesions eymeriozo turkey-invasions histomonoznoyu

OpenAIRE

CHARIV I.

2011-01-01

The immune system of animals and birds provides resistance against bacterial and viral infections. In the intestinal mucosa and eymeriyi histomonady produce metabolic products that are toxic to different systems and tissues of turkeys. They parasitizing in the intestine, suppress specific phase of immunity provided by antibodies (humoral type), reduce activity sensitized cells (cell type), slow phase of nonspecific immunity, which is represented by various immune cells.

The Role of the Immune System Beyond the Fight Against Infection.

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Sattler, Susanne

2017-01-01

The immune system was identified as a protective factor during infectious diseases over a century ago. Current definitions and textbook information are still largely influenced by these early observations, and the immune system is commonly presented as a defence machinery. However, host defence is only one manifestation of the immune system's overall function in the maintenance of tissue homeostasis and system integrity. In fact, the immune system is integral part of fundamental physiological processes such as development, reproduction and wound healing, and a close crosstalk between the immune system and other body systems such as metabolism, the central nervous system and the cardiovascular system is evident. Research and medical professionals in an expanding range of areas start to recognise the implications of the immune system in their respective fields.This chapter provides a brief historical perspective on how our understanding of the immune system has evolved from a defence system to an overarching surveillance machinery to maintain tissue integrity. Current perspectives on the non-defence functions of classical immune cells and factors will also be discussed.

The role of intestinal microbiota and the immune system.

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Purchiaroni, F; Tortora, A; Gabrielli, M; Bertucci, F; Gigante, G; Ianiro, G; Ojetti, V; Scarpellini, E; Gasbarrini, A

2013-02-01

The human gut is an ecosystem consisting of a great number of commensal bacteria living in symbiosis with the host. Several data confirm that gut microbiota is engaged in a dynamic interaction with the intestinal innate and adaptive immune system, affecting different aspects of its development and function. To review the immunological functions of gut microbiota and improve knowledge of its therapeutic implications for several intestinal and extra-intestinal diseases associated to dysregulation of the immune system. Significant articles were identified by literature search and selected based on content, including atopic diseases, inflammatory bowel diseases and treatment of these conditions with probiotics. Accumulating evidence indicates that intestinal microflora has protective, metabolic, trophic and immunological functions and is able to establish a "cross-talk" with the immune component of mucosal immunity, comprising cellular and soluble elements. When one or more steps in this fine interaction fail, autoimmune or auto-inflammatory diseases may occur. Furthermore, it results from the data that probiotics, used for the treatment of the diseases caused by the dysregulation of the immune system, can have a beneficial effect by different mechanisms. Gut microbiota interacts with both innate and adaptive immune system, playing a pivotal role in maintenance and disruption of gut immune quiescence. A cross talk between the mucosal immune system and endogenous microflora favours a mutual growth, survival and inflammatory control of the intestinal ecosystem. Based on these evidences, probiotics can be used as an ecological therapy in the treatment of immune diseases.  

[The liver and the immune system].

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Jakab, Lajos

2015-07-26

The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row "endothelium", stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes

Nociception and role of immune system in pain.

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Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

2015-09-01

Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

Integration of the immune system: a complex adaptive supersystem

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Crisman, Mark V.

2001-10-01

Immunity to pathogenic organisms is a complex process involving interacting factors within the immune system including circulating cells, tissues and soluble chemical mediators. Both the efficiency and adaptive responses of the immune system in a dynamic, often hostile, environment are essential for maintaining our health and homeostasis. This paper will present a brief review of one of nature's most elegant, complex adaptive systems.

The deconvolution of complex spectra by artificial immune system

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Galiakhmetova, D. I.; Sibgatullin, M. E.; Galimullin, D. Z.; Kamalova, D. I.

2017-11-01

An application of the artificial immune system method for decomposition of complex spectra is presented. The results of decomposition of the model contour consisting of three components, Gaussian contours, are demonstrated. The method of artificial immune system is an optimization method, which is based on the behaviour of the immune system and refers to modern methods of search for the engine optimization.

Role of Cortistatin in the Stressed Immune System.

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Delgado, Mario; Gonzalez-Rey, Elena

2017-01-01

The immune system is faced with the daunting job of defending the organism against invading pathogens, while at the same time preserving the body integrity and maintaining tolerance to its own tissues. Loss of self-tolerance compromises immune homeostasis and leads to the onset of autoimmune disorders. The identification of endogenous factors that control immune tolerance and inflammation is a key goal for immunologists. Evidences from the last decade indicate that the neuropeptide cortistatin is one of the endogenous factors. Cortistatin is produced by immune cells and through its binding to various receptors, it exerts potent anti-inflammatory actions and participates in the maintenance of immune tolerance at multiple levels, especially in immunological disorders. Cortistatin emerges as a key element in the bidirectional communication between the neuroendocrine and immune systems aimed at regulating body homeostasis. © 2017 S. Karger AG, Basel.

Regulation of vitamin D homeostasis: implications for the immune system.

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van Etten, Evelyne; Stoffels, Katinka; Gysemans, Conny; Mathieu, Chantal; Overbergh, Lut

2008-10-01

Vitamin D homeostasis in the immune system is the focus of this review. The production of both the activating (25- and 1alpha-hydroxylase) and the metabolizing (24-hydroxylase) enzymes by cells of the immune system itself, indicates that 1,25(OH)(2)D(3) can be produced locally in immune reaction sites. Moreover, the strict regulation of these enzymes by immune signals is highly suggestive for an autocrine/paracrine role in the immune system, and opens new treatment possibilities.

3D ultrasound system to investigate intraventricular hemorrhage in preterm neonates

International Nuclear Information System (INIS)

Kishimoto, J; Lawrence, K St; De Ribaupierre, S; Fenster, A; Lee, D S C; Mehta, R

2013-01-01

Intraventricular hemorrhage (IVH) is a common disorder among preterm neonates that is routinely diagnosed and monitored by 2D cranial ultrasound (US). The cerebral ventricles of patients with IVH often have a period of ventricular dilation (ventriculomegaly). This initial increase in ventricle size can either spontaneously resolve, which often shows clinically as a period of stabilization in ventricle size and eventual decline back towards a more normal size, or progressive ventricular dilation that does not stabilize and which may require interventional therapy to reduce symptoms relating to increased intracranial pressure. To improve the characterization of ventricle dilation, we developed a 3D US imaging system that can be used with a conventional clinical US scanner to image the ventricular system of preterm neonates at risk of ventriculomegaly. A motorized transducer housing was designed specifically for hand-held use inside an incubator using a transducer commonly used for cranial 2D US scans. This system was validated using geometric phantoms, US/MRI compatible ventricle volume phantoms, and patient images to determine 3D reconstruction accuracy and inter- and intra-observer volume estimation variability. 3D US geometric reconstruction was found to be accurate with an error of 3 for a single observer. Results from ANOVA for three observers segmenting three patients of IVH grade II did not show any significant differences (p > 0.05) for the measured ventricle volumes between observers. This 3D US system can reliably produce 3D US images of the neonatal ventricular system. There is the potential to use this system to monitor the progression of ventriculomegaly over time in patients with IVH. (paper)

Immune system investigations for radiation workers

International Nuclear Information System (INIS)

Obreja, Doina; Tulbure, Rodica; Marinescu, Irina

2001-01-01

During the last decade a great deal of attention has been paid to the research in the field of the immune system. Some important steps forward have been achieved in understanding the mechanisms of action and control of the immunologic responses. At the same time the concern for the possible health effects of exposure to ionizing radiation has considerably increased. On the purpose of the evaluation of the modifications induced by the ionizing radiation for radiation workers, we have applied the method of lymphocytic subpopulations, a method that evinces the proportions for the various subtypes of lymphocytes having different roles within the immune system. A number of 62 persons, employees of the Institute of Physics and Nuclear Engineering at Bucharest - Magurele were involved in this study. All radiation workers from 2 departments characterized by a high exposure to ionizing radiation were included, as follows: Group no. 1, consisting of 20 persons working at RWTS (Radioactive Waste Treating Station), thus presenting both external and internal irradiation; Group no. 2, consisting of 18 persons working at RPC (Radioactive Isotopes Preparing Center), a place where besides the radioactive contamination, the chemical risk was also present. The control group (consisting of 24 persons) was formed of employees from the same institute, with the difference that they were not radiation workers. For the statistical processing of the results the programs EPI INFO 6 and CIA were used. Significantly, when analyzing globally the lymphocytic modifications for TT and/or B lymphocytes (either increments or decrements when compared to the normal values), a noticeable statistical difference among the groups in terms of the frequency of the immune system modifications (Hi square test p=0.001) occurs. The results are in accordance to those in special literature mentioning age as a factor having a role in the appearance of the immune modifications. The obtained results indicate a

Evidence for a common mucosal immune system in the pig.

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Wilson, Heather L; Obradovic, Milan R

2015-07-01

The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

The immune self: a selectionist theory of recognition, learning, and remembering within the immune system.

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Kradin, R L

1995-01-01

In this paper, I have briefly explored metaphors shared by the immune and nervous systems and shown that this exercise can lead to the elucidation of common principles of organization, as well as to predictions concerning how the immune system functions. Metaphor itself undoubtedly reflects the way in which we categorize and retrieve information 44], so it is not surprising that the deep processes of language tend to sample information from related data categories. Although the nervous and immune systems are obviously not the same and metaphors are indeed just that, my primary goal has been to suggest that by virtue of their having evolved in parallel over millions of years, the nervous and immune systems currently use the same archetypal principles and strategies to address related challenges in information processing and retrieval. Ultimately, nature is conservative. One need only look at a tree, a river, the airways, or the vascular bed in order to see how a fractal pattern of repetitive dichotomous branching has been used by each, in order to optimize the transport of fluids over large distances [45]. While each system has had to adopt different materials in order to solve the problem, the shape of their solutions is remarkably alike. In the immune and nervous systems, the elements used to produce optimal functional responses are also quite different, but again the solutions have been achieved by comparable strategies. I am certain that these two great systems of information processing, each responding with vastly different kinetics, will prove to be far more integrally interdependent than has been previously recognized. For example, should a swift response by the immune system be required in an overwhelming invasion by microbial pathogens, the immune system may be able to cooperate with the rapidly reacting nervous system to rid the host of the invaders. In this regard, we have shown that the beta-adrenergic hormone epinephrine rapidly increases the traffic of

The University Immune System: Overcoming Resistance to Change

Science.gov (United States)

Gilley, Ann; Godek, Marisha; Gilley, Jerry W.

2009-01-01

A university, similar to any other organization, has an immune system that erects a powerful barrier against change. This article discusses the university immune system and what can be done to counteract its negative effects and thereby allow change to occur.

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,

Autopolyreactivity Confers a Holistic Role in the Immune System.

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Avrameas, S

2016-04-01

In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B-cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non-self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far-reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host-microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self-antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system. © 2016 The Foundation for the Scandinavian Journal of Immunology.

Impact of aging immune system on neurodegeneration and potential immunotherapies.

Science.gov (United States)

Liang, Zhanfeng; Zhao, Yang; Ruan, Linhui; Zhu, Linnan; Jin, Kunlin; Zhuge, Qichuan; Su, Dong-Ming; Zhao, Yong

2017-10-01

The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of a flat panel digital radiographic system for low-dose portable imaging of neonates

International Nuclear Information System (INIS)

Samei, Ehsan; Hill, Jeanne G.; Frey, G. Donald; Southgate, W. Michael; Mah, Eugene; Delong, David

2003-01-01

The purpose of this study was to evaluate the clinical utility of an investigational flat-panel digital radiography system for low-dose portable neonatal imaging. Thirty image-pairs from neonatal intensive care unit patients were acquired with a commercial Computed Radiography system (Agfa, ADC 70), and with the investigational system (Varian, Paxscan 2520) at one-quarter of the exposure. The images were evaluated for conspicuity and localization of the endings of ancillary catheters and tubes in two observer performance experiments with three pediatric radiologists and three neonatologists serving as observers. The results indicated no statistically significant difference in diagnostic quality between the images from the investigational system and from CR. Given the investigational system's superior resolution and noise characteristics, observer results suggest that the high detective quantum efficiency of flat-panel digital radiography systems can be utilized to decrease the radiation dose/exposure to neonatal patients, although post-processing of the images remains to be optimized. The rapid availability of flat-panel images in portable imaging was found to be an added advantage for timely clinical decision-making

Effects of ionizing radiation on the immune system

International Nuclear Information System (INIS)

Dubois, J.B.

1986-01-01

After reviewing the different lymphoid organs and the essential phases of the immune response, we studied the morphological and functional effects of ionizing radiation on the immunological system. Histologic changes in the lymph nodes, spleen, thymus, and different lymphocyte subpopulations were studied in relation with the radiation dose and irradiated volume (whole body irradiation, localized irradiation). Functional changes in the immune system induced by ionizing radiation were also investigated by a study of humoral-mediated immunity (antibody formation) and cell-mediated immunity (behavior of macrophages, B-cells, T suppressor cells, T helper cells, T effector cells, and natural killer cells). A study into the mechanisms of action of ionizing radiation and the immune processes it interferes with suggests several likely hypotheses (direct action on the immune cells, on their precursors, on seric mediators or on cell mediators). The effects on cancer patients' immune reactions of low radiation doses delivered to the various lymphoid organs are discussed, as well as the relationships between the host and the evolution of the tumor [fr

Investigating Relationships between Reproduction, Immune Defenses, and Cortisol in Dall Sheep

Directory of Open Access Journals (Sweden)

Cynthia J. Downs

2018-01-01

Full Text Available Life-history theory is fundamental to understanding how animals allocate resources among survival, development, and reproduction, and among traits within these categories. Immediate trade-offs occur within a short span of time and, therefore, are more easily detected. Trade-offs, however, can also manifest across stages of the life cycle, a phenomenon known as carryover effects. We investigated trade-offs on both time scales in two populations of Dall sheep (Ovis dalli dalli in Southcentral Alaska. Specifically, we (i tested for glucocorticoid-mediated carryover effects from the breeding season on reproductive success and immune defenses during parturition and (ii tested for trade-offs between immune defenses and reproduction within a season. We observed no relationship between cortisol during mating and pregnancy success; however, we found marginal support for a negative relationship between maternal cortisol and neonate birth weights. Low birth weights, resulting from high maternal cortisol, may result in low survival or low fecundity for the neonate later in life, which could result in overall population decline. We observed a negative relationship between pregnancy and bacterial killing ability, although we observed no relationship between pregnancy and haptoglobin. Study site affected bactericidal capacity and the inflammatory response, indicating the influence of external factors on immune responses, although we could not test hypotheses about the cause of those differences. This study helps advance our understanding of the plasticity and complexity of the immune system and provides insights into the how individual differences in physiology may mediate differences in fitness.

The role of the adaptive immune system in regulation of gut microbiota.

Science.gov (United States)

Kato, Lucia M; Kawamoto, Shimpei; Maruya, Mikako; Fagarasan, Sidonia

2014-07-01

The gut nourishes rich bacterial communities that affect profoundly the functions of the immune system. The relationship between gut microbiota and the immune system is one of reciprocity. The microbiota contributes to nutrient processing and the development, maturation, and function of the immune system. Conversely, the immune system, particularly the adaptive immune system, plays a key role in shaping the repertoire of gut microbiota. The fitness of host immune system is reflected in the gut microbiota, and deficiencies in either innate or adaptive immunity impact on diversity and structures of bacterial communities in the gut. Here, we discuss the mechanisms that underlie this reciprocity and emphasize how the adaptive immune system via immunoglobulins (i.e. IgA) contributes to diversification and balance of gut microbiota required for immune homeostasis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Design of wireless sensor system for neonatal monitoring

NARCIS (Netherlands)

Chen, W.; Nguyen, S.T.; Bouwstra, S.; Coops, R.; Brown, L.; Bambang Oetomo, S.; Feijs, L.M.G.

2011-01-01

In this paper, we present the application of wireless sensor technology and the advantages it will inherently have for neonatal care and monitoring at Neonatal Intensive Care Units (NICU). An electrocardiography (ECG) readout board and a wireless transceiver module developed by IMEC at the Holst

The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

Science.gov (United States)

McGrath-Morrow, Sharon A; Hayashi, Madoka; Aherrera, Angela; Lopez, Armando; Malinina, Alla; Collaco, Joseph M; Neptune, Enid; Klein, Jonathan D; Winickoff, Jonathan P; Breysse, Patrick; Lazarus, Philip; Chen, Gang

2015-01-01

Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth. Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG) or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI) method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml). After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (pE-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

Obesity, Fat Mass and Immune System: Role for Leptin

Directory of Open Access Journals (Sweden)

Vera Francisco

2018-06-01

Full Text Available Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

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

Immune system modulation in the central nervous system: A possible role for endocannabinoids

International Nuclear Information System (INIS)

Abd-Allah, Adel R.A.

2007-01-01

The immune system is designed to protect the body from infection and tumor formation. To perform this function, cells of the immune system can be dangerous for the survival and function of the neuronal network in the brain under the influence of infection or immune imbalance. An attack of immune cells inside the brain includes the potential for severe neuronal damage or cell death and therefore impairment of the CNS function. To avoid such undesirable action of the immune system, the CNS performs a cascade of cellular and molecular mechanisms enabling strict control of immune reactions i mmune privilege . Under inflammatory and patholological conditions, uncontrolled immune system results in the activation of neuronal damage that is frequently associated with neurological diseases. On the other hand, processes of neuroprotection and neurorepair after neuronal damage depend on a steady and tightly controlled immunesurvelliance. Many immunoprotectants play a role to imbalance the immune reactions in the CNS and other organs which presents an important therapeutic target. It has been reported recently that endocannabinoids are secreted in abundance in the CNS following neuronal insult, probably for its protection. There are at least two types of cannabinoid receptors, CB1 and CB2. Both are coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. Endogenous agonists for cannabinoid receptors (endocannabinoids), have been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol (2AG), and 2-archidonyl glyceryl ether. Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. Therapeutic uses of cannabinoid receptor agonists/antagonists include the management of many disease conditions. They are also involved in immune system suppression and in cell to cell communication

CMV immune evasion and manipulation of the immune system with aging.

Science.gov (United States)

Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

2017-06-01

Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

Neonatal pain management

Directory of Open Access Journals (Sweden)

Tarun Bhalla

2014-01-01

Full Text Available The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.

Efficacy of a low-cost bubble CPAP system in treatment of respiratory distress in a neonatal ward in Malawi.

Directory of Open Access Journals (Sweden)

Kondwani Kawaza

Full Text Available Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care.We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups.87 neonates (62 bCPAP, 25 controls were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62 compared with 44.0% (11/25 for controls. 65.5% (19/29 of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13 of controls. 64.6% (31/48 of neonates with respiratory distress syndrome (RDS receiving bCPAP survived to discharge, compared to 23.5% (4/17 of controls. 61.5% (16/26 of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived.Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.

Efficacy of a low-cost bubble CPAP system in treatment of respiratory distress in a neonatal ward in Malawi.

Science.gov (United States)

Kawaza, Kondwani; Machen, Heather E; Brown, Jocelyn; Mwanza, Zondiwe; Iniguez, Suzanne; Gest, Al; Smith, E O'Brian; Oden, Maria; Richards-Kortum, Rebecca R; Molyneux, Elizabeth

2014-01-01

Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP) is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care. We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups. 87 neonates (62 bCPAP, 25 controls) were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62) compared with 44.0% (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48) of neonates with respiratory distress syndrome (RDS) receiving bCPAP survived to discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived. Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.

Maintenance of systemic immune functions prevents accelerated presbycusis.

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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.

The Immune System: Basis of so much Health and Disease: 4. Immunocytes.

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Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

2017-05-01

The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers cells of the immune system (immunocytes). Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

An agent based architecture for high-risk neonate management at neonatal intensive care unit.

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Malak, Jaleh Shoshtarian; Safdari, Reza; Zeraati, Hojjat; Nayeri, Fatemeh Sadat; Mohammadzadeh, Niloofar; Farajollah, Seide Sedighe Seied

2018-01-01

In recent years, the use of new tools and technologies has decreased the neonatal mortality rate. Despite the positive effect of using these technologies, the decisions are complex and uncertain in critical conditions when the neonate is preterm or has a low birth weight or malformations. There is a need to automate the high-risk neonate management process by creating real-time and more precise decision support tools. To create a collaborative and real-time environment to manage neonates with critical conditions at the NICU (Neonatal Intensive Care Unit) and to overcome high-risk neonate management weaknesses by applying a multi agent based analysis and design methodology as a new solution for NICU management. This study was a basic research for medical informatics method development that was carried out in 2017. The requirement analysis was done by reviewing articles on NICU Decision Support Systems. PubMed, Science Direct, and IEEE databases were searched. Only English articles published after 1990 were included; also, a needs assessment was done by reviewing the extracted features and current processes at the NICU environment where the research was conducted. We analyzed the requirements and identified the main system roles (agents) and interactions by a comparative study of existing NICU decision support systems. The Universal Multi Agent Platform (UMAP) was applied to implement a prototype of our multi agent based high-risk neonate management architecture. Local environment agents interacted inside a container and each container interacted with external resources, including other NICU systems and consultation centers. In the NICU container, the main identified agents were reception, monitoring, NICU registry, and outcome prediction, which interacted with human agents including nurses and physicians. Managing patients at the NICU units requires online data collection, real-time collaboration, and management of many components. Multi agent systems are applied as

How (and why) the immune system makes us sleep.

Science.gov (United States)

Imeri, Luca; Opp, Mark R

2009-03-01

Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.

[The role of the innate immune system in atopic dermatitis].

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Volz, T; Kaesler, S; Skabytska, Y; Biedermann, T

2015-02-01

The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

The effects of early life adversity on the immune system.

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Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

2017-08-01

Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Immune System in Hypertension

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Trott, Daniel W.; Harrison, David G.

2014-01-01

While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

The Immune System of HIV-Exposed Uninfected Infants.

Science.gov (United States)

Abu-Raya, Bahaa; Kollmann, Tobias R; Marchant, Arnaud; MacGillivray, Duncan M

2016-01-01

Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, haemophilus influenzae type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored.

Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.

Science.gov (United States)

Dantzer, Robert

2018-01-01

Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous

Role of the Immune System in Hypertension.

Science.gov (United States)

Rodriguez-Iturbe, Bernardo; Pons, Hector; Johnson, Richard J

2017-07-01

High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease. Copyright © 2017 the American Physiological Society.

The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

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Sharon A McGrath-Morrow

Full Text Available Electronic cigarette (E-cigarettes emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth.Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml. After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (p<.054 trial 1; p<.006 trial 2. These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths.

Science.gov (United States)

Agrawal, Madhur; Kern, Philip A; Nikolajczyk, Barbara S

2017-08-15

Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically. However, new evidence also suggests that the immune system is equally vital for adipocyte differentiation and protection from ectopic lipid deposition. Furthermore, roles of anti-inflammatory immune cells such as regulatory T cells, "M2-like" macrophages, eosinophils, and mast cells are being explored, primarily due to promise of immunotherapeutic applications. Both immune responses and AT distribution are strongly influenced by factors like sex and race, which have been largely underappreciated in the field of metabolically-associated inflammation, or meta-flammation. More studies are required to recognize factors that switch inflammation from controlled to uncontrolled in obesity-associated pathogenesis and to integrate the combined effects of meta-flammation and immunometabolism. It is critical to recognize that the AT-associated immune system can be alternately beneficial and destructive; therefore, simply blocking immune responses early in obesity may not be the best clinical approach. The dearth of information on gender and race-associated disparities in metabolism, AT distribution, and the immune system suggest that a greater understanding of such differences will be critical to develop personalized treatments for obesity and the associated metabolic dysfunction.

Systems biology of neutrophil differentiation and immune response

DEFF Research Database (Denmark)

Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

2005-01-01

Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis).

Science.gov (United States)

Korolevskaya, Larisa B; Shmagel, Konstantin V; Shmagel, Nadezhda G; Saidakova, Evgeniya V

2016-03-01

Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modulating the immune system through nanotechnology.

Science.gov (United States)

Dacoba, Tamara G; Olivera, Ana; Torres, Dolores; Crecente-Campo, José; Alonso, María José

2017-12-01

Nowadays, nanotechnology-based modulation of the immune system is presented as a cutting-edge strategy, which may lead to significant improvements in the treatment of severe diseases. In particular, efforts have been focused on the development of nanotechnology-based vaccines, which could be used for immunization or generation of tolerance. In this review, we highlight how different immune responses can be elicited by tuning nanosystems properties. In addition, we discuss specific formulation approaches designed for the development of anti-infectious and anti-autoimmune vaccines, as well as those intended to prevent the formation of antibodies against biologicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regional specialization within the intestinal immune system

DEFF Research Database (Denmark)

Mowat, Allan M.; Agace, William Winston

2014-01-01

The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

Direct and Electronic Health Record Access to the Clinical Decision Support for Immunizations in the Minnesota Immunization Information System.

Science.gov (United States)

Rajamani, Sripriya; Bieringer, Aaron; Wallerius, Stephanie; Jensen, Daniel; Winden, Tamara; Muscoplat, Miriam Halstead

2016-01-01

Immunization information systems (IIS) are population-based and confidential computerized systems maintained by public health agencies containing individual data on immunizations from participating health care providers. IIS hold comprehensive vaccination histories given across providers and over time. An important aspect to IIS is the clinical decision support for immunizations (CDSi), consisting of vaccine forecasting algorithms to determine needed immunizations. The study objective was to analyze the CDSi presentation by IIS in Minnesota (Minnesota Immunization Information Connection [MIIC]) through direct access by IIS interface and by access through electronic health records (EHRs) to outline similarities and differences. The immunization data presented were similar across the three systems examined, but with varying ability to integrate data across MIIC and EHR, which impacts immunization data reconciliation. Study findings will lead to better understanding of immunization data display, clinical decision support, and user functionalities with the ultimate goal of promoting IIS CDSi to improve vaccination rates.

Effects of prebiotics on immune system and cytokine expression.

Science.gov (United States)

Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Navidshad, Bahman; Liang, Juan Boo

2017-02-01

Nowadays, use of prebiotics as feed and food additives has received increasing interest because of the beneficial effects of prebiotics on the health of animals and humans. One of the beneficial effects of prebiotics is stimulation of immune system, which can be direct or indirect through increasing population of beneficial microbes or probiotics, especially lactic acid bacteria and bifidobacteria, in the gut. An important mechanism of action of probiotics and prebiotics, by which they can affect the immune system, is changing the expression of cytokines. The present review tried to summarize the findings of studies that investigated the effects of prebiotics on immune system with focusing on their effects on cytokine expression. Generally, most of reviewed studies indicated beneficial effects for prebiotics in terms of improving immune system, by increasing the expression of anti-inflammatory cytokines, while reducing the expressions of proinflammatory cytokines. However, most of studies mainly considered the indirect effects of prebiotics on the immune system (through changing the composition and population of gut microbiota), and their direct effects still need to be further studied using prebiotics with different degree of polymerization in different hosts.

Thermodynamics as the driving principle behind the immune system

Directory of Open Access Journals (Sweden)

Eduardo Finger

2012-09-01

Full Text Available Over the last 120 years, few things contributed more to ourunderstanding of immune system than the study of its behavior inthe host/parasite relationship. Despite the advances though, a fewquestions remain, such as what drives the immune system? Whatare its guiding principles? If we ask these questions randomly, mostwill immediately answer “defend the body from external threats,” butwhat exactly do we defend ourselves from? How do these threatsharm us? What criteria define what constitutes a threat? On theother hand, if the immune system evolved to defend us againstexternal threats, how does its action against “internal” processes,such as neoplasms, qualify? Why do we die from cancer? Or frominfection? Or even, why do we die at all? These apparently obviousquestions are nor simple neither trivial, and the difficulty answeringthem reveals the complex reality that the immune system handles.The objective of this article is to articulate for the reader something that he instinctively already knows: that the decisions of the immune system are thermodynamically driven. Additionally, we will discuss how this apparent change in paradigm alters concepts such as health, disease, and therapeutics.

Artificial immune system applications in computer security

CERN Document Server

Tan, Ying

2016-01-01

This book provides state-of-the-art information on the use, design, and development of the Artificial Immune System (AIS) and AIS-based solutions to computer security issues. Artificial Immune System: Applications in Computer Security focuses on the technologies and applications of AIS in malware detection proposed in recent years by the Computational Intelligence Laboratory of Peking University (CIL@PKU). It offers a theoretical perspective as well as practical solutions for readers interested in AIS, machine learning, pattern recognition and computer security. The book begins by introducing the basic concepts, typical algorithms, important features, and some applications of AIS. The second chapter introduces malware and its detection methods, especially for immune-based malware detection approaches. Successive chapters present a variety of advanced detection approaches for malware, including Virus Detection System, K-Nearest Neighbour (KNN), RBF networ s, and Support Vector Machines (SVM), Danger theory, ...

Subcutaneous or oral immunization of mice with Lactococcus lactis expressing F4 fimbrial adhesin FaeG.

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Liu, Shujie; Li, Yongming; Xu, Ziwei; Wang, Yicheng

2013-01-01

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in neonatal and postweaning piglets. Fimbrial adhesion of ETEC has been considered an important colonization factor with antigenicity. To safely and effectively deliver the F4 (K88) fimbrial adhesin FaeG to the immune system, we have previously constructed the secretory expression vector pNZ8112-faeG, and FaeG was produced in cytoplasmic form in Lactococcus lactis. In this work, BALB/c mice were immunized with recombinant L. lactis to further determine the immunogenicity of recombinant FaeG (rFaeG) via the subcutaneous or oral route. Subcutaneous immunization in mice with recombinant L. lactis induced a significant increase in the F4-specific serum IgG titer and the number of antibody-secreting cells (ASCs) in the spleen. Oral immunization of mice with recombinant L. lactis induced mucosal and systemic F4-specific immune responses and increased the number of ASCs in the spleen, mesenteric lymph nodes and Peyer's patches. High-dose (2.8 × 10(11) CFU) recombinant strains and adjuvant cholera toxin B subunit enhanced specific mucosal immune responses. The results suggest the feasibility of delivering rFaeG expressed in L. lactis to the immune system in order to induce an F4-specific immune response.

Single-cell technologies to study the immune system.

Science.gov (United States)

Proserpio, Valentina; Mahata, Bidesh

2016-02-01

The immune system is composed of a variety of cells that act in a coordinated fashion to protect the organism against a multitude of different pathogens. The great variability of existing pathogens corresponds to a similar high heterogeneity of the immune cells. The study of individual immune cells, the fundamental unit of immunity, has recently transformed from a qualitative microscopic imaging to a nearly complete quantitative transcriptomic analysis. This shift has been driven by the rapid development of multiple single-cell technologies. These new advances are expected to boost the detection of less frequent cell types and transient or intermediate cell states. They will highlight the individuality of each single cell and greatly expand the resolution of current available classifications and differentiation trajectories. In this review we discuss the recent advancement and application of single-cell technologies, their limitations and future applications to study the immune system. © 2015 The Authors. Immunology Published by John Wiley & Sons Ltd.

MRI of neonatal encephalopathy

International Nuclear Information System (INIS)

Khong, P.L.; Lam, B.C.C.; Tung, H.K.S.; Wong, V.; Chan, F.L.; Ooi, G.C.

2003-01-01

We present the magnetic resonance imaging (MRI) findings in neonatal encephalopathy, including hypoxic-ischaemic encephalopathy, perinatal/neonatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital central nervous system infections and birth trauma. The applications of advanced MRI techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy are emphasized

Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.

Science.gov (United States)

Robson, Matthew J; Quinlan, Meagan A; Blakely, Randy D

2017-05-17

Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.

Mind-Body Medicine and Immune System Outcomes: A Systematic Review

OpenAIRE

Wahbeh, Helané; Haywood, Ashley; Kaufman, Karen; Zwickey, Heather

2009-01-01

This study is a systematic review of mind-body interventions that used immune outcomes in order to: 1) characterize mind-body medicine studies that assessed immune outcomes, 2) evaluate the quality of mind-body medicine studies measuring immune system effects, and 3) systematically evaluate the evidence for mind-body interventions effect on immune system outcomes using existing formal tools. 111 studies with 4,777 subjects were reviewed. The three largest intervention type categories were Rel...

Protective effect of enterovirus‑71 (EV71) virus‑like particle vaccine against lethal EV71 infection in a neonatal mouse model.

Science.gov (United States)

Cao, Lei; Mao, Fengfeng; Pang, Zheng; Yi, Yao; Qiu, Feng; Tian, Ruiguang; Meng, Qingling; Jia, Zhiyuan; Bi, Shengli

2015-08-01

Enterovirus-71 (EV71) is a viral pathogen that causes severe cases of hand, foot and mouth disease (HFMD) among young children, with significant mortality. Effective vaccines against HFMD are urgently required. Several EV71 virus-like particle (VLP) vaccine candidates were found to be protective in the neonatal mouse EV71 challenge model. However, to what extent the VLP vaccine protects susceptible organs against EV71 infection in vivo has remained elusive. In the present study, the comprehensive immunogenicity of a potential EV71 vaccine candidate based on VLPs was evaluated in a neonatal mouse model. Despite lower levels of neutralizing antibodies to EV71 in the sera of VLP-immunized mice compared with those in mice vaccinated with inactivated EV71, the VLP-based vaccine was shown to be able to induce immunoglobulin (Ig)G and IgA memory-associated cellular immune responses to EV71. Of note, the EV71 VLP vaccine candidate was capable of inhibiting viral proliferation in cardiac muscle, skeletal muscle, lung and intestine of immunized mice and provided effective protection against the pathological damage caused by viral attack. In particular, the VLP vaccine was able to inhibit the transportation of EV71 from the central nervous system to the muscle tissue and greatly protected muscle tissue from infection, along with recovery from the viral infection. This led to nearly 100% immunoprotective efficacy, enabling neonatal mice delivered by VLP-immunized female adult mice to survive and grow with good health. The present study provided valuable additional knowledge of the specific protective efficacy of the EV71 VLP vaccine in vivo, which also indicated that it is a promising potential candidate for being developed into an EV71 vaccine.

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

Science.gov (United States)

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

2008-01-01

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

The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

Science.gov (United States)

Mendes, Fernando; Domingues, Cátia; Rodrigues-Santos, Paulo; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Estrela, Jéssica; Encarnação, João; Pires, Ana Salomé; Laranjo, Mafalda; Alves, Vera; Teixo, Ricardo; Sarmento, Ana Bela; Botelho, Maria Filomena; Rosa, Manuel Santos

2016-04-01

Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Soluble CD14 in human breast milk and its role in innate immune responses.

Science.gov (United States)

Vidal, K; Labéta, M O; Schiffrin, E J; Donnet-Hughes, A

2001-10-01

Immune factors secreted in milk are important for health in the neonatal gut. We have detected the bacterial pattern recognition receptor, soluble CD14 (sCD14) in human breast milk at different times during lactation. The molecule occurs in a single form in milk, in contrast to human serum, in which there are two isoforms. Produced by mammary epithelial cells, milk sCD14 mediates secretion of innate immune response molecules such as interleukin-8, tumor necrosis factor-alpha, and epithelial neutrophil activator-78 by CD14-negative intestinal epithelial cells exposed to lipopolysaccharide (LPS) or bacteria. Although present at low concentrations in milk, LPS-binding protein may be implicated in the biological effects observed. Our findings support the premise that milk sCD14 acts as a 'sentinel' molecule and immune modulator in homeostasis and in the defense of the neonatal intestine. In so doing, it may prevent the immune and inflammatory conditions of the gut to which non-breastfed infants are predisposed.

Breakdown of the innate immune system by bacterial proteases

NARCIS (Netherlands)

Laarman, A.J.

2011-01-01

Bacteria have developed many strategies to circumvent our immune system to survive and colonize human tissues. One of these strategies is by secreting proteases that specifically target the innate immune system. Aureolysin is a metalloprotease from Staphylococcus aureus which target the main

Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

Science.gov (United States)

LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

2006-03-15

The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

Outgrowing the Immaturity Myth: The Cost of Defending From Neonatal Infectious Disease

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Danny Harbeson

2018-05-01

Full Text Available Newborns suffer high rates of mortality due to infectious disease—this has been generally regarded to be the result of an “immature” immune system with a diminished disease-fighting capacity. However, the immaturity dogma fails to explain (i greater pro-inflammatory responses than adults in vivo and (ii the ability of neonates to survive a significantly higher blood pathogen burden than of adults. To reconcile the apparent contradiction of clinical susceptibility to disease and the host immune response findings when contrasting newborn to adult, it will be essential to capture the entirety of available host-defense strategies at the newborn’s disposal. Adults focus heavily on the disease resistance approach: pathogen reduction and elimination. Newborn hyperactive innate immunity, sensitivity to immunopathology, and the energetic requirements of growth and development (immune and energy costs, however, preclude them from having an adult-like resistance response. Instead, newborns also may avail themselves of disease tolerance (minimizing immunopathology without reducing pathogen load, as a disease tolerance approach provides a counterbalance to the dangers of a heightened innate immunity and has lower-associated immune costs. Further, disease tolerance allows for the establishment of a commensal bacterial community without mounting an unnecessarily dangerous immune resistance response. Since disease tolerance has its own associated costs (immune suppression leading to unchecked pathogen proliferation, it is the maintenance of homeostasis between disease tolerance and disease resistance that is critical to safe and effective defense against infections in early life. This paradigm is consistent with nearly all of the existing evidence.

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

Parental satisfaction in the traditional system of neonatal intensive ...

African Journals Online (AJOL)

Neonatal intensive care unit (NICU) admission is a time of significant stress for the ... depression, both during the neonate's hospitalisation and in the post- ... directly, as the expressed breastmilk is fed to the baby by nursing staff as per its need ...

Country Immunization Information System Assessments - Kenya, 2015 and Ghana, 2016.

Science.gov (United States)

Scott, Colleen; Clarke, Kristie E N; Grevendonk, Jan; Dolan, Samantha B; Ahmed, Hussein Osman; Kamau, Peter; Ademba, Peter Aswani; Osadebe, Lynda; Bonsu, George; Opare, Joseph; Diamenu, Stanley; Amenuvegbe, Gregory; Quaye, Pamela; Osei-Sarpong, Fred; Abotsi, Francis; Ankrah, Joseph Dwomor; MacNeil, Adam

2017-11-10

The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between child registers and facility tally sheets (Kenya = 0%, Ghana = 3%). In Kenya, systemic challenges included limited supportive supervision and lack of resources to access electronic reporting systems; in Ghana, challenges included a poorly defined subdistrict administrative level. Data quality improvement plans (DQIPs) based on assessment findings are being implemented in both countries. IISAs can help countries identify and address root causes of poor immunization data to provide a stronger evidence base for future investments in immunization programs.

Artificial immune system algorithm in VLSI circuit configuration

Science.gov (United States)

Mansor, Mohd. Asyraf; Sathasivam, Saratha; Kasihmuddin, Mohd Shareduwan Mohd

2017-08-01

In artificial intelligence, the artificial immune system is a robust bio-inspired heuristic method, extensively used in solving many constraint optimization problems, anomaly detection, and pattern recognition. This paper discusses the implementation and performance of artificial immune system (AIS) algorithm integrated with Hopfield neural networks for VLSI circuit configuration based on 3-Satisfiability problems. Specifically, we emphasized on the clonal selection technique in our binary artificial immune system algorithm. We restrict our logic construction to 3-Satisfiability (3-SAT) clauses in order to outfit with the transistor configuration in VLSI circuit. The core impetus of this research is to find an ideal hybrid model to assist in the VLSI circuit configuration. In this paper, we compared the artificial immune system (AIS) algorithm (HNN-3SATAIS) with the brute force algorithm incorporated with Hopfield neural network (HNN-3SATBF). Microsoft Visual C++ 2013 was used as a platform for training, simulating and validating the performances of the proposed network. The results depict that the HNN-3SATAIS outperformed HNN-3SATBF in terms of circuit accuracy and CPU time. Thus, HNN-3SATAIS can be used to detect an early error in the VLSI circuit design.

New insights into innate immune control of systemic candidiasis

Science.gov (United States)

Lionakis, Michail S.

2014-01-01

Systemic infection caused by Candida species is the fourth leading cause of nosocomial bloodstream infection in modern hospitals and carries high morbidity and mortality despite antifungal therapy. A recent surge of immunological studies in the mouse models of systemic candidiasis and the parallel discovery and phenotypic characterization of inherited genetic disorders in antifungal immune factors that are associated with enhanced susceptibility or resistance to the infection have provided new insights into the cellular and molecular basis of protective innate immune responses against Candida. In this review, the new developments in our understanding of how the mammalian immune system responds to systemic Candida challenge are synthesized and important future research directions are highlighted. PMID:25023483

Maternal, Fetal and Neonatal Outcomes in Pregnant Women with Systemic Lupus Erythematosus: A Comprehensive Review Study

Directory of Open Access Journals (Sweden)

Fatemeh Zahra Karimi

2017-11-01

Full Text Available Background:Systemic lupus erythematosus (SLE is an autoimmune disease with multiple organ involvement and periods of relapse and remission that mainly affects young women of childbearing age. In this regard the reproductive health is an important issue. Although diagnosis, treatment and management of pregnancy in SLE women have been improved recently, but the main concern is effects of SLE on maternal, fetal and neonatal outcomes. This study aimed to investigate the maternal, fetal and neonatal outcomes in pregnant women with SLE. Materials and Methods: The databases of PubMed, Medline, Scopus and Web of Science as well as domestic database (Persian such as SID, Magiran, Irandoc, and Google Scholar were searched with using keywords such as" Systemic lupus erythematosus"; "Pregnancy"; "Neonatal lupus"; "maternal, fetus or neonatal outcome";  and equivalent Persian words. Included were all Persian and English articles, published between 2000 and May 2017. Finally, a total of 77 studies were included. Results: Adverse perinatal outcomes increase in pregnancies with lupus. Outcomes include respiratory, cardiovascular, blood and skin disorders in mothers; stillbirth, spontaneous, and recurrent abortion in fetuses and neonatal lupus, prematurity, intrauterine growth restriction (IUGR, and small for gestational age (SGA in neonates, respectively. Conclusion: Pregnant women with SLE are at high risk due to increased complications for both mother and fetus. It seems broad control of the women before fertilization, so that they be at full remission in the beginning of pregnancy and the disease activity be in complete control, it can help to improve outcomes of pregnancy and so better results can be expected.

The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates

Directory of Open Access Journals (Sweden)

Kludka-Sternik M

2010-04-01

Full Text Available The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendriticcells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty ninehealthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. Theexpression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performedusing a non-parametric test (Mann-Whitney U-Test. The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4expressions were significantly higher in peripheral blood of healthy adults (p<0.00003. It was either observed that the percentageof BDCA-2+ dendritic cells with the expression of B7-H4 molecules was significantly higher in peripheral blood ofhealthy adults in comparison with umbilical cord blood (p<0.02. Decreased percentages of dendritic cells and co-stimulatorymolecules indicate that neonates have immature immune system. Depletion of co-stimulatory B7-H1 and B7-H4 moleculesenable appropriate development of immune response.

The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates.

Directory of Open Access Journals (Sweden)

S Radej

2011-04-01

Full Text Available The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty nine healthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. The expression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performed using a non-parametric test (Mann-Whitney U-Test. The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4 expressions were significantly higher in peripheral blood of healthy adults (p<0.00003. It was either observed that the percentage of BDCA-2+ dendritic cells with the expression of B7-H4 molecules was significantly higher in peripheral blood of healthy adults in comparison with umbilical cord blood (p<0.02. Decreased percentages of dendritic cells and co-stimulatory molecules indicate that neonates have immature immune system. Depletion of co-stimulatory B7-H1 and B7-H4 molecules enable appropriate development of immune response.

IMMUNE SYSTEM MATURITY AND SENSITIVITY TO CHEMICAL EXPOSURE

Science.gov (United States)

It is well established that human diseases associated with abnormal immune function, including some common infectious diseases and asthma, are considerably more prevalent at younger ages. The immune system continues to mature after birth, and functional immaturity accounts for m...

Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100-Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

NARCIS (Netherlands)

Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2013-01-01

Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery

Chronic grouped social restriction triggers long-lasting immune system adaptations.

Science.gov (United States)

Tian, Rui; Hou, Gonglin; Song, Liuwei; Zhang, Jianming; Yuan, Ti-Fei

2017-05-16

Chronic stress triggers rigorous psychological and physiological changes, including immunological system adaptations. However, the effects of long-term social restriction on human immune system have not been investigated. The present study is to investigate the effect of chronic stress on immune changes in human blood, with the stress stimuli controlled.10 male volunteers were group isolated from the modern society in a 50-meter-square room for 150 days, with enriched nutrition and good living conditions provided. Serum examination of immune system markers demonstrated numerous changes in different aspects of the immune functions. The changes were observed as early as 30 days and could last for another 150 days after the termination of the restriction period (300 days' time point). The results strongly argued for the adaptation of immunological system under chronic social restriction stress in adult human, preceding a clear change in psychological conditions. The changes of these immune system factors could as well act as the serum biomarkers in clinical early-diagnosis of stress-related disorders.

Modulation of systemic immune responses through commensal gastrointestinal microbiota.

Directory of Open Access Journals (Sweden)

Kyle M Schachtschneider

Full Text Available Colonization of the gastrointestinal (GI tract is initiated during birth and continually seeded from the individual's environment. Gastrointestinal microorganisms play a central role in developing and modulating host immune responses and have been the subject of investigation over the last decades. Animal studies have demonstrated the impact of GI tract microbiota on local gastrointestinal immune responses; however, the full spectrum of action of early gastrointestinal tract stimulation and subsequent modulation of systemic immune responses is poorly understood. This study explored the utility of an oral microbial inoculum as a therapeutic tool to affect porcine systemic immune responses. For this study a litter of 12 pigs was split into two groups. One group of pigs was inoculated with a non-pathogenic oral inoculum (modulated, while another group (control was not. DNA extracted from nasal swabs and fecal samples collected throughout the study was sequenced to determine the effects of the oral inoculation on GI and respiratory microbial communities. The effects of GI microbial modulation on systemic immune responses were evaluated by experimentally infecting with the pathogen Mycoplasma hyopneumoniae. Coughing levels, pathology, toll-like receptors 2 and 6, and cytokine production were measured throughout the study. Sequencing results show a successful modulation of the GI and respiratory microbiomes through oral inoculation. Delayed type hypersensitivity responses were stronger (p = 0.07, and the average coughing levels and respiratory TNF-α variance were significantly lower in the modulated group (p<0.0001 and p = 0.0153, respectively. The M. hyopneumoniae infection study showed beneficial effects of the oral inoculum on systemic immune responses including antibody production, severity of infection and cytokine levels. These results suggest that an oral microbial inoculation can be used to modulate microbial communities, as well as

Graphene and the immune system: Challenges and potentiality.

Science.gov (United States)

Orecchioni, Marco; Ménard-Moyon, Cécilia; Delogu, Lucia Gemma; Bianco, Alberto

2016-10-01

In the growing area of nanomedicine, graphene-based materials (GBMs) are some of the most recent explored nanomaterials. For the majority of GBM applications in nanomedicine, the immune system plays a fundamental role. It is necessary to well understand the complexity of the interactions between GBMs, the immune cells, and the immune components and how they could be of advantage for novel effective diagnostic and therapeutic approaches. In this review, we aimed at painting the current picture of GBMs in the background of the immune system. The picture we have drawn looks like a cubist image, a sort of Picasso-like portrait looking at the topic from all perspectives: the challenges (due to the potential toxicity) and the potentiality like the conjugation of GBMs to biomolecules to develop advanced nanomedicine tools. In this context, we have described and discussed i) the impact of graphene on immune cells, ii) graphene as immunobiosensor, and iii) antibodies conjugated to graphene for tumor targeting. Thanks to the huge advances on graphene research, it seems realistic to hypothesize in the near future that some graphene immunoconjugates, endowed of defined immune properties, can go through preclinical test and be successfully used in nanomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapies for neonates with congenital malformations admitted to a neonatal unit

Directory of Open Access Journals (Sweden)

Maria Vera Lúcia Moreira Leitão Cardoso

2015-03-01

Full Text Available The aim of this study was to characterize the treatments applied to newborns with congenital malformation hospitalized in a neonatal unit and to identify whether there is an association among the treatments used and the type of malformation. A descriptive, prospective and quantitative study was developed in a public institution in Fortaleza, Ceará, Brazil. Data were collected using the medical records of 30 neonates with congenital malformations. The incidence of malformations was higher among females, regardless of the mother’s age, gestational age or weight at birth; malformations of the central nervous and musculoskeletal systems prevailed. The treatments used varied according to the clinical evolution of the neonate. The data collected did not present statistical significance when associated with the variable of congenital malformation and the treatments used (p>0.05. The treatments are not directly related to the type of malformation, but to the clinical condition of the neonate.

T helper cell 2 immune skewing in pregnancy/early life

DEFF Research Database (Denmark)

McFadden, J P; Thyssen, J P; Basketter, D A

2015-01-01

During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation - Th2 cells...... that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider...... the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore further promote the persistence of a Th2 bias in neonates. Furthermore, we propose...

Molecular mechanisms of aging and immune system regulation in Drosophila.

Science.gov (United States)

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

Under Pressure: Interactions between Commensal Microbiota and the Teleost Immune System

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Cecelia Kelly

2017-05-01

Full Text Available Commensal microorganisms inhabit every mucosal surface of teleost fish. At these surfaces, microorganisms directly and indirectly shape the teleost immune system. This review provides a comprehensive overview of how the microbiota and microbiota-derived products influence both the mucosal and systemic immune system of fish. The cross talk between the microbiota and the teleost immune system shifts significantly under stress or disease scenarios rendering commensals into opportunists or pathogens. Lessons learnt from germ-free fish models as well as from oral administration of live probiotics to fish highlight the vast impact that microbiota have on immune development, antibody production, mucosal homeostasis, and resistance to stress. Future studies should dissect the specific mechanisms by which different members of the fish microbiota and the metabolites they produce interact with pathogens, with other commensals, and with the teleost immune system.

Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System.

Science.gov (United States)

Cerullo, Vincenzo; Capasso, Cristian; Vaha-Koskela, Markus; Hemminki, Otto; Hemminki, Akseli

2018-01-01

Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen- presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit. Tackling these questions will give us further insight in how to manipulate adenovirus-mediated immune responses for enhancement of anti-tumor efficacy. In this review, we first highlight how oncolytic adenovirus interacts with the innate immune system and its receptors such as Toll-like receptors, nucleotide-binding and oligomerization domain (NOD)- like receptors and other immune sensors. Then we describe the effect of these interactions on the adaptive immune system and its cells, especially B and T lymphocytes. Finally, we summarize the most significant preclinical and clinical results in the field of gene therapy where researchers have engineered adenovirus to manipulate the host immune system by expressing cytokines and signalingmediators. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Computed radiography in neonatal intensive care

International Nuclear Information System (INIS)

Merlo, L.; Bighi, S.; Cervi, P.M.; Lupi, L.

1991-01-01

The Authors report their experience in the employment of a computerized digital radiographic system in Neonatal Intensive Care. The analog screen-film system is replaced by photosensitive imaging plates, scanned after X-ray exposure by a laser that releases the digital image, which can then be manipulated on computer work-stations. In a period of twelve months about 200 chest-abdomen X-ray examinations in Neonatal Intensive Care have been performed using this method with good technical and diagnostic results. The use of digital radiography in the neonatal area is of high interest: this system produces good quality images, there is a reduction in radiation dose and 'retakes', the system allows selective enhancement of different structures and their magnification. (orig.)

Role of neuropilin-2 in the immune system.

Science.gov (United States)

Schellenburg, S; Schulz, A; Poitz, D M; Muders, M H

2017-10-01

Neuropilins (NRPs) are single transmembrane receptors with short cytoplasmic tails and are dependent on receptors like VEGF receptors or Plexins for signal transduction. NRPs are known to be important in angiogenesis, lymphangiogenesis, and axon guidance. The Neuropilin-family consists of two members, Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). They are up to 44 % homologous and conserved in all vertebrates. High levels of NRP2 are found on immune cells. Current research is very limited regarding the functions of NRP2 on these cells. Recent evidence suggests that NRP2 is important for migration, antigen presentation, phagocytosis and cell-cell contact within the immune system. Additionally, posttranslational NRP2 modifications like polysialylation are crucial for the function of some immune cells. This review is an overview about expression and functions of NRP2 in the immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age-Dependent Differences in Systemic and Cell-Autonomous Immunity to L. monocytogenes

Directory of Open Access Journals (Sweden)

Ashley M. Sherrid

2013-01-01

Full Text Available Host defense against infection can broadly be categorized into systemic immunity and cell-autonomous immunity. Systemic immunity is crucial for all multicellular organisms, increasing in importance with increasing cellular complexity of the host. The systemic immune response to Listeria monocytogenes has been studied extensively in murine models; however, the clinical applicability of these findings to the human newborn remains incompletely understood. Furthermore, the ability to control infection at the level of an individual cell, known as “cell-autonomous immunity,” appears most relevant following infection with L. monocytogenes; as the main target, the monocyte is centrally important to innate as well as adaptive systemic immunity to listeriosis. We thus suggest that the overall increased risk to suffer and die from L. monocytogenes infection in the newborn period is a direct consequence of age-dependent differences in cell-autonomous immunity of the monocyte to L. monocytogenes. We here review what is known about age-dependent differences in systemic innate and adaptive as well as cell-autonomous immunity to infection with Listeria monocytogenes.

Characterization of acoustic noise in a neonatal intensive care unit MRI system

Energy Technology Data Exchange (ETDEWEB)

Tkach, Jean A.; Li, Yu; Pratt, Ronald G.; Loew, Wolfgang; Daniels, Barret R.; Giaquinto, Randy O.; Dumoulin, Charles L. [Cincinnati Children' s Hospital Medical Center, Imaging Research Center, Department of Radiology, Cincinnati, OH (United States); Baroch, Kelly A. [Cincinnati Children' s Hospital Medical Center, Division of Audiology, Cincinnati, OH (United States); Merhar, Stephanie L. [Cincinnati Children' s Hospital Medical Center, Division of Neonatology and Pulmonary Biology, Perinatal Institute, Cincinnati, OH (United States); Kline-Fath, Beth M. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

2014-08-15

To eliminate the medical risks and logistical challenges of transporting infants from the neonatal intensive care unit (NICU) to the radiology department for magnetic resonance imaging, a small-footprint 1.5-T MRI scanner has been developed for neonatal imaging within the NICU. MRI is known to be noisy, and exposure to excessive acoustic noise has the potential to elicit physiological distress and impact development in the term and preterm infant. To measure and compare the acoustic noise properties of the NICU MRI system against those of a conventional 1.5-T MRI system. We performed sound pressure level measurements in the NICU MRI scanner and in a conventional adult-size whole-body 1.5-T MRI system. Sound pressure level measurements were made for six standard clinical MR imaging protocols. The average sound pressure level value, reported in unweighted (dB) and A-weighted (dBA) decibels for all six imaging pulse sequences, was 73.8 dB and 88 dBA for the NICU scanner, and 87 dB and 98.4 dBA for the conventional MRI scanner. The sound pressure level values measured on the NICU scanner for each of the six MR imaging pulse sequences were consistently and significantly (P = 0.03) lower, with an average difference of 14.2 dB (range 10-21 dB) and 11 dBA (range 5-18 dBA). The sound pressure level frequency response of the two MR systems showed a similar harmonic structure above 200 Hz for all imaging sequences. The amplitude, however, was appreciably lower for the NICU scanner, by as much as 30 dB, for frequencies below 200 Hz. The NICU MRI system is quieter than conventional MRI scanners, improving safety for the neonate and facilitating siting of the unit within the NICU. (orig.)

Characterization of acoustic noise in a neonatal intensive care unit MRI system

International Nuclear Information System (INIS)

Tkach, Jean A.; Li, Yu; Pratt, Ronald G.; Loew, Wolfgang; Daniels, Barret R.; Giaquinto, Randy O.; Dumoulin, Charles L.; Baroch, Kelly A.; Merhar, Stephanie L.; Kline-Fath, Beth M.

2014-01-01

To eliminate the medical risks and logistical challenges of transporting infants from the neonatal intensive care unit (NICU) to the radiology department for magnetic resonance imaging, a small-footprint 1.5-T MRI scanner has been developed for neonatal imaging within the NICU. MRI is known to be noisy, and exposure to excessive acoustic noise has the potential to elicit physiological distress and impact development in the term and preterm infant. To measure and compare the acoustic noise properties of the NICU MRI system against those of a conventional 1.5-T MRI system. We performed sound pressure level measurements in the NICU MRI scanner and in a conventional adult-size whole-body 1.5-T MRI system. Sound pressure level measurements were made for six standard clinical MR imaging protocols. The average sound pressure level value, reported in unweighted (dB) and A-weighted (dBA) decibels for all six imaging pulse sequences, was 73.8 dB and 88 dBA for the NICU scanner, and 87 dB and 98.4 dBA for the conventional MRI scanner. The sound pressure level values measured on the NICU scanner for each of the six MR imaging pulse sequences were consistently and significantly (P = 0.03) lower, with an average difference of 14.2 dB (range 10-21 dB) and 11 dBA (range 5-18 dBA). The sound pressure level frequency response of the two MR systems showed a similar harmonic structure above 200 Hz for all imaging sequences. The amplitude, however, was appreciably lower for the NICU scanner, by as much as 30 dB, for frequencies below 200 Hz. The NICU MRI system is quieter than conventional MRI scanners, improving safety for the neonate and facilitating siting of the unit within the NICU. (orig.)

The role of the immune system in Alzheimer disease: Etiology and treatment.

Science.gov (United States)

Jevtic, Stefan; Sengar, Ameet S; Salter, Michael W; McLaurin, JoAnne

2017-11-01

The immune system is now considered a major factor in Alzheimer Disease (AD). This review seeks to demonstrate how various aspects of the immune system, both in the brain and peripherally, interact to contribute to AD. We highlight classical nervous system immune components, such as complement and microglia, as well as novel aspects of the peripheral immune system that can influence disease, such as monocytes and lymphocytes. By detailing the roles of various immune cells in AD, we summarize an emerging perspective for disease etiology and future therapeutic targets. Copyright © 2017. Published by Elsevier B.V.

Prevalence and pattern of congenital malformations among neonates in the neonatal unit of a teaching hospital

International Nuclear Information System (INIS)

Hussain, S.; Sabir, M.; Tarar, S. H.; Mushtaq, R.; Asghar, I.; Chattha, M. N.

2014-01-01

Objective: To determine the prevalence and pattern of congenital malformations among neonates in a teaching hospital. Methods: The prospective hospital-based study was conducted over a period of 18 months in the neonatal unit of Combined Military Hospital, Kharian, from September 2011 to February 2013. All neonates from newborn to 28 days of age admitted to the unit irrespective of their condition comprised the study population. Neonatal examination was done by the Registrar at the time of admission followed by neonatologist/paediatrician. Information regarding gender, weight, gestational age, mode of delivery, consanguinity, maternal age, antenatal visit record and family history were recorded on a predesigned proforma. After clinical examination, if required, relevant investigations like ultrasonography, radiology, echocardiography, laboratory and genetic studies were done to confirm diagnosis. Data was statistically analysed by using SPSS 20. Results: Out of 3,210 total admissions, 226 (7%) neonates were congenitally malformed. Of them, 130 (57.52 %) were male and 96 (42.47 %) females. Among different body systems affected, anomalies related to the central nervous system were 46(20.35%) musculoskeletal 42(18.58%), genitourinary 34 (15.04%), cardiovascular system 30 (13.27%), ear, eye, face, neck 27(11.94%), digestive system 19 (8.40%), syndromes and skin 14 (6.19%) each. Conclusion: Congenital Malformations are not rare in our community and central nervous system is the most commonly affected system. Healthcare managers must stress upon primary prevention in the form of vaccination, nutrition and drugs to decrease preventable share of congenital malformations. (author)

Neural Control of the Immune System

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Sundman, Eva; Olofsson, Peder S.

2014-01-01

Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have…

Roles of Zinc Signaling in the Immune System.

Science.gov (United States)

Hojyo, Shintaro; Fukada, Toshiyuki

2016-01-01

Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells.

Immune algorithm based active PID control for structure systems

International Nuclear Information System (INIS)

Lee, Young Jin; Cho, Hyun Cheol; Lee, Kwon Soon

2006-01-01

An immune algorithm is a kind of evolutional computation strategies, which is developed in the basis of a real immune mechanism in the human body. Recently, scientific or engineering applications using this scheme are remarkably increased due to its significant ability in terms of adaptation and robustness for external disturbances. Particularly, this algorithm is efficient to search optimal parameters against complicated dynamic systems with uncertainty and perturbation. In this paper, we investigate an immune algorithm embedded Proportional Integral Derivate (called I P ID) control, in which an optimal parameter vector of the controller is determined offline by using a cell-mediated immune response of the immunized mechanism. For evaluation, we apply the proposed control to mitigation of vibrations for nonlinear structural systems, cased by external environment load such as winds and earthquakes. Comparing to traditional controls under same simulation scenarios, we demonstrate the innovation control is superior especially in robustness aspect

Sympathetic neural modulation of the immune system

International Nuclear Information System (INIS)

Madden, K.S.

1989-01-01

One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125 iododeoxyuridine ( 125 IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125 IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51 Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

Clonal Selection Based Artificial Immune System for Generalized Pattern Recognition

Science.gov (United States)

Huntsberger, Terry

2011-01-01

The last two decades has seen a rapid increase in the application of AIS (Artificial Immune Systems) modeled after the human immune system to a wide range of areas including network intrusion detection, job shop scheduling, classification, pattern recognition, and robot control. JPL (Jet Propulsion Laboratory) has developed an integrated pattern recognition/classification system called AISLE (Artificial Immune System for Learning and Exploration) based on biologically inspired models of B-cell dynamics in the immune system. When used for unsupervised or supervised classification, the method scales linearly with the number of dimensions, has performance that is relatively independent of the total size of the dataset, and has been shown to perform as well as traditional clustering methods. When used for pattern recognition, the method efficiently isolates the appropriate matches in the data set. The paper presents the underlying structure of AISLE and the results from a number of experimental studies.

The ontogeny of the porcine immune system

Czech Academy of Sciences Publication Activity Database

Šinkora, Marek; Butler, J. E.

2009-01-01

Roč. 33, č. 3 (2009), s. 273-283 ISSN 0145-305X R&D Projects: GA ČR GA524/07/0087; GA ČR GA523/07/0088 Institutional research plan: CEZ:AV0Z50200510 Keywords : ontogeny of the porcine immune system * swine adaptive immunity * development of alpha beta and gamma delta T cells Subject RIV: EC - Immunology Impact factor: 3.290, year: 2009

Neonatal Death

Science.gov (United States)

... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...

Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

Science.gov (United States)

Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

2009-04-01

Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

Science.gov (United States)

Barrangou, Rodolphe; Marraffini, Luciano A

2014-04-24

Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control. Copyright © 2014 Elsevier Inc. All rights reserved.

CRISPR-Cas systems: prokaryotes upgrade to adaptive immunity

Science.gov (United States)

Barrangou, Rodolphe; Marraffini, Luciano A.

2014-01-01

Summary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing, and can be repurposed for numerous DNA targeting applications including transcriptional control. PMID:24766887

Genome-wide analysis of immune system genes by EST profiling

Science.gov (United States)

Giallourakis, Cosmas; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Zukerberg, Lawrence R.; Daly, Mark J.; Rioux, John D.; Xavier, Ramnik J.

2013-01-01

Profiling studies of mRNA and miRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some instances, functional studies have been subsequently pursued. Recent efforts such as ENCODE have demonstrated the benefit of coupling RNA-Seq analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including non-coding RNAs. As a result, we have established the Immunogene database, representing an integrated EST “road map” of gene expression in human immune cells, which can be used to further investigate the function of coding and non-coding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes. PMID:23616578

Is immune system-related hypertension associated with ovarian hormone deficiency?

Science.gov (United States)

Sandberg, Kathryn; Ji, Hong; Einstein, Gillian; Au, April; Hay, Meredith

2016-03-01

What is the topic of this review? This review summarizes recent data on the role of ovarian hormones and sex in inflammation-related hypertension. What advances does it highlight? The adaptive immune system has recently been implicated in the development of hypertension in males but not in females. The role of the immune system in the development of hypertension in women and its relationship to ovarian hormone production are highlighted. The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Vascular, glial, and lymphatic immune gateways of the central nervous system

NARCIS (Netherlands)

Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

Prenatal and neonatal adaptations with a focus on the respiratory system.

Science.gov (United States)

Vannucchi, C I; Silva, L C G; Lúcio, C F; Regazzi, F M; Veiga, G A L; Angrimani, D S

2012-12-01

Among the modifications that occur during the neonatal period, pulmonary development is the most critical. The neonate's lungs must be able to perform adequate gas exchange, which was previously accomplished by the placenta. Neonatal respiratory distress syndrome is defined as insufficient surfactant production or pulmonary structural immaturity and is specifically relevant to preterm newborns. Prenatal maternal betamethasone treatment of bitches at 55 days of gestation leads to structural changes in the neonatal lung parenchyma and consequently an improvement in the preterm neonatal respiratory condition, but not to an increase in pulmonary surfactant production. Parturition represents an important challenge to neonatal adaptation, as the uterine and abdominal contractions during labour provoke intermittent hypoxia. Immediately after birth, puppies present venous mixed acidosis (low blood pH and high dioxide carbon saturation) and low but satisfactory Apgar scores. Thus, the combination of physiological hypoxia during birth and the initial effort of filling the pulmonary alveoli with oxygen results in anaerobiosis. As a neonatal adaptation follow-up, the Apgar analysis indicates a tachypnoea response after 1 h of life, which leads to a shift in the blood acid-base status to metabolic acidosis. One hour is sufficient for canine neonates to achieve an ideal Apgar score; however, a haemogasometric imbalance persists. Dystocia promotes a long-lasting bradycardia effect, slows down Apgar score progression and aggravates metabolic acidosis and stress. The latest data reinforce the need to accurately intervene during canine parturition and offer adequate medical treatment to puppies that underwent a pathological labour. © 2012 Blackwell Verlag GmbH.

An MR-compatible neonatal incubator.

Science.gov (United States)

Paley, M N J; Hart, A R; Lait, M; Griffiths, P D

2012-07-01

To develop a neonatal MR-compatible incubator for transporting babies between a neonatal intensive care unit and an MRI unit that is within the same hospital but geographically separate. The system was strapped to a standard MR-compatible patient trolley, which provides space for resuscitation outside the incubator. A constant-temperature exothermic heat pad was used to maintain temperature together with a logging fluoro-optic temperature monitor and alarm system. The system has been designed to accommodate standard knee-sized coils from the major MR manufacturers. The original incubator was constructed from carbon fibre, but this required modification to prevent radiofrequency shading artefacts due to the conducting properties of the carbon fibre. A high-tensile polyester material was used, which combined light weight with high impact strength. The system could be moved onto the patient bed with the coils and infant in place by one technologist. Studies in eight neonatal patients produced high quality 1.5 T MR images with low motion artefacts. The incubator should also be compatible with imaging in 3 T MR systems, although further work is required to establish this. Images were acquired using both rapid and high-resolution sequences, including three-dimensional volumes, proton spectra and diffusion weighting. The incubator provides a safe, quiet environment for neonates during transport and imaging, at low cost.

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder

Institute of Scientific and Technical Information of China (English)

Anne Masi; Nicholas Glozier; Russell Dale; Adam J.Guastella

2017-01-01

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Heterogeneity of presentation is a hallmark.Investigations of immune system problems in ASD,including aberrations in cytokine profiles and signaling,have been increasing in recent times and are the subject of ongoing interest.With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD,or function as an objective measure of response to treatment,this review summarizes the role of the immune system,discusses the relationship between the immune system,the brain,and behavior,and presents previouslyidentified immune system abnormalities in ASD,specifically addressing the role of cytokines in these aberrations.The roles and identification of biomarkers are also addressed,particularly with respect to cytokine profiles in ASD.

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

Science.gov (United States)

Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

2017-04-01

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

A Service Oriented Architecture Approach to Achieve Interoperability between Immunization Information Systems in Iran.

Science.gov (United States)

Hosseini, Masoud; Ahmadi, Maryam; Dixon, Brian E

2014-01-01

Clinical decision support (CDS) systems can support vaccine forecasting and immunization reminders; however, immunization decision-making requires data from fragmented, independent systems. Interoperability and accurate data exchange between immunization information systems (IIS) is an essential factor to utilize Immunization CDS systems. Service oriented architecture (SOA) and Health Level 7 (HL7) are dominant standards for web-based exchange of clinical information. We implemented a system based on SOA and HL7 v3 to support immunization CDS in Iran. We evaluated system performance by exchanging 1500 immunization records for roughly 400 infants between two IISs. System turnaround time is less than a minute for synchronous operation calls and the retrieved immunization history of infants were always identical in different systems. CDS generated reports were accordant to immunization guidelines and the calculations for next visit times were accurate. Interoperability is rare or nonexistent between IIS. Since inter-state data exchange is rare in United States, this approach could be a good prototype to achieve interoperability of immunization information.

Metabolites: messengers between the microbiota and the immune system.

Science.gov (United States)

Levy, Maayan; Thaiss, Christoph A; Elinav, Eran

2016-07-15

The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases. © 2016 Levy et al.; Published by Cold Spring Harbor Laboratory Press.

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

The major histocompatibility complex (MHC) class I related receptor, the neonatal Fc receptor (FcRn), rescues immunoglobulin G (IgG) and albumin from lysosomal degradation by recycling in endothelial cells. FcRn also contributes to passive immunity by mediating transport of IgG from mother to fetus...

Quantifying adaptive evolution in the Drosophila immune system.

Directory of Open Access Journals (Sweden)

Darren J Obbard

2009-10-01

Full Text Available It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, and as organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a likely cause. To quantify the effect, and to identify which genes and pathways are most likely to be involved in the host-parasite arms race, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of the McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. We find the rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host-parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution in both species, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. In summary, our data provide quantitative estimates of the elevated rate of adaptive evolution in immune system genes relative to the rest of the genome, and they suggest that adaptation to parasites is an important force driving molecular evolution.

Schizophrenia and the immune system: pathophysiology, prevention, and treatment.

Science.gov (United States)

Richard, Michelle D; Brahm, Nancy C

2012-05-01

Published evidence on established and theoretical connections between immune system dysfunction and schizophrenia is reviewed, with a discussion of developments in the search for immunologically-targeted treatments. A growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia. A literature search identified more than 100 articles pertaining to suspected immunologic influences on schizophrenia published over the past 15 years. Schizophrenia researchers have explored a wide range of potential immune system-related causal or contributory factors, including neurobiological and neuroanatomical disorders, genetic abnormalities, and environmental influences such as maternal perinatal infection. Efforts to establish an immunologic basis for schizophrenia and identify reliable immune markers continue to be hindered by sampling challenges and methodological problems. In aggregate, the available evidence indicates that at least some cases of schizophrenia have an immunologic component, suggesting that immune-focused prevention strategies (e.g., counseling of pregnant women to avoid immune stressors) and close monitoring of at-risk children are appropriate. While antipsychotics remain the standard treatments for schizophrenia, a variety of drugs with immunologic effects have been investigated as adjunctive therapies, with variable and sometimes conflicting results; these include the cyclooxygenase-2 inhibitor celecoxib, immune-modulating agents (e.g., azathioprine and various anticytokine agents such as atlizumab, anakinra, and tumor necrosis factor-α blockers), and an investigational anti-interferon-γ agent. The published evidence indicates that immune system dysfunction related to genetic, environmental, and neurobiological influences may play a role in the etiology of schizophrenia in a subset of patients.

The role of the immune system in the generation of neuropathic pain.

Science.gov (United States)

Calvo, Margarita; Dawes, John M; Bennett, David L H

2012-07-01

Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

Directory of Open Access Journals (Sweden)

Dyah Ayu Hewajuli

2015-09-01

Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

The conservative physiology of the immune system

Directory of Open Access Journals (Sweden)

N.M. Vaz

2003-01-01

Full Text Available Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies. Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

When carbon nanotubes encounter the immune system: desirable and undesirable effects.

Science.gov (United States)

Dumortier, Hélène

2013-12-01

The role of our immune system is to bring efficient protection against invasion by foreign elements, not only pathogens but also any material it may be in contact with. Nanoparticles may enter the body and encounter the immune system either intentionally (e.g. administration for biomedical application) or not (e.g. respiratory occupational exposure). Therefore, it is of fundamental importance to get a thorough knowledge of the way they interact with immune cells and all related consequences. Among nanomaterials, carbon nanotubes (CNTs) are of special interest because of their tremendous field of applications. Consequently, their increasing production, processing and eventual incorporation into new types of composites and/or into biological systems have raised fundamental issues regarding their potential impact on health. This review aims at giving an overview of the known desirable and undesirable effects of CNTs on the immune system, i.e. beneficial modulation of immune cells by CNTs engineered for biomedical applications versus toxicity, inflammation and unwanted immune reactions triggered by CNTs themselves. © 2013 Elsevier B.V. All rights reserved.

The contribution of the immune system to parturition

Directory of Open Access Journals (Sweden)

R. De Jongh

1996-01-01

Full Text Available The immune system plays a central role before and during parturition, including the main physiological processes of parturition: uterine contractions and cervical ripening. The immune system comprises white blood cells and their secretions. Polymorphonuclear cells and macrophages invade the cervical tissue and release compounds, such as oxygen radicals and enzymes, which break down the cervical matrix to allow softening and dilatation. During this inflammatory process, white blood cells undergo chemotaxis, adherence to endothelial cells, diapedesis, migration and activation. Factors that regulate white blood cell invasion and secretion include cytokines such as tumour necrosis factor and interleukins. Glucocorticoids, sex hormones and prostaglandins, affect cytokine synthesis. They also modulate the target cells, resulting in altered responses to cytokines. On the other hand, the immune system has profound effects on the hormonal system and prostaglandin synthesis. In animals, nitric oxide has marked effects on uterine quiescence during gestation. At the same time, it plays an important role in regulating the vascular tone of uterine arteries and has anti-adhesive effects on leukocytes. Cytokines are found in amniotic fluid, and in maternal and foetal serum at term and preterm. Several intrauterine cells have been shown to produce these cytoldnes. Since neither white blood cells, cytokines nor nitric oxide seem to be the ultimate intermediate for human parturition, the immune system is an additional but obligatory and underestimated component in the physiology of delivery. Scientists, obstetricians and anaesthesiologists must thus be aware of these processes.

Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer.

Science.gov (United States)

Marelli, Giulia; Howells, Anwen; Lemoine, Nicholas R; Wang, Yaohe

2018-01-01

Oncolytic viral therapy is a new promising strategy against cancer. Oncolytic viruses (OVs) can replicate in cancer cells but not in normal cells, leading to lysis of the tumor mass. Beside this primary effect, OVs can also stimulate the immune system. Tumors are an immuno-suppressive environment in which the immune system is silenced in order to avoid the immune response against cancer cells. The delivery of OVs into the tumor wakes up the immune system so that it can facilitate a strong and durable response against the tumor itself. Both innate and adaptive immune responses contribute to this process, producing an immune response against tumor antigens and facilitating immunological memory. However, viruses are recognized by the immune system as pathogens and the consequent anti-viral response could represent a big hurdle for OVs. Finding a balance between anti-tumor and anti-viral immunity is, under this new light, a priority for researchers. In this review, we provide an overview of the various ways in which different components of the immune system can be allied with OVs. We have analyzed the different immune responses in order to highlight the new and promising perspectives leading to increased anti-tumor response and decreased immune reaction to the OVs.

Neonatal tetanus elimination in Pakistan: progress and challenges.

Science.gov (United States)

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and

Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity.

Science.gov (United States)

Le Doare, Kirsty; Holder, Beth; Bassett, Aisha; Pannaraj, Pia S

2018-01-01

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant's developing mucosal immune system. It is believed that bacteria from the mother's intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

OpenAIRE

Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor ...

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.

Biological Immune System Applications on Mobile Robot for Disabled People

Directory of Open Access Journals (Sweden)

Songmin Jia

2014-01-01

Full Text Available To improve the service quality of service robots for the disabled, immune system is applied on robot for its advantages such as diversity, dynamic, parallel management, self-organization, and self-adaptation. According to the immune system theory, local environment condition sensed by robot is considered an antigen while robot is regarded as B-cell and possible node as antibody, respectively. Antibody-antigen affinity is employed to choose the optimal possible node to ensure the service robot can pass through the optimal path. The paper details the immune system applications on service robot and gives experimental results.

CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

Science.gov (United States)

Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

2018-06-01

To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

Science.gov (United States)

Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

2015-10-27

The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of

The enkephalinergic nervous system and its immunomodulation on the developing immune system during the ontogenesis of oyster Crassostrea gigas.

Science.gov (United States)

Liu, Zhaoqun; Zhou, Zhi; Wang, Lingling; Song, Xiaorui; Chen, Hao; Wang, Weilin; Liu, Rui; Wang, Mengqiang; Wang, Hao; Song, Linsheng

2015-08-01

Enkephalinergic neuroendocrine-immune regulatory system is one of the most important neuroendocrine-immune systems in both vertebrates and invertebrates for its significant role in the immune regulation. In the present study, the early onset of enkephalinergic nervous system and its immunomodulation on the developing immune system during the ontogenesis of oyster Crassostrea gigas were investigated to illustrate the function of neural regulation on the innate immune system in oyster larvae. [Met(5)]-enkephalin (Met-ENK) was firstly observed on the marginal of the dorsal half of D-hinged larvae. Six immune-related molecules, including four PRRs (CgCTL-1, CgCTL-2, CgCTL-4, CgNatterin-3) and two immune effectors (CgTNF-1 and CgEcSOD) were detected in the early developmental stages of trochophore, D-hinged and umbo larvae of oyster. After incubated with [Met(5)]-enkephalin, the mRNA expression level of all the PRRs changed significantly (p immune effectors were up-regulated significantly at 3 h and 6 h in trochophore larvae (p system of oyster was firstly appeared in D-hinged larvae, while the primitive immune defense system existed in the region of prototroch in trochophore larvae and developed maturely after D-hinged larvae. The developing immune system could be regulated by the neurotransmitter [Met(5)]-enkephalin released by the neuroendocrine system in oyster C. gigas. Copyright © 2015 Elsevier Ltd. All rights reserved.

Archaeal CRISPR-based immune systems

DEFF Research Database (Denmark)

Garrett, Roger A; Vestergaard, Gisle Alberg; Shah, Shiraz Ali

2011-01-01

CRISPR (clustered regularly interspaced short palindromic repeats)-based immune systems are essentially modular with three primary functions: the excision and integration of new spacers, the processing of CRISPR transcripts to yield mature CRISPR RNAs (crRNAs), and the targeting and cleavage...... of foreign nucleic acid. The primary target appears to be the DNA of foreign genetic elements, but the CRISPR/Cmr system that is widespread amongst archaea also specifically targets and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and complex. Here we examine evidence...... of CRISPR loci and the evidence for intergenomic exchange of CRISPR systems....

Optimal approximation of linear systems by artificial immune response

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

This paper puts forward a novel artificial immune response algorithm for optimal approximation of linear systems. A quaternion model of artificial immune response is proposed for engineering computing. The model abstracts four elements, namely, antigen, antibody, reaction rules among antibodies, and driving algorithm describing how the rules are applied to antibodies, to simulate the process of immune response. Some reaction rules including clonal selection rules, immunological memory rules and immune regulation rules are introduced. Using the theorem of Markov chain, it is proofed that the new model is convergent. The experimental study on the optimal approximation of a stable linear system and an unstable one show that the approximate models searched by the new model have better performance indices than those obtained by some existing algorithms including the differential evolution algorithm and the multi-agent genetic algorithm.

Endocrine and Local IGF-I in the Bony Fish Immune System.

Science.gov (United States)

Franz, Anne-Constance; Faass, Oliver; Köllner, Bernd; Shved, Natallia; Link, Karl; Casanova, Ayako; Wenger, Michael; D'Cotta, Helena; Baroiller, Jean-François; Ullrich, Oliver; Reinecke, Manfred; Eppler, Elisabeth

2016-01-26

A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

Endocrine and Local IGF-I in the Bony Fish Immune System

Directory of Open Access Journals (Sweden)

Anne-Constance Franz

2016-01-01

Full Text Available A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived, which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

Dermatology in the Darwin anniversary. Part 2: Evolution of the skin-associated immune system.

Science.gov (United States)

Wölfle, Ute; Martin, Stefan; Emde, Matthias; Schempp, Christoph

2009-10-01

The present review highlights the evolution of the skin-associated immune system from the invertebrates to the vertebrates and man. In the invertebrates a non-specific humoral immune response dominates. It includes antimicrobial peptides, oxidases, lysozyme, agglutinins, coagulins and melanin. The cellular immune system initially consists of undifferentiated mesenchymal stem cells. Later migrating phagocytes and natural killer cells occur. From the fishes on, dendritic cells are present, linking innate and adaptive immune responses. In addition to this unspecific but highly effective immune system, the specific immune response, based on genetic recombination, is present in the vertebrates starting with the chondral fishes. The adaptive immune system possesses unlimited numbers of highly specific antibodies and T-cell receptors, increasingly tissue specific MHC restriction, and cellular memory. Elements of the skin-associated adaptive immune system are first detectable in the teleost fishes in the form of intraepithelial IgM positive lymphocytes and dendritic cells. Moving up to mammals and man, the skin-associated immune system became more and more complex and effective.

Cerebral blood oxygenation measurements in neonates with optoacoustic technique

Science.gov (United States)

Herrmann, Stephen; Petrov, Irene Y.; Petrov, Yuriy; Richardson, C. Joan; Fonseca, Rafael A.; Prough, Donald S.; Esenaliev, Rinat O.

2017-03-01

Cerebral hypoxia is a major contributor to neonatal/infant mortality and morbidity including severe neurological complications such as mental retardation, cerebral palsy, motor impairment, and epilepsy. Currently, no technology is capable of accurate monitoring of neonatal cerebral oxygenation. We proposed to use optoacoustics for this application by probing the superior sagittal sinus (SSS), a large central cerebral vein. We developed and built a multi-wavelength, optical parametric oscillator (OPO) and laser diode optoacoustic systems for measurement of SSS blood oxygenation in the reflection mode through open anterior or posterior fontanelles and in the transmission mode through the skull in the occipital area. In this paper we present results of initial tests of the laser diode system for neonatal cerebral oxygenation measurements. First, the system was tested in phantoms simulating neonatal SSS. Then, using the data obtained in the phantoms, we optimized the system's hardware and software and tested it in neonates admitted in the Neonatal Intensive Care Unit. The laser diode system was capable of detecting SSS signals in the reflection mode through the open anterior and posterior fontanelles as well as in the transmission mode through the skull with high signal-to-noise ratio. Using the signals measured at different wavelengths and algorithms developed for oxygenation measurements, the laser diode system provided real-time, continuous oxygenation monitoring with high precision at all these locations.

The reaction of the immune system of fish to vaccination

NARCIS (Netherlands)

Lamers, C.H.J.

1985-01-01

The studies presented in this thesis deal with the effect of bacterial antigens of Yersinia ruckeri and Aeromonashydrophila on the immune system of carp. The antigens were administered by injection or by bath treatment. The effect on the immune system was studied by

Neonatal irradiation sensitizes mice to delayed pulmonary challenge.

Science.gov (United States)

Johnston, Carl J; Manning, Casey M; Rangel-Moreno, Javier; Randall, Troy D; Hernady, Eric; Finkelstein, Jacob N; Williams, Jacqueline P

2013-04-01

Significant differences exist between the physiology of the immature, neonatal lung compared to that of the adult lung that may affect acute and late responses to irradiation. Identifying these differences is critical to developing successful mitigation strategies for this special population. Our current hypothesis proposes that irradiation during the neonatal period will alter developmental processes, resulting in long-term consequences, including altered susceptibility to challenge with respiratory pathogens. C57BL/6J mice, 4 days of age, received 5 Gy whole-body irradiation. At subsequent time points (12, 26 and 46 weeks postirradiation), mice were intranasally infected with 120 HAU of influenza A virus. Fourteen days later, mice were sacrificed and tissues were collected for examination. Morbidity was monitored following changes in body weight and survival. The magnitude of the pulmonary response was determined by bronchoalveolar lavage, histological examination and gene expression of epithelial and inflammatory markers. Viral clearance was assessed 7 days post-influenza infection. Following influenza infection, irradiated animals that were infected at 26 and 46 weeks postirradiation lost significantly more weight and demonstrated reduced survival compared with those infected at 12 weeks postirradiation, with the greatest deleterious effect seen at the late time point. The results of these experiments suggest that radiation injury during early life may affect the lung's response to a subsequent pathogenic aerial challenge, possibly through a chronic and progressive defect in the immune system. This finding may have implications for the development of countermeasures in the context of systemic radiation exposure.

Dosing antibiotics in neonates: review of the pharmacokinetic data.

Science.gov (United States)

Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G

2017-09-01

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

The Mucosal Immune System of Teleost Fish

Directory of Open Access Journals (Sweden)

Irene Salinas

2015-08-01

Full Text Available Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT of teleosts are the gut-associated lymphoid tissue (GALT, skin-associated lymphoid tissue (SALT, the gill-associated lymphoid tissue (GIALT and the recently discovered nasopharynx-associated lymphoid tissue (NALT. Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT+ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture.

The Role of the Immune System in Metabolic Health and Disease.

Science.gov (United States)

Zmora, Niv; Bashiardes, Stavros; Levy, Maayan; Elinav, Eran

2017-03-07

In addition to the immune system's traditional roles of conferring anti-infectious and anti-neoplastic protection, it has been recently implicated in the regulation of systemic metabolic homeostasis. This cross-talk between the immune and the metabolic systems is pivotal in promoting "metabolic health" throughout the life of an organism and plays fundamental roles in its adaptation to ever-changing environmental makeups and nutritional availability. Perturbations in this intricate immune-metabolic cross-talk contribute to the tendency to develop altered metabolic states that may culminate in metabolic disorders such as malnutrition, obesity, type 2 diabetes mellitus (T2DM), and other features of the metabolic syndrome. Regulators of immune-metabolic interactions include host genetics, nutritional status, and the intestinal microbiome. In this Perspective, we highlight current understanding of immune-metabolism interactions, illustrate differences among individuals and between populations in this respect, and point toward future avenues of research possibly enabling immune harnessing as means of personalized treatment for common metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

High-Density Lipoproteins and the Immune System

Directory of Open Access Journals (Sweden)

Hidesuke Kaji

2013-01-01

Full Text Available High-density lipoprotein (HDL plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases.

Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

Science.gov (United States)

Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

2015-01-01

Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.

Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

Science.gov (United States)

Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

2016-05-01

Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

A mathematical model of radiation effect on the immunity system

International Nuclear Information System (INIS)

Smirnova, O.A.

1984-01-01

A mathematical model, simulating the effect of ionizing radiation on the dynamics of humoral immune reaction is suggested. It represents the system of nonlinear differential equations and is realized in the form of program in Fortran computer language. The model describes the primary immune reaction of nonirradiated organism on T-independent antigen, reflects the postradiation lymphopoiesis dynamics in nonimmunized mammals, simulates the processes of injury and recovery of the humoral immunity system under the combined effect of ionizing radiation and antigenic stimulation. The model can be used for forecasting imminity state in irradiated mammals

Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

LENUS (Irish Health Repository)

McCarron, Mark

2012-02-01

In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

Why the Immune System Should Be Concerned by Nanomaterials?

Directory of Open Access Journals (Sweden)

Marc J. Pallardy

2017-05-01

Full Text Available Particles possess huge specific surface area and therefore nanomaterials exhibit unique characteristics, such as special physical properties and chemical hyper-reactivity, which make them particularly attractive but also raise numerous questions concerning their safety. Interactions of nanomaterials with the immune system can potentially lead to immunosuppression, hypersensitivity (allergy, immunogenicity and autoimmunity, involving both innate and adaptive immune responses. Inherent physical and chemical NP characteristics may influence their immunotoxicity, i.e., the adverse effects that can result from exposure. This review will focus on the possible interaction of nanomaterials including protein aggregates with the innate immune system with specific emphasis on antigen-presenting cells, i.e., dendritic cells, macrophages and monocytes.

[The role of protein glycosylation in immune system].

Science.gov (United States)

Ząbczyńska, Marta; Pocheć, Ewa

2015-01-01

Glycosylation is one of the most frequent post-translational modifications of proteins. The majority of cell surface and secreted proteins involved in immune response is glycosylated. The structural diversity of glycans depends on monosaccharide composition, type of glycosidic linkage and branching. These structural modifications determine a great variability of glycoproteins. The oligosaccharide components of proteins are regulated mostly by expression of glycosyltransferases and glycosidases and many environmental factors. Glycosylation influences the function of all immune cells. Glycans play a crucial role in intercellular contacts and leukocytes migration. These interactions are important in activation and proliferation of leukocytes and during immune response. The key immune proteins, such as TCR, MHC, TLR and antibodies are glycosylated. Sugars on the surface of pathogens and self-surface glycoproteins are recognized by special carbohydrate binding proteins called lectins. Changes of glycan structure are common in many pathological processes occurring in immune system, therefore they are used as molecular markers of different diseases.

Web-based e-learning and virtual lab of human-artificial immune system.

Science.gov (United States)

Gong, Tao; Ding, Yongsheng; Xiong, Qin

2014-05-01

Human immune system is as important in keeping the body healthy as the brain in supporting the intelligence. However, the traditional models of the human immune system are built on the mathematics equations, which are not easy for students to understand. To help the students to understand the immune systems, a web-based e-learning approach with virtual lab is designed for the intelligent system control course by using new intelligent educational technology. Comparing the traditional graduate educational model within the classroom, the web-based e-learning with the virtual lab shows the higher inspiration in guiding the graduate students to think independently and innovatively, as the students said. It has been found that this web-based immune e-learning system with the online virtual lab is useful for teaching the graduate students to understand the immune systems in an easier way and design their simulations more creatively and cooperatively. The teaching practice shows that the optimum web-based e-learning system can be used to increase the learning effectiveness of the students.

The risks of using allogeneic cell lines for vaccine production : The example of Bovine Neonatal Pancytopenia

NARCIS (Netherlands)

Benedictus, Lindert; Bell, Charlotte R

2017-01-01

INTRODUCTION: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for

The placental immune milieu is characterized by a Th2- and anti-inflammatory transcription profile, regardless of maternal allergy, and associates with neonatal immunity.

Science.gov (United States)

Abelius, Martina S; Janefjord, Camilla; Ernerudh, Jan; Berg, Göran; Matthiesen, Leif; Duchén, Karel; Nilsson, Lennart J; Jenmalm, Maria C

2015-05-01

How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear. Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring. Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Framework of Complex Adaptive Systems: Parents As Partners in the Neonatal Intensive Care Unit.

Science.gov (United States)

DʼAgata, Amy L; McGrath, Jacqueline M