The perioperative period and promotion of cancer metastasis: New outlooks on mediating mechanisms and immune involvement

PubMed Central

Neeman, Elad; Ben-Eliyahu, Shamgar

2012-01-01

Surgery for the removal of a primary tumor presents an opportunity to eradicate cancer or arrest its progression, but is also believed to promote the outbreak of pre-existing micrometastases and the initiation of new metastases. These deleterious effects of surgery are mediated through various mechanisms, including psychological and physiological neuroendocrine and paracrine stress responses elicited by surgery. In this review we (i) describe the many risk factors that arise during the perioperative period, acting synergistically to make this short timeframe critical for determining long-term cancer recurrence, (ii) present newly identified potent immunocyte populations that can destroy autologous tumor cells that were traditionally considered immune-resistant, thus invigorating the notion of immune-surveillance against cancer metastasis, (iii) describe in vivo evidence in cancer patients that support a role for anti-cancer immunity, (iv) indicate neuroendocrine and paracrine mediating mechanisms of stress- and surgery-induced promotion of cancer progression, focusing on the prominent role of catecholamines and prostaglandins through their impact on anti-cancer immunity, and through direct effects on the malignant tissue and its surrounding, (v) discuss the impact of different anesthetic approaches and other intra-operative procedures on immunity and cancer progression, and (vi) suggest prophylactic measures against the immunosuppressive and cancer promoting effects of surgery. PMID:22504092

Extinguishing visible photoluminescence of porous silicon stimulated by antigen-antibody immunocomplex formation

NASA Astrophysics Data System (ADS)

Starodub, Nickolaj F.; Fedorenko, Leonid L.; Starodub, Valentyna M.; Dikiy, S. P.; Svechnikov, Sergey V.

1997-02-01

The photoluminescence of the porous silicon obtained by special procedure with the usage of the chemical and laser beam treatment of silicon crystal was investigated in water, buffer and solution containing sodium chloride. It was demonstrated that the intensity of the photoluminescence did not practically change at the above mentioned conditions as well as after antigen or antibody immobilization on the porous silicon surface. But this parameter of the photoluminescence dramatically decreased in case of specific immune complex formation on the silicon surface. The level of the photoluminescence extinguishing depended on duration and intensity of immune reaction. It is proposed to use discovered effect for creation of the immunosensors based on the direct registration of immunocomplex formation.

Generation of anti-porcine CD69 monoclonal antibodies and their usefulness to evaluate early activation of cellular immunity by flow cytometric analysis.

PubMed

Hayashi, Yumiko; Okutani, Mie; Ogawa, Shohei; Tsukahara, Takamitsu; Inoue, Ryo

2018-05-01

T cell-mediated cellular immunity and humoral immunity are equally important for the prevention of diseases. To assess activation of human and mouse cellular immunity, early activation markers of lymphocytes are often used in flow cytometry targeting expression of CD69 molecules. Response of humoral immunity against infection or vaccination has been well investigated in pigs, but that of cellular immunity has been largely neglected due to lack of direct evaluation tools. Thus, in pig research a proper assay of antibody reacted with porcine CD69 is still unavailable. In the present study, two anti-porcine CD69 mAb-producing mouse hybridomas, 01-14-22-51 (IgG2b-κ) and 01-22-44-102 (IgG2a-κ), both showing fine reactivity with phorbol 12-myristate 13-acetate (PMA) and ionomycin-stimulated porcine peripheral blood lymphocytes in flow cytometry, were established. When porcine peripheral blood lymphocytes were activated with PMA and ionomycin and analyzed by flow cytometry, it was found that both mAbs generated in this study stained about 70% of lymphocytes. In contrast, after an identical procedure, only 5% and 13.5% of lymphocytes were stained with anti-interferon-γ mAb and anti-tumor necrosis factor-α mAb, respectively. These results indicate that evaluation of cellular immunity activation turns more sensitive after using our newly generated mAbs. © 2018 Japanese Society of Animal Science.

T cells for viral infections after allogeneic hematopoietic stem cell transplant

PubMed Central

Heslop, Helen E.

2016-01-01

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing “off the shelf” approaches. PMID:27207801

28 CFR 35.178 - State immunity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 1 2013-07-01 2013-07-01 false State immunity. 35.178 Section 35.178 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY IN STATE AND LOCAL GOVERNMENT SERVICES Compliance Procedures § 35.178 State immunity. A State shall not be immune...

28 CFR 35.178 - State immunity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false State immunity. 35.178 Section 35.178 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY IN STATE AND LOCAL GOVERNMENT SERVICES Compliance Procedures § 35.178 State immunity. A State shall not be immune...

28 CFR 35.178 - State immunity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 1 2012-07-01 2012-07-01 false State immunity. 35.178 Section 35.178 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY IN STATE AND LOCAL GOVERNMENT SERVICES Compliance Procedures § 35.178 State immunity. A State shall not be immune...

28 CFR 35.178 - State immunity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false State immunity. 35.178 Section 35.178 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY IN STATE AND LOCAL GOVERNMENT SERVICES Compliance Procedures § 35.178 State immunity. A State shall not be immune...

28 CFR 35.178 - State immunity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false State immunity. 35.178 Section 35.178 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION ON THE BASIS OF DISABILITY IN STATE AND LOCAL GOVERNMENT SERVICES Compliance Procedures § 35.178 State immunity. A State shall not be immune...

Music Therapy as Procedural Support for Young Children Undergoing Immunizations: A Randomized Controlled Study.

PubMed

Yinger, Olivia Swedberg

2016-01-01

Children undergoing routine immunizations frequently experience severe distress, which may be improved through music therapy as procedural support. The purpose of this study was to examine effects of live, cognitive-behavioral music therapy during immunizations on (a) the behaviors of children, their parents, and their nurses; and (b) parental perceptions. Participants were children between the ages of 4 and 6 years (N = 58) who underwent immunizations, their parents (N = 62), and the nurses who administered the procedure (N = 19). Parent/child dyads were randomly assigned to receive music therapy (n = 29) or standard care (n = 29) during their immunization. Afterward, each parent rated their child's level of pain and the distress their child experienced compared to previous medical experiences. All procedures were videotaped and later viewed by trained observers, who classified child, parent, and nurse behaviors using the categories of the Child-Adult Medical Procedure Interaction Scale-Revised (CAMPIS-R). Significant differences between the music therapy and control groups were found in rates of child coping and distress behaviors and parent distress-promoting behaviors. Parents of children who received music therapy reported that their child's level of distress was less than during previous medical experiences, whereas parents of children in the control group reported that their child's level of distress was greater. No significant differences between groups were found in parents' ratings of children's pain or in rates of nurse behavior. Live, cognitive-behavioral music therapy has potential benefits for young children and their parents during immunizations. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed against Prostate Cancer

DTIC Science & Technology

2017-08-01

Award Number: W81XWH-15-1-0328 TITLE: Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed against...1 August 2016 - 31 July 2017 4. TITLE AND SUBTITLE Targeting Peripheral-Derived Regulatory T Cells as a Means of Enhancing Immune Responses Directed...discovered that a subset of regulatory T cells (Tregs), termed peripheral-derived Tregs (pTregs), impair immune responses directed against tumor

Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.

PubMed

Pomié, Céline; Blasco-Baque, Vincent; Klopp, Pascale; Nicolas, Simon; Waget, Aurélie; Loubières, Pascale; Azalbert, Vincent; Puel, Anthony; Lopez, Frédéric; Dray, Cédric; Valet, Philippe; Lelouvier, Benjamin; Servant, Florence; Courtney, Michael; Amar, Jacques; Burcelin, Rémy; Garidou, Lucile

2016-06-01

To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.

Mechanisms and applications of interleukins in cancer immunotherapy.

PubMed

Anestakis, Doxakis; Petanidis, Savvas; Kalyvas, Spyridon; Nday, Christiane M; Tsave, Olga; Kioseoglou, Efrosini; Salifoglou, Athanasios

2015-01-13

Over the past years, advances in cancer immunotherapy have resulted in innovative and novel approaches in molecular cancer diagnostics and cancer therapeutic procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in tumor immunity, the clinical benefits are quite restricted. The goal of this review is to evaluate the major cytokines-interleukins involved in cancer immunotherapy and project their basic biochemical and clinical applications. Emphasis will be given to new cytokines in pre-clinical development, and potential directions for future investigation using cytokines. Furthermore, current interleukin-based approaches and clinical trial data from combination cancer immunotherapies will also be discussed. It appears that continuously increasing comprehension of cytokine-induced effects, cancer stemness, immunoediting, immune-surveillance as well as understanding of molecular interactions emerging in the tumor microenvironment and involving microRNAs, autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA methylation processes may hold much promise in improving anti-tumor immunity. To this end, the emerging in-depth knowledge supports further studies on optimal synergistic combinations and additional adjuvant therapies to realize the full potential of cytokines as immunotherapeutic agents.

Mechanisms and Αpplications of Ιnterleukins in Cancer Immunotherapy

PubMed Central

Anestakis, Doxakis; Petanidis, Savvas; Kalyvas, Spyridon; Nday, Christiane M.; Tsave, Olga; Kioseoglou, Efrosini; Salifoglou, Athanasios

2015-01-01

Over the past years, advances in cancer immunotherapy have resulted in innovative and novel approaches in molecular cancer diagnostics and cancer therapeutic procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in tumor immunity, the clinical benefits are quite restricted. The goal of this review is to evaluate the major cytokines-interleukins involved in cancer immunotherapy and project their basic biochemical and clinical applications. Emphasis will be given to new cytokines in pre-clinical development, and potential directions for future investigation using cytokines. Furthermore, current interleukin-based approaches and clinical trial data from combination cancer immunotherapies will also be discussed. It appears that continuously increasing comprehension of cytokine-induced effects, cancer stemness, immunoediting, immune-surveillance as well as understanding of molecular interactions emerging in the tumor microenvironment and involving microRNAs, autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA methylation processes may hold much promise in improving anti-tumor immunity. To this end, the emerging in-depth knowledge supports further studies on optimal synergistic combinations and additional adjuvant therapies to realize the full potential of cytokines as immunotherapeutic agents. PMID:25590298

Genes In Space-5

NASA Image and Video Library

2018-04-13

iss055e020319 (April 13, 2018) --- Flight Engineer Ricky Arnold processes of samples inside the Miniature Polymerase Chain Reaction (miniPCR) for the Genes In Space-5 experiment. The research gathered from Genes in Space-5 may be valuable in the development of procedures to maintain astronaut health and prevent an increased risk of cancer on deep space missions. The investigation also provides a deeper understanding of the human immune system, while giving student researchers a direct connection to the space program and offering hands-on educational experiences on Earth and promoting involvement in STEM fields.

T cells for viral infections after allogeneic hematopoietic stem cell transplant.

PubMed

Bollard, Catherine M; Heslop, Helen E

2016-06-30

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

Mechanism of Innate Resistance to Viral Encephalitis.

DTIC Science & Technology

1976-12-01

contrast, local inhabitants would likely be immune to infection from previous contact. Moreover, effective vaccination procedures for most neurotropic...individuals and, 3) developing a rational procedure for vaccin - ation. Prevailing explanations for innate genetic resistance to lethal flaviviral...He mice infected the same way (Table 7). We began to examine the responses of He and RV mice to immunization with formalinized Banzi virus vaccine (BV

Construction of High-Quality Camel Immune Antibody Libraries.

PubMed

Romão, Ema; Poignavent, Vianney; Vincke, Cécile; Ritzenthaler, Christophe; Muyldermans, Serge; Monsion, Baptiste

2018-01-01

Single-domain antibodies libraries of heavy-chain only immunoglobulins from camelids or shark are enriched for high-affinity antigen-specific binders by a short in vivo immunization. Thus, potent binders are readily retrieved from relatively small-sized libraries of 10 7 -10 8 individual transformants, mostly after phage display and panning on a purified target. However, the remaining drawback of this strategy arises from the need to generate a dedicated library, for nearly every envisaged target. Therefore, all the procedures that shorten and facilitate the construction of an immune library of best possible quality are definitely a step forward. In this chapter, we provide the protocol to generate a high-quality immune VHH library using the Golden Gate Cloning strategy employing an adapted phage display vector where a lethal ccdB gene has to be substituted by the VHH gene. With this procedure, the construction of the library can be shortened to less than a week starting from bleeding the animal. Our libraries exceed 10 8 individual transformants and close to 100% of the clones harbor a phage display vector having an insert with the length of a VHH gene. These libraries are also more economic to make than previous standard approaches using classical restriction enzymes and ligations. The quality of the Nanobodies that are retrieved from immune libraries obtained by Golden Gate Cloning is identical to those from immune libraries made according to the classical procedure.

Effect of Bacillus subtilis-based direct-fed microbials on immune status in broiler chickens raised on fresh or used litter

USDA-ARS?s Scientific Manuscript database

The type of dietary direct-fed microbials (DFMs) or poultry litter could directly influence the composition of gut microbiota. Gut microbiota play an important role in shaping the developing immune system and maintaining homeostasis of the mature immune system in mammal and chickens. The present stu...

Parent Knowledge and Attitudes About School-Based Hepatitis B Immunization Programs.

ERIC Educational Resources Information Center

Middleman, Amy B.; Guajardo, Andrea D.; Sunwoo, Edward; Sansaricq, Kim M.

2002-01-01

Surveyed parents of students in the Houston Independent School District to determine preferences regarding immunization clinic site and preferred consent procedures for a Hepatitis B immunization program. Results indicated a significant lack of parent knowledge regarding the Hepatitis B virus. Demographic variables influenced parents' knowledge…

Immunizations under sedation at a paediatric hospital in Melbourne, Australia from 2012-2016.

PubMed

Cheng, Daryl R; Elia, Sonja; Perrett, Kirsten P

2018-05-09

Sedation for immunizations is of particular importance in a subset of paediatric patients with anxiety disorders, needle phobia, developmental or behavioural disorders. The Royal Children's Hospital (RCH) Melbourne offers a unique immunization under sedation service for these patients. We aimed to evaluate the number and types of patients using inpatient sedation for immunizations, distraction and sedation techniques used, and outcomes of these procedures. A medical record review was conducted on all patients who had immunization under sedation between January 2012 to December 2016 in the RCH Day Medical Unit (DMU). A total of 139 children and adolescents had 213 vaccination encounters. More than half of the vaccination encounters involved multiple vaccines. A total of 400 vaccines were administered. One third of patients (32.3%) had multiple DMU admissions for vaccinations. The median age of patients was 13 years. There were only 10 (4.7%) failed attempts at vaccination; all due to patient non-compliance with prescribed sedation. The majority of patients (58.9%) had a diagnosis of needle phobia. Sedation was most commonly adequately achieved with inhaled nitrous oxide (54.7% sole agent). Midazolam was often used as an adjunct therapy (42.8%). Local anaesthetic cream or play therapy, were used in only 5.9% and 3.9% of patients respectively, although this may reflect poor documentation rather than actual practice. For a subset of paediatric patients for which standard immunization procedures have failed, distraction techniques and conscious sedation enable immunizations to be given safely and effectively. Future research will develop protocols to streamline immunization procedures under sedation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanical stress induces neuroendocrine and immune responses of sea cucumber ( Apostichopus japonicus)

NASA Astrophysics Data System (ADS)

Tan, Jie; Li, Fenghui; Sun, Huiling; Gao, Fei; Yan, Jingping; Gai, Chunlei; Chen, Aihua; Wang, Qingyin

2015-04-01

Grading procedure in routine sea cucumber hatchery production is thought to affect juvenile sea cucumber immunological response. The present study investigated the impact of a 3-min mechanical perturbation mimicking the grading procedure on neuroendocrine and immune parameters of the sea cucumber Apostichopus japonicus. During the application of stress, concentrations of noradrenaline and dopamine in coelomic fluid increased significantly, indicating that the mechanical perturbation resulted in a transient state of stress in sea cucumbers. Coelomocytes concentration in coelomic fluid increased transiently after the beginning of stressing, and reached the maximum in 1 h. Whereas, coelomocytes phagocytosis at 3 min, superoxide anion production from 3 min to 0.5 h, acid phosphatase activity at 0.5 h, and phenoloxidase activity from 3 min to 0.5 h were all significantly down-regulated. All of the immune parameters recovered to baseline levels after the experiment was conducted for 8 h, and an immunostimulation occurred after the stress considering the phagocytosis and acid phosphatase activity. The results suggested that, as in other marine invertebrates, neuroendocrine/immune connections exist in sea cucumber A. japonicus. Mechanical stress can elicit a profound influence on sea cucumber neuroendocrine system. Neuroendocrine messengers act in turn to modulate the immunity functions. Therefore, these effects should be considered for developing better husbandry procedures.

Solar photovoltaic powered refrigerators/freezers for medical use in remote geographic locations

NASA Technical Reports Server (NTRS)

Darkazalli, G.; Hein, G. F.

1983-01-01

One of the obstacles preventing widespread immunication against disease is the virtual absence of reliable, low maintenance refrigeration systems for storage of vaccines in remote geographic locations. A system which consists of a solar photovoltaic cell array and an integrated refrigerator/freezer-energy storage unit is discussed herein. The array converts solar radiation into direct current (DC) electricity with no moving parts and no intermediate steps. A detailed description of the refrigeration system, its design and an analysis thereof, performance test procedures, and test results are presented. A system schematic is also provided.

The effects of chemotherapeutics on cellular metabolism and consequent immune recognition.

PubMed

Newell, M Karen; Melamede, Robert; Villalobos-Menuey, Elizabeth; Swartzendruber, Douglas; Trauger, Richard; Camley, Robert E; Crisp, William

2004-02-02

Awidely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest that effective oncolytic agents sensitize immunologically altered tumor cells to immune recognition and immune-directed cell death.

The effects of chemotherapeutics on cellular metabolism and consequent immune recognition

PubMed Central

Newell, M Karen; Melamede, Robert; Villalobos-Menuey, Elizabeth; Swartzendruber, Douglas; Trauger, Richard; Camley, Robert E; Crisp, William

2004-01-01

A widely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest that effective oncolytic agents sensitize immunologically altered tumor cells to immune recognition and immune-directed cell death. PMID:14756899

The role of the immune system in kidney disease.

PubMed

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.

Gene expression profiling of immunomagnetically separated cells directly from stabilized whole blood for multicenter clinical trials

PubMed Central

2014-01-01

Background Clinically useful biomarkers for patient stratification and monitoring of disease progression and drug response are in big demand in drug development and for addressing potential safety concerns. Many diseases influence the frequency and phenotype of cells found in the peripheral blood and the transcriptome of blood cells. Changes in cell type composition influence whole blood gene expression analysis results and thus the discovery of true transcript level changes remains a challenge. We propose a robust and reproducible procedure, which includes whole transcriptome gene expression profiling of major subsets of immune cell cells directly sorted from whole blood. Methods Target cells were enriched using magnetic microbeads and an autoMACS® Pro Separator (Miltenyi Biotec). Flow cytometric analysis for purity was performed before and after magnetic cell sorting. Total RNA was hybridized on HGU133 Plus 2.0 expression microarrays (Affymetrix, USA). CEL files signal intensity values were condensed using RMA and a custom CDF file (EntrezGene-based). Results Positive selection by use of MACS® Technology coupled to transcriptomics was assessed for eight different peripheral blood cell types, CD14+ monocytes, CD3+, CD4+, or CD8+ T cells, CD15+ granulocytes, CD19+ B cells, CD56+ NK cells, and CD45+ pan leukocytes. RNA quality from enriched cells was above a RIN of eight. GeneChip analysis confirmed cell type specific transcriptome profiles. Storing whole blood collected in an EDTA Vacutainer® tube at 4°C followed by MACS does not activate sorted cells. Gene expression analysis supports cell enrichment measurements by MACS. Conclusions The proposed workflow generates reproducible cell-type specific transcriptome data which can be translated to clinical settings and used to identify clinically relevant gene expression biomarkers from whole blood samples. This procedure enables the integration of transcriptomics of relevant immune cell subsets sorted directly from whole blood in clinical trial protocols. PMID:25984272

The Isolation and Enrichment of Large Numbers of Highly Purified Mouse Spleen Dendritic Cell Populations and Their In Vitro Equivalents.

PubMed

Vremec, David

2016-01-01

Dendritic cells (DCs) form a complex network of cells that initiate and orchestrate immune responses against a vast array of pathogenic challenges. Developmentally and functionally distinct DC subtypes differentially regulate T-cell function. Importantly it is the ability of DC to capture and process antigen, whether from pathogens, vaccines, or self-components, and present it to naive T cells that is the key to their ability to initiate an immune response. Our typical isolation procedure for DC from murine spleen was designed to efficiently extract all DC subtypes, without bias and without alteration to their in vivo phenotype, and involves a short collagenase digestion of the tissue, followed by selection for cells of light density and finally negative selection for DC. The isolation procedure can accommodate DC numbers that have been artificially increased via administration of fms-like tyrosine kinase 3 ligand (Flt3L), either directly through a series of subcutaneous injections or by seeding with an Flt3L secreting murine melanoma. Flt3L may also be added to bone marrow cultures to produce large numbers of in vitro equivalents of the spleen DC subsets. Total DC, or their subsets, may be further purified using immunofluorescent labeling and flow cytometric cell sorting. Cell sorting may be completely bypassed by separating DC subsets using a combination of fluorescent antibody labeling and anti-fluorochrome magnetic beads. Our procedure enables efficient separation of the distinct DC subsets, even in cases where mouse numbers or flow cytometric cell sorting time is limiting.

Prebiotics as immunostimulants in aquaculture: a review.

PubMed

Song, Seong Kyu; Beck, Bo Ram; Kim, Daniel; Park, John; Kim, Jungjoon; Kim, Hyun Duk; Ringø, Einar

2014-09-01

Prebiotics are indigestible fibers that increase beneficial gut commensal bacteria resulting in improvements of the host's health. The beneficial effects of prebiotics are due to the byproducts generated from their fermentation by gut commensal bacteria. In this review, the direct effects of prebiotics on the innate immune system of fish are discussed. Prebiotics, such as fructooligosaccharide, mannanoligosaccharide, inulin, or β-glucan, are called immunosaccharides. They directly enhance innate immune responses including: phagocytic activation, neutrophil activation, activation of the alternative complement system, increased lysozyme activity, and more. Immunosaccharides directly activate the innate immune system by interacting with pattern recognition receptors (PRR) expressed on innate immune cells. They can also associate with microbe associated molecular patterns (MAMPs) to activate innate immune cells. However, the underlying mechanisms involved in innate immune cell activation need to be further explored. Many studies have indicated that immunosaccharides are beneficial to both finfish and shellfish. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimization of a gene electrotransfer procedure for efficient intradermal immunization with an hTERT-based DNA vaccine in mice

PubMed Central

Calvet, Christophe Y; Thalmensi, Jessie; Liard, Christelle; Pliquet, Elodie; Bestetti, Thomas; Huet, Thierry; Langlade-Demoyen, Pierre; Mir, Lluis M

2014-01-01

DNA vaccination consists in administering an antigen-encoding plasmid in order to trigger a specific immune response. This specific vaccine strategy is of particular interest to fight against various infectious diseases and cancer. Gene electrotransfer is the most efficient and safest non-viral gene transfer procedure and specific electrical parameters have been developed for several target tissues. Here, a gene electrotransfer protocol into the skin has been optimized in mice for efficient intradermal immunization against the well-known telomerase tumor antigen. First, the luciferase reporter gene was used to evaluate gene electrotransfer efficiency into the skin as a function of the electrical parameters and electrodes, either non-invasive or invasive. In a second time, these parameters were tested for their potency to generate specific cellular CD8 immune responses against telomerase epitopes. These CD8 T-cells were fully functional as they secreted IFNγ and were endowed with specific cytotoxic activity towards target cells. This simple and optimized procedure for efficient gene electrotransfer into the skin using the telomerase antigen is to be used in cancer patients for the phase 1 clinical evaluation of a therapeutic cancer DNA vaccine called INVAC-1. PMID:26015983

Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and Can Impart Th1 Immunity to Th2-Biased Recipients

PubMed Central

Ghosh, Mrinal K.; Muller, H. Konrad

2017-01-01

We have previously demonstrated lactational transfer of T cell–based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup’s thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we investigated lactational transfer of immunity to Mycobacterium tuberculosis in MHC class I–mismatched animals, as well as from Th1-biased dams to Th2-biased foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized BALB/cJ foster pups resulted in much greater immunity than direct immunization in 5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen-responding cells in the pup spleen were produced through maternal educational immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal cells in the spleen and thymus but a much larger percentage was Foxp3+, resulting in equivalent immunity to direct immunization. Depletion of maternal Foxp3+ cells from pup splenocytes illustrated a substantial role for lactationally transferred dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross MHC class I barriers and that Th1 immunity can be imparted to Th2-biased offspring; in some instances, it can be greater than that achieved by direct immunization. PMID:28747348

Effects of FVIII immunity on hepatocyte and hematopoietic stem cell–directed gene therapy of murine hemophilia A

PubMed Central

Lytle, Allison M; Brown, Harrison C; Paik, Na Yoon; Knight, Kristopher A; Wright, J Fraser; Spencer, H Trent; Doering, Christopher B

2016-01-01

Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV. PMID:26909355

Report of the American Animal Hospital Association (AAHA) Canine Vaccine Task Force: executive summary and 2003 canine vaccine guidelines and recommendations.

PubMed

Paul, Michael A; Appel, Max; Barrett, Ralph; Carmichael, Leland E; Childers, Henry; Cotter, Susan; Davidson, Autumn; Ford, Richard; Keil, Dan; Lappin, Michael; Schultz, Ronald D; Thacker, Eileen; Trumpeter, Janice L; Welborn, Link

2003-01-01

The AAHA has undertaken the development of this document in an effort to inform veterinary practitioners, clarify misunderstandings held by veterinarians, and encourage practitioners to recognize that immunization of patients is a medical procedure. As such, it is bound by the same tenets that govern the recommendation of other medical procedures-principally, that it be tailored to the needs of the individual patient. Many diseases we immunize against are ubiquitous. Many are serious and some even life threatening. Some are of limited demographic concern given the exposure risk for each patient. These factors have all been considered in developing the AAHA Canine Vaccination Guidelines. In the end, each veterinarian must do what he or she determines to be in the best interest of the patient. Vaccination of individual animals produces not only individual immunity but also population or herd immunity. Since we have no readily available and reliable way to determine if each patient has developed an adequate immune response, we encourage the practice philosophy of vaccinating more patients while vaccinating each patient no more than needed.

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

PubMed

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.

Cancer-derived extracellular vesicles: friend and foe of tumour immunosurveillance.

PubMed

Dörsam, Bastian; Reiners, Kathrin S; von Strandmann, Elke Pogge

2018-01-05

Extracellular vesicles (EVs) are important players of intercellular signalling mechanisms, including communication with and among immune cells. EVs can affect the surrounding tissue as well as peripheral cells. Recently, EVs have been identified to be involved in the aetiology of several diseases, including cancer. Tumour cell-released EVs or exosomes have been shown to promote a tumour-supporting environment in non-malignant tissue and, thus, benefit metastasis. The underlying mechanisms are numerous: loss of antigen expression, direct suppression of immune effector cells, exchange of nucleic acids, alteration of the recipient cells' transcription and direct suppression of immune cells. Consequently, tumour cells can subvert the host's immune detection as well as suppress the immune system. On the contrary, recent studies reported the existence of EVs able to activate immune cells, thus promoting the tumour-directed immune response. In this article, the immunosuppressive capabilities of EVs, on the one hand, and their potential use in immunoactivation and therapeutic potential, on the other hand, are discussed.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'. © 2017 The Authors.

Transient Peripheral Immune Activation follows Elective Sigmoidoscopy or Circumcision in a Cohort Study of MSM at Risk of HIV Infection.

PubMed

Lama, Javier R; Karuna, Shelly T; Grant, Shannon P; Swann, Edith M; Ganoza, Carmela; Segura, Patricia; Montano, Silvia M; Lacherre, Martin; De Rosa, Stephen C; Buchbinder, Susan; Sanchez, Jorge; McElrath, M Juliana; Lemos, Maria P

2016-01-01

Rectal and genital sampling in HIV prevention trials permits assessments at the site of HIV entry. Yet the safety and acceptability of circumcision and sigmoidoscopy (and associated abstinence recommendations) are unknown in uncircumcised men who have sex with men (MSM) at high risk of HIV infection. Twenty-nine HIV-seronegative high-risk Peruvian MSM agreed to elective sigmoidoscopy biopsy collections (weeks 2 and 27) and circumcision (week 4) in a 28-week cohort study designed to mimic an HIV vaccine study mucosal collection protocol. We monitored adherence to abstinence recommendations, procedure-related complications, HIV infections, peripheral immune activation, and retention. Twenty-three (79.3%) underwent a first sigmoidoscopy, 21 (72.4%) were circumcised, and 16 (55.2%) completed a second sigmoidoscopy during the study period. All who underwent procedures completed the associated follow-up safety visits. Those completing the procedures reported they were well tolerated, and complication rates were similar to those reported in the literature. Immune activation was detected during the healing period (1 week post-sigmoidoscopy, 6 weeks post-circumcision), including increases in CCR5+CD4+T cells and α4β7+CD4+T cells. Most participants adhered to post-circumcision abstinence recommendations whereas reduced adherence occurred post-sigmoidoscopy. Rectosigmoid mucosal and genital tissue collections were safe in high-risk MSM. Although the clinical implications of the post-procedure increase in peripheral immune activation markers are unknown, they reinforce the need to provide ongoing risk reduction counseling and support for post-procedure abstinence recommendations. Future HIV vaccine studies should also consider the effects of mucosal and tissue collections on peripheral blood endpoints in trial design and analysis. ClinicalTrials.gov NCT02630082.

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

NASA Technical Reports Server (NTRS)

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

2007-01-01

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

Engineering synthetic vaccines using cues from natural immunity

PubMed Central

Irvine, Darrell J.; Swartz, Melody A.; Szeto, Gregory L.

2014-01-01

Vaccines aim to protect against or treat diseases through manipulation of the immune response, promoting either immunity or tolerance. The former generate antibodies and T-cells poised to protect against future pathogen encounter or attack diseased cells such as tumors; the latter, which are far less developed, block pathogenic autoreactive T-cells and autoantibodies that target self tissue. Enormous challenges remain, however, as a consequence of our incomplete understanding of human immunity. A rapidly growing field of research is the design of synthetic materials in vaccines to 1) target organs, tissues, cells, or intracellular compartments; 2) co-deliver immunomodulatory signals that control the quality of the immune response; or 3) directly act as immune regulators, and there exists great potential for well-defined materials to further our understanding of immunity. Here we describe recent advances in the design of synthetic materials to direct immune responses, highlighting successes and challenges in prophylactic, therapeutic, and tolerance-inducing vaccines. PMID:24150416

Non-celiac gluten sensitivity: Time for sifting the grain.

PubMed

Elli, Luca; Roncoroni, Leda; Bardella, Maria Teresa

2015-07-21

In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.

Validation of Procedures for Monitoring Crewmember Immune Function

NASA Technical Reports Server (NTRS)

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

2008-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk (if any) from prolonged immune dysregulation during exploration-class space flight has not yet been determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight status of immunity as it resolves over prolonged flight. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess immunity, latent viral reactivation and physiological stress during both short and long duration flights. Upon completion, it is expected that any clinical risks resulting from the adverse effects of space flight on the human immune system will have been determined. In addition, a flight-compatible immune monitoring strategy will have been developed with which countermeasures validation could be performed. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers' immune systems. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter R+0 assessments. The overall status of the immune system during flight (activation, deficiency, dysregulation) and the response of the immune system to specific latent virus reactivation (known to occur during space flight) will be thoroughly assessed. The first in-flight activity for integrated immunity very recently occurred during the STS-120 Space Shuttle mission. The protocols functioned well from a technical perspective, and accurate in-flight data was obtained from 1 Shuttle and 2 ISS crewmembers. Crew participation rates for the study continue to be robust.

The simultaneous isolation of multiple high and low frequent T-cell populations from donor peripheral blood mononuclear cells using the major histocompatibility complex I-Streptamer isolation technology.

PubMed

Roex, Marthe C J; Hageman, Lois; Heemskerk, Matthias T; Veld, Sabrina A J; van Liempt, Ellis; Kester, Michel G D; Germeroth, Lothar; Stemberger, Christian; Falkenburg, J H Frederik; Jedema, Inge

2018-04-01

Adoptive transfer of donor-derived T cells can be applied to improve immune reconstitution in immune-compromised patients after allogeneic stem cell transplantation. The separation of beneficial T cells from potentially harmful T cells can be achieved by using the major histocompatibility complex (MHC) I-Streptamer isolation technology, which has proven its feasibility for the fast and pure isolation of T-cell populations with a single specificity. We have analyzed the feasibility of the simultaneous isolation of multiple antigen-specific T-cell populations in one procedure by combining different MHC I-Streptamers. First, the effect of combining different amounts of MHC I-Streptamers used in the isolation procedure on the isolation efficacy of target antigen-specific T cells and on the number of off-target co-isolated contaminating cells was assessed. The feasibility of this approach was demonstrated in large-scale validation procedures targeting both high and low frequent T-cell populations using the Good Manufacturing Practice (GMP)-compliant CliniMACS Plus device. T-cell products targeting up to 24 different T-cell populations could be isolated in one, simultaneous MHC I-Streptamer procedure, by adjusting the amount of MHC I- Streptamers per target antigen-specific T-cell population. Concurrently, the co-isolation of potentially harmful contaminating T cells remained below our safety limit. This technology allows the reproducible isolation of high and low frequent T-cell populations. However, the expected therapeutic relevance of direct clinical application without in vitro expansion of these low frequent T-cell populations is questionable. This study provides a feasible, fast and safe method for the generation of highly personalized MHC I-Streptamer isolated T-cell products for adoptive immunotherapy. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits.

PubMed

Hamamoto, Shinichi; Okuma, Tomohisa; Yamamoto, Akira; Kageyama, Ken; Takeshita, Toru; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio

2013-05-01

To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity. © RSNA, 2013.

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential Effects of Controllable and Uncontrollable Stress on Immune Function in Humans

DTIC Science & Technology

1989-02-24

illness, divorce, unemploy - ment, and academic examination periods, humans tend to exhibit signs of altered immunity (e.g., Arnetz et al., 1987; Bartrop...the separation were responsible for the occurrence of these immune ., ., 15 differences. Arnetz et al. (1987) studied 17 unemployed women and 8...subjects; however, sampling procedures were not symmetrical and sub- jects were studied at different times of the year. rhe women bad been unemployed

Engineering synthetic vaccines using cues from natural immunity.

PubMed

Irvine, Darrell J; Swartz, Melody A; Szeto, Gregory L

2013-11-01

Vaccines aim to protect against or treat diseases through manipulation of the immune response, promoting either immunity or tolerance. In the former case, vaccines generate antibodies and T cells poised to protect against future pathogen encounter or attack diseased cells such as tumours; in the latter case, which is far less developed, vaccines block pathogenic autoreactive T cells and autoantibodies that target self tissue. Enormous challenges remain, however, as a consequence of our incomplete understanding of human immunity. A rapidly growing field of research is the design of vaccines based on synthetic materials to target organs, tissues, cells or intracellular compartments; to co-deliver immunomodulatory signals that control the quality of the immune response; or to act directly as immune regulators. There exists great potential for well-defined materials to further our understanding of immunity. Here we describe recent advances in the design of synthetic materials to direct immune responses, highlighting successes and challenges in prophylactic, therapeutic and tolerance-inducing vaccines.

Engineering synthetic vaccines using cues from natural immunity

NASA Astrophysics Data System (ADS)

Irvine, Darrell J.; Swartz, Melody A.; Szeto, Gregory L.

2013-11-01

Vaccines aim to protect against or treat diseases through manipulation of the immune response, promoting either immunity or tolerance. In the former case, vaccines generate antibodies and T cells poised to protect against future pathogen encounter or attack diseased cells such as tumours; in the latter case, which is far less developed, vaccines block pathogenic autoreactive T cells and autoantibodies that target self tissue. Enormous challenges remain, however, as a consequence of our incomplete understanding of human immunity. A rapidly growing field of research is the design of vaccines based on synthetic materials to target organs, tissues, cells or intracellular compartments; to co-deliver immunomodulatory signals that control the quality of the immune response; or to act directly as immune regulators. There exists great potential for well-defined materials to further our understanding of immunity. Here we describe recent advances in the design of synthetic materials to direct immune responses, highlighting successes and challenges in prophylactic, therapeutic and tolerance-inducing vaccines.

Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Ogonek, Justyna; Kralj Juric, Mateja; Ghimire, Sakhila; Varanasi, Pavankumar Reddy; Holler, Ernst; Greinix, Hildegard; Weissinger, Eva

2016-01-01

The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT. PMID:27909435

ACTION OF TRITIATED TETANUS TOXIN AND TOXOID UPTON THE NERVOUS SYSTEM AND UPON THE ANTIBOYD FORMING MECHANISM. Period covered: April 1, 1959-March 31, 1961

DOE Office of Scientific and Technical Information (OSTI.GOV)

Speirs, R.S.

1961-10-31

>Progress is reported in studies on the action of tritiated tetanus toxin and toxoid upon the nervous system and upon the antibody forming mechanisms in mice. Procedures are described for the preparation of purified tritiated tetanus toxin. The tritiated toxin was injected into mice immunized to tetanus toxoid. Distinct differences were noted in the cellular reaction to the tritiated antigen in immunized and control animals. The data suggest that antibody-producing cells contain antigen at the time antibody is being produced. A quantitative procedure was developed for determining the number of cells responding during an inflammation. Procedures were developed for themore » automatic processing of radioautograms. ( C.H.)« less

Innate and adaptive immunity at Mucosal Surfaces of the Female Reproductive Tract: Stratification and Integration of Immune Protection against the Transmission of Sexually Transmitted Infections

PubMed Central

Hickey, DK; Patel, MV; Fahey, JV; Wira, CR

2011-01-01

This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract. PMID:21353708

Exosomes and their roles in immune regulation and cancer.

PubMed

Greening, David W; Gopal, Shashi K; Xu, Rong; Simpson, Richard J; Chen, Weisan

2015-04-01

Exosomes, a subset of extracellular vesicles (EVs), function as a mode of intercellular communication and molecular transfer. Exosomes facilitate the direct extracellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. The immunological activities of exosomes affect immunoregulation mechanisms including modulating antigen presentation, immune activation, immune suppression, immune surveillance, and intercellular communication. Besides immune cells, cancer cells secrete immunologically active exosomes that influence both physiological and pathological processes. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has enforced the way these membranous vesicles are being considered as potential immunotherapeutic reagents. Indeed, tumour- and immune cell-derived exosomes have been shown to carry tumour antigens and promote immunity, leading to eradication of established tumours by CD8(+) T cells and CD4(+) T cells, as well as directly suppressing tumour growth and resistance to malignant tumour development. Further understanding of these areas of exosome biology, and especially of molecular mechanisms involved in immune cell targeting, interaction and manipulation, is likely to provide significant insights into immunorecognition and therapeutic intervention. Here, we review the emerging roles of exosomes in immune regulation and the therapeutic potential in cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-celiac gluten sensitivity: Time for sifting the grain

PubMed Central

Elli, Luca; Roncoroni, Leda; Bardella, Maria Teresa

2015-01-01

In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined. PMID:26217073

Engineering Immunity: Modulating Dendritic Cell Subsets and Lymph Node Response to Direct Immune-polarization and Vaccine Efficacy

PubMed Central

Leleux, Jardin; Atalis, Alexandra; Roy, Krishnendu

2017-01-01

While successful vaccines have been developed against many pathogens, there are still many diseases and pathogenic infections that are highly evasive to current vaccination strategies. Thus, more sophisticated approaches to control the type and quality of vaccine-induced immune response must be developed. Dendritic cells (DCs) are the sentinels of the body and play a critical role in immune response generation and direction by bridging innate and adaptive immunity. It is now well recognized that DCs can be separated into many subgroups, each of which has a unique function. Better understanding of how various DC subsets, in lymphoid organs and in the periphery, can be targeted through controlled delivery; and how these subsets modulate and control the resulting immune response could greatly enhance our ability to develop new, effective vaccines against complex diseases. In this review, we provide an overview of DC subset biology and discuss current immunotherapeutic strategies that utilize DC targeting to modulate and control immune responses. PMID:26489733

Autophagy dictates metabolism and differentiation of inflammatory immune cells

PubMed Central

Riffelmacher, Thomas; Richter, Felix Clemens; Simon, Anna Katharina

2018-01-01

ABSTRACT The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. In particular, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation. This concept is strengthened through novel molecular insights into how AMPK and MTOR signaling cascades affect both autophagy and metabolism. In this review, we discuss direct and indirect evidence linking autophagy, metabolic pathways and immune cell differentiation including T, B, and innate lymphocytes as well as in myeloid cells that are direct mediators of inflammation. Herein, we propose a model for autophagy-driven immunometabolism controlling immune cell differentiation. PMID:28806133

75 FR 69005 - Flumioxazin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-10

... reproduction studies indicated an effect on the nervous systems. Based on the lack of evidence of... flumioxazin does not directly impact the nervous system or directly target the immune system. The Agency does... to indicate that flumioxazin targets the nervous system or the immune system. Further, EPA has...

Just-in-time training of dental responders in a simulated pandemic immunization response exercise.

PubMed

Colvard, Michael D; Hirst, Jeremy L; Vesper, Benjamin J; DeTella, George E; Tsagalis, Mila P; Roberg, Mary J; Peters, David E; Wallace, Jimmy D; James, James J

2014-06-01

The reauthorization of the Pandemic and All-Hazards Preparedness Act in 2013 incorporated the dental profession and dental professionals into the federal legislation governing public health response to pandemics and all-hazard situations. Work is now necessary to expand the processes needed to incorporate and train oral health care professionals into pandemic and all-hazard response events. A just-in-time (JIT) training exercise and immunization drill using an ex vivo porcine model system was conducted to demonstrate the rapidity to which dental professionals can respond to a pandemic influenza scenario. Medical history documentation, vaccination procedures, and patient throughput and error rates of 15 dental responders were evaluated by trained nursing staff and emergency response personnel. The average throughput (22.33/hr) and medical error rates (7 of 335; 2.08%) of the dental responders were similar to those found in analogous influenza mass vaccination clinics previously conducted using certified public health nurses. The dental responder immunization drill validated the capacity and capability of dental professionals to function as a valuable immunization resource. The ex vivo porcine model system used for JIT training can serve as a simple and inexpensive training tool to update pandemic responders' immunization techniques and procedures supporting inoculation protocols.

Diet Modifies the Neuroimmune System by Influencing Macrophage Activation

ERIC Educational Resources Information Center

Sherry, Christina Lynn

2009-01-01

It has long been appreciated that adequate nutrition is required for proper immune function and it is now recognized that dietary components contribute to modulation of immune cells, subsequently impacting the whole body's response during an immune challenge. Macrophage activation plays a critical role in the immune system and directs the…

Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activity in Nociceptors

DTIC Science & Technology

2016-06-01

BSCB will permit blood-borne mye- loid and lymphoid immune cells to enter the spinal cord parenchyma and exert direct inflammatory actions on central...primitive innate immune system is the first line of defense against pathogens and toxins; it is always present and it depends upon diverse cell types that...adaptive immune system, the innate immune system does not em- ploy antigen-specific humoral and cell -mediated immunity mecha- nisms. Two innate immune

Cellular Immunosenescence in Adult Male Crickets, Gryllus assimilis

USDA-ARS?s Scientific Manuscript database

Ecological immunity studies in invertebrates, particularly insects, have generated new insights into trade-offs between immune functions and other physiological parameters. These studies document physiologically-directed reallocations of immune costs to other high-cost areas of physiology. Immunos...

Health and Safety in Day Care.

ERIC Educational Resources Information Center

Sells, Clifford J.; Paeth, Susan

1987-01-01

Basic health and day care policies and procedures should be implemented and closely monitored with the help of a health consultant, particularly in terms of respiratory tract, enteric, skin, invasive bacterial, and multiple system infections; Acquired Immune Deficiency Syndrome; vaccine preventable diseases; and general safety procedures.…

AIDS: Acquired Immune Deficiency Syndrome, Information and Procedural Guidelines for Providing Services to Persons with AIDS/HTLV-III.

ERIC Educational Resources Information Center

Montana State Dept. of Health and Environmental Sciences, Helena.

This manual presents information about the disease, Acquired Immune Deficiency Syndrome (AIDS), and guidelines for service delivery to Montana residents who have been diagnosed with AIDS or related disorders. The first section describes the disease's causes, symptoms, and transmission; risk factors; high-risk populations; prevention suggestions;…

Crosstalk between cancer and the neuro-immune system.

PubMed

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.

Engineering vaccines and niches for immune modulation.

PubMed

Purwada, Alberto; Roy, Krishnendu; Singh, Ankur

2014-04-01

Controlled modulation of immune response, especially the balance between immunostimulatory and immunosuppressive responses, is critical for a variety of clinical applications, including immunotherapies against cancer and infectious diseases, treatment of autoimmune disorders, transplant surgeries, regenerative medicine, prosthetic implants, etc. Our ability to precisely modify both innate and adaptive immune responses could provide new therapeutic directions in a variety of diseases. In the context of vaccines and immunotherapies, the interplay between antigen-presenting cells (e.g. dendritic cells and macrophages), B cells, T helper and killer subtypes, and regulatory T- and B-cell responses is critical for generating effective immunity against cancer, infectious diseases and autoimmune diseases. In recent years, immunoengineering has emerged as a new field that uses quantitative engineering tools to understand molecular-, cellular- and system-level interactions of the immune system and to develop design-driven approaches to control and modulate immune responses. Biomaterials are an integral part of this engineering toolbox and can exploit the intrinsic biological and mechanical cues of the immune system to directly modulate and train immune cells and direct their response to a particular phenotype. A large body of literature exists on strategies to evade or suppress the immune response in implants, transplantation and regenerative medicine. This review specifically focuses on the use of biomaterials for immunostimulation and controlled modulation, especially in the context of vaccines and immunotherapies against cancer, infectious diseases and autoimmune disorders. Bioengineering smart systems that can simultaneously deliver multiple bioactive agents in a controlled manner or can work as a niche for in situ priming and modulation of the immune system could significantly enhance the efficacy of next-generation immunotherapeutics. In this review, we describe our perspective on the important design aspects for the development of biomaterials that can actively modulate immune responses by stimulating receptor complexes and cells, and delivering multiple immunomodulatory biomolecules. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Innate Immunity and Breast Milk.

PubMed

Cacho, Nicole Theresa; Lawrence, Robert M

2017-01-01

Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant's intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant's gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges

PubMed Central

Coughlan, Lynda; Lambe, Teresa

2015-01-01

Influenza A virus is a respiratory pathogen which causes both seasonal epidemics and occasional pandemics; infection continues to be a significant cause of mortality worldwide. Current influenza vaccines principally stimulate humoral immune responses that are largely directed towards the variant surface antigens of influenza. Vaccination can result in an effective, albeit strain-specific antibody response and there is a need for vaccines that can provide superior, long-lasting immunity to influenza. Vaccination approaches targeting conserved viral antigens have the potential to provide broadly cross-reactive, heterosubtypic immunity to diverse influenza viruses. However, the field lacks consensus on the correlates of protection for cellular immunity in reducing severe influenza infection, transmission or disease outcome. Furthermore, unlike serological methods such as the standardized haemagglutination inhibition assay, there remains a large degree of variation in both the types of assays and method of reporting cellular outputs. T-cell directed immunity has long been known to play a role in ameliorating the severity and/or duration of influenza infection, but the precise phenotype, magnitude and longevity of the requisite protective response is unclear. In order to progress the development of universal influenza vaccines, it is critical to standardize assays across sites to facilitate direct comparisons between clinical trials. PMID:26343189

[Secondary immune blood transfusion shock in calves due to the donor immune erythrocyte isoantibodies].

PubMed

Golemanov, D

1980-01-01

Experiments were carried out on 2 cows, used as donors and 10 calves at the age from 1 to 6 months, taken in the experiment as recipients. The calves were made a blood-transfusion in a dose of 9 cm(3)/kg T. from donors whose serum contained immune erythroantibodies with a titer of 1:4--1:64, directed against their erythrocytes. The recipients had not had antibodies, directed against the donors' erythrocytes. For the purposes of the investigations were used a hemalitic test and an agglutination in a vidal test-tube. The post-transfusional immune reactions and complications observed were related to the hematransfusional shock as a result of a collision between the donor's immune isoerythroantibodies and their corresponding erythrocytic antigens in the recipients. This shock is of great practical value for transfusional hematology in calves. The immune isoerythroantibodies, built up after blood transfusion of immunized, in advance, donors, were formed in 60% of the cases on the 7th--9th days afer the blood-transfusion and disappeared from peripheral blood on the 30ieth day afterwards.

Coping strategies and immune neglect in affective forecasting: Direct evidence and key moderators

PubMed Central

Hoerger, Michael

2012-01-01

Affective forecasting skills have important implications for decision making. However, recent research suggests that immune neglect – the tendency to overlook coping strategies that reduce future distress – may lead to affective forecasting problems. Prior evidence for immune neglect has been indirect. More direct evidence and a deeper understanding of immune neglect are vital to informing the design of future decision-support interventions. In the current study, young adults (N = 325) supplied predicted, actual, and recollected reactions to an emotionally-evocative interpersonal event, Valentine’s Day. Based on participants’ qualitative descriptions of the holiday, a team of raters reliably coded the effectiveness of their coping strategies. Supporting the immune neglect hypothesis, participants overlooked the powerful role of coping strategies when predicting their emotional reactions. Immune neglect was present not only for those experiencing the holiday negatively (non-daters) but also for those experiencing it positively (daters), suggesting that the bias may be more robust than originally theorized. Immune neglect was greater for immediate emotional reactions than more enduring reactions. Further, immune neglect was conspicuously absent from recollected emotional reactions. Implications for decision-support interventions are discussed. PMID:22375161

Characterization and storage of malaria antigens: Localization and chemical characterization of Plasmodium knowlesi schizont antigens

PubMed Central

Deans, J. A.; Cohen, S.

1979-01-01

The identification of malarial antigens that induce protective immunity could provide a rational basis for developing an effective antimalarial vaccine as well as specific serodiagnostic tests indicative of clinical immune status. Since protective immunity is probably induced by stage-dependent rather than stage-independent antigens, the antigenic composition of different stages of Plasmodium knowlesi has been compared, and a limited chemical characterization undertaken. This information should provide some insight into the types of preparative procedure appropriate for the purification of functionally important malarial antigens. PMID:120777

Old and new facts about hyperthermia-induced modulations of the immune system.

PubMed

Frey, Benjamin; Weiss, Eva-Maria; Rubner, Yvonne; Wunderlich, Roland; Ott, Oliver J; Sauer, Rolf; Fietkau, Rainer; Gaipl, Udo S

2012-01-01

Hyperthermia (HT) is a potent sensitiser for radiotherapy (RT) and chemotherapy (CT) and has been proven to modulate directly or indirectly cells of the innate and adaptive immune system. We will focus in this article on how anti-tumour immunity can be induced by HT. In contrast to some in vitro assays, in vivo examinations showed that natural killer cells and phagocytes like granulocytes are directly activated against the tumour by HT. Since heat also activates dendritic cells (DCs), HT should be combined with further death stimuli (RT, CT or immune therapy) to allocate tumour antigen, derived from, for example, necrotic tumour cells, for uptake by DCs. We will outline that induction of immunogenic tumour cells and direct tumour cell killing by HT in combination with other therapies contributes to immune activation against the tumour. Studies will be presented showing that non-beneficial effects of HT on immune cells are mostly timely restricted. A special focus is set on immune activation mediated by extracellular present heat shock proteins (HSPs) carrying tumour antigens and further danger signals released by dying tumour cells. Local HT treatment in addition to further stress stimuli exerts abscopal effects and might be considered as in situ tumour vaccination. An increased natural killer (NK) cell activity, lymphocyte infiltration and HSP-mediated induction of immunogenic tumour cells have been observed in patients. Treatments with the addition of HT therefore can be considered as a personalised cancer treatment approach by specifically activating the immune system against the individual unique tumour.

Role of TIRAP in Myelodysplastic Syndromes

DTIC Science & Technology

2015-04-01

process of examining other publically available sequencing data on MDS or myeloproliferative neoplasm patients for innate immune signaling gene mutations...evidence showing the presence of somatic mutations in the innate immune signaling genes in myeloid neoplasm , there is evidence of dysregulation of the...this procedure. To characterize TIRAP-induced myeloproliferation in IFNγ-KO mice, to determine the transplantability of the myeloprolifation , and to

AIDS: Acquired Immune Deficiency Syndrome; Information and Procedural Guidelines for Providing Services to Persons with AIDS/HIV. Revised.

ERIC Educational Resources Information Center

Montana State Dept. of Health and Environmental Sciences, Helena. Health Education Bureau.

This volume consists of updated information to be inserted into a Montana AIDS Project manual on providing services to persons with acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV), originally published in December 1985. The updates are mainly statistics and terminology, along with the addition of several new sections.…

Prior Corneal Scarification and Injection of Immune Serum are Not Required Before Ocular HSV-1 Infection for UV-B-Induced Virus Reactivation and Recurrent Herpetic Corneal Disease in Latently Infected Mice

PubMed Central

BenMohamed, Lbachir; Osorio, Nelson; Khan, Arif A.; Srivastava, Ruchi; Huang, Lei; Krochmal, John J.; Garcia, Jairo M.; Simpson, Jennifer L.; Wechsler, Steven L.

2017-01-01

Purpose Blinding ocular herpetic disease in humans is due to spontaneous reactivation of herpes simplex virus type 1 (HSV-1) from latency, rather than to primary acute infection. Mice latently infected with HSV-1 undergo little or no in vivo spontaneous reactivation with accompanying virus shedding in tears. HSV-1 reactivation can be induced in latently infected mice by several in vivo procedures, with UV-B-induced reactivation being one commonly used method. In the UV-B model, corneas are scarified (lightly scratched) just prior to ocular infection to increase efficiency of the primary infection and immune serum containing HSV-1 neutralizing antibodies is injected intraperitoneally (i.p.) to increase survival and decrease acute corneal damage. Since scarification can significantly alter host gene transcription in the cornea and in the trigeminal ganglia (TG; the site of HSV-1 latency) and since injection of immune serum likely modulates innate and adaptive herpes immunity, we investigated eliminating both treatments. Material and Methods Mice were infected with HSV-1 with or without corneal scarification and immune serum. HSV-1 reactivation and recurrent disease were induced by UV-B irradiation. Results When corneal scarification and immune serum were both eliminated, UV-B irradiation still induced both HSV-1 reactivation, as measured by shedding of reactivated virus in tears and herpetic eye disease, albeit at reduced levels compared to the original procedure. Conclusion Despite the reduced reactivation and disease, avoidance of both corneal scarification and immune serum should improve the clinical relevance of the UV-B mouse model. PMID:26398722

Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

PubMed Central

2014-01-01

Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma).

PubMed Central

Kondo, H; Rabin, B S; Rodnan, G P

1976-01-01

Cell-mediated immunity to skin extracts was studied by the macrophage migration inhibition test, lymphocyte transformation, and direct cytotoxicity to skin fibroblasts, in normal individuals and patients with progressive systemic sclerosis. The latter included 18 individuals with diffuse scleroderma and 12 with the CREST syndrome, a variant form of systemic sclerosis in which there is more limited involvement of the skin. Controls consisted of 13 patients with other connective tissue diseases and 16 normal individuals. Phosphate-buffered saline and 3 M KCl extracts of both normal and sclerodermatous skin were used as antigens. No evidence of lymphocyte reactivity was found by the lymphocyte transformation and direct cytotoxicity test procedures. However, the lymphocytes of patients with diffuse scleroderma did respond to extracts of both normal and sclerodermatous skin in the migration inhibition assay. 10 of 16 patients (62.5%) had migration indices below 2 SD of the normal range, 1 of 10 CREST patients and 1 of 13 patients with other connective tissue diseases showed similar reactivity. Antisera specific for immunoglobulin-bearing lymphocytes (B lymphocytes) and T lymphocytes were used to characterize the lymphocytes found in skin biopsies of patients with diffuse scleroderma. T lymphocytes made up the majority of lymphocytes in the skin infiltrates. These findings suggest that lymphocytes sensitized to skin extracts are present in patients with diffuse scleroderma. The cell-mediated immune reaction to skin antigens may be a factor in the pathogenesis of diffuse scleroderma. Images PMID:791970

Guidelines for standard preclinical experiments in the mouse model of myasthenia gravis induced by acetylcholine receptor immunization.

PubMed

Tuzun, Erdem; Berrih-Aknin, Sonia; Brenner, Talma; Kusner, Linda L; Le Panse, Rozen; Yang, Huan; Tzartos, Socrates; Christadoss, Premkumar

2015-08-01

Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one of the standard animal models. Although numerous compounds have been recently proposed for MG mostly by using the active immunization EAMG model, only a few have been proven to be effective in MG patients. The variability in the experimental design, immunization methods and outcome measurements of pre-clinical EAMG studies make it difficult to interpret the published reports and assess the potential for application to MG patients. In an effort to standardize the active immunization EAMG model, we propose standard procedures for animal care conditions, sampling and randomization of mice, experimental design and outcome measures. Utilization of these standard procedures might improve the power of pre-clinical EAMG experiments and increase the chances for identifying promising novel treatment methods that can be effectively translated into clinical trials for MG. Copyright © 2015 Elsevier Inc. All rights reserved.

Combining tabular, rule-based, and procedural knowledge in computer-based guidelines for childhood immunization.

PubMed

Miller, P L; Frawley, S J; Sayward, F G; Yasnoff, W A; Duncan, L; Fleming, D W

1997-06-01

IMM/Serve is a computer program which implements the clinical guidelines for childhood immunization. IMM/Serve accepts as input a child's immunization history. It then indicates which vaccinations are due and which vaccinations should be scheduled next. The clinical guidelines for immunization are quite complex and are modified quite frequently. As a result, it is important that IMM/Serve's knowledge be represented in a format that facilitates the maintenance of that knowledge as the field evolves over time. To achieve this goal, IMM/Serve uses four representations for different parts of its knowledge base: (1) Immunization forecasting parameters that specify the minimum ages and wait-intervals for each dose are stored in tabular form. (2) The clinical logic that determines which set of forecasting parameters applies for a particular patient in each vaccine series is represented using if-then rules. (3) The temporal logic that combines dates, ages, and intervals to calculate recommended dates, is expressed procedurally. (4) The screening logic that checks each previous dose for validity is performed using a decision table that combines minimum ages and wait intervals with a small amount of clinical logic. A knowledge maintenance tool, IMM/Def, has been developed to help maintain the rule-based logic. The paper describes the design of IMM/Serve and the rationale and role of the different forms of knowledge used.

Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activity in Nociceptors

DTIC Science & Technology

2014-10-01

disruption of the BSCB will permit blood-borne mye- loid and lymphoid immune cells to enter the spinal cord parenchyma and exert direct inflammatory actions...recently evolved adaptive immune system, the innate immune system does not em- ploy antigen-specific humoral and cell -mediated immunity mecha- nisms. Two... innate immune functions have been emphasized traditionally: 1) the recruitment of cells and proteins to destroy pathogens and toxins, and 2) increases

31 CFR 357.23 - Judicial proceedings-sovereign immunity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Judicial proceedings-sovereign immunity. 357.23 Section 357.23 Money and Finance: Treasury Regulations Relating to Money and Finance... Securities System (Legacy Treasury Direct) § 357.23 Judicial proceedings—sovereign immunity. (a) Department...

Rab GTPases in Immunity and Inflammation.

PubMed

Prashar, Akriti; Schnettger, Laura; Bernard, Elliott M; Gutierrez, Maximiliano G

2017-01-01

Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.

Environmental proxies of antigen exposure explain variation in immune investment better than indices of pace of life.

PubMed

Horrocks, Nicholas P C; Hegemann, Arne; Ostrowski, Stéphane; Ndithia, Henry; Shobrak, Mohammed; Williams, Joseph B; Matson, Kevin D; Tieleman, B I

2015-01-01

Investment in immune defences is predicted to covary with a variety of ecologically and evolutionarily relevant axes, with pace of life and environmental antigen exposure being two examples. These axes may themselves covary directly or inversely, and such relationships can lead to conflicting predictions regarding immune investment. If pace of life shapes immune investment then, following life history theory, slow-living, arid zone and tropical species should invest more in immunity than fast-living temperate species. Alternatively, if antigen exposure drives immune investment, then species in antigen-rich tropical and temperate environments are predicted to exhibit higher immune indices than species from antigen-poor arid locations. To test these contrasting predictions we investigated how variation in pace of life and antigen exposure influence immune investment in related lark species (Alaudidae) with differing life histories and predicted risks of exposure to environmental microbes and parasites. We used clutch size and total number of eggs laid per year as indicators of pace of life, and aridity, and the climatic variables that influence aridity, as correlates of antigen abundance. We quantified immune investment by measuring four indices of innate immunity. Pace of life explained little of the variation in immune investment, and only one immune measure correlated significantly with pace of life, but not in the predicted direction. Conversely, aridity, our proxy for environmental antigen exposure, was predictive of immune investment, and larks in more mesic environments had higher immune indices than those living in arid, low-risk locations. Our study suggests that abiotic environmental variables with strong ties to environmental antigen exposure can be important correlates of immunological variation.

Concentration and detection of bacteria in virtual environmental samples based on non-immunomagnetic separation and quantum dots by using a laboratory-made system

NASA Astrophysics Data System (ADS)

Cheng, Zhi; Wu, Taihu; Chen, Feng; Du, Yaohua; Gu, Biao; Li, Chao; Yang, Zijian

2012-03-01

This study investigated a method that simultaneously detects three bacteria, Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus via an approach that combines un-immunized magnetic nanoparticles for the enrichment and antibody-conjugated quantum dots (QDs) as fluorescence markers, by using a laboratory-made system. In the enrichment procedure, the un-immunized superparamagnetic polymer nanoparticles and the three bacteria formed "beadcell" complex. Magnetic nanoparticles with different size were used and some interferents were added into the bacteria suspension respectively to check the influence on concentration efficiency. In the immuno-fluorescence labeling procedure, QDs with different emission wavelenghs were immobilized with antibody. Antibody conjugated QDs capture the bacteria selectively and specifically so that "sandwich" complex were formed. The suspension of the labeled bacteria was trickled onto a microporous membrane. A 450nm semiconductor laser was used as a part of the laboratory-made system to excite the QDs. Three PMT detectors were utilized to detect the fluorescence intensity. These un-immunized magnetic nanoparticles can be applied in nonspecific separation and enrichment of bacteria from environmental samples, and this method, of which the detection procedures are completed within 2 h, can be applied to the cost-effective and rapid detecting of bacterial contamination.

Immunization in Texas: Progress and Challenges [and] Teacher's Guide.

ERIC Educational Resources Information Center

Smith, David R.

Two documents are presented here. One is a report of the Texas state health department concerning the immunization needs of the state's population, the extent of federal, state, and private financial support for public vaccination programs, legislation and current efforts to extend immunization to all children, and future directions for…

Parental Vaccine Beliefs and Child's School Type

ERIC Educational Resources Information Center

Kennedy, Allison M.; Gust, Deborah A.

2005-01-01

The school system plays an important role in a child's vaccination status, whether by directly offering immunization services, maintaining immunization records, or providing an incentive for up-to-date immunizations through the enforcement of school entry laws. Within the American educational system, however, children do not all attend the same…

Immune Abnormalities in Patients with Autism.

ERIC Educational Resources Information Center

Warren, Reed P.; And Others

1986-01-01

A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

Acute changes in serum immune markers due to swimming in a chlorinated pool.

PubMed

Vlaanderen, Jelle; van Veldhoven, Karin; Font-Ribera, Laia; Villanueva, Cristina M; Chadeau-Hyam, Marc; Portengen, Lützen; Grimalt, Joan O; Zwiener, Christian; Heederik, Dick; Zhang, Xiangru; Vineis, Paolo; Kogevinas, Manolis; Vermeulen, Roel

2017-08-01

Exposure to disinfectants and disinfection byproducts (DBPs) due to swimming in chlorinated water has been associated with allergic and respiratory health effects, including asthma. Biological mechanisms contributing to these associations are largely unknown. We hypothesized a potential pathway involving modulation of the immune system. We assessed levels of immune markers (CCL11, CCL22, CXCL10, CRP, EGF, GCSF, IL-8, IL-17, IL-1RA, MPO, VEGF, Periostin) in serum collected from 30 women and 29 men before and after 40min of swimming in a chlorinated pool. Exposure to DBPs was assessed by measuring bromodichloromethane, bromoform, chloroform, and dibromochloromethane in exhaled breath before and after swimming. Covariate data including information on physical activity was available through questionnaires and measurements. We assessed the association between indicators of swimming in a chlorinated pool and changes in serum immune marker concentrations using linear regression with bivariate normal distributions and adjusted for multiple comparisons by applying the Benjamini-Hochberg procedure. We observed a significant decrease in serum concentrations of IL-8 (-12.53%; q=2.00e-03), CCL22 (-7.28%; q=4.00e-04), CCL11 (-7.15%; q=9.48e-02), CRP (-7.06%; q=4.68e-05), and CXCL10 (-13.03%; q=6.34e-14) and a significant increase in IL-1RA (20.16%; q=4.18e-06) from before to after swimming. Associations with quantitative measurements of DBPs or physical activity were similar in direction and strength. Most of the observed associations became non-significant when we adjusted the effects of exposure to DBPs for physical activity or vice-versa. Our study indicates that swimming in a chlorinated pool induces perturbations of the immune response through acute alterations of patterns of cytokine and chemokine secretion. The observed effects could not be uniquely attributed to either exposure to DBPs or physical activity. Evidence in the literature suggests that observed decreases in immune markers are possibly due to an immunosuppressive effect of DBPs, while the increase in IL-1RA might be due to physical activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses

PubMed Central

Fertey, Jasmin; Bayer, Lea; Grunwald, Thomas; Pohl, Alexandra; Beckmann, Jana; Gotzmann, Gaby; Casado, Javier Portillo; Schönfelder, Jessy; Rögner, Frank-Holm; Wetzel, Christiane; Thoma, Martin; Bailer, Susanne M.; Hiller, Ekkehard; Rupp, Steffen; Ulbert, Sebastian

2016-01-01

Inactivated vaccines are commonly produced by incubating pathogens with chemicals such as formaldehyde or β-propiolactone. This is a time-consuming process, the inactivation efficiency displays high variability and extensive downstream procedures are often required. Moreover, application of chemicals alters the antigenic components of the viruses or bacteria, resulting in reduced antibody specificity and therefore stimulation of a less effective immune response. An alternative method for inactivation of pathogens is ionizing radiation. It acts very fast and predominantly damages nucleic acids, conserving most of the antigenic structures. However, currently used irradiation technologies (mostly gamma-rays and high energy electrons) require large and complex shielding constructions to protect the environment from radioactivity or X-rays generated during the process. This excludes them from direct integration into biological production facilities. Here, low-energy electron irradiation (LEEI) is presented as an alternative inactivation method for pathogens in liquid solutions. LEEI can be used in normal laboratories, including good manufacturing practice (GMP)- or high biosafety level (BSL)-environments, as only minor shielding is necessary. We show that LEEI efficiently inactivates different viruses (influenza A (H3N8), porcine reproductive and respiratory syndrome virus (PRRSV), equine herpesvirus 1 (EHV-1)) and bacteria (Escherichia coli) and maintains their antigenicity. Moreover, LEEI-inactivated influenza A viruses elicit protective immune responses in animals, as analyzed by virus neutralization assays and viral load determination upon challenge. These results have implications for novel ways of developing and manufacturing inactivated vaccines with improved efficacy. PMID:27886076

Mice are actively immunized after passive monoclonal antibody prophylaxis and ricin toxin challenge. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemley, P.V.; Wright, D.C.

1992-12-31

Mice passively immunized by a protective, anti-ricin A-chain monoclonal antibody, then challenged intravenously with ricin, were protected from a subsequent ricin challenge, and were actively immunized. Two significant advantages accrued from this experiment: the monoclonal antibody neutralized the toxicity of the ricin immunogen, and active immunization was achieved with very low antigen load (approx. 0.5 micrograms/mouse). We ruled out the possibility that residual monoclonal antibody provided the protection by using three independent criteria. There was significant (four orders of magnitude) enhancement of the immune response in the presence of the monoclonal antibody; control immunizations of mice with ricin A-chain, ricinmore » B-chain or either chain with the monoclonal antibody did not induce active immunity; and the active immunization could not be replicated when protective goat polyclonal antibody was substituted for the monoclonal antibody. Because high titers were achieved rapidly without any adjuvant, we are currently investigating haptenized ricin to determine if anti-hapten monoclonal antibodies can be produced by this refined procedure.« less

SIRT1 and HIF1α signaling in metabolism and immune responses.

PubMed

Yu, Qing; Dong, Lin; Li, Yan; Liu, Gaungwei

2018-04-01

SIRT1 and HIF1α are regarded as two key metabolic sensors in cellular metabolism pathways and play vital roles in influencing immune responses. SIRT1 and HIF1α regulate immune responses in metabolism-dependent and -independent ways. Here, we summarized the recent knowledge of SIRT1 and HIF1α signaling in metabolism and immune responses. HIF1α is a direct target of SIRT1. Sometimes, SIRT1 and HIF1α cooperate or act separately to mediate immune responses. In innate immune responses, SIRT1 can regulate the glycolytic activity of myeloid-derived suppressor cells (MDSCs) and influence MDSC functional differentiation. SIRT1 can regulate monocyte function through NF-κB and PGC-1, accompanying an increased NAD + level. The SIRT1-HIF1α axis bridges the innate immune signal to an adaptive immune response by directing cytokine production of dendritic cells in a metabolism-independent manner, promoting the differentiation of CD4 + T cells. For adaptive immune cells, SIRT1 can mediate the differentiation of inflammatory T cell subsets in a NAD + -dependent manner. HIF1α can stimulate some glycolysis-associated genes and regulate the ATP and ROS generations. In addition, SIRT1-and HIF1α-associated metabolism inhibits the activity of mTOR, thus negatively regulating the differentiation and function of Th9 cells. As immune cells are crucial in controlling immune-associated diseases, SIRT1-and HIF1α associated-metabolism is closely linked to immune-associated diseases, including infection, tumors, allergic airway inflammation, and autoimmune diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Epigenetic modifiers in immunotherapy: a focus on checkpoint inhibitors.

PubMed

Terranova-Barberio, Manuela; Thomas, Scott; Munster, Pamela N

2016-06-01

Immune surveillance should be directed to suppress tumor development and progression, involving a balance of coinhibitory and costimulatory signals that amplify immune response without overwhelming the host. Immunotherapy confers durable clinical benefit in 'immunogenic tumors', whereas in other tumors the responses are modest. Thus, immune checkpoint inhibitors may need to be combined with strategies to boost immune response or increase the tumor immune profile. Epigenetic aberrations contribute significantly to carcinogenesis. Recent findings suggest that epigenetic drugs prime the immune response by increasing expression of tumor-associated antigens and immune-related genes, as well as modulating chemokines and cytokines involved in immune system activation. This review describes our current understanding regarding epigenetic and immunotherapy combination, focusing on immune response priming to checkpoint blockade.

Aviation Safety Reporting System: Process and Procedures

NASA Technical Reports Server (NTRS)

Connell, Linda J.

1997-01-01

The Aviation Safety Reporting System (ASRS) was established in 1976 under an agreement between the Federal Aviation Administration (FAA) and the National Aeronautics and Space Administration (NASA). This cooperative safety program invites pilots, air traffic controllers, flight attendants, maintenance personnel, and others to voluntarily report to NASA any aviation incident or safety hazard. The FAA provides most of the program funding. NASA administers the program, sets its policies in consultation with the FAA and aviation community, and receives the reports submitted to the program. The FAA offers those who use the ASRS program two important reporting guarantees: confidentiality and limited immunity. Reports sent to ASRS are held in strict confidence. More than 350,000 reports have been submitted since the program's beginning without a single reporter's identity being revealed. ASRS removes all personal names and other potentially identifying information before entering reports into its database. This system is a very successful, proof-of-concept for gathering safety data in order to provide timely information about safety issues. The ASRS information is crucial to aviation safety efforts both nationally and internationally. It can be utilized as the first step in safety by providing the direction and content to informed policies, procedures, and research, especially human factors. The ASRS process and procedures will be presented as one model of safety reporting feedback systems.

The Distinctive Sensitivity to Microgravity of Immune Cell Subpopulations

NASA Astrophysics Data System (ADS)

Chen, Hui; Luo, Haiying; Liu, Jing; Wang, Peng; Dong, Dandan; Shang, Peng; Zhao, Yong

2015-11-01

Immune dysfunction in astronauts is well documented after spaceflights. Microgravity is one of the key factors directly suppressing the function of immune system. However, it is unclear which subpopulations of immune cells including innate and adaptive immune cells are more sensitive to microgravity We herein investigated the direct effects of modeled microgravity (MMg) on different immune cells in vitro. Mouse splenocytes, thymocytes and bone marrow cells were exposed to MMg for 16 hrs. The survival and the phenotypes of different subsets of immune cells including CD4+T cells, CD8+T cells, CD4+Foxp3+ regulatory T cells (Treg), B cells, monocytes/macrophages, dendritic cells (DCs), natural killer cells (NK) were determined by flow cytometry. After splenocytes were cultured under MMg for 16h, the cell frequency and total numbers of monocytes, macrophages and CD4+Foxp3+T cells were significantly decreased more than 70 %. MMg significantly decreased the cell numbers of CD8+ T cells, B cells and neutrophils in splenocytes. The cell numbers of CD4+T cells and NK cells were unchanged significantly when splenocytes were cultured under MMg compared with controls. However, MMg significantly increased the ratio of mature neutrophils to immature neutrophils in bone marrow and the cell number of DCs in splenocytes. Based on the cell survival ability, monocytes, macrophages and CD4+Foxp3+Treg cells are most sensitive to microgravity; CD4+T cells and NK cells are resistant to microgravity; CD8+T cells and neutrophils are impacted by short term microgravity exposure. Microgravity promoted the maturation of neutrophils and development of DCs in vitro. The present studies offered new insights on the direct effects of MMg on the survival and homeostasis of immune cell subsets.

Basics of cancer immunotherapy.

PubMed

Fujioka, Yuki; Nishikawa, Hiroyoshi

2016-01-01

The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19 + acute lymphocytic leukemia. In sharp contrast to conventional anti-cancer reagents which directly kill cancer cells, cancer immunotherapy activates various types of immune effector cells to attack cancer cells. However, more than half of the treated patients showed no activation of anti-tumor CD8 + killer T cells and CD4 + helper T cells and failed to respond to immune therapies such as immune checkpoint blockade, even when administered in combination regimens. Thus, development of novel immunotherapies to achieve more effective activation of anti-cancer immunity and immuno-monitoring of biomarkers, allowing proper evaluation of immune responses in cancer patients in order to detect responders, are urgent issues. Additionally, we must pay attention to characteristic immunological side effects not observed following treatment with conventional anti-cancer reagents. Herein, we present a summary outline and discuss the future direction of cancer immunotherapy.

Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy.

PubMed

Willemze, Rose A; Luyer, Misha D; Buurman, Wim A; de Jonge, Wouter J

2015-06-01

Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes. Sympathetic immune modulation and reflexes are well described, and in the past decade the parasympathetic efferent vagus nerve has been added to this immune-regulation network. This system, designated 'the inflammatory reflex', comprises an afferent arm that senses inflammation and an efferent arm that inhibits innate immune responses. Intervention in this system as an innovative principle is currently being tested in pioneering trials of vagus nerve stimulation using implantable devices to treat IBD. Patients benefit from this treatment, but some of the working mechanisms remain to be established, for instance, treatment is effective despite the vagus nerve not always directly innervating the inflamed tissue. In this Review, we will focus on the direct neuronal regulatory mechanisms of immunity in the intestine, taking into account current advances regarding the innervation of the spleen and lymphoid organs, with a focus on the potential for treatment in IBD and other gastrointestinal pathologies.

Immune Regulatory Activity of Vitamin D3 in Head and Neck Cancer

PubMed Central

Young, M. Rita I.; Day, Terry A.

2013-01-01

While vitamin D exhibits a multitude of cellular effects that can impact on cancer development and progression, this review focuses on its immune modulatory effects. These immune modulatory effects can be both direct and indirect. Compared to other cancer types, head and neck squamous cell carcinomas (HNSCC) have received less attention, but are a fascination immunologically because of the profound extent to which they inhibit immune defenses. This review describes the mechanisms of some of these immune inhibitory processes and how vitamin D can help overcome aspects of this immune suppression. PMID:24202334

Increased Plasma Levels of Danger-Associated Molecular Patterns Are Associated With Immune Suppression and Postoperative Infections in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PubMed

Leijte, Guus P; Custers, Hettie; Gerretsen, Jelle; Heijne, Amon; Roth, Johannes; Vogl, Thomas; Scheffer, Gert J; Pickkers, Peter; Kox, Matthijs

2018-01-01

Danger-associated molecular patterns (DAMPs) can elicit immune responses and may subsequently induce an immune-suppressed state. Previous work showed that increased plasma levels of DAMPs are associated with immune suppression and increased susceptibility toward infections in trauma patients. Like trauma, major surgical procedures, such as cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), are also thought to cause profound DAMP release. Furthermore, the incidence of postoperative infections in these patients, ranging from 10 to 36%, is very high compared to that observed in patients undergoing other major surgical procedures. We hypothesized that the double hit of surgical trauma (CRS) in combination with HIPEC causes excessive DAMP release, which in turn contributes to the development of immune suppression. To investigate this, we assessed DAMP release in patients undergoing CRS-HIPEC, and investigated its relationship with immune suppression and postoperative infections. In 20 patients undergoing CRS-HIPEC, blood was obtained at five time points: just before surgery (baseline), after CRS, after HIPEC, at ICU admission, and 1 day after surgery. Circulating levels of DAMPs [heat shock protein (HSP)70, high mobility group box (HMGB)1, S100A12, S100A8/S100A9, nuclear (n)DNA, mitochondrial (mt)DNA, lactate dehydrogenase (LDH), a marker of unscheduled cell death], and cytokines [tumor necrosis factor (TNF)α, IL-6, IL-8, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and MCP-1] were measured. The extent of immune suppression was determined by measuring HLA-DR gene expression and ex vivo leukocytic cytokine production capacity. Plasma levels of DAMPs (maximum fold increases of HSP70: 2.1 [1.5-2.8], HMGB1: 5.9 [3.2-9.8], S100A8/S100A9: 3.6 [1.8-5.6], S100A12: 2.6 [1.8-4.3], nDNA 3.9 [1.0-10.8], LDH 1.7 [1.2-2.5]), and all measured cytokines increased profoundly following CRS-HIPEC. Evidence of immune suppression was already apparent during the procedure, illustrated by a decrease of HLA-DR expression compared with baseline (0.5-fold [0.3-0.9]) and diminished ex vivo pro-inflammatory cytokine production capacity. The increase in HMGB1 levels correlated with the decrease in HLA-DR expression ( r  = -0.46, p  = 0.04), and peak HMGB1 concentrations were significantly higher in the five patients who went on to develop a postoperative infection (p = 0.04). CRS-HIPEC is associated with profound DAMP release and immune suppression, and plasma HMGB1 levels are related with the occurrence of postoperative infections in these patients.

Transfer of T-cell mediated immunity to Hymenolepis nana from mother mice to their neonates.

PubMed

Asano, K; Okamoto, K

1992-01-15

Administration of lymph node cells from Hymenolepis nana-infected mice into lactating mothers, or directly suckling neonates successfully transferred immunity to the neonates. The capacity of lymph node cells to transfer immunity was completely abrogated by pretreatment with anti-Thy-1.2 monoclonal antibody and complement.

Effects of prebiotics on immune system and cytokine expression.

PubMed

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.

The Transcription Factor EB Links Cellular Stress to the Immune Response



PubMed Central

Nabar, Neel R.; Kehrl, John H.

2017-01-01

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB’s function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation. PMID:28656016

[Neuroendocrine immunomodulation].

PubMed

Uchakin, P N; Uchakina, O N; Tobin, B V; Ershov, F I

2007-01-01

Close interaction between the immune and nervous systems is well documented. The ability of immunocompetent cells to express receptors to neuroendocrine mediators as well as secrete many of them is proved. The current literature suggests that the hormones of the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonodal axes play the most significant role in the regulation of immune responsiveness. On the other hand, the immune system communicates with the CNS directly through the cytokines that are able to cross the blood-brain barrier, or directly via the nervus vagus, as well as via secondary messengers. Receptors to a number of cytokines have been found in the nervous tissue. Moreover, glial cells are able to secrete cytokines in the amount significant enough for at least autocrine action. In this article, the authors review the role of the "major" stress hormones such as cortisol, DHEA, growth hormone in the regulation of immune response, as well as neuro- and psychotropic properties of two major groups of cytokines that support cell-mediated (Type 1) and humoral (Type 2) immune reactions. This review emphasizes neuro-endocrine-immune interactions in response to infection both under laboratory and clinical conditions.

The Transcription Factor EB Links Cellular Stress to the Immune Response

.

PubMed

Nabar, Neel R; Kehrl, John H

2017-06-01

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB's function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation.

Neuroimmunomodulation in unipolar depression: a focus on chronobiology and chronotherapeutics.

PubMed

Eyre, Harris; Baune, Bernhard T

2012-10-01

The rising burden of unipolar depression along with its often related sleep disturbances, as well as increasing rates of sleep restriction in modern society, make the search for an extended understanding of the aetiology and pathophysiology of depression necessary. Accumulating evidence suggests an important role for the immune system in mediating disrupted neurobiological and chronobiological processes in depression. This review aims to provide an overview of the neuroimmunomodulatory processes involved with depression and antidepressant treatments with a special focus on chronobiology, chronotherapeutics and the emerging field of immune-circadian bi-directional crosstalk. Increasing evidence suggests that chronobiological disruption can mediate immune changes in depression, and likewise, immune processes can mediate chronobiological disruption. This may suggest a bi-directional relationship in immune-circadian crosstalk. Furthermore, given the immunomodulatory effects of antidepressants and chronotherapeutics, as well as their associated beneficial effects on circadian disturbance, we--and others--suggest that these therapeutic agents may exert their chronobiotic effects partially via the neuroimmune system. Further research is required to better elucidate the mechanisms of immune involvement in the chronobiology of depression.

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

PubMed

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.

Modulation of innate and adaptive cellular immunity relevant to HIV-1 vaccine design by seminal plasma.

PubMed

Selva, Kevin J; Kent, Stephen J; Parsons, Matthew S

2017-01-28

Mucosal exposure to HIV-1 infection generally occurs in the presence of semen. Immunomodulation by seminal plasma is well described in the reproductive biology literature. Little is known, however, about the impact of seminal plasma on innate and adaptive anti-HIV-1 cellular immunity. The study investigated the effects of seminal plasma on immune responses considered important for prophylactic HIV-1 vaccine development, namely innate and adaptive cellular immunity mediated by natural killer (NK) cells and T cells, respectively. The ability of seminal plasma to modulate direct, antibody-dependent and cytokine-stimulated NK cell activation was assessed utilizing intracellular cytokine staining. Direct and antibody-dependent cellular cytotoxicity was assessed using lactate dehydrogenase release assays. The effects of seminal plasma on T-cell activation upon stimulation with staphylococcus enterotoxin B or HIV-1 Gag peptides were assessed by intracellular cytokine staining. The impact of seminal plasma on redirected cytolysis mediated by T cells was measured using lactate dehydrogenase release assays. Both direct and antibody-dependent NK cell activation were dramatically impaired by the presence of either HIV-1-uninfected or HIV-1-infected seminal plasma in a dose-dependent manner. Additionally, seminal plasma suppressed both direct and antibody-dependent NK cell-mediated cytolysis, including anti-HIV-1 antibody-dependent cytolysis of gp120-pulsed CEM.NKr-CCR5 cells. Finally, seminal plasma attenuated both HIV-1 Gag-specific and staphylococcus enterotoxin B-induced CTL activation. Semen contains potent immunosuppressors of both NK cell and CD8 T-cell-mediated anti-HIV-1 immune responses. This could impede attempts to provide vaccine-induced immunity to HIV-1.

Epigenetic regulation of immune checkpoints: another target for cancer immunotherapy?

PubMed

Ali, Mahmoud A; Matboli, Marwa; Tarek, Marwa; Reda, Maged; Kamal, Kamal M; Nouh, Mahmoud; Ashry, Ahmed M; El-Bab, Ahmed Fath; Mesalam, Hend A; Shafei, Ayman El-Sayed; Abdel-Rahman, Omar

2017-01-01

Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion. Many forms of epigenetic inheritance mechanisms may play a role in regulation of immune checkpoints including: covalent modifications, noncoding RNA and histone modifications. In this review, we will show how the potential interaction between epigenetic and immune modulation may lead to new approaches for specific epigenome/immunome-targeted therapies for cancer.

Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection

PubMed Central

Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

2015-01-01

Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close “neighborhood” of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa. PMID:26327290

Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection.

PubMed

Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

2015-01-01

Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close "neighborhood" of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa.

Innate Immunity and Breast Milk

PubMed Central

Cacho, Nicole Theresa; Lawrence, Robert M.

2017-01-01

Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant. PMID:28611768

Immunotherapy in ovarian cancer.

PubMed

Odunsi, K

2017-11-01

Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells. In an effort to understand whether the immune system plays a role in controlling ovarian cancer, our group and others demonstrated that the presence of tumor infiltrating lymphocytes (TILs) is associated with improved clinical outcome in ovarian cancer patients. Recently, we hypothesized that the quality of infiltrating T cells could also be a critical determinant of outcome in ovarian cancer patients. In the past decade, several immune-based interventions have gained regulatory approval in many solid tumors and hematologic malignancies. These interventions include immune checkpoint blockade, cancer vaccines, and adoptive cell therapy. There are currently no approved immune therapies for ovarian cancer. Immunotherapy in ovarian cancer will have to consider the immune suppressive networks within the ovarian tumor microenvironment; therefore, a major direction is to develop biomarkers that would predict responsiveness to different types of immunotherapies, and allow for treatment selection based on the results. Moreover, such biomarkers would allow rational combination of immunotherapies, while minimizing toxicities. In this review, the current understanding of the host immune response in ovarian cancer patients will be briefly reviewed, progress in immune therapies, and future directions for exploiting immune based strategies for long lasting durable cure. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Training pharmacy technicians to administer immunizations.

PubMed

McKeirnan, Kimberly C; Frazier, Kyle R; Nguyen, Maryann; MacLean, Linda Garrelts

To evaluate the effectiveness of an immunization training program for pharmacy technicians on technicians' self-reported confidence, knowledge, and number of vaccines administered. A one-group pre- and posttest study was conducted with certified pharmacy technicians from Albertsons and Safeway community pharmacies in Idaho. Thirty pharmacy technicians were recruited to participate in an immunization administration training program comprising a 2-hour home study and a 2-hour live training. Pharmacy technician scores on a 10-question knowledge assessment, responses on a pre- and posttraining survey, and number of immunizations administered in the 6-month period following the training were collected. Twenty-five pharmacy technicians completed the home study and live portions of the immunization training program. All 29 pharmacy technicians who took the home study assessment passed with greater than 70% competency on the first attempt. Technicians self-reported increased confidence with immunization skills between the pretraining survey and the posttraining survey. From December 2016 to May 2017, the technicians administered 953 immunizations with 0 adverse events reported. For the first time, pharmacy technicians have legally administered immunizations in the United States. Trained pharmacy technicians demonstrated knowledge of vaccination procedures and self-reported improved confidence in immunization skills and administered immunizations after participating in a 4-hour training program. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

PubMed

Klein, B; Schuppe, H-C; Bergmann, M; Hedger, M P; Loveland, B E; Loveland, K L

2017-07-01

Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6 production by seminoma cells may be a practical target for early diagnosis and/or treatment of TGCT. © 2017 American Society of Andrology and European Academy of Andrology.

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

PubMed

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.

PERSISTENT ANTIGENIC VARIATION OF INFLUENZA A VIRUSES AFTER INCOMPLETE NEUTRALIZATION IN OVO WITH HETEROLOGOUS IMMUNE SERUM

PubMed Central

Archetti, Italo; Horsfall, Frank L.

1950-01-01

Antigenic variants of influenza A virus strains emerge on serial passage in ovo in the presence of immune serum against different but related strains. An old laboratory strain (PR8) which had been through hundreds of animal passages was as readily modified by this procedure as recently recovered strains. Such variants apparently can be obtained at will and show antigenic patterns which are reproducible and appear to be predictable in terms of the immune serum used for their selection. Variant strains retain their new antigenic patterns on serial passage in ovo in the absence of immune serum. Limited serial passage in ovo of strains in the absence of immune serum did not result in the emergence of antigenic variants. Similarly, serial passages of strains in ovo in the presence of immune serum against widely different strains, which failed to show significant cross-neutralization, did not lead to the appearance of antigenic variants. PMID:14778924

Influences on immunization rates: Vaccination coverage of mumps, measles, rubella and varicella before and after the STIKO intervention 2011 - A retrospective study.

PubMed

Sanftenberg, Linda; Schrörs, Hans-Jürgen; Schelling, Jörg

2016-07-25

In September 2011, the German Standing Committee on Vaccinations (STIKO) changed their recommendation regarding the mumps-measles-rubella-varicella vaccination (MMRV). We compared the immunization rates against MMRV in Germany before and after the STIKO intervention. We recorded the immunization status of children born between 09/2008 and 08/2012 in 35 selected doctor's surgeries in Germany. After the STIKO intervention, the ratio of the combined MMRV vaccine as the first dose immunization was reduced to approximately 25% of the initial value. A slight increase in the number of children not sufficiently vaccinated against varicella (1.2%) was observed, but the immunization rates against measles, mumps, rubella and varicella did not significantly decrease. The STIKO intervention led to a significant change in physicians' vaccination procedures. The separate administration MMR+V vaccination may be a helpful option to improve the immunization rates in general. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methods for Posttranslational Induction of Polyreactivity of Antibodies.

PubMed

Lecerf, Maxime; Jarossay, Annaelle; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien; Dimitrov, Jordan D

2017-01-01

An antibody molecule that recognizes multiple unrelated antigens is defined as polyreactive. Polyreactivity is an intrinsic characteristic of immune repertoires. Degenerated antigen binding diversifies the repertoire of specificities, thus contributing to immune defense and immune regulation. Immune repertoire contains also a fraction of immunoglobulins, which acquire polyreactivity only following contact with various protein-destabilizing or pro-oxidative substances. Posttranslational induction of the antibody polyreactivity may have important repercussion for laboratory practice, as well as in cases of pathological conditions accompanied by liberation of large quantities of pro-oxidative substances such as heme, labile iron, or reactive oxygen species. Antibodies with induced polyreactivity have been demonstrated to exert pathogen neutralization and immune regulatory potential in inflammatory conditions, suggesting that this phenomenon may be exploited for design of therapeutic strategies. In this article, we provide description of the basic procedures for uncovering of the cryptic polyreactivity of antibodies by heme, ferrous ions, and acid pH solution.

Immunizing children who fear and resist needles: is it a problem for nurses?

PubMed

Ives, Mary; Melrose, Sherri

2010-01-01

Despite increasing evidence that immunization procedures can be stressful for children, little is known about what the experience of immunizing frightened and needle-resistant children can be like for nurses. This article presents findings from a qualitative research project designed to explore public health nurses' feelings toward immunizing needle-resistant children. A constructivist theoretical perspective and an action research approach framed the study. Data sources included two survey questions and audio-recorded transcribed data from three focus groups. Participants included 35 public health nurses from five different health units in one Canadian province. The data were analyzed for themes and were confirmed with participants through ongoing member checking. The following four overarching themes were identified and are used to explain and describe significant features of the immunization experience that were stressful and problematic for nurses: (a) nurses experience stress when immunizing children who fear and resist needle injection; (b) the strength of child resistance and some adult behavior creates an ethical dilemma for nurses; (c) some adult responses make immunizing difficult and unsafe; and (d) resources to help nurses cope with these situations are inconsistent.

Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA L74 on human enterocytes.

PubMed

Paparo, L; Aitoro, R; Nocerino, R; Fierro, C; Bruno, C; Canani, R Berni

2018-01-29

Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA L74 stimulated cell growth and differentiation, tight junction proteins and mucin 2 expression, and mucus layer thickness in a dose-dependent fashion. A significant stimulation of HBD-2 and LL-37 synthesis, associated with a modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and immune defence mechanisms through a direct interaction with the enterocytes. These effects could be involved in the preventive action against infectious diseases demonstrated by this fermented product in children.

Pattern Recognition Receptors in Innate Immunity, Host Defense, and Immunopathology

ERIC Educational Resources Information Center

Suresh, Rahul; Mosser, David M.

2013-01-01

Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue.…

Effects of cortisol and lipopolysaccharide on expression of select growth-, stress- and immune-related genes in rainbow trout liver

USDA-ARS?s Scientific Manuscript database

Many studies have shown that stress-induced cortisol levels negatively influence growth and immunity in finfish. Despite this knowledge, few studies have assessed the direct effects of cortisol on liver immune function in finfish. Using real-time PCR, the expression of three cortisol-responsive ge...

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

PubMed

Macho, Alberto P

2016-04-01

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

Nutritionally mediated programming of the developing immune system.

PubMed

Palmer, Amanda C

2011-09-01

A growing body of evidence highlights the importance of a mother's nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a "layered" expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease.

Invasion of Peripheral Immune Cells into Brain Parenchyma after Cardiac Arrest and Resuscitation.

PubMed

Zhang, Can; Brandon, Nicole R; Koper, Kerryann; Tang, Pei; Xu, Yan; Dou, Huanyu

2018-06-01

Although a direct link has long been suspected between systemic immune responses and neuronal injuries after stroke, it is unclear which immune cells play an important role. A question remains as to whether the blood brain barrier (BBB) is transiently disrupted after circulatory arrest to allow peripheral immune cells to enter brain parenchyma. Here, we developed a clinically relevant cardiac arrest and resuscitation model in mice to investigate the BBB integrity using noninvasive magnetic resonance imaging. Changes in immune signals in the brain and periphery were assayed by immunohistochemistry and flow cytometry. Quantitative variance maps from T1-weighted difference images before and after blood-pool contrast clearance revealed BBB disruptions immediately after resuscitation and one day after reperfusion. Time profiles of hippocampal CA1 neuronal injuries correlated with the morphological changes of microglia activation. Cytotoxic T cells, CD11b + CD11c + dendritic cells, and CD11b + CD45 +hi monocytes and macrophages were significantly increased in the brain three days after cardiac arrest and resuscitation, suggesting direct infiltration of these cells following the BBB disruption. Importantly, these immune cell changes were coupled with a parallel increase in the same subset of immune cell populations in the bone marrow and blood. We conclude that neurovascular breakdown during the initial reperfusion phase contributes to the systemic immune cell invasion and subsequent neuropathogenesis affecting the long-term outcome after cardiac arrest and resuscitation.

Metformin: Candidate host-directed therapy for tuberculosis in diabetes and non-diabetes patients.

PubMed

Restrepo, Blanca I

2016-12-01

Despite major advances in tuberculosis (TB) control, TB continues to be a leading cause of death worldwide. The discovery of new anti-TB treatment drugs and regimens that target drug-sensitive and drug-resistant TB are being complemented with a search for adjunct host-directed therapies that synergize for Mycobacterium tuberculosis (Mtb) elimination. The goal of host-directed therapies is to boost immune mechanisms that diminish excess inflammation to reduce lung tissue damage and limit Mtb growth. Metformin is the most commonly-used medication for type 2 diabetes, and a candidate for host-directed therapy for TB. Preliminary data suggests metformin may be beneficial for TB control by reducing the deleterious inflammation associated with immune pathology and enhancing the anti-mycobacterial activity of immune cells. In this review I summarize current findings, knowledge gaps and the potential benefits as well as points of caution for using metformin as adjunct therapy for TB in patients with and without type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measuring coverage in MNCH: design, implementation, and interpretation challenges associated with tracking vaccination coverage using household surveys.

PubMed

Cutts, Felicity T; Izurieta, Hector S; Rhoda, Dale A

2013-01-01

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.

Immunotherapy

MedlinePlus

... CSF) Interleukin-2 (IL-2) Interferon Donor lymphocyte infusion Some blood cancer patients, especially those with chronic ... from an immune cell treatment called donor lymphocyte infusion. During this procedure, doctors transfer lymphocytes (a type ...

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease.

PubMed

Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

2017-09-21

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

Natural selection on immune defense: A field experiment.

PubMed

Langeloh, Laura; Behrmann-Godel, Jasminca; Seppälä, Otto

2017-02-01

Predicting the evolution of phenotypic traits requires an understanding of natural selection on them. Despite its indispensability in the fight against parasites, selection on host immune defense has remained understudied. Theory predicts immune traits to be under stabilizing selection due to associated trade-offs with other fitness-related traits. Empirical studies, however, report mainly positive directional selection. This discrepancy could be caused by low phenotypic variation in the examined individuals and/or variation in host resource level that confounds trade-offs in empirical studies. In a field experiment where we maintained Lymnaea stagnalis snails individually in cages in a lake, we investigated phenotypic selection on two immune defense traits, phenoloxidase (PO)-like activity and antibacterial activity, in hemolymph. We used a diverse laboratory population and manipulated snail resource level by limiting their food supply. For six weeks, we followed immune activity, growth, and two fitness components, survival and fecundity of snails. We found that PO-like activity and growth were under stabilizing selection, while antibacterial activity was under positive directional selection. Selection on immune traits was mainly driven by variation in survival. The form of selection on immune defense apparently depends on the particular trait, possibly due to its importance for countering the present parasite community. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

PubMed Central

Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

2017-01-01

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date. PMID:28934123

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities.

PubMed

Diegeler, Sebastian; Hellweg, Christine E

2017-01-01

Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

Validation of Procedures for Monitoring Crewmember Immune Function

NASA Technical Reports Server (NTRS)

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

2010-01-01

The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles, viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. To date, 18 short duration (now completed) and 8 long-duration crewmembers have completed the study. The long-duration phase of this study is ongoing. For this presentation, the final data set for the short duration subjects will be discussed.

Potentiation of an anthrax DNA vaccine with electroporation.

PubMed

Luxembourg, A; Hannaman, D; Nolan, E; Ellefsen, B; Nakamura, G; Chau, L; Tellez, O; Little, S; Bernard, R

2008-09-19

DNA vaccines are a promising method of immunization against biothreats and emerging infections because they are relatively easy to design, manufacture, store and distribute. However, immunization with DNA vaccines using conventional delivery methods often fails to induce consistent, robust immune responses, especially in species larger than the mouse. Intramuscular (i.m.) delivery of a plasmid encoding anthrax toxin protective antigen (PA) using electroporation (EP), a potent DNA delivery method, rapidly induced anti-PA IgG and toxin neutralizing antibodies within 2 weeks following a single immunization in multiple experimental species. The delivery procedure is particularly dose efficient and thus favorable for achieving target levels of response following vaccine administration in humans. These results suggest that EP may be a valuable platform technology for the delivery of DNA vaccines against anthrax and other biothreat agents.

Stressor Controllability and Immune Function

DTIC Science & Technology

1986-10-17

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

Active targeted delivery of immune therapeutics to lymph nodes.

PubMed

Bahmani, Baharak; Vohra, Ishaan; Kamaly, Nazila; Abdi, Reza

2018-02-01

Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.

Neuro-Immune Mechanisms in Response to Venezuelan Equine Encephalitis Virus Infection

DTIC Science & Technology

2000-01-01

iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine ...3. DATES COVERED - 4. TITLE AND SUBTITLE NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION 5a. CONTRACT

Immune failure reveals vulnerability of populations exposed to pollution in the bioindicator species Hediste diversicolor.

PubMed

Cuvillier-Hot, Virginie; Gaudron, Sylvie Marylène; Massol, François; Boidin-Wichlacz, Céline; Pennel, Timothée; Lesven, Ludovic; Net, Sopheak; Papot, Claire; Ravaux, Juliette; Vekemans, Xavier; Billon, Gabriel; Tasiemski, Aurélie

2018-02-01

Human activities on the shoreline generate a growing pollution, creating deleterious habitats in coastal zones. Some species nevertheless succeed in such harsh milieus, raising the question of their tolerance to environmental stress. The annelid Hediste diversicolor lives buried in the sediments, directly exposed to contaminants trapped in the mud. After verifying the similarity of their genetic contexts, we compared reproductive output and individual immune resistance measures of populations living in polluted vs. 'clean' sediments, and related these assessments with measures of phthalates and metal pollution, and associated toxicity indices. Chemical analyses predicted no toxicity to the local infauna, and phenological studies evidenced no direct cost of living in noxious habitats. However, populations exposed to pollutants showed a significantly reduced survival upon infection with a local pathogen. Surprisingly, physiological studies evidenced a basal overinflammatory state in the most exposed populations. This over-activated baseline immune phenotype likely generates self-damage leading to enhanced immune cell death rate and immune failure. Monitoring the immune status of individual worms living in anthropic areas could thus be used as a reliable source of information regarding the actual health of wild populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Steroids and Autoimmunity.

PubMed

Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio

2017-01-01

From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.

Multiple functions of the E3 ubiquitin ligase CHIP in immunity.

PubMed

Zhan, Shaohua; Wang, Tianxiao; Ge, Wei

2017-09-03

The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner. In addition, through tight regulation of the protein level of its substrates, CHIP plays important roles in many physiological and pathological conditions, including cancers, neurological disorders, cardiac diseases, bone metabolism, immunity, and so on. Nonetheless, the precise mechanisms underlying the regulation of the immune system by CHIP are still poorly understood despite accumulating developments in our understanding of the regulatory roles of CHIP in both innate and adaptive immune responses. In this review, we also aim to provide a view of CHIP-mediated regulation of immune responses and the signaling pathways involved in the model described. Finally, we discuss the roles of CHIP in immune-related diseases.

[Researches in immunological responses after burn injury in China].

PubMed

Peng, Dai-zhi

2008-10-01

For five decades it has been recognized that severe burn injury may precipitate in marked alterations in immune function, resulting in life-threatening systemic infections, sepsis, multiple organ failure, and even death. Extensive and deep burns exert widespread and profound impacts on various cells and molecules of the immune system. The general characteristics of abnormal immune responses following major burns are hyperinflammatory response and hypoimmune response of innate and adaptive immunity. These are recognized as postburn immune dysfunction (PID). The stress reaction, massive necrotic tissue, shock, infection, malnutrition and various therapeutic procedures after burns alter the microenvironment of the immune cells and molecules in which they reside, and consequently result in the changes in immune cells and their secretions in quantity and/or activity, and also aberrant signal transduction in different immune cells. These events constitute the cellular and molecular bases in the pathogenesis of PID. The main clinical consequences of PID include tissue damages and increased susceptibility to opportunistic pathogens caused by refractory inflammation and suppressed adaptive immunity. In order to decrease the morbidity of these lethal complications, efforts to improve the immune dysfunction after burn injury have been made not only at the integral level of etiological factors, but also at the cellular and molecular levels of its mechanisms. In this review, all these above-mentioned aspects of PID are comprehensively discussed.

Rapid Waterborne Pathogen Detection with Mobile Electronics.

PubMed

Wu, Tsung-Feng; Chen, Yu-Chen; Wang, Wei-Chung; Kucknoor, Ashwini S; Lin, Che-Jen; Lo, Yu-Hwa; Yao, Chun-Wei; Lian, Ian

2017-06-09

Pathogen detection in water samples, without complex and time consuming procedures such as fluorescent-labeling or culture-based incubation, is essential to public safety. We propose an immunoagglutination-based protocol together with the microfluidic device to quantify pathogen levels directly from water samples. Utilizing ubiquitous complementary metal-oxide-semiconductor (CMOS) imagers from mobile electronics, a low-cost and one-step reaction detection protocol is developed to enable field detection for waterborne pathogens. 10 mL of pathogen-containing water samples was processed using the developed protocol including filtration enrichment, immune-reaction detection and imaging processing. The limit of detection of 10 E. coli O157:H7 cells/10 mL has been demonstrated within 10 min of turnaround time. The protocol can readily be integrated into a mobile electronics such as smartphones for rapid and reproducible field detection of waterborne pathogens.

Vaccination against bacterial kidney disease: Chapter 22

USGS Publications Warehouse

Elliott, Diane G.; Wiens, Gregory D.; Hammell, K. Larry; Rhodes, Linda D.; Edited by Gudding, Roar; Lillehaug, Atle; Evensen, Øystein

2014-01-01

Bacterial kidney disease (BKD) of salmonid fishes, caused by Renibacterium salmoninarum, has been recognized as a serious disease in salmonid fishes since the 1930s. This chapter discusses the occurrence and significance, etiology, and pathogenesis of BKD. It then describes the different vaccination procedures and the effects and side-effects of vaccination. Despite years of research, however, only a single vaccine has been licensed for prevention of BKD, and has demonstrated variable efficacy. Therefore, in addition to a presentation of the current status of BKD vaccination, a discussion of potential future directions for BKD vaccine development is included in the chapter. This discussion is focused on the unique characteristics of R. salmoninarum and its biology, as well as aspects of the salmonid immune system that might be explored specifically to develop more effective vaccines for BKD prevention.

Anandamide and Δ9-Tetrahydrocannabinol Directly Inhibit Cells of the Immune System via CB2 Receptors

PubMed Central

Eisenstein, Toby K.; Meissler, Joseph J.; Wilson, Qiana; Gaughan, John P.; Adler, Martin W.

2007-01-01

This study shows that two cannabinoids, Δ9-tetrahydrocannabinol (THC) and anandamide, induce dose related immunosuppression in both the primary and secondary in vitro plaque-forming cell assays of antibody formation. The immunosuppression induced by both compounds could be blocked by SR144528, an antagonist specific for the CB2 receptor, but not by SR141716, a CB1 antagonist. These studies are novel in that they show that both anadamide and THC are active in the nanomolar to picomolar (for anandamide) range in these assays of immune function, and that both mediate their effects directly on cells of the immune system through the CB2 receptor. PMID:17640739

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

PubMed

Candotti, Fabio; Shaw, Kit L; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F; Weinberg, Kenneth I; Crooks, Gay M; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S; Rosenblatt, Howard M; Davis, Carla M; Hanson, Celine; Rishi, Radha G; Wang, Xiaoyan; Gjertson, David; Yang, Otto O; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A; Engel, Barbara C; Podsakoff, Gregory M; Hershfield, Michael S; Blaese, R Michael; Parkman, Robertson; Kohn, Donald B

2012-11-01

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans

PubMed Central

Candotti, Fabio; Shaw, Kit L.; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F.; Weinberg, Kenneth I.; Crooks, Gay M.; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S.; Rosenblatt, Howard M.; Davis, Carla M.; Hanson, Celine; Rishi, Radha G.; Wang, Xiaoyan; Gjertson, David; Yang, Otto O.; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A.; Engel, Barbara C.; Podsakoff, Gregory M.; Hershfield, Michael S.; Blaese, R. Michael; Parkman, Robertson

2012-01-01

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m2). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. PMID:22968453

Nutritionally Mediated Programming of the Developing Immune System12

PubMed Central

Palmer, Amanda C.

2011-01-01

A growing body of evidence highlights the importance of a mother’s nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a “layered” expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease. PMID:22332080

Isolation of a Soluble Component of Plasmodium berghei Which Induces Immunity in Rats

PubMed Central

Grothaus, G. D.; Kreier, J. P.

1980-01-01

Soluble material was obtained from sonically freed plasmodiae by three procedures. Two procedures, cryo-impacting and freeze-thawing, were evaluated for their ability to disrupt the parasites and release soluble material. The soluble materials obtained by these procedures were compared to materials washed from the surfaces of sonically freed parasites. Between 35 and 40% of the total parasite protein was solubilized by freeze-thawing or cryo-impacting. One cycle of freeze-thawing released nearly as much protein as could be released by this method, and additional cycles of freeze-thawing had little additional effect. Cryo-impacting solubilized only a small amount of protein in addition to that which was released by the cycle of freeze-thawing inherent in the procedure. Reductions in the packed cell volume of the material remaining after freeze-thawing or cryo-impacting indicate that the insoluble fragments are broken into smaller pieces as treatment is extended. Electron microscopy of 30-s cryo-impacted and three-times freeze-thawed parasites revealed membrane fragments similar in appearance. Patterns obtained by polyacrylamide gel electrophoresis of the soluble material from freeze-thawed and cryo-impacted parasites were also similar, and approximately 13 protein bands were demonstrated. The material washed from the surfaces of the free parasites, on the other hand, resolved into only two to four major bands on the gel columns. In immunization studies, the soluble and insoluble fractions obtained by freeze-thawing or cryo-impacting and the material washed from the surfaces of the parasites all stimulated a protective immune response. On the basis of the amount of protein required to stimulate roughly comparable immunity, the soluble fraction obtained by freeze-thawing or cryo-impacting free parasites was about twice as potent an immunogen as was the insoluble fraction. The material obtained by gentle washing of the freed parasites was approximately 20 times as potent an immunogen as were the freed parasites and about 7 times as potent as the soluble material obtained by freeze-thawing or cryo-impacting. Images Fig. 1 Fig. 2 PMID:6991439

Merkel cells and permanent disesthesia in the oral mucosa after soft tissue grafts.

PubMed

Aimetti, M; Romano, F; Cricenti, L; Perotto, S; Gotti, S; Panzica, G; Graziano, A

2010-07-01

Connective tissue grafts are routinely procedures in the treatment of gingival defects. The clinical success of the gingival tissue graft procedures anyway should ensure not only the aesthetic integration between the tissues but also the physiological activity of the graft in terms of sensitivity and immunity because the skin and the mucosae constitute the first natural aspecific borders against pathogens. The aim of this paper was to investigate nervous net recovery after connective graft procedure, in relation with sensorial alteration in the injured area. Results showed that there is a close link among the number of Merkel cells and the alteration of sensations. Merkel cells can be found isolated standing in the basal layer, supposed to have neuroendocrine functions in the epithelia or in larger group not associated with nerves; when found in association with nerves they are named Merkel complexes, acting as slow adapter mechanical receptor. Our data can be explained in two ways: Merkel cells increase as a consequence of tissue injury, a sort of "SOS cells" that secrete neuroendocrine signals to guide tissue healing; as an alternative the presence of the Merkel cells could be read as a derailment of tissue regeneration with the stop of cellular differentiation in the direction of an abnormal proliferation, a sort of mad stem cell. (c) 2010 Wiley-Liss, Inc.

Impact of carbon nanotubes and graphene on immune cells.

PubMed

Orecchioni, Marco; Bedognetti, Davide; Sgarrella, Francesco; Marincola, Francesco M; Bianco, Alberto; Delogu, Lucia Gemma

2014-05-21

It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.

Development of a Fluorescent Bodipy Probe for Visualization of the Serotonin 5-HT1A Receptor in Native Cells of the Immune System.

PubMed

Hernández-Torres, Gloria; Enríquez-Palacios, Ernesto; Mecha, Miriam; Feliú, Ana; Rueda-Zubiaurre, Ainoa; Angelina, Alba; Martín-Cruz, Leticia; Martín-Fontecha, Mar; Palomares, Oscar; Guaza, Carmen; Peña-Cabrera, Eduardo; López-Rodríguez, María L; Ortega-Gutiérrez, Silvia

2018-05-14

Serotonin (5-HT) modulates key aspects of the immune system. However, its precise function and the receptors involved in the observed effects have remained elusive. Among the different serotonin receptors, 5-HT 1A plays an important role in the immune system given its presence in cells involved in both the innate and adaptive immune responses, but its actual levels of expression under different conditions have not been comprehensively studied due to the lack of suitable tools. To further clarify the role of 5-HT 1A receptor in the immune system, we have developed a fluorescent small molecule probe that enables the direct study of the receptor levels in native cells. This probe allows direct profiling of the receptor expression in immune cells using flow cytometry. Our results show that important subsets of immune cells including human monocytes and dendritic cells express functional 5-HT 1A and that its activation is associated with anti-inflammatory signaling. Furthermore, application of the probe to the experimental autoimmune encephalomyelitis model of multiple sclerosis demonstrates its potential to detect the specific overexpression of the 5-HT 1A receptor in CD4+ T cells. Accordingly, the probe reported herein represents a useful tool whose use can be extended to study the levels of 5-HT 1A receptor in ex vivo samples of different immune system conditions.

Impact of carbon nanotubes and graphene on immune cells

PubMed Central

2014-01-01

It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine. PMID:24885781

ACTIVE IMMUNIZATION AGAINST POLIOMYELITIS IN MONKEYS.

PubMed

Brodie, M; Goldbloom, A

1931-05-31

1. A combination of poliomyelitis virus and specific human serum is effective for the production of active immunity. 2. For each gram of active virus given intradermally as an emulsion, 6 cc. of human immune serum, injected subcutaneously, was required in our experiments to protect a monkey from paralysis. Some degree of active immunity was induced. 3. Immunity, without symptom of the disease, was secured when the serum was given at the time of inoculation, or within 3 days preceding or following inoculation of the virus. 4. For the production of immunity, virus, preceded by serum administration, is probably less effective than when it is given simultaneously with, or before, the injection of serum. 5. The virus neutralization test is more sensitive than the direct intracerebral test for determining the production of immunity.

Therapy of Human Papillomavirus-Related Disease

PubMed Central

Stern, Peter L.; van der Burg, Sjoerd H.; Hampson, Ian N.; Broker, Thomas; Fiander, Alison; Lacey, Charles J.; Kitchener, Henry C.; Einstein, Mark H.

2014-01-01

This chapter reviews the current treatment of chronic and neoplastic HPV-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPV-associated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, preneoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66–79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50–60%) in treatment of high grade vulvar intraepithelial neoplasia. Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after “successful” treatment is 30–40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the anti-apoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this correlated with strong and broad systemic HPV-specific T cell response and modulation of key local immune factors. Treatments that can shift the balance of immune effectors locally in combination with vaccination are now being tested. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012. PMID:23199967

Vaccine adjuvants: Tailor-made mast-cell granules

NASA Astrophysics Data System (ADS)

Gunzer, Matthias

2012-03-01

Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

21st Nantes Actualités Transplantation: "When Stem Cells Meet Immunology".

PubMed

Anegon, Ignacio; Nguyen, Tuan Huy

2017-01-01

"When Stem Cells Meet Immunology" has been the topic of the 21st annual "Nantes Actualités en Transplantation" meeting (June 9-10, 2016, Nantes, France). This meeting brought together pioneers and leading experts in the fields of stem cells, biomaterials and immunoregulation. Presentations covered multipotent (mesenchymal and hematopoietic) and pluripotent stem cells (embryonic and induced) for regenerative medicine of incurable diseases, immunotherapy and blood transfusions. An additional focus had been immune rejections and responses of allogeneic or autologous stem cells. Conversely, stem cells are also able to directly modulate the immune response through the production of immunoregulatory molecules. Moreover, stem cells may also provide an unlimited source of immune cells (DCs, NK cells, B cells, and T cells) that can operate as "super" immune cells, for example, through genetic engineering with chimeric antigen receptors.This meeting report puts presentations into an overall context highlighting new potential biomarkers for potency prediction of mesenchymal stem cell-derived and pluripotent stem cell-derived multicellular organoids. Finally, we propose future directions arising from the flourishing encounter of stem cell and immune biology.

Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: Direct effect of Vpr on T cell activation and immune function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkatachari, Narasimhan J.; Majumder, Biswanath; Ayyavoo, Velpandi

2007-02-20

Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal host cellular immune pathways thus exploiting the cellular machinery for replication, survival and to escape host immune attack. Here we evaluated the direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr specifically downregulated the expression of CD28 and increased the expression of CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR was observed. Interferon gamma (IFN-{gamma}) production in T cells was evaluated as a measure of the downstream effector functions. Results indicate that Vpr significantly inhibited IFN-{gamma} production and this may, in part,more » due to Vpr's ability to inhibit the nuclear translocation of NF-{kappa}B, and its transcriptional regulation. Together these results support that HIV-1 Vpr selectively dysregulates the immune functions at multiple levels and exerts its inhibitory effects in the presence of other viral proteins.« less

PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1.

PubMed

Yoh, Sunnie M; Schneider, Monika; Seifried, Janna; Soonthornvacharin, Stephen; Akleh, Rana E; Olivieri, Kevin C; De Jesus, Paul D; Ruan, Chunhai; de Castro, Elisa; Ruiz, Pedro A; Germanaud, David; des Portes, Vincent; García-Sastre, Adolfo; König, Renate; Chanda, Sumit K

2015-06-04

Dendritic cells (DCs) play a critical role in the immune response to viral infection through the facilitation of cell-intrinsic antiviral activity and the activation of adaptive immunity. HIV-1 infection of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS). We report the results of a targeted RNAi screen utilizing primary human monocyte-derived DCs (MDDCs) to identify immune regulators that directly interface with HIV-1-encoded features to initiate this innate response. Polyglutamine binding protein 1 (PQBP1) emerged as a strong candidate through this analysis. We found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. MDDCs derived from Renpenning syndrome patients, who harbor mutations in the PQBP1 locus, possess a severely attenuated innate immune response to HIV-1 challenge, underscoring the role of PQBP1 as a proximal innate sensor of a HIV-1 infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Food-mediated modulation of immunity in a phytophagous insect: An effect of nutrition rather than parasitic contamination.

PubMed

Vogelweith, Fanny; Moreau, Jérôme; Thiéry, Denis; Moret, Yannick

2015-06-01

Inherent to the cost of immunity, the immune system itself can exhibit tradeoffs between its arms. Phytophagous insects face a wide range of microbial and eukaryotic parasites, each activating different immune pathways that could compromise the activity of the others. Feeding larvae are primarily exposed to microbes, which growth is controlled by antibiotic secondary metabolites produced by the host plant. The resulting variation in abundance of microbes on plants is expected to differentially stimulate the insect antimicrobial immune defenses. Under the above tradeoff hypothesis, stimulation of the insect antimicrobial defenses is expected to compromise immune activity against eukaryote parasites. In the European grape berry moth, Eupoecilia ambiguella, immune effectors directed towards microbes are negatively correlated to those directed towards eukaryotic parasites among host plants. Here, we hypothesize this relationship is caused by a variable control of the microbial community among host plants by their antibiotic metabolites. To test this hypothesis, we first quantified antimicrobial activity in berries of several grape varieties. We then measured immune defenses of E. ambiguella larvae raised on artificial diets in which we mimicked levels of antimicrobial activity of grape berries using tetracycline to control the abundance of growing microbes. Another group of larvae was raised on artificial diets made of berry extracts only to control for the effect of nutrition. We found that controlling microbe abundance with tetracycline in diets did not explain variation in the immune function whereas the presence of berry extracts did. This suggests that variation in immune defenses of E. ambiguella among grape varieties is caused by nutritional difference among host plants rather than microbe abundance. Further study of the effects of berry compounds on larval immune parameters will be needed to explain the observed tradeoff among immune system components. Copyright © 2015 Elsevier Ltd. All rights reserved.

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

PubMed

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

Active and passive immunization for cancer.

PubMed

Baxter, David

2014-01-01

Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers - proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types - the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review.

Active and passive immunization for cancer

PubMed Central

Baxter, David

2014-01-01

Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers – proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types – the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review. PMID:25424829

Interactions of the innate and adaptive arms of the immune system in the pathogenesis of spondyloarthritis

PubMed Central

Stoll, Matthew L

2011-01-01

The immune system can be divided into the innate and adaptive arms. Historically, most of the research into the pathogenesis of spondyloarthritis (SpA) and other types of chronic arthritis focused on the adaptive immune system. Recently, the pendulum has shifted, and much current work in SpA focuses on innate immunity. Herein, I summarize evidence demonstrating that both the innate and the adaptive arms of the immune system are involved in the pathogenesis of SpA, propose a mechanism in which both arms interact to maintain chronic arthritis, and discuss potential research directions. PMID:21269576

Immunity to Salmonella typhi: considerations relevant to measurement of cellular immunity in typhoid-endemic regions.

PubMed Central

Murphy, J R; Wasserman, S S; Baqar, S; Schlesinger, L; Ferreccio, C; Lindberg, A A; Levine, M M

1989-01-01

Experiments were performed in Baltimore, Maryland and in Santiago, Chile, to determine the level of Salmonella typhi antigen-driven in vitro lymphocyte replication response which signifies specific acquired immunity to this bacterium and to determine the best method of data analysis and form of data presentation. Lymphocyte replication was measured as incorporation of 3H-thymidine into desoxyribonucleic acid. Data (ct/min/culture) were analyzed in raw form and following log transformation, by non-parametric and parametric statistical procedures. A preference was developed for log-transformed data and discriminant analysis. Discriminant analysis of log-transformed data revealed 3H-thymidine incorporation rates greater than 3,433 for particulate S. typhi, Ty2 antigen stimulated cultures signified acquired immunity at a sensitivity and specificity of 82.7; for soluble S. typhi O polysaccharide antigen-stimulated cultures, ct/min/culture values of greater than 1,237 signified immunity (sensitivity and specificity 70.5%). PMID:2702777

The use of breast-feeding for pain relief during neonatal immunization injections.

PubMed

Efe, Emine; Ozer, Zeynep Canli

2007-02-01

The objective of this study was to examine the pain-relieving effect of breast-feeding during immunization injections in healthy neonates. Sixty-six healthy infants returning to a clinic for their second-, third-, or fourth-month immunization with intramuscular diphtheria, tetanus, and pertussis were randomized to be breast-fed before, during, and after the injection or to be given the injection according to routine clinic procedure (no breast-feeding). To assess the pain responses of the neonates during and after immunization, we noted their heart rates, oxygen saturation levels, and length of crying. The crying time was shorter in the experimental (breast-feeding) group (M +/- SD duration, 35.85 +/- 40.11 seconds) than in the control group (M +/- SD duration, 76.24 +/- 49.61 seconds; p = .001). The heart rate and oxygen saturation levels were almost the same in both groups. We concluded that breast-feeding, maternal holding, and skin-to-skin contact significantly reduced crying in infants receiving an immunization injection for diphtheria, tetanus, and pertussis.

Do infant behaviors following immunization predict attachment? An exploratory study.

PubMed

Horton, Rachel; Pillai Riddell, Rebecca; Moran, Greg; Lisi, Diana

2016-01-01

The relationship between infant behaviors during routine immunization, pre- and post-needle, and infant attachment was explored. A total of 130 parent-infant dyads were recruited from a larger longitudinal study and videotaped during routine immunization at 12 months and the Strange Situation Procedure (SSP) at 14 months. Six infant behaviors were coded for 1-minute pre-needle and 3-minutes post-needle. Attachment was operationalized according to the secure/avoidant/resistant/disorganized categories. As expected, none of the pre-needle behaviors predicted attachment. Proximity-seeking post-needle significantly discriminated attachment categorizations. Secure infants were more likely to seek proximity to caregivers post-needle in comparison with avoidant and disorganized infants. Proximity-seeking following immunization was positively correlated with proximity-seeking during the SSP and negatively correlated with avoidance and disorganization during the SSP. Infant proximity-seeking during immunization is associated with attachment security and parallels behaviors observed during the SSP. More research is needed to identify behavioral markers of disorganization.

Standardized Methods for Detection of Poliovirus Antibodies.

PubMed

Weldon, William C; Oberste, M Steven; Pallansch, Mark A

2016-01-01

Testing for neutralizing antibodies against polioviruses has been an established gold standard for assessing individual protection from disease, population immunity, vaccine efficacy studies, and other vaccine clinical trials. Detecting poliovirus specific IgM and IgA in sera and mucosal specimens has been proposed for evaluating the status of population mucosal immunity. More recently, there has been a renewed interest in using dried blood spot cards as a medium for sample collection to enhance surveillance of poliovirus immunity. Here, we describe the modified poliovirus microneutralization assay, poliovirus capture IgM and IgA ELISA assays, and dried blood spot polio serology procedures for the detection of antibodies against poliovirus serotypes 1, 2, and 3.

Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis▿

PubMed Central

Mao, Huawei; Tu, Wenwei; Qin, Gang; Law, Helen Ka Wai; Sia, Sin Fun; Chan, Ping-Lung; Liu, Yinping; Lam, Kwok-Tai; Zheng, Jian; Peiris, Malik; Lau, Yu-Lung

2009-01-01

Influenza is an acute respiratory viral disease that is transmitted in the first few days of infection. Evasion of host innate immune defenses, including natural killer (NK) cells, is important for the virus's success as a pathogen of humans and other animals. NK cells encounter influenza viruses within the microenvironment of infected cells and are important for host innate immunity during influenza virus infection. It is therefore important to investigate the direct effects of influenza virus on NK cells. In this study, we demonstrated for the first time that influenza virus directly infects and replicates in primary human NK cells. Viral entry into NK cells was mediated by both clathrin- and caveolin-dependent endocytosis rather than through macropinocytosis and was dependent on the sialic acids on cell surfaces. In addition, influenza virus infection induced a marked apoptosis of NK cells. Our findings suggest that influenza virus can directly target and kill NK cells, a potential novel strategy of influenza virus to evade the NK cell innate immune defense that is likely to facilitate viral transmission and may also contribute to virus pathogenesis. PMID:19587043

Direct fed microbial supplementation repartitions host energy to the immune system.

PubMed

Qiu, R; Croom, J; Ali, R A; Ballou, A L; Smith, C D; Ashwell, C M; Hassan, H M; Chiang, C-C; Koci, M D

2012-08-01

Direct fed microbials and probiotics are used to promote health in livestock and poultry; however, their mechanism of action is still poorly understood. We previously reported that direct fed microbial supplementation in young broilers reduced ileal respiration without changing whole-body energy expenditure. The current studies were conducted to further investigate the effects of a direct fed microbial on energy metabolism in different tissues of broilers. One hundred ninety-two 1-d-old broiler chicks (16 chicks/pen) were randomly assigned to 2 dietary groups: standard control starter diet (CSD) and CSD plus direct fed microbial (DFMD; 0.3%) with 6 pens/treatment. Body weight, feed consumption, whole-body energy expenditure, organ mass, tissue respiration rates, and peripheral blood mononuclear cell (PBMC) ATP concentrations were measured to estimate changes in energy metabolism. No differences in whole body energy expenditure or BW gain were observed; however, decreased ileal O(2) respiration (P < 0.05) was measured in DFMD fed broilers. In contrast, the respiration rate of the thymus in those broilers was increased (P < 0.05). The PBMC from DFMD fed broilers had increased ATP concentrations and exhibited increased ATP turnover (P < 0.01). To determine if the increased energy consumption by PBMC corresponded with an altered immune response, broilers were immunized with sheep red blood cells (SRBC) and assayed for differences in their humoral response. The DFMD-fed broilers had a faster rate of antigen specific IgG production (P < 0.05) and an increase in total IgA (P < 0.05). Collectively, these data indicate that supplementation with the direct fed microbial used in this study resulted in energy re-partitioning to the immune system and an increase in antibody production independent of changes in whole body metabolism or growth performance.

The Split Virus Influenza Vaccine rapidly activates immune cells through Fcγ receptors.

PubMed

O'Gorman, William E; Huang, Huang; Wei, Yu-Ling; Davis, Kara L; Leipold, Michael D; Bendall, Sean C; Kidd, Brian A; Dekker, Cornelia L; Maecker, Holden T; Chien, Yueh-Hsiu; Davis, Mark M

2014-10-14

Seasonal influenza vaccination is one of the most common medical procedures and yet the extent to which it activates the immune system beyond inducing antibody production is not well understood. In the United States, the most prevalent formulations of the vaccine consist of degraded or "split" viral particles distributed without any adjuvants. Based on previous reports we sought to determine whether the split influenza vaccine activates innate immune receptors-specifically Toll-like receptors. High-dimensional proteomic profiling of human whole-blood using Cytometry by Time-of-Flight (CyTOF) was used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response ex vivo. This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature quite distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza virus "splitting" inactivates any potential adjuvants endogenous to influenza, such as RNA, but in previously exposed individuals can elicit a potent immune response by facilitating the rapid formation of immune complexes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification and Characterization of Novel Immunomodulatory Bursal-derived Pentapeptide-II (BPP-II)*

PubMed Central

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-01-01

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement. PMID:22184121

Identification and characterization of novel immunomodulatory bursal-derived pentapeptide-II (BPP-II).

PubMed

Feng, Xiu-Li; Liu, Qing-Tao; Cao, Rui-Bing; Zhou, Bin; Ma, Zhi-Yong; Deng, Wen-Lei; Wei, Jian-Chao; Qiu, Ya-Feng; Wang, Fang-Quan; Gu, Jin-Yan; Wang, Feng-Juan; Zheng, Qi-Sheng; Ishag, Hassan; Chen, Pu-Yan

2012-02-03

The bursa of Fabricius, the acknowledged central humoral immune organ, plays a vital role in B lymphocyte differentiation. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of bursal-derived peptides. In this paper, a novel bursal-derived pentapeptide-II (BPP-II, MTLTG) was isolated and exerted immunomodulatory functions on antibody responses in vitro. Gene microarray analyses demonstrated that BPP-II regulated expression of 2478 genes in a mouse-derived hybridoma cell line. Immune-related gene ontology functional procedures were employed for further functional analysis. Furthermore, the majority of BPP-II-regulated pathways were associated with immune responses and tumor processes. Moreover, BPP-II exhibited immunomodulatory effects on antigen-specific immune responses in vivo, including enhancement of avian influenza virus (H9N2 subtype)-specific antibody and cytokine production and modification of T cell immunophenotypes and lymphocyte proliferation. Finally, BPP-II triggered p53 expression and stabilization and selectively inhibited tumor cell proliferation. These data identified the multifunctional factor, BPP-II, as a novel biomaterial representing an important linking between the humoral central immune system and immune induction, including antitumor. Information generated in this study elucidates further the mechanisms involved in humoral immune system and represents the potential basis of effective immunotherapeutic strategies for treating human tumors and immune improvement.

A semi-direct procedure using a local relaxation factor and its application to an internal flow problem

NASA Technical Reports Server (NTRS)

Chang, S. C.

1984-01-01

Generally, fast direct solvers are not directly applicable to a nonseparable elliptic partial differential equation. This limitation, however, is circumvented by a semi-direct procedure, i.e., an iterative procedure using fast direct solvers. An efficient semi-direct procedure which is easy to implement and applicable to a variety of boundary conditions is presented. The current procedure also possesses other highly desirable properties, i.e.: (1) the convergence rate does not decrease with an increase of grid cell aspect ratio, and (2) the convergence rate is estimated using the coefficients of the partial differential equation being solved.

Active System for Electromagnetic Perturbation Monitoring in Vehicles

NASA Astrophysics Data System (ADS)

Matoi, Adrian Marian; Helerea, Elena

Nowadays electromagnetic environment is rapidly expanding in frequency domain and wireless services extend in terms of covered area. European electromagnetic compatibility regulations refer to limit values regarding emissions, as well as procedures for determining susceptibility of the vehicle. Approval procedure for a series of cars is based on determining emissions/immunity level for a few vehicles picked randomly from the entire series, supposing that entire vehicle series is compliant. During immunity assessment, the vehicle is not subjected to real perturbation sources, but exposed to electric/magnetic fields generated by laboratory equipment. Since current approach takes into account only partially real situation regarding perturbation sources, this paper proposes an active system for determining electromagnetic parameters of vehicle's environment, that implements a logical diagram for measurement, satisfying the imposed requirements. This new and original solution is useful for EMC assessment of hybrid and electrical vehicles.

Characterization of DUT impedance in immunity test setups

NASA Astrophysics Data System (ADS)

Hassanpour Razavi, Seyyed Ali; Frei, Stephan

2016-09-01

Several immunity test procedures for narrowband radiated electromagnetic energy are available for automotive components. The ISO 11452 series describes the most commonly used test methods. The absorber line shielded enclosure (ALSE) is often considered as the most reliable method. However, testing with the bulk current injection (BCI) can be done with less efforts and is often preferred. As the test setup in both procedures is quite similar, there were several trials for finding appropriate modifications to the BCI in order to increase the matching to the ALSE. However, the lack of knowledge regarding the impedance of the tested component, makes it impossible to find the equivalent current to be injected by the BCI and a good match cannot be achieved. In this paper, three approaches are proposed to estimate the termination impedance indirectly by using different current probes.

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

PubMed

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 the Pathogenesis of Ovarian Cancer

PubMed Central

Charbonneau, Bridget; Goode, Ellen L.; Kalli, Kimberly R.; Knutson, Keith L.; DeRycke, Melissa S.

2014-01-01

Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks. PMID:23582060

Plant immunity: a lesson from pathogenic bacterial effector proteins.

PubMed

Cui, Haitao; Xiang, Tingting; Zhou, Jian-Min

2009-10-01

Phytopathogenic bacteria inject an array of effector proteins into host cells to alter host physiology and assist the infection process. Some of these effectors can also trigger disease resistance as a result of recognition in the plant cell by cytoplasmic immune receptors. In addition to effector-triggered immunity, plants immunity can be triggered upon the detection of Pathogen/Microbe-Associated Molecular Patterns by surface-localized immune receptors. Recent progress indicates that many bacterial effector proteins use a variety of biochemical properties to directly attack key components of PAMP-triggered immunity and effector-triggered immunity, providing new insights into the molecular basis of plant innate immunity. Emerging evidence indicate that the evolution of disease resistance in plants is intimately linked to the mechanism by which bacterial effectors promote parasitism. This review focuses on how these studies have conceptually advanced our understanding of plant-pathogen interactions.

Drosophila as a model system to unravel the layers of innate immunity to infection

PubMed Central

Kounatidis, Ilias; Ligoxygakis, Petros

2012-01-01

Summary Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host–pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions. PMID:22724070

Drosophila as a model system to unravel the layers of innate immunity to infection.

PubMed

Kounatidis, Ilias; Ligoxygakis, Petros

2012-05-01

Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host-pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

49 CFR 389.39 - Direct final rulemaking procedures

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Direct final rulemaking procedures 389.39 Section 389.39 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER... PROCEDURES-FEDERAL MOTOR CARRIER SAFETY REGULATIONS Procedures for Adoption of Rules § 389.39 Direct final...

49 CFR 389.39 - Direct final rulemaking procedures

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Direct final rulemaking procedures 389.39 Section 389.39 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER... PROCEDURES-FEDERAL MOTOR CARRIER SAFETY REGULATIONS Procedures for Adoption of Rules § 389.39 Direct final...

Platelets as Cellular Effectors of Inflammation in Vascular Diseases

PubMed Central

Rondina, Matthew T.; Weyrich, Andrew S.; Zimmerman, Guy A.

2013-01-01

Platelets are chief effector cells in hemostasis. In addition, they are multifaceted inflammatory cells with functions that span the continuum from innate immune responses to adaptive immunity. Activated platelets have key “thromboinflammatory” activities in a variety of vascular disorders and vasculopathies. Recently-identified inflammatory and immune activities provide insights into the biology of these versatile blood cells that are directly relevant to human vascular diseases. PMID:23704217

Cryotherapy with concurrent CpG oligonucleotide treatment controls local tumor recurrence and modulates HER2/neu immunity.

PubMed

Veenstra, Jesse J; Gibson, Heather M; Littrup, Peter J; Reyes, Joyce D; Cher, Michael L; Takashima, Akira; Wei, Wei-Zen

2014-10-01

Percutaneous cryoablation is a minimally invasive procedure for tumor destruction, which can potentially initiate or amplify antitumor immunity through the release of tumor-associated antigens. However, clinically efficacious immunity is lacking and regional recurrences are a limiting factor relative to surgical excision. To understand the mechanism of immune activation by cryoablation, comprehensive analyses of innate immunity and HER2/neu humoral and cellular immunity following cryoablation with or without peritumoral CpG injection were conducted using two HER2/neu(+) tumor systems in wild-type (WT), neu-tolerant, and SCID mice. Cryoablation of neu(+) TUBO tumor in BALB/c mice resulted in systemic immune priming, but not in neu-tolerant BALB NeuT mice. Cryoablation of human HER2(+) D2F2/E2 tumor enabled the functionality of tumor-induced immunity, but secondary tumors were refractory to antitumor immunity if rechallenge occurred during the resolution phase of the cryoablated tumor. A step-wise increase in local recurrence was observed in WT, neu-tolerant, and SCID mice, indicating a role of adaptive immunity in controlling residual tumor foci. Importantly, local recurrences were eliminated or greatly reduced in WT, neu tolerant, and SCID mice when CpG was incorporated in the cryoablation regimen, showing significant local control by innate immunity. For long-term protection, however, adaptive immunity was required because most SCID mice eventually succumbed to local tumor recurrence even with combined cryoablation and CpG treatment. This improved understanding of the mechanisms by which cryoablation affects innate and adaptive immunity will help guide appropriate combination of therapeutic interventions to improve treatment outcomes. ©2014 American Association for Cancer Research.

DNA Methylation and Demethylation in Plant Immunity.

PubMed

Deleris, A; Halter, T; Navarro, L

2016-08-04

Detection of plant and animal pathogens triggers a massive transcriptional reprogramming, which is directed by chromatin-based processes, and ultimately results in antimicrobial immunity. Although the implication of histone modifications in orchestrating biotic stress-induced transcriptional reprogramming has been well characterized, very little was known, until recently, about the role of DNA methylation and demethylation in this process. In this review, we summarize recent findings on the dynamics and biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathogens. In particular, we report the implications of these epigenetic regulatory processes in the transcriptional and co-transcriptional control of immune-responsive genes and discuss their relevance in fine-tuning antimicrobial immune responses. Finally, we discuss the possible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerational immune priming, and de novo epiallelism, which could be adaptive.

Dendritic Cell Immune Responses in HIV-1 Controllers.

PubMed

Martin-Gayo, Enrique; Yu, Xu G

2017-02-01

Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.

Concerted Activity of IgG1 Antibodies and IL-4/IL-25-Dependent Effector Cells Trap Helminth Larvae in the Tissues following Vaccination with Defined Secreted Antigens, Providing Sterile Immunity to Challenge Infection

PubMed Central

Hewitson, James P.; Filbey, Kara J.; Esser-von Bieren, Julia; Camberis, Mali; Schwartz, Christian; Murray, Janice; Reynolds, Lisa A.; Blair, Natalie; Robertson, Elaine; Harcus, Yvonne; Boon, Louis; Huang, Stanley Ching-Cheng; Yang, Lihua; Tu, Yizheng; Miller, Mark J.; Voehringer, David; Le Gros, Graham; Harris, Nicola; Maizels, Rick M.

2015-01-01

Over 25% of the world's population are infected with helminth parasites, the majority of which colonise the gastrointestinal tract. However, no vaccine is yet available for human use, and mechanisms of protective immunity remain unclear. In the mouse model of Heligmosomoides polygyrus infection, vaccination with excretory-secretory (HES) antigens from adult parasites elicits sterilising immunity. Notably, three purified HES antigens (VAL-1, -2 and -3) are sufficient for effective vaccination. Protection is fully dependent upon specific IgG1 antibodies, but passive transfer confers only partial immunity to infection, indicating that cellular components are also required. Moreover, immune mice show greater cellular infiltration associated with trapping of larvae in the gut wall prior to their maturation. Intra-vital imaging of infected intestinal tissue revealed a four-fold increase in extravasation by LysM+GFP+ myeloid cells in vaccinated mice, and the massing of these cells around immature larvae. Mice deficient in FcRγ chain or C3 complement component remain fully immune, suggesting that in the presence of antibodies that directly neutralise parasite molecules, the myeloid compartment may attack larvae more quickly and effectively. Immunity to challenge infection was compromised in IL-4Rα- and IL-25-deficient mice, despite levels of specific antibody comparable to immune wild-type controls, while deficiencies in basophils, eosinophils or mast cells or CCR2-dependent inflammatory monocytes did not diminish immunity. Finally, we identify a suite of previously uncharacterised heat-labile vaccine antigens with homologs in human and veterinary parasites that together promote full immunity. Taken together, these data indicate that vaccine-induced immunity to intestinal helminths involves IgG1 antibodies directed against secreted proteins acting in concert with IL-25-dependent Type 2 myeloid effector populations. PMID:25816012

The New Cellular Immunology

ERIC Educational Resources Information Center

Claman, Henry N.

1973-01-01

Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

γδ T Cells Are a Component of Early Immunity against Preerythrocytic Malaria Parasites

PubMed Central

McKenna, Kyle C.; Tsuji, Moriya; Sarzotti, Marcella; Sacci, John B.; Witney, Adam A.; Azad, Abdu F.

2000-01-01

We tested the hypothesis that γδ T cells are a component of an early immune response directed against preerythrocytic malaria parasites that are required for the induction of an effector αβ T-cell immune response generated by irradiated-sporozoite (irr-spz) immunization. γδ T-cell-deficient (TCRδ−/−) mice on a C57BL/6 background were challenged with Plasmodium yoelii (17XNL strain) sporozoites, and then liver parasite burden was measured at 42 h postchallenge. Liver parasite burden was measured by quantification of parasite-specific 18S rRNA in total liver RNA by quantitative-competitive reverse transcription-PCR and by an automated 5′ exonuclease PCR. Sporozoite-challenged TCRδ−/− mice showed a significant (P < 0.01) increase in liver parasite burden compared to similarly challenged immunocompetent mice. In support of this result, TCRδ−/− mice were also found to be more susceptible than immunocompetent mice to a sporozoite challenge when blood-stage parasitemia was used as a readout. A greater percentage of TCRδ−/− mice than of immunocompetent mice progressed to a blood-stage infection when challenged with five or fewer sporozoites (odds ratio = 2.35, P = 0.06). TCRδ−/− mice receiving a single irr-spz immunization showed percent inhibition of liver parasites comparable to that of immunized immunocompetent mice following a sporozoite challenge. These data support the hypothesis that γδ T cells are a component of early immunity directed against malaria preerythrocytic parasites and suggest that γδ T cells are not required for the induction of an effector αβ T-cell immune response generated by irr-spz immunization. PMID:10722623

Neonatal Immunization: Rationale, Current State, and Future Prospects.

PubMed

Whittaker, Elizabeth; Goldblatt, David; McIntyre, Peter; Levy, Ofer

2018-01-01

Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies. Despite distinct immunity and reduced responses to some vaccines, several vaccines have proven safe and effective at birth. While some vaccines such as polysaccharide vaccines have little effectiveness at birth, hepatitis B vaccine can prime at birth and requires multiple doses to achieve protection, whereas the live-attenuated Bacille Calmette-Guérin (BCG), may offer single shot protection, potentially in part via heterologous ("non-specific") beneficial effects. Additional vaccines have been studied at birth including those directed against pertussis, pneumococcus, Haemophilus influenza type B and rotavirus providing important lessons. Current areas of research in neonatal vaccinology include characterization of early life immune ontogeny, heterogeneity in and heterologous effects of BCG vaccine formulations, applying systems biology and systems serology, in vitro platforms that model age-specific human immunity and discovery and development of novel age-specific adjuvantation systems. These approaches may inform, de-risk, and accelerate development of novel vaccines for use in early life. Key stakeholders, including the general public, should be engaged in assessing the opportunities and challenges inherent to neonatal immunization.

Neonatal Immunization: Rationale, Current State, and Future Prospects

PubMed Central

Whittaker, Elizabeth; Goldblatt, David; McIntyre, Peter; Levy, Ofer

2018-01-01

Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies. Despite distinct immunity and reduced responses to some vaccines, several vaccines have proven safe and effective at birth. While some vaccines such as polysaccharide vaccines have little effectiveness at birth, hepatitis B vaccine can prime at birth and requires multiple doses to achieve protection, whereas the live-attenuated Bacille Calmette–Guérin (BCG), may offer single shot protection, potentially in part via heterologous (“non-specific”) beneficial effects. Additional vaccines have been studied at birth including those directed against pertussis, pneumococcus, Haemophilus influenza type B and rotavirus providing important lessons. Current areas of research in neonatal vaccinology include characterization of early life immune ontogeny, heterogeneity in and heterologous effects of BCG vaccine formulations, applying systems biology and systems serology, in vitro platforms that model age-specific human immunity and discovery and development of novel age-specific adjuvantation systems. These approaches may inform, de-risk, and accelerate development of novel vaccines for use in early life. Key stakeholders, including the general public, should be engaged in assessing the opportunities and challenges inherent to neonatal immunization. PMID:29670610

Measuring Coverage in MNCH: Design, Implementation, and Interpretation Challenges Associated with Tracking Vaccination Coverage Using Household Surveys

PubMed Central

Cutts, Felicity T.; Izurieta, Hector S.; Rhoda, Dale A.

2013-01-01

Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis. PMID:23667334

The Role of Probiotics and Prebiotics in Inducing Gut Immunity

PubMed Central

Vieira, Angélica T.; Teixeira, Mauro M.; Martins, Flaviano S.

2013-01-01

The gut immune system is influenced by many factors, including dietary components and commensal bacteria. Nutrients that affect gut immunity and strategies that restore a healthy gut microbial community by affecting the microbial composition are being developed as new therapeutic approaches to treat several inflammatory diseases. Although probiotics (live microorganisms) and prebiotics (food components) have shown promise as treatments for several diseases in both clinical and animal studies, an understanding of the molecular mechanisms behind the direct and indirect effects on the gut immune response will facilitate better and possibly more efficient therapy for diseases. In this review, we will first describe the concept of prebiotics, probiotics, and symbiotics and cover the most recently well-established scientific findings regarding the direct and indirect mechanisms by which these dietary approaches can influence gut immunity. Emphasis will be placed on the relationship of diet, the microbiota, and the gut immune system. Second, we will highlight recent results from our group, which suggest a new dietary manipulation that includes the use of nutrient products (organic selenium and Lithothamnium muelleri) and probiotics (Saccharomyces boulardii UFMG 905 and Bifidobacterium sp.) that can stimulate and manipulate the gut immune response, inducing intestinal homeostasis. Furthermore, the purpose of this review is to discuss and translate all of this knowledge into therapeutic strategies and into treatment for extra-intestinal compartment pathologies. We will conclude by discussing perspectives and molecular advances regarding the use of prebiotics or probiotics as new therapeutic strategies that manipulate the microbial composition and the gut immune responses of the host. PMID:24376446

Engineering Vaccines to Reprogram Immunity against Head and Neck Cancer.

PubMed

Tan, Y S; Sansanaphongpricha, K; Prince, M E P; Sun, D; Wolf, G T; Lei, Y L

2018-06-01

The recent Food and Drug Administration's approval of monoclonal antibodies targeting immune checkpoint receptors (ICRs) for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) offers exciting promise to improve patient outcome and reduce morbidities. A favorable response to ICR blockade relies on an extensive collection of preexisting tumor-specific T cells in the tumor microenvironment (TME). ICR blockade reinvigorates exhausted CD8 + T cells and enhances immune killing. However, resistance to ICR blockade is observed in about 85% of patients with HNSCC, therefore highlighting the importance of characterizing the mechanisms underlying HNSCC immune escape and exploring combinatorial strategies to sensitize hypoimmunogenic cold HNSCC to ICR inhibition. Cancer vaccines are designed to bypass the cold TME and directly deliver cancer antigens to antigen-presenting cells (APCs); these vaccines epitomize a priming strategy to synergize with ICR inhibitors. Cancer cells are ineffective antigen presenters, and poor APC infiltration as well as the M2-like polarization in the TME further dampens antigen uptake and processing, both of which render ineffective innate and adaptive immune detection. Cancer vaccines directly activate APC and expand the tumor-specific T-cell repertoire. In addition, cancer vaccines often contain an adjuvant, which further improves APC function, promotes epitope spreading, and augments host intrinsic antitumor immunity. Thus, the vaccine-induced immune priming generates a pool of effectors whose function can be enhanced by ICR inhibitors. In this review, we summarize the major HNSCC immune evasion strategies, the ongoing effort toward improving HNSCC vaccines, and the current challenges limiting the efficacy of cancer vaccines.

Role of CD4+ T cells in a protective immune response against Cryptococcus neoformans in the central nervous system.

PubMed

Uicker, William C; McCracken, James P; Buchanan, Kent L

2006-02-01

Cryptococcosis is a life-threatening disease caused by the encapsulated yeast, Cryptococcus neoformans. Although infection with C. neoformans is initiated in the lungs, morbidity and mortality is mostly associated with infections of the central nervous system (CNS). Individuals with deficiencies in cell-mediated immunity, such as patients with AIDS, are more susceptible to disseminated cryptococcosis, highlighting the importance of cell-mediated immunity and CD4+ T cells in host resistance against C. neoformans. Using a mouse model of cryptococcal meningoencephalitis, we have shown that immunization of mice with a cryptococcal antigen induced a protective immune response that crossed the blood-brain barrier and initiated an immune response directly in the CNS if C. neoformans was present. The regional protective response was characteristic of a Type-1 (Th1) response in the types of cells present at the site of infection and in the cytokines and chemokines expressed. Here, we extend those findings and report that CD4+ T cells are required for survival of immune mice infected directly in the brain with C. neoformans and sensitized CD4 + T cells can transfer partial protection to naive mice infected intracerebrally with C. neoformans. Furthermore, CD4 + T cells were also important for optimal infiltration of inflammatory cells at the site of infection and in the expression of cytokines and chemokines associated with protection in the brain. Lastly, CD4+ T cells were required for optimal regional production and secretion of IFNgamma and in the significantly increased expression of iNOS in C. neoformans-infected brains of immune mice.

Interactions Between Macrophages of Guinea Pigs and Salmonellae III. Bactericidal Action and Cytophilic Antibodies of Macrophages of Infected Guinea Pigs

PubMed Central

Hsu, H. S.; Mayo, Donald R.

1973-01-01

The fate of virulent Salmonella typhimurium within macrophages of guinea pigs was assessed by a suspended cell culture procedure. The present study confirmed that macrophages of normal guinea pigs were capable of inactivating the ingested salmonellae. Macrophages of previously infected guinea pigs were not endowed with any significant increase in their ability to eliminate the ingested pathogen. However, the immune macrophages were observed to clump together tightly when they were exposed to salmonellae. This phenomenon was attributed to the presence of specific cytophilic antibodies on the immune macrophages. When immune macrophages were inactivated with Merthiolate, they agglutinated with both the H and the O antigens of S. typhimurium, but not with the O antigens of other species of Salmonella nor with the O antigens of Escherichia coli. Cytophilic antibodies could be eluted from immune macrophages by incubation in the absence of immune serum. Conversely, cytophilic antibodies could be passively transferred onto normal macrophages by incubation in the presence of immune serum. Furthermore, using immune serum previously adsorbed with the O antigens of S. typhimurium, cytophilic antibodies against the H antigens alone could be transferred onto normal macrophages, or those against the O antigens alone could be eluted from immune macrophages. These data suggest that immune macrophages possess specific cytophilic antibodies against both the H and the O antigens of S. typhimurium. It is proposed that the presence of cytophilic antibodies on immune macrophages represents an expression of antibacterial cellular immunity by enhanced clumping and phagocytic activities of the macrophages. PMID:4579899

24 CFR 291.210 - Direct sales procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Direct sales procedures. 291.210... URBAN DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF HUD-ACQUIRED SINGLE FAMILY PROPERTY Sales Procedures § 291.210 Direct sales procedures. When HUD conducts the sales listed in § 291.90(c), it will sell...

24 CFR 291.210 - Direct sales procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Direct sales procedures. 291.210... URBAN DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF HUD-ACQUIRED SINGLE FAMILY PROPERTY Sales Procedures § 291.210 Direct sales procedures. When HUD conducts the sales listed in § 291.90(c), it will sell...

24 CFR 291.210 - Direct sales procedures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Direct sales procedures. 291.210... URBAN DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF HUD-ACQUIRED SINGLE FAMILY PROPERTY Sales Procedures § 291.210 Direct sales procedures. When HUD conducts the sales listed in § 291.90(c), it will sell...

Targeting innate immunity to downmodulate adaptive immunity and reverse type 1 diabetes

PubMed Central

Itoh, Arata; Ridgway, William M

2017-01-01

Type 1 diabetes (T1D) is characterized by specific destruction of pancreatic insulin-producing beta cells accompanied by evidence of beta-cell-directed autoimmunity such as autoreactive T cells and islet autoantibodies (IAAs). Currently, T1D cannot be prevented or reversed in humans. T1D is easy to prevent in the nonobese diabetic (NOD) spontaneous mouse model but reversing new-onset T1D in mice is more difficult. Since the discovery of the T-cell receptor in the 1980s and the subsequent identification of autoreactive T cells directed toward beta-cell antigens (eg, insulin, glutamic acid decarboxylase), the dream of antigen-specific immunotherapy has dominated the field with its promise of specificity and limited side effects. While such approaches have worked in the NOD mouse, however, dozens of human trials have failed. Broader immunosuppressive approaches (originally cyclosporine, subsequently anti-CD3 antibody) have shown partial successes (e.g., prolonged C peptide preservation) but no major therapeutic efficacy or disease reversal. Human prevention trials have failed, despite the ease of such approaches in the NOD mouse. In the past 50 years, the incidence of T1D has increased dramatically, and one explanation is the “hygiene hypothesis”, which suggests that decreased exposure of the innate immune system to environmental immune stimulants (e.g., bacterial products such as Toll-like receptor (TLR) 4-stimulating lipopolysaccharide [LPS]) dramatically affects the adaptive immune system and increases subsequent autoimmunity. We have tested the role of innate immunity in autoimmune T1D by treating acute-onset T1D in NOD mice with anti-TLR4/MD-2 agonistic antibodies and have shown a high rate of disease reversal. The TLR4 antibodies do not directly stimulate T cells but induce tolerogenic antigen-presenting cells (APCs) that mediate decreased adaptive T-cell responses. Here, we review our current knowledge and suggest future prospects for targeting innate immunity in T1D immunotherapy. PMID:28580341

Thymol and Carvacrol Affect Hybrid Tilapia through the Combination of Direct Stimulation and an Intestinal Microbiota-Mediated Effect: Insights from a Germ-Free Zebrafish Model.

PubMed

Ran, Chao; Hu, Jun; Liu, Wenshu; Liu, Zhi; He, Suxu; Dan, Bui Chau Truc; Diem, Nguyen Ngoc; Ooi, Ei Lin; Zhou, Zhigang

2016-05-01

Essential oils (EOs) are commonly used as animal feed additives. Information is lacking on the mechanisms driving the beneficial effects of EOs in animals, especially the role played by the intestinal microbiota of the host. The purpose of this study was to clarify the relative contribution of direct effects of EOs on the physiology and immune system of tilapia and indirect effects mediated by the intestinal microbiota by using a germ-free zebrafish model. Juvenile hybrid tilapia were fed a control diet or 1 of 4 treatment diets containing 60-800 mg Next Enhance 150 (NE) (an EO product containing equal levels of thymol and carvacrol)/kg for 6 wk. The key humoral and cellular innate immune parameters were evaluated after the feeding period. In another experiment, the gut microbiota of tilapia fed a control or an NE diet (200 mg/kg) for 2 wk were transferred to 3-d postfertilization (dpf) germ-free (GF) zebrafish, and the expression of genes involved in innate immunity and tight junctions was evaluated in zebrafish at 6 dpf. Lastly, NE was directly applied to 3-dpf GF zebrafish at 3 doses ranging from 0.2 to 20 mg/L, and the direct effect of NE on zebrafish was evaluated after 1 and 3 d. NE supplementation at 200 mg/kg enhanced phagocytosis activity of head kidney macrophages (×1.36) (P < 0.05) and plasma lysozyme activity (×1.69) of tilapia compared with the control (P < 0.001), indicating an immunostimulatory effect. Compared with those colonized with control microbiota, GF zebrafish colonized with NE microbiota showed attenuated induction of immune response marker genes serum amyloid a (Saa; ×0.62), interleukin 1β (Il1β; ×0.29), and interleukin 8 (Il8; ×0.62) (P < 0.05). NE treatment of GF zebrafish at 2 and 20 mg/L for 1 d upregulated the expression of Il1β (×2.44) and Claudin1 (×1.38), respectively (P < 0.05), whereas at day 3 the expression of Occludin2 was higher (×3.30) in the 0.2-mg NE/L group compared with the GF control (P < 0.05). NE may affect the immunity of tilapia through a combination of factors, i.e., primarily through a direct effect on host tissue (immune-stimulating) but also an indirect effect mediated by microbial changes (immune-relieving). © 2016 American Society for Nutrition.

Molecular mechanisms mediating immune priming in Anopheles gambiae mosquitos

USDA-ARS?s Scientific Manuscript database

The Anopheles gambiae immune priming response is triggered when Plasmodium ookinetes invade the mosquito midgut and the microbiota comes in direct contact with injured cells. This is a long-lasting response that confers the challenged mosquito enhanced ability to control subsequent Plasmodium infect...

MicroRNA-466l inhibits antiviral innate immune response by targeting interferon-alpha

PubMed Central

Li, Yingke; Fan, Xiaohua; He, Xingying; Sun, Haijing; Zou, Zui; Yuan, Hongbin; Xu, Haitao; Wang, Chengcai; Shi, Xueyin

2012-01-01

Effective recognition of viral infections and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs (miRNAs). A previous study showed that miR-466l upregulates IL-10 expression in macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. However, the ability of miR-466l to regulate antiviral immune responses remains unknown. Here, we found that interferon-alpha (IFN-α) expression was repressed in Sendai virus (SeV)- and vesicular stomatitis virus (VSV)-infected macrophages and in dendritic cells transfected with miR-466l expression. Moreover, multiple IFN-α species can be directly targeted by miR-466l through their 3′ untranslated region (3′UTR). This study has demonstrated that miR-466l could directly target IFN-α expression to inhibit host antiviral innate immune response. PMID:23042536

Eosinophils in mucosal immune responses

PubMed Central

Travers, J; Rothenberg, M E

2015-01-01

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

[Hypnotherapy of atopic dermatitis in an adult. Case report].

PubMed

Perczel, Kristóf; Gál, János

2016-01-17

Hypnosis is well known for its modulatory effects on immune and inflammatory processes, and it is a therapeutic option for certain diseases of such pathogenesis. The authors report treatment of an adult patient with extensive atopic dermatitis, who was only minimally responsive to conservative treatment. In a 15 session hypnotherapy the authors combined the use of direct, symptom-oriented suggestive techniques with hypnotic procedures to identify and modify comorbid psychological issues. To monitor the effect of the treatment, patient diaries (quality and quantity of sleep, intensity of pain and itch) and repeated psychometric tests were used. At the end of treatment there were improvements in all measured dimensions (itch, pain, insomnia, activity, anxiety and emotional state) both clinically and psychometrically. The authors conclude, that hypnosis can be an effective adjunctive therapy in atopic dermatitis, and in certain severe cases may constitute a salvage therapy.

[Learning from the US immunization administration].

PubMed

Kamiya, Hajime; Kamiya, Hitoshi

2008-10-01

The US federal government has been providing support to state and local health departments for immunization program since 1920' s. Many government and nongovernment organizations, groups and personnel are involved in the process of the US immunization program. These organizations and groups are moving towards the same direction under the policy of "reducing the incidence of vaccine preventable diseases and to increase the safe usage of vaccines and related biological products". Thus every organization keeps step with the others, which will make states and other local government easier to follow the recommendations. In this review, we will introduce the system and structure of the US immunization administration and indicate why the US has succeeded to decrease vaccine preventable disease with immunization.

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis | Center for Cancer Research

Cancer.gov

We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high

Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System

PubMed Central

Symowski, Cornelia; Voehringer, David

2017-01-01

Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell–cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system. PMID:29163497

Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System.

PubMed

Symowski, Cornelia; Voehringer, David

2017-01-01

Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell-cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system.

The potential roles of endogenous retroviruses in autoimmunity.

PubMed

Nakagawa, K; Harrison, L C

1996-08-01

Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs. ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue-specific or differentiation-dependent expression. In fact, retrovirus-like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms. ERVs may lead to immune dysregulation as insertional mutagens or cis-regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T-lymphotrophic virus type I (HTLV-I) or tat in human immunodeficiency virus-I (HIV-I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non-specific immunosuppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV protein not expressed in the thymus during acquisition of immune tolerance, may lead to its perception as a neoantigen. Paraneoplastic syndromes raise the possibility that novel ERV-encoded epitopes expressed by a tumour elicit immunity to cross-reactive epitopes in normal tissues. Recombination events between different but related ERVs, to whose products the host is immunologically tolerant, may also generate new antigenic determinants. Frequently reported humoral immunity to exogenous retrovirus proteins in autoimmune disease could be elicited by cross-reactive ERV proteins. A review of the evidence implicating ERVs in immune dysfunction leads to the conclusion that direct molecular studies are likely to establish a pathogenic role for ERVs in autoimmune disease.

Developing a Novel Parameter Estimation Method for Agent-Based Model in Immune System Simulation under the Framework of History Matching: A Case Study on Influenza A Virus Infection

PubMed Central

Li, Tingting; Cheng, Zhengguo; Zhang, Le

2017-01-01

Since they can provide a natural and flexible description of nonlinear dynamic behavior of complex system, Agent-based models (ABM) have been commonly used for immune system simulation. However, it is crucial for ABM to obtain an appropriate estimation for the key parameters of the model by incorporating experimental data. In this paper, a systematic procedure for immune system simulation by integrating the ABM and regression method under the framework of history matching is developed. A novel parameter estimation method by incorporating the experiment data for the simulator ABM during the procedure is proposed. First, we employ ABM as simulator to simulate the immune system. Then, the dimension-reduced type generalized additive model (GAM) is employed to train a statistical regression model by using the input and output data of ABM and play a role as an emulator during history matching. Next, we reduce the input space of parameters by introducing an implausible measure to discard the implausible input values. At last, the estimation of model parameters is obtained using the particle swarm optimization algorithm (PSO) by fitting the experiment data among the non-implausible input values. The real Influeza A Virus (IAV) data set is employed to demonstrate the performance of our proposed method, and the results show that the proposed method not only has good fitting and predicting accuracy, but it also owns favorable computational efficiency. PMID:29194393

Developing a Novel Parameter Estimation Method for Agent-Based Model in Immune System Simulation under the Framework of History Matching: A Case Study on Influenza A Virus Infection.

PubMed

Li, Tingting; Cheng, Zhengguo; Zhang, Le

2017-12-01

Since they can provide a natural and flexible description of nonlinear dynamic behavior of complex system, Agent-based models (ABM) have been commonly used for immune system simulation. However, it is crucial for ABM to obtain an appropriate estimation for the key parameters of the model by incorporating experimental data. In this paper, a systematic procedure for immune system simulation by integrating the ABM and regression method under the framework of history matching is developed. A novel parameter estimation method by incorporating the experiment data for the simulator ABM during the procedure is proposed. First, we employ ABM as simulator to simulate the immune system. Then, the dimension-reduced type generalized additive model (GAM) is employed to train a statistical regression model by using the input and output data of ABM and play a role as an emulator during history matching. Next, we reduce the input space of parameters by introducing an implausible measure to discard the implausible input values. At last, the estimation of model parameters is obtained using the particle swarm optimization algorithm (PSO) by fitting the experiment data among the non-implausible input values. The real Influeza A Virus (IAV) data set is employed to demonstrate the performance of our proposed method, and the results show that the proposed method not only has good fitting and predicting accuracy, but it also owns favorable computational efficiency.

Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells.

PubMed

Manda, Katrin; Glasow, Annegret; Paape, Daniel; Hildebrandt, Guido

2012-01-01

Dendritic cells (DCs), as professional antigen-presenting cells, are members of the innate immune system and function as key players during the induction phase of adaptive immune responses. Uptake, processing, and presentation of antigens direct the outcome toward either tolerance or immunity. The cells of the immune system are among the most highly radiosensitive cells in the body. For high doses of ionizing radiation (HD-IR) both immune-suppressive effects after whole body irradiation and possible immune activation during tumor therapy were observed. On the other hand, the effects of low doses of ionizing radiation (LD-IR) on the immune system are controversial and seem to show high variability among different individuals and species. There are reports revealing that protracted LD-IR can result in radioresistance. But immune-suppressive effects of chronic LD-IR are also reported, including the killing or sensitizing of certain cell types. This article shall review the current knowledge of radiation-induced effects on the immune system, paying special attention to the interaction of DCs and T cells.

Probiotics and prebiotics associated with aquaculture: A review.

PubMed

Akhter, Najeeb; Wu, Bin; Memon, Aamir Mahmood; Mohsin, Muhammad

2015-08-01

There is a rapidly growing literature, indicating success of probiotics and prebiotics in immunomodulation, namely the stimulation of innate, cellular and humoral immune response. Probiotics are considered to be living microorganisms administered orally and lead to health benefits. These Probiotics are microorganisms in sufficient amount to alter the microflora (by implantation or colonization) in specific host's compartment exerting beneficial health effects at this host. Nevertheless, Prebiotics are indigestible fiber which enhances beneficial commensally gut bacteria resulting in improved health of the host. The beneficial effects of prebiotics are due to by-products derived from the fermentation of intestinal commensal bacteria. Among the many health benefits attributed to probiotics and prebiotics, the modulation of the immune system is one of the most anticipated benefits and their ability to stimulate systemic and local immunity, deserves attention. They directly enhance the innate immune response, including the activation of phagocytosis, activation of neutrophils, activation of the alternative complement system, an increase in lysozyme activity, and so on. Prebiotics acting as immunosaccharides directly impact on the innate immune system of fish and shellfish. Therefore, both probiotics and prebiotics influence the immunomodulatory activity boosting up the health benefits in aquatic animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation

PubMed Central

Jones, Charles H.; Chen, Mingfu; Ravikrishnan, Anitha; Reddinger, Ryan; Zhang, Guojian; Hakansson, Anders P.; Pfeifer, Blaine A.

2014-01-01

Given the rise of antibiotic resistance and other difficult-to-treat diseases, genetic vaccination is a promising preventative approach that can be tailored and scaled according to the vector chosen for gene delivery. However, most vectors currently utilized rely on ubiquitous delivery mechanisms that ineffectively target important immune effectors such as antigen presenting cells (APCs). As such, APC targeting allows the option for tuning the direction (humoral vs cell-mediated) and strength of the resulting immune responses. In this work, we present the development and assessment of a library of mannosylated poly(beta-amino esters) (PBAEs) that represent a new class of easily synthesized APC-targeting cationic polymers. Polymeric characterization and assessment methodologies were designed to provide a more realistic physiochemical profile prior to in vivo evaluation. Gene delivery assessment in vitro showed significant improvement upon PBAE mannosylation and suggested that mannose-mediated uptake and processing influence the magnitude of gene delivery. Furthermore, mannosylated PBAEs demonstrated a strong, efficient, and safe in vivo humoral immune response without use of adjuvants when compared to genetic and protein control antigens. In summary, the gene delivery effectiveness provided by mannosylated PBAE vectors offers specificity and potency in directing APC activation and subsequent immune responses. PMID:25453962

Recognition and Blocking of Innate Immunity Cells by Candida albicans Chitin ▿ †

PubMed Central

Mora-Montes, Héctor M.; Netea, Mihai G.; Ferwerda, Gerben; Lenardon, Megan D.; Brown, Gordon D.; Mistry, Anita R.; Kullberg, Bart Jan; O'Callaghan, Chris A.; Sheth, Chirag C.; Odds, Frank C.; Brown, Alistair J. P.; Munro, Carol A.; Gow, Neil A. R.

2011-01-01

Chitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ultrapurified chitin from Candida albicans cell walls did not stimulate cytokine production directly but blocked the recognition of C. albicans by human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficient C. albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls. PMID:21357722

Effect of breast-feeding on pain relief during infant immunization injections.

PubMed

Abdel Razek, Aida; Az El-Dein, Nagwa

2009-04-01

Using a quasi-experimental design, this study was conducted in two maternal & child health centres in Jordan to examine the effects of breast-feeding on pain relief during neonatal immunization injections. Inclusion criteria were first year of age, breast-fed and no concurrent illness. Infants were divided into two groups (of 60 infants for each). One is intervention group: mothers were taken to a private room, seated and reclined on a comfortable chair with their infants awake in their arms, without cloth and with clean diapers. The mothers cradled their infants during breast-feeding to maintain full-body skin-to-skin contact during immunization injections. The other is control group: infants were observed during routine immunization in maternal & child health centres. Pain responses of infants during and after immunization were assessed by using Facial Pain Rating Scale and Neonatal/Infant Pain Scale (NIPS), before, during and after the procedure. Infants' heart rates and duration of crying for both groups were calculated. Findings revealed that the crying time was shorter in intervention (breast-fed) group than in the control group with a statistically significant difference in the duration of crying during and after immunization. We concluded that, breast-feeding and skin-to-skin contact significantly reduced crying in infants receiving immunization.

Cell-to-cell transmission of retroviruses: Innate immunity and interferon-induced restriction factors

PubMed Central

Jolly, Clare

2011-01-01

It has been known for some time that retroviruses can disseminate between immune cells either by conventional cell-free transmission or by directed cell-to-cell spread. Over the past few years there has been increasing interest in how retroviruses may use cell-to-cell spread to promote more rapid infection kinetics and circumvent humoral immunity. Effective humoral immune responses are intimately linked with innate immunity and the interplay between retroviruses and innate immunity is a rapidly expanding area of research that has been advanced considerably by the identification of cellular restriction factors that provide barriers to retroviral infection. The effect of innate immunity and restriction factors on retroviral cell-to-cell spread has been comparatively little studied; however recent work suggests this maybe changing. Here I will review some recent advances in what is a budding area of retroviral research. PMID:21247613

Designing natural and synthetic immune tissues

NASA Astrophysics Data System (ADS)

Gosselin, Emily A.; Eppler, Haleigh B.; Bromberg, Jonathan S.; Jewell, Christopher M.

2018-06-01

Vaccines and immunotherapies have provided enormous improvements for public health, but there are fundamental disconnects between where most studies are performed—in cell culture and animal models—and the ultimate application in humans. Engineering immune tissues and organs, such as bone marrow, thymus, lymph nodes and spleen, could be instrumental in overcoming these hurdles. Fundamentally, designed immune tissues could serve as in vitro tools to more accurately study human immune function and disease, while immune tissues engineered for implantation as next-generation vaccines or immunotherapies could enable direct, on-demand control over generation and regulation of immune function. In this Review, we discuss recent interdisciplinary strategies that are merging materials science and immunology to create engineered immune tissues in vitro and in vivo. We also highlight the hurdles facing these approaches and the need for comparison to existing clinical options, relevant animal models, and other emerging technologies.

Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

PubMed Central

Man, Yan-gao; Stojadinovic, Alexander; Mason, Jeffrey; Avital, Itzhak; Bilchik, Anton; Bruecher, Bjoern; Protic, Mladjan; Nissan, Aviram; Izadjoo, Mina; Zhang, Xichen; Jewett, Anahid

2013-01-01

It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness. PMID:23386907

Advances of Immune Checkpoint Inhibitors in Tumor Immunotherapy

NASA Astrophysics Data System (ADS)

Guo, Qiao

2018-01-01

Immune checkpoints are cell surface molecules that can fine-tune the immune responses, they are crucial for modulating the duration and amplitude of immune reactions while maintaining self-tolerance in order to minimize autoimmune responses. Numerous studies have demonstrated that tumors cells can directly express immune-checkpoint molecules, or induce many inhibitory molecules expression in the tumor microenvironment to inhibit the anti-tumor immunity. Releasing these brakes has emerged as an exciting strategy to cure cancer. In the past few years, clinical trials with therapeutic antibodies targeting to the checkpoint molecules CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. In contrast to the conventional treatment, checkpoint inhibitors induce broad and durable antitumor responses. In the future, treatment may involve combination therapy to target different checkpoint molecules and stages of the adaptive immune responses. In this review, we summarized the recent advances of the study and development of other checkpoint molecules in tumor immunotherapy.

Activation of the innate immune receptor Dectin-1 upon formation of a “phagocytic synapse”

PubMed Central

Goodridge, Helen S.; Reyes, Christopher N.; Becker, Courtney A.; Katsumoto, Tamiko R.; Ma, Jun; Wolf, Andrea J.; Bose, Nandita; Chan, Anissa S. H.; Magee, Andrew S.; Danielson, Michael E.; Weiss, Arthur; Vasilakos, John P.; Underhill, David M.

2011-01-01

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 is a pattern recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular anti-microbial activity, including phagocytosis and production of reactive oxygen species1, 2. In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 are excluded (Supplementary Figure 1). The “phagocytic synapse” now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular anti-microbial responses only when they are required. PMID:21525931

Age-dependent trade-offs between immunity and male, but not female, reproduction.

PubMed

McNamara, Kathryn B; van Lieshout, Emile; Jones, Therésa M; Simmons, Leigh W

2013-01-01

Immune function is costly and must be traded off against other life-history traits, such as gamete production. Studies of immune trade-offs typically focus on adult individuals, yet the juvenile stage can be a highly protracted period when reproductive resources are acquired and immune challenges are ubiquitous. Trade-offs during development are likely to be important, yet no studies have considered changes in adult responses to immune challenges imposed at different stages of juvenile development. By manipulating the timing of a bacterial immune challenge to the larvae of the cotton bollworm moth, we examined potential trade-offs between investment into immunity at different stages of juvenile development (early or late) and subsequent adult reproductive investment into sperm or egg production. Our data reveal an age-dependent trade-off between juvenile immune function and adult male reproductive investment. Activation of the immune response during late development resulted in a reduced allocation of resources to eupyrene (fertilizing) sperm production. Immune activation from the injection procedure itself (irrespective of whether individuals were injected with an immune elicitor or a control solution) also caused reproductive trade-offs; males injected early in development produced fewer apyrene (nonfertilizing) sperm. Contrary to many other studies, our study demonstrates these immune trade-offs under ad libitum nutritional conditions. No trade-offs were observed between female immune activation and adult reproductive investment. We suggest the differences in trade-offs observed between male sperm types and the absence of reproductive trade-offs in females may be the result of ontogenetic differences in gamete production in this species. Our data reveal developmental windows when trade-offs between immune function and gametic investment are made, and highlight the importance of considering multiple developmental periods when making inferences regarding the fundamental trade-offs expected between immune function and reproduction. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

[The clinical economic analysis of application of immune correcting preparations to prevent respiratory infections and their complications in frequently ill children of early school age].

PubMed

Maiorov, R V; Derbenov, D P

2014-01-01

The article presents the results of clinical economic analysis of effect of different immune correcting preparations on rate of respiratory infections in 548 frequently ill children of early school age. It is established that preventive immune correction with lysates of bacteria or glucosaminyl muramyl dipeptide in aggregate with vitamin mineral complex results in statistically significant decreasing of rate of respiratory infections and dramatic decreasing of direct and indirect costs of treatment of infectious diseases of respiratory ways. The preventive application of juice of cone-flower herb or interferon in aggregate with vitamnin mineral complex statistically significantly decreases rate of respiratory infections and negligibly decreases direct and indirect costs of their treatment.

ImmunoScenarios: A Game for the Immune System.

ERIC Educational Resources Information Center

Taylor, Mark F.; Jackson, Sally W.

1996-01-01

Describes a board game, ImmunoScenarios, which was developed to reinforce the ideas about the immune system discussed in lecture classes. Emphasizes important characteristics of the body's specific defense system including specificity, cooperation among various cells, and memory. Includes directions for playing, student handouts, and scenarios.…

Detection of cell mediated immune response to avian influenza viruses

USDA-ARS?s Scientific Manuscript database

In birds, lymphomyeloid tissues develop from epithelial (Bursa of Fabricus or thymus) or mesenchymal tissue which are populated by heamatopoietic stem cells. These stem cells develop directly into immunologically competent B (bursa) and T (thymus) cells. Cell-mediated immunity (CMI) is a part of the...

Low-dose intradermal and intramuscular vaccination against hepatitis B.

PubMed

Bryan, J P; Sjogren, M H; Perine, P L; Legters, L J

1992-03-01

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Cutaneous immunization: an evolving paradigm in influenza vaccines

PubMed Central

Gill, Harvinder S; Kang, Sang-Moo; Quan, Fu-Shi; Compans, Richard W

2014-01-01

Introduction Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate route of vaccination that has potential to be painless and could even lead to dose reduction of vaccines. Recently, microneedles have emerged as a novel painless approach for delivery of influenza vaccines via the skin. Areas covered In this review, we briefly summarize the approaches and devices used for skin vaccination, and then focus on studies of skin immunization with influenza vaccines using microneedles. We discuss both the functional immune response and the nature of this immune response following vaccination with microneedles. Expert opinion The cutaneous administration of influenza vaccines using microneedles offers several advantages: it is painless, elicits stronger immune responses in preclinical studies and could improve responses in high-risk populations. These dry formulations of vaccines provide enhanced stability, a property of high importance in enabling their rapid global distribution in response to possible outbreaks of pandemic influenza and newly emerging infectious diseases. PMID:24521050

Priming of innate antimycobacterial immunity by heat-killed Listeria monocytogenes induces sterilizing response in the adult zebrafish tuberculosis model

PubMed Central

Luukinen, Hanna; Vanha-aho, Leena-Maija; Svorjova, Aleksandra; Kantanen, Laura; Järvinen, Sampsa; Dufour, Eric; Rämet, Mika; Hytönen, Vesa Pekka

2018-01-01

ABSTRACT Mycobacterium tuberculosis remains one of the most problematic infectious agents, owing to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming to optimize immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model system to study induced protective immune responses in mycobacterial infection. We show that priming adult zebrafish with heat-killed Listeria monocytogenes (HKLm) at 1 day prior to M. marinum infection leads to significantly decreased mycobacterial loads in the infected zebrafish. Using rag1−/− fish, we show that the protective immunity conferred by HKLm priming can be induced through innate immunity alone. At 24 h post-infection, HKLm priming leads to a significant increase in the expression levels of macrophage-expressed gene 1 (mpeg1), tumor necrosis factor α (tnfa) and nitric oxide synthase 2b (nos2b), whereas superoxide dismutase 2 (sod2) expression is downregulated, implying that HKLm priming increases the number of macrophages and boosts intracellular killing mechanisms. The protective effects of HKLm are abolished when the injected material is pretreated with nucleases or proteinase K. Importantly, HKLm priming significantly increases the frequency of clearance of M. marinum infection by evoking sterilizing immunity (25 vs 3.7%, P=0.0021). In this study, immune priming is successfully used to induce sterilizing immunity against mycobacterial infection. This model provides a promising new platform for elucidating the mechanisms underlying sterilizing immunity and to develop host-directed treatment or prevention strategies against tuberculosis. This article has an associated First Person interview with the first author of the paper. PMID:29208761

From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system.

PubMed

Dhouib, Ines; Jallouli, Manel; Annabi, Alya; Marzouki, Soumaya; Gharbi, Najoua; Elfazaa, Saloua; Lasram, Mohamed Montassar

2016-05-01

The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC

PubMed Central

Falcao‐Pires, Ines; Balligand, Jean‐Luc; Bauersachs, Johann; Brutsaert, Dirk; Ciccarelli, Michele; Dawson, Dana; de Windt, Leon J.; Giacca, Mauro; Hamdani, Nazha; Hilfiker‐Kleiner, Denise; Hirsch, Emilio; Leite‐Moreira, Adelino; Mayr, Manuel; Thum, Thomas; Tocchetti, Carlo G.; van der Velden, Jolanda; Varricchi, Gilda; Heymans, Stephane

2018-01-01

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. PMID:29333691

Implications for registry-based vaccine effectiveness studies from an evaluation of an immunization registry: a cross-sectional study.

PubMed

Mahon, Barbara E; Shea, Kimberly M; Dougherty, Nancy N; Loughlin, Anita M

2008-05-14

Population-based electronic immunization registries create the possibility of using registry data to conduct vaccine effectiveness studies which could have methodological advantages over traditional observational studies. For study validity, the base population would have to be clearly defined and the immunization status of members of the population accurately recorded in the registry. We evaluated a city-wide immunization registry, focusing on its potential as a tool to study pertussis vaccine effectiveness, especially in adolescents. We conducted two evaluations - one in sites that were active registry participants and one in sites that had implemented an electronic medical record with plans for future direct data transfer to the registry - of the ability to match patients' medical records to registry records and the accuracy of immunization records in the registry. For each site, records from current pediatric patients were chosen randomly. Data regarding pertussis-related immunizations, clinic usage, and demographic and identifying information were recorded; for 11-17-year-old subjects, information on MMR, hepatitis B, and varicella immunizations was also collected. Records were then matched, when possible, to registry records. For records with a registry match, immunization data were compared. Among 350 subjects from sites that were current registry users, 307 (87.7%) matched a registry record. Discrepancies in pertussis-related data were common for up-to-date status (22.6%), number of immunizations (34.7%), dates (10.2%), and formulation (34.4%). Among 442 subjects from sites that planned direct electronic transfer of immunization data to the registry, 393 (88.9%) would have matched a registry record; discrepancies occurred frequently in number of immunizations (11.9%), formulation (29.1%), manufacturer (94.4%), and lot number (95.1%.) Inability to match and immunization discrepancies were both more common in subjects who were older at their first visit to the provider site. For 11-17-year-old subjects, discrepancies were also common for MMR, hepatitis B, and varicella vaccination data. Provider records frequently could not be matched to registry records or had discrepancies in key immunization data. These issues were more common for older children and were present even with electronic data transfer. These results highlight general challenges that may face investigators wishing to use registry-based immunization data for vaccine effectiveness studies, especially in adolescents.

Implications for registry-based vaccine effectiveness studies from an evaluation of an immunization registry: A cross-sectional study

PubMed Central

Mahon, Barbara E; Shea, Kimberly M; Dougherty, Nancy N; Loughlin, Anita M

2008-01-01

Background Population-based electronic immunization registries create the possibility of using registry data to conduct vaccine effectiveness studies which could have methodological advantages over traditional observational studies. For study validity, the base population would have to be clearly defined and the immunization status of members of the population accurately recorded in the registry. We evaluated a city-wide immunization registry, focusing on its potential as a tool to study pertussis vaccine effectiveness, especially in adolescents. Methods We conducted two evaluations – one in sites that were active registry participants and one in sites that had implemented an electronic medical record with plans for future direct data transfer to the registry – of the ability to match patients' medical records to registry records and the accuracy of immunization records in the registry. For each site, records from current pediatric patients were chosen randomly. Data regarding pertussis-related immunizations, clinic usage, and demographic and identifying information were recorded; for 11–17-year-old subjects, information on MMR, hepatitis B, and varicella immunizations was also collected. Records were then matched, when possible, to registry records. For records with a registry match, immunization data were compared. Results Among 350 subjects from sites that were current registry users, 307 (87.7%) matched a registry record. Discrepancies in pertussis-related data were common for up-to-date status (22.6%), number of immunizations (34.7%), dates (10.2%), and formulation (34.4%). Among 442 subjects from sites that planned direct electronic transfer of immunization data to the registry, 393 (88.9%) would have matched a registry record; discrepancies occurred frequently in number of immunizations (11.9%), formulation (29.1%), manufacturer (94.4%), and lot number (95.1%.) Inability to match and immunization discrepancies were both more common in subjects who were older at their first visit to the provider site. For 11–17-year-old subjects, discrepancies were also common for MMR, hepatitis B, and varicella vaccination data. Conclusion Provider records frequently could not be matched to registry records or had discrepancies in key immunization data. These issues were more common for older children and were present even with electronic data transfer. These results highlight general challenges that may face investigators wishing to use registry-based immunization data for vaccine effectiveness studies, especially in adolescents. PMID:18479517

Commensal microbiome effects on mucosal immune system development in the ruminant gastrointestinal tract.

PubMed

Taschuk, Ryan; Griebel, Philip J

2012-06-01

Commensal microflora play many roles within the mammalian gastrointestinal tract (GIT) that benefit host physiology by way of direct or indirect interactions with mucosal surfaces. Commensal flora comprises members across all microbial phyla, although predominantly bacterial, with population dynamics varying with host species, genotype, and environmental factors. Little is known, however, about the complex mechanisms regulating host-commensal interactions that underlie this mutually beneficial relationship and how alterations in the microbiome may influence host development and susceptibility to infection. Research into the gut microbiome has intensified as it becomes increasingly evident that symbiont-host interactions have a significant impact on mucosal immunity and health. Furthermore, evidence that microbial populations vary significantly throughout the GIT suggest that regional differences in the microbiome may also influence immune function within distinct compartments of the GIT. Postpartum colonization of the GIT has been shown to have a direct effect on mucosal immune system development, but information is limited regarding regional effects of the microbiome on the development, activation, and maturation of the mucosal immune system. This review discusses factors influencing the colonization and establishment of the microbiome throughout the GIT of newborn calves and the evidence that regional differences in the microbiome influence mucosal immune system development and maturation. The implications of this complex interaction are also discussed in terms of possible effects on responses to enteric pathogens and vaccines.

The ontogeny of immunity: development of innate immune strength in the honey bee (Apis mellifera).

PubMed

Wilson-Rich, Noah; Dres, Stephanie T; Starks, Philip T

2008-01-01

Honey bees (Apis mellifera) are of vital economic and ecological importance. These eusocial animals display temporal polyethism, which is an age-driven division of labor. Younger adult bees remain in the hive and tend to developing brood, while older adult bees forage for pollen and nectar to feed the colony. As honey bees mature, the types of pathogens they experience also change. As such, pathogen pressure may affect bees differently throughout their lifespan. We provide the first direct tests of honey bee innate immune strength across developmental stages. We investigated immune strength across four developmental stages: larvae, pupae, nurses (1-day-old adults), and foragers (22-30 days old adults). The immune strength of honey bees was quantified using standard immunocompetence assays: total hemocyte count, encapsulation response, fat body quantification, and phenoloxidase activity. Larvae and pupae had the highest total hemocyte counts, while there was no difference in encapsulation response between developmental stages. Nurses had more fat body mass than foragers, while phenoloxidase activity increased directly with honey bee development. Immune strength was most vigorous in older, foraging bees and weakest in young bees. Importantly, we found that adult honey bees do not abandon cellular immunocompetence as has recently been proposed. Induced shifts in behavioral roles may increase a colony's susceptibility to disease if nurses begin foraging activity prematurely.

Epstein-Barr virus lymphoproliferative disease after solid organ transplantation.

PubMed

Prockop, Susan E; Vatsayan, Anant

2017-11-01

Epstein-Barr virus (EBV) was the first identified human oncovirus and is also one of the most ubiquitous viral infections known with established infections in more than 90% of individuals by early adulthood. EBV establishes latency by controlling expression of the viral genome making it silent to immune surveillance. In immunocompetent individuals, up to 1% of circulating T cells are directed at maintaining control over EBV replication. In addition to being involved in oncogenesis of lymphoid and epithelial tumors in immune-competent individuals, loss of immune surveillance over EBV predisposes individuals to EBV malignancies. Lymphoid proliferations from EBV-infected B cells arise in up to 20% of recipients of solid organ transplants (SOTs). One question not answered is why, when EBV requires such active immune surveillance, EBV malignancies are not even more prevalent in severely immune-compromised individuals. A better understanding of who develops complications related to EBV and what the immunologic risks are will ultimately make it feasible to perform prophylactic trials in those at highest risk. This review summarizes our current understanding of factors in SOT recipients that predispose them to the development of an EBV malignancy and that predict response to initial therapy. We then review the current landscape of those therapies, focusing on the goal of restoring long-term EBV-directed immunity to patients at risk. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

PubMed

Hemmink, Johanneke D; Morgan, Sophie B; Aramouni, Mario; Everett, Helen; Salguero, Francisco J; Canini, Laetitia; Porter, Emily; Chase-Topping, Margo; Beck, Katy; Loughlin, Ronan Mac; Carr, B Veronica; Brown, Ian H; Bailey, Mick; Woolhouse, Mark; Brookes, Sharon M; Charleston, Bryan; Tchilian, Elma

2016-10-20

Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.

Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice.

PubMed

Liu, Chengwen; Lou, Yanyan; Lizée, Gregory; Qin, Hong; Liu, Shujuan; Rabinovich, Brian; Kim, Grace J; Wang, Yi-Hong; Ye, Yang; Sikora, Andrew G; Overwijk, Willem W; Liu, Yong-Jun; Wang, Gang; Hwu, Patrick

2008-03-01

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-gamma production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells.

Effect of the Various Steps in the Processing of Human Milk in the Concentrations of IgA, IgM, and Lactoferrin.

PubMed

Arroyo, Gerardo; Ortiz Barrientos, Kevin Alexander; Lange, Karla; Nave, Federico; Miss Mas, Gabriela; Lam Aguilar, Pamela; Soto Galindo, Miguel Angel

2017-09-01

Human milk immune components are unique and important for the development of the newborn. Milk processing at the Human Milk Banks (HMB), however, causes partial destruction of immune proteins. The objective of this study was to determine the effects that heating during the milk processing procedure at the HMB had on the concentrations of IgA, IgM, and lactoferrin at three critical points in time. Fifty milk samples (150 mL) were collected from voluntary donors at the HMB at the Hospital Nacional Pedro de Bethancourt, located in Antigua Guatemala. Samples from three critical points in time during the milk processing procedure were selected for analysis: freezing/thawing I, freezing/thawing II, and pasteurization. IgA, IgM, and lactoferrin concentrations were determined during each critical point and compared with a baseline concentration. After milk processing, IgA, IgM, and lactoferrin mean concentrations were reduced by 30.0%, 36.0%, and 70.0%, respectively (p < 0.001). Reduction of biological activity was mainly attributed to pasteurization for IgA and lactoferrin (p < 0.001); the first freezing/thawing processes before pasteurization showed no significant reduction difference between mean concentrations of IgA (p = 0.160) and lactoferrin (p = 0.345) but showed a significant effect on IgM concentration (p = 0.016), and the second freezing/thawing procedure only showed a significant effect on IgA (p < 0.001). The effects of milk processing on the immune proteins that were evaluated in this study demonstrated a significant reduction.

Comparative analysis of signature genes in PRRSV-infected porcine monocyte-derived cells at differential activation statuses

USDA-ARS?s Scientific Manuscript database

Activation statuses of monocytic cells are critically important for antiviral immunity. Devastating viruses like porcine reproductive and respiratory syndrome virus (PRRSV) are capable of directly infecting these cells, subverting host immunity. Monocyte-derived DCs (mDCs) are major target cells in ...

Selection of broilers with improved innate immune responsiveness to reduce on-farm infection by foodborne pathogens: A review

USDA-ARS?s Scientific Manuscript database

Economic pressure on the modern poultry industry has directed the selection process towards fast-growing broilers that have a reduced feed conversion ratio. Selection based heavily on growth characteristics could adversely affect immune competence leaving chickens more susceptible to disease. Sinc...

Grantee Spotlight: Manuel L. Penichet, M.D., Ph.D. - Reprogramming the Immune System to Kill Cancer

Cancer.gov

Dr. Manuel L. Penichet, former CURE K01 trainee and NCI R01 grantee, aims to genetically engineer antibodies that can be used to directly target and eliminate cancer cells and also stimulate the body’s immune system to fight and destroy cancer.

Advancing Cancer Therapy with Present and Emerging Immuno-Oncology Approaches

PubMed Central

Kamta, Jeff; Chaar, Maher; Ande, Anusha; Altomare, Deborah A.; Ait-Oudhia, Sihem

2017-01-01

Immuno-oncology (I-O) is a young and growing field on the frontier of cancer therapy. Contrary to cancer therapies that directly target malignant cells, I-O therapies stimulate the body’s immune system to target and attack the tumor, which is otherwise invisible to, or inhibiting the immune response. To this end, several methods have been developed: First, passive therapies that enable T-cells to fight the tumor without direct manipulation, typically through binding and modifying the intracellular signaling of surface receptors. Checkpoint inhibitors, perhaps the most well known of I-O therapies; are an example of such. These are monoclonal antibodies that block binding of the tumor cell at receptors that inactivate the T-cell. A variety of small molecules can achieve the same effect by affecting metabolic or signaling pathways to boost the immune response or prevent its attenuation. Drugs originally formulated for unrelated disease states are now being used to treat cancer under the I-O approach. Second, active therapies which often involve direct manipulations that occur in vitro and once introduced to the patient will directly attack the tumor. Adoptive cell transfer is the oldest of these methods. It involves the removal of T-cells from the body, which are then expanded and genetically modified for specificity toward tumor-associated antigens (TAAs), and then reintroduced to the patient. A similar approach is taken with cancer vaccines, where TAAs are identified and reintroduced with adjuvants to stimulate an immune response, sometimes in the context of antigen-presenting cells or viral vectors. Oncolytic viruses are genetically modified natural viruses for selectivity toward tumor cells. The resulting cytotoxicity has the potential to elicit an immune response that furthers tumor cell killing. A final active approach is bi-specific T-cell engagers. These modified antibodies act to link a T-cell and tumor cell through surface receptors and thereby forcibly generate immune recognition. The therapies in each of these subfields are all still very new and ongoing clinical trials could provide even further additions. The full therapeutic potential of the aforementioned therapies, alone or in combination, has yet to be realized, but holds great promise for the future of cancer treatment. PMID:28459041

Opioids and the immune system: what is their mechanism of action?

PubMed

Eisenstein, Toby K

2011-12-01

There is a significant amount of literature showing that morphine and other opioids modulate immune responses. The findings support many mechanisms by which this may occur. In vitro experiments provide evidence for direct actions of opioids on immune cells using a variety of functional end points. When these drugs are given in vivo, a plethora of immune parameters are also altered. The paper in this issue of the journal by Zhang et al. provides new information on morphine alteration of immune cell subsets in the spleen and thymus of mice and the potential role of glucocorticoids in these observed phenomena. This Commentary reviews the in vitro activities of morphine on leucocytes, as well as other documented mechanisms by which morphine can alter immune function in vivo. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models

PubMed Central

Watson, Alan M.; Klimstra, William B.

2017-01-01

The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus. PMID:28398253

Dynamic two-photon imaging of the immune response to Toxoplasma gondii infection.

PubMed

Luu, L; Coombes, J L

2015-03-01

Toxoplasma gondii is a highly successful parasite that can manipulate host immune responses to optimize its persistence and spread. As a result, a highly complex relationship exists between T. gondii and the immune system of the host. Advances in imaging techniques, and in particular, the application of two-photon microscopy to mouse infection models, have made it possible to directly visualize interactions between parasites and the host immune system as they occur in living tissues. Here, we will discuss how dynamic imaging techniques have provided unexpected new insight into (i) how immune responses are dynamically regulated by cells and structures in the local tissue environment, (ii) how protective responses to T. gondii are generated and (iii) how the parasite exploits the immune system for its own benefit. © 2014 John Wiley & Sons Ltd.

Targeting Antitumor Immune Response for Enhancing the Efficacy of Photodynamic Therapy of Cancer: Recent Advances and Future Perspectives

PubMed Central

2016-01-01

Photodynamic therapy (PDT) is a minimally invasive therapeutic strategy for cancer treatment, which can destroy local tumor cells and induce systemic antitumor immune response, whereas, focusing on improving direct cytotoxicity to tumor cells treated by PDT, there is growing interest in developing approaches to further explore the immune stimulatory properties of PDT. In this review we summarize the current knowledge of the innate and adaptive immune responses induced by PDT against tumors, providing evidence showing PDT facilitated-antitumor immunity. Various immunotherapeutic approaches on different cells are reviewed for their effectiveness in improving the treatment efficiency in concert with PDT. Future perspectives are discussed for further enhancing PDT efficiency via intracellular targetable drug delivery as well as optimized experimental model development associated with the study of antitumor immune response. PMID:27672421

Candidate immune biomarkers for radioimmunotherapy.

PubMed

Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

2017-08-01

Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.

PubMed

Watson, Alan M; Klimstra, William B

2017-04-11

The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus.

Trans-Golgi network/early endosome: a central sorting station for cargo proteins in plant immunity.

PubMed

LaMontagne, Erica D; Heese, Antje

2017-12-01

In plants, the trans-Golgi network (TGN) functionally overlaps with the early endosome (EE), serving as a central sorting hub to direct newly synthesized and endocytosed cargo to the cell surface or vacuole. Here, we focus on the emerging role of the TGN/EE in sorting of immune cargo proteins for effective plant immunity against pathogenic bacteria and fungi. Specific vesicle coat and regulatory components at the TGN/EE ensure that immune cargoes are correctly sorted and transported to the location of their cellular functions. Our understanding of the identity of immune cargoes and the underlying cellular mechanisms regulating their sorting are still rudimentary, but this knowledge is essential to understanding the physiological contribution of the TGN/EE to effective immune responses. Copyright © 2017. Published by Elsevier Ltd.

Macrobiota — helminths as active participants and partners of the microbiota in host intestinal homeostasis

PubMed Central

Gause, William C; Maizels, Rick M

2016-01-01

Important insights have recently been gained in our understanding of the intricate relationship in the intestinal milieu between the vertebrate host mucosal immune response, commensal bacteria, and helminths. Helminths are metazoan worms (macrobiota) and trigger immune responses that include potent regulatory components capable of controlling harmful inflammation, protecting barrier function and mitigating tissue damage. They can secrete a variety of products that directly affect immune regulatory function but they also have the capacity to influence the composition of microbiota, which can also then impact immune function. Conversely, changes in microbiota can affect susceptibility to helminth infection, indicating that crosstalk between these two disparate groups of endobiota can play an essential role in host intestinal immune function and homeostasis. PMID:27116368

Beneficial Autoimmunity at Body Surfaces – Immune Surveillance and Rapid Type 2 Immunity Regulate Tissue Homeostasis and Cancer

PubMed Central

Dalessandri, Tim; Strid, Jessica

2014-01-01

Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis. PMID:25101088

A Novel Energy-Efficient Multi-Sensor Fusion Wake-Up Control Strategy Based on a Biomimetic Infectious-Immune Mechanism for Target Tracking.

PubMed

Zhou, Jie; Liang, Yan; Shen, Qiang; Feng, Xiaoxue; Pan, Quan

2018-04-18

A biomimetic distributed infection-immunity model (BDIIM), inspired by the immune mechanism of an infected organism, is proposed in order to achieve a high-efficiency wake-up control strategy based on multi-sensor fusion for target tracking. The resultant BDIIM consists of six sub-processes reflecting the infection-immunity mechanism: occurrence probabilities of direct-infection (DI) and cross-infection (CI), immunity/immune-deficiency of DI and CI, pathogen amount of DI and CI, immune cell production, immune memory, and pathogen accumulation under immunity state. Furthermore, a corresponding relationship between the BDIIM and sensor wake-up control is established to form the collaborative wake-up method. Finally, joint surveillance and target tracking are formulated in the simulation, in which we show that the energy cost and position tracking error are reduced to 50.8% and 78.9%, respectively. Effectiveness of the proposed BDIIM algorithm is shown, and this model is expected to have a significant role in guiding the performance improvement of multi-sensor networks.

Using Video Modeling with Voiceover Instruction Plus Feedback to Train Staff to Implement Direct Teaching Procedures.

PubMed

Giannakakos, Antonia R; Vladescu, Jason C; Kisamore, April N; Reeve, Sharon A

2016-06-01

Direct teaching procedures are often an important part of early intensive behavioral intervention for consumers with autism spectrum disorder. In the present study, a video model with voiceover (VMVO) instruction plus feedback was evaluated to train three staff trainees to implement a most-to-least direct (MTL) teaching procedure. Probes for generalization were conducted with untrained direct teaching procedures (i.e., least-to-most, prompt delay) and with an actual consumer. The results indicated that VMVO plus feedback was effective in training the staff trainees to implement the MTL procedure. Although additional feedback was required for the staff trainees to show mastery of the untrained direct teaching procedures (i.e., least-to-most and prompt delay) and with an actual consumer, moderate to high levels of generalization were observed.

Neuron-directed autoimmunity in the central nervous system: entities, mechanisms, diagnostic clues, and therapeutic options.

PubMed

Melzer, Nico; Meuth, Sven G; Wiendl, Heinz

2012-06-01

The human central nervous system (CNS) can mistakenly be the target of adaptive cellular and humoral immune responses causing both functional and structural impairment. We here provide an overview of neuron-directed autoimmunity as a novel class of inflammatory CNS disorders, their differential diagnoses, clinical hallmarks, imaging features, characteristic laboratory, electrophysiological, cerebrospinal fluid and neuropathological findings, cellular and molecular disease mechanisms, as well as therapeutic options. A growing number of immune-mediated CNS disorders of both autoimmune and paraneoplastic origin have emerged, in which neurons seem to be the target of the immune response. Antibodies binding to a variety of synaptic and extrasynaptic antigens located on the neuronal surface membrane can define distinct entities. Clinically, these disorders are characterized by subacute CNS-related [and sometimes peripheral nervous system (PNS)-related] symptoms involving a variety of cortical and subcortical gray matter areas, which often reflect the expression pattern and function of the respective target antigen. Antibodies seem to be pathogenic and cause (reversible) disturbance of synaptic transmission and neuronal excitability by selective functional inhibition or crosslinking and internalization of their antigen in the absence of overt cytotoxicity, at least at early disease stages. Whether at later disease stages antibody-mediated cytotoxicity, cytotoxic CD8+ T cells, or other detrimental immune mechanisms contribute to neuronal impairment is unclear at present. Adaptive humoral autoimmunity directed to neuronal cell-surface antigens offers first and unique insights and provokes further investigation into the systemic, cellular, and molecular consequences of immune-mediated disruption of distinct neuronal signaling pathways within the living human CNS.

Medical Versus Nonmedical Immunization Exemptions for Child Care and School Attendance.

PubMed

2016-09-01

Routine childhood immunizations against infectious diseases are an integral part of our public health infrastructure. They provide direct protection to the immunized individual and indirect protection to children and adults unable to be immunized via the effect of community immunity. All 50 states, the District of Columbia, and Puerto Rico have regulations requiring proof of immunization for child care and school attendance as a public health strategy to protect children in these settings and to secondarily serve as a mechanism to promote timely immunization of children by their caregivers. Although all states and the District of Columbia have mechanisms to exempt school attendees from specific immunization requirements for medical reasons, the majority also have a heterogeneous collection of regulations and laws that allow nonmedical exemptions from childhood immunizations otherwise required for child care and school attendance. The American Academy of Pediatrics (AAP) supports regulations and laws requiring certification of immunization to attend child care and school as a sound means of providing a safe environment for attendees and employees of these settings. The AAP also supports medically indicated exemptions to specific immunizations as determined for each individual child. The AAP views nonmedical exemptions to school-required immunizations as inappropriate for individual, public health, and ethical reasons and advocates for their elimination. Copyright © 2016 by the American Academy of Pediatrics.

Absence of regulation of human polymorphonuclear oxidative burst by interleukin-10, interleukin-4, interleukin-13 and transforming growth factor-beta in whole blood.

PubMed

Réglier-Poupet, H; Hakim, J; Gougerot-Pocidalo, M A; Elbim, C

1998-12-01

Cytokines such as IL-10, IL-4, IL-13 and TGF-beta play a major role in the regulation of immune responses and are considered as anti-inflammatory agents mainly due to their actions on monocytes. These cytokines are also known to participate in the regulation of PMN activities. However, few and contradictory results have been reported on their direct and priming effects on the PMN oxidative burst, which is essential for killing bacteria. We used a flow cytometry method to study the effects of these cytokines on the PMN oxidative burst; we also used whole blood to avoid PMN activation related to isolation procedures and in order to simulate the in vivo situation more closely. None of the cytokines tested had direct or priming effects on PMN H2O2 production. We also show for the first time that these cytokines do not modulate TNF priming of the PMN oxidative burst in response to N-formyl peptides (fMLP). These results show that the anti-bacterial activity of PMN, in terms of the PMN respiratory burst, is not down regulated by these anti-inflammatory cytokines in whole blood.

Distinct regions of the Pseudomonas syringae coiled-coil effector AvrRps4 are required for activation of immunity

PubMed Central

Sohn, Kee Hoon; Hughes, Richard K.; Piquerez, Sophie J.; Jones, Jonathan D. G.; Banfield, Mark J.

2012-01-01

Gram-negative phytopathogenic bacteria translocate effector proteins into plant cells to subvert host defenses. These effectors can be recognized by plant nucleotide-binding–leucine-rich repeat immune receptors, triggering defense responses that restrict pathogen growth. AvrRps4, an effector protein from Pseudomonas syringae pv. pisi, triggers RPS4-dependent immunity in resistant accessions of Arabidopsis. To better understand the molecular basis of AvrRps4-triggered immunity, we determined the crystal structure of processed AvrRps4 (AvrRps4C, residues 134–221), revealing that it forms an antiparallel α-helical coiled coil. Structure-informed mutagenesis reveals an electronegative surface patch in AvrRps4C required for recognition by RPS4; mutations in this region can also uncouple triggering of the hypersensitive response from disease resistance. This uncoupling may result from a lower level of defense activation, sufficient for avirulence but not for triggering a hypersensitive response. Natural variation in AvrRps4 reveals distinct recognition specificities that involve a surface-exposed residue. Recently, a direct interaction between AvrRps4 and Enhanced Disease Susceptibility 1 has been implicated in activation of immunity. However, we were unable to detect direct interaction between AvrRps4 and Enhanced Disease Susceptibility 1 after coexpression in Nicotiana benthamiana or in yeast cells. How intracellular plant immune receptors activate defense upon effector perception remains an unsolved problem. The structure of AvrRps4C, and identification of functionally important residues for its activation of plant immunity, advances our understanding of these processes in a well-defined model pathosystem. PMID:22988101

Reproductive immunology: current status and future directions (part I).

PubMed

Peeva, Elena

2010-12-01

Extensive research work over the past couple of decades has indicated a series of intricate relations between immune and reproductive systems. A range of reproductive immunology topics including the roles of adoptive and innate immunity in infertility and pregnancy, the immune system's role in induction of labor and preterm delivery, and immuno-modulatory effects of the female sex hormones will be discussed in this and the next issue of the Journal. The implications of this research on the development of novel therapeutic approaches are also addressed.

Impact of the CDC's Section 317 Immunization Grants Program funding on childhood vaccination coverage.

PubMed

Rein, David B; Honeycutt, Amanda A; Rojas-Smith, Lucia; Hersey, James C

2006-09-01

The Centers for Disease Control and Prevention's Section 317 Grants Program is the main source of funding for state and jurisdictional immunization programs, yet no study has evaluated its direct impact on vaccination coverage rates. Therefore, we used a fixed-effects model and data collected from 56 US jurisdictions to estimate the impact of Section 317 financial assistance immunization grants on childhood vaccination coverage rates from 1997 to 2003. Our results showed that increases in Section 317 funding were significantly and meaningfully associated with higher rates of vaccination coverage; a 10 dollars increase in per capita funding corresponded with a 1.6-percentage-point increase in vaccination coverage. Policymakers charged with funding public health programs should consider this study's findings, which indicate that money allocated to vaccine activities translates directly into higher vaccine coverage rates.

Lipopolysaccharide immune stimulation but not β-mannanase supplementation affects maintenance energy requirements in young weaned pigs.

PubMed

Huntley, Nichole F; Nyachoti, C Martin; Patience, John F

2018-01-01

Pathogen or diet-induced immune activation can partition energy and nutrients away from growth, but clear relationships between immune responses and the direction and magnitude of energy partitioning responses have yet to be elucidated. The objectives were to determine how β-mannanase supplementation and lipopolysaccharide (LPS) immune stimulation affect maintenance energy requirements (MEm) and to characterize immune parameters, digestibility, growth performance, and energy balance. In a randomized complete block design, 30 young weaned pigs were assigned to either the control treatment (CON; basal corn, soybean meal and soybean hulls diet), the enzyme treatment (ENZ; basal diet + 0.056% β-mannanase), or the immune system stimulation treatment (ISS; basal diet + 0.056% β-mannanase, challenged with repeated increasing doses of Escherichia coli LPS). The experiment consisted of a 10-d adaptation period, 5-d digestibility and nitrogen balance measurement, 22 h of heat production (HP) measurements, and 12 h of fasting HP measurements in indirect calorimetry chambers. The immune challenge consisted of 4 injections of either LPS (ISS) or sterile saline (CON and ENZ), one every 48 h beginning on d 10. Blood was collected pre- and post-challenge for complete blood counts with differential, haptoglobin and mannan binding lectin, 12 cytokines, and glucose and insulin concentrations. Beta-mannanase supplementation did not affect immune status, nutrient digestibility, growth performance, energy balance, or ME m . The ISS treatment induced fever, elevated proinflammatory cytokines and decreased leukocyte concentrations ( P  < 0.05). The ISS treatment did not impact nitrogen balance or nutrient digestibility ( P  > 0.10), but increased total HP (21%) and ME m (23%), resulting in decreased lipid deposition (-30%) and average daily gain (-18%) ( P  < 0.05). This experiment provides novel data on β-mannanase supplementation effects on immune parameters and energy balance in pigs and is the first to directly relate decreased ADG to increased ME m independent of changes in feed intake in immune challenged pigs. Immune stimulation increased energy partitioning to the immune system by 23% which limited lipid deposition and weight gain. Understanding energy and nutrient partitioning in immune-stressed pigs may provide insight into more effective feeding and management strategies.

An Education in Contrast: State-by-State Assessment of School Immunization Records Requirements

PubMed Central

Jessop, Amy B.; Field, Robert I.

2014-01-01

Objectives. We reviewed the complexities of school-related immunization policies, their relation to immunization information systems (IIS) and immunization registries, and the historical context to better understand this convoluted policy system. Methods. We used legal databases (Lexis-Nexis and Westlaw) to identify school immunization records policies for 50 states, 5 cities, and the District of Columbia (Centers for Disease Control and Prevention “grantees”). The original search took place from May to September 2010 (cross-referenced in July 2013 with the list on http://www.immunize.org/laws). We describe the requirements, agreement with IIS policies, and penalties for policy violations. Results. We found a complex web of public health, medical, and education-directed policies, which complicates immunization data sharing. Most (79%) require records of immunizations for children to attend school or for a child-care institution licensure, but only a few (11%) require coordination between IIS and schools or child-care facilities. Conclusions. To realize the full benefit of IIS investment, including improved immunization and school health program efficiencies, IIS and school immunization records policies must be better coordinated. States with well-integrated policies may serve as models for effective harmonization. PMID:25122033

Receptor signaling clusters in the immune synapse(in eng)

DOE PAGES

Dustin, Michael L.; Groves, Jay T.

2012-02-23

Signaling processes between various immune cells involve large-scale spatial reorganization of receptors and signaling molecules within the cell-cell junction. These structures, now collectively referred to as immune synapses, interleave physical and mechanical processes with the cascades of chemical reactions that constitute signal transduction systems. Molecular level clustering, spatial exclusion, and long-range directed transport are all emerging as key regulatory mechanisms. The study of these processes is drawing researchers from physical sciences to join the effort and represents a rapidly growing branch of biophysical chemistry. Furthermore, recent advances in physical and quantitative analyses of signaling within the immune synapses are reviewedmore » here.« less

Cytokines and their STATs in cutaneous and visceral leishmaniasis.

PubMed

Cummings, Hannah E; Tuladhar, Rashmi; Satoskar, Abhay R

2010-01-01

Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis.

Innate immunity in rice

PubMed Central

Chen, Xuewei; Ronald, Pamela C.

2011-01-01

Advances in studies of rice innate immunity have led to the identification and characterization of host sensors encoding receptor kinases that perceive conserved microbial signatures. The non-RD domain, a newly recognized hallmark of these receptor kinases is highly expanded in rice (Oryza sativa) compared with Arabidopsis (Arabidopsis thaliana). Researchers have also identified a diverse array of microbial effectors from bacterial and fungal pathogens that triggers immune responses upon perception. These include both, effectors that indirectly target host Nucleotide binding site/Leucine rice repeat (NBS-LRR) proteins and transcription activator-like (TAL) effectors that directly bind promoters of host genes. Here we review the recognition and signaling events that govern rice innate immunity. PMID:21602092

Receptor signaling clusters in the immune synapse (in eng)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dustin, Michael L.; Groves, Jay T.

2012-02-23

Signaling processes between various immune cells involve large-scale spatial reorganization of receptors and signaling molecules within the cell-cell junction. These structures, now collectively referred to as immune synapses, interleave physical and mechanical processes with the cascades of chemical reactions that constitute signal transduction systems. Molecular level clustering, spatial exclusion, and long-range directed transport are all emerging as key regulatory mechanisms. The study of these processes is drawing researchers from physical sciences to join the effort and represents a rapidly growing branch of biophysical chemistry. Furthermore, recent advances in physical and quantitative analyses of signaling within the immune synapses are reviewedmore » here.« less

Exploring a regulatory role for mast cells: 'MCregs'?

PubMed

Frossi, Barbara; Gri, Giorgia; Tripodo, Claudio; Pucillo, Carlo

2010-03-01

Regulatory cells can mould the fate of the immune response by direct suppression of specific subsets of effector cells, or by redirecting effectors against invading pathogens and infected or neoplastic cells. These functions have been classically, although not exclusively, ascribed to different subsets of T cells. Recently, mast cells have been shown to regulate physiological and pathological immune responses, and thus to act at the interface between innate and adaptive immunity assuming different functions and behaviors at discrete stages of the immune response. Here, we focus on these poorly defined, and sometimes apparently conflicting, functions of mast cells. Copyright 2010 Elsevier Ltd. All rights reserved.

Nanomaterials in the Context of Type 2 Immune Responses—Fears and Potentials

PubMed Central

Himly, Martin; Mills-Goodlet, Robert; Geppert, Mark; Duschl, Albert

2017-01-01

The type 2 immune response is an adaptive immune program involved in defense against parasites, detoxification, and wound healing, but is predominantly known for its pathophysiological effects, manifesting as allergic disease. Engineered nanoparticles (NPs) are non-self entities that, to our knowledge, do not stimulate detrimental type 2 responses directly, but have the potential to modulate ongoing reactions in various ways, including the delivery of substances aiming at providing a therapeutic benefit. We review, here, the state of knowledge concerning the interaction of NPs with type 2 immune responses and highlight their potential as a multifunctional platform for therapeutic intervention. PMID:28487697

Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.

PubMed

Einstein, Ofira; Fainstein, Nina; Touloumi, Olga; Lagoudaki, Roza; Hanya, Ester; Grigoriadis, Nikolaos; Katz, Abram; Ben-Hur, Tamir

2018-01-01

Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro. LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs. sedentary recipient mice. ET inhibits immune system responses to an auto-antigen to attenuate EAE, rather than generally suppressing the immune system, but does not induce a direct neuro-protective effect against EAE. Copyright © 2017 Elsevier Inc. All rights reserved.

Observations Illustrating the Use of Health Informatics to Link Public Health Immunization Registries and Pharmacies to Increase Adult Immunization Rates and Improve Population Health Outcomes.

PubMed

Popovich, Michael; Altstadter, Brandy; Popovich, Lara Hargraves

2016-01-01

The Health Information Technology for Economic and Clinical Health (HITECH) Act encourages health information exchange between clinical care and public health through Meaningful Use measures. Meaningful Use specifically identifies objectives to support a number of public health programs including immunizations, cancer registries, syndromic surveillance, and disease case reports. The objective is to improve public and population health. Stage 2 of Meaningful Use focused on compliance to sending of information to public health. The next phase focuses on bi-directional information exchange to support immunization intelligence and to empower providers, pharmacists, and the consumer. The HITECH Act Stage 2 initiative provided incentive and motivation for healthcare providers to encourage their Electronic Medical Record (EMR) vendors to implement data exchanges with public health, with the expected result being timely awareness of health risks. The empowerment nugget in the HITECH Act is not in the compliance reporting to public health. The nugget is the ability for a provider to receive relevant information on the patient or consumer currently in front of them or to those they will connect to through their outreach efforts. The ability for public health to retain current immunization records of individuals from a variety of providers supports their program goals to increase immunization rates and mitigate the risk of vaccine-preventable disease (VPD). The ability for providers to receive at the point of service more complete immunization histories integrated with decision support enhances their delivery of care, thereby reducing the risk of VPD to their patients. Indirectly payers benefit through healthcare cost savings and when the focus is expanded from a health model to a business model, there are significant return on investment (ROI) opportunities that exponentially increase the value of a bi-directional immunization data exchange. This paper will provide descriptions of case examples to demonstrate the value of electronic data exchanges when pharmacy immunization providers and public health work together.

Increased rates of cesarean sections and large families: a potentially dangerous combination.

PubMed

Saleh, Ahmed M; Dudenhausen, Joachim W; Ahmed, Badreldeen

2017-07-26

Rates of cesarean sections have been on the rise over the past three decades all over the world, despite the ideal rate of 10-15% that had been set by the World Health Organization (WHO) in 1985, in Fortaleza, Brazil. This epidemic increase in the rate of cesarean delivery is due to many factors which include, cesarean delivery on request, advanced maternal age at first pregnancy, decrease in number of patients who are willing to try vaginal birth after cesarean delivery, virtual disappearance of vaginal breech delivery, perceived increase in the weight of the fetus and increase in the number of women with chronic medical conditions such as Diabetes Mellitus and congenital heart disease in the reproductive age. There is no doubt that cesarean delivery is a safe procedure and it is getting safer and safer for many reasons. However, like all other surgical procedures it is not without risks both to the mother and the new born. There is a substantial increase in the incidence of morbidly adherent placenta and the risk of scar pregnancy. In the Middle East and many African and Asian countries women tend to have large families. The number of previous cesarean section deliveries is directly proportional to the risk of developing morbidly adherent placenta. Morbidly adherent placenta is the most common cause of emergency postpartum hysterectomy, which is often associated with multiple surgical complications, severe maternal morbidity and mortality. The increased rates of cesarean sections lead to increased rates of scar pregnancies, which can have lethal consequences. Cesarean delivery has a negative impact on the infant immune system. This effect on the infant led to the introduction of a new concept called "Vaginal seeding". This refers to the practice of transferring some maternal vaginal fluid to the infant born via cesarean section in an effort to enhance its immune system.

[Prevention of accidental needle sticks before the Directive 2010/32/EU in a sample of Italian hospitals].

PubMed

Di Bari, Virginia; De Carli, Gabriella; Puro, Vincenzo

2015-05-04

Needlesticks and cuts are the most common occupational injuries in healthcare workers (HCWs). Directive 2010/32/EU defines principles and preventive interventions. To assess, in hospitals participating in the Italian Study on Occupational Risk of HIV (SIROH) project, which are very active in prevention, the degree of application of the measures provided for by the Directive, prior to its incorporation into Italian law. An open questionnaire covering the 9 focal points of the Directive, as a guide for a presentation at the SIROH meeting in 2013. Of 100 SIROH hospitals, 97% and 96% respectively provide specific information and education initiatives (54% and 73% of which expressly for new employees). All centres reinforce the ban on recapping, and 30 monitor its application by inspecting sharps containers; all hospitals place containers on mobile trolleys and 78 provide operating procedures for their replacement; all introduced at least one needlestick-prevention device (NPD; 4 on average, range 1-11), most frequently intravenous catheters (91%) and winged needles (87%), but 39% only in selected units; 14 centres implemented initiatives to eliminate unnecessary needles. Regarding hepatitis B, all centres screen and vaccinate HCWs but only 78% monitor their response: 89% of HCWs were immunized. Post-exposure management protocols, although based on the same rationale, differ significantly causing considerable differences in  costs. Most of the preventive interventions covered by the Directive were implemented in SIROH hospitals. It is necessary to invest in NPD availability and dissemination, elimination of unnecessary needles, and streamline post-exposure protocols. The situation in the remaining Italian facilities should be investigated.

Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors.

PubMed

Bliska, James B; Wang, Xiaoying; Viboud, Gloria I; Brodsky, Igor E

2013-10-01

The innate immune system of mammals responds to microbial infection through detection of conserved molecular determinants called 'pathogen-associated molecular patterns' (PAMPs). Pathogens use virulence factors to counteract PAMP-directed responses. The innate immune system can in turn recognize signals generated by virulence factors, allowing for a heightened response to dangerous pathogens. Many Gram-negative bacterial pathogens encode type III secretion systems (T3SSs) that translocate effector proteins, subvert PAMP-directed responses and are critical for infection. A plasmid-encoded T3SS in the human-pathogenic Yersinia species translocates seven effectors into infected host cells. Delivery of effectors by the T3SS requires plasma membrane insertion of two translocators, which are thought to form a channel called a translocon. Studies of the Yersinia T3SS have provided key advances in our understanding of how innate immune responses are generated by perturbations in plasma membrane and other signals that result from translocon insertion. Additionally, studies in this system revealed that effectors function to inhibit innateimmune responses resulting from insertion of translocons into plasma membrane. Here, we review these advances with the goal of providing insight into how a T3SS can activate and inhibit innate immune responses, allowing a virulent pathogen to bypass host defences. © 2013 John Wiley & Sons Ltd.

Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity.

PubMed

Hamilton, Gerhard; Rath, Barbara

2017-04-01

Immune checkpoint inhibition holds great promise for selected tumors. The human monoclonal antibody (mAB) avelumab is directed to programmed death ligand-1 (PD-L1) and is supposed to inhibit the immunosuppressive PD-L1/PD-1 interaction and, furthermore, effect antibody-dependent cytotoxicity (ADCC) lysis of tumor cells. Areas covered: This article presents an overview of the current means to activate the antitumor immune defense by targeting PD-1 or PD-L1 with mABs and their possible role in ADCC-mediated tumor cell elimination. Expert opinion: Avelumab contains a Fc region which can bind cognate receptors on immune effector cells and induce ADCC-mediated tumor cell lysis, in contrast to other mABs directed to PD-1/PD-L1 which lack the ability to trigger ADCC due to belonging to the IgG4 subclass or possessing a mutated Fc region. Preclinical and clinical data indicate that avelumab can be safely administered to cancer patients with a toxicity profile comparable to other mABs and without lysis of PD-L1-positive activated immune cells. This antibody yielded durable responses in a phase II trial in advanced Merkel cell carcinoma patients. Tumor cell lysis by avelumab prevents cells from resorting to alternative checkpoints as shown by targeting PD-1 and the upregulation of TIM-3.

Innate lymphoid cells in tissue homeostasis and diseases.

PubMed

Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

2017-08-18

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

Immunotherapy and gene therapy as novel treatments for cancer

PubMed Central

Rangel-Sosa, Martha Montserrat; Aguilar-Córdova, Estuardo

2017-01-01

Abstract The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is an anti-CTLA-4 antibody which demonstrated good results when administered to patients with melanoma. Gene therapy has also shown promising results in clinical trials. Particularly, Herpes simplex virus (HSV)-mediated delivery of the HSV thymidine kinase (TK) gene to tumor cells in combination with ganciclovir (GCV) may provide an effective suicide gene therapy for destruction of glioblastomas, prostate tumors and other neoplasias by recruiting tumor-infiltrating lymphocytes into the tumor. The development of new treatment strategies or combination of available innovative therapies to improve cell cytotoxic T lymphocytes trafficking into the tumor mass and the production of inhibitory molecules blocking tumor tissue immune-tolerance are crucial to improve the efficacy of cancer therapy. PMID:29213157

Inflammatory Monocytes Orchestrate Innate Antifungal Immunity in the Lung

PubMed Central

Dutta, Orchi; Kasahara, Shinji; Donnelly, Robert; Du, Peicheng; Rosenfeld, Jeffrey; Leiner, Ingrid; Chen, Chiann-Chyi; Ron, Yacov; Hohl, Tobias M.; Rivera, Amariliz

2014-01-01

Aspergillus fumigatus is an environmental fungus that causes invasive aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor-2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2+Mo) and their derivatives initiate adaptive pulmonary immune responses, their role in coordinating innate immune responses in the lung remain poorly defined. Using conditional and antibody-mediated cell ablation strategies, we found that CCR2+Mo and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE) conidia that report fungal cell association and viability in vivo, we identify two mechanisms by which CCR2+Mo and Mo-DCs exert innate antifungal activity. First, CCR2+Mo and Mo-DCs condition the lung inflammatory milieu to augment neutrophil conidiacidal activity. Second, conidial uptake by CCR2+Mo temporally coincided with their differentiation into Mo-DCs, a process that resulted in direct conidial killing. Our findings illustrate both indirect and direct functions for CCR2+Mo and their derivatives in innate antifungal immunity in the lung. PMID:24586155

Immune response in the lungs following oral immunization with bacterial lysates of respiratory pathogens.

PubMed Central

Ruedl, C; Frühwirth, M; Wick, G; Wolf, H

1994-01-01

We have investigated the local immune response of the BALB/c mouse respiratory tract after oral immunization with a bacterial lysate of seven common respiratory pathogens. After two immunization on five consecutive days, we examined the immunoglobulin (immunoglobulin G [IgG], IgM, and IgA) secretion rates of cells isolated from the lungs and compared them with those of spleen cells of orally immunized and nonimmunized animals by using a new test system based on time-resolved fluorescence. The procedure followed the principle of the classical ELISPOT test with nitrocellulose-bottomed microtiter plates, but europium (Eu3+)-linked streptavidin rather than enzyme-conjugated streptavidin was used, with the advantage of quantifying secreted immunoglobulins instead of detecting single antibody-secreting cells. Lymphocytes isolated from the lungs of treated animals revealed significant increases in total and antigen-specific IgA synthesis compared with the rates of the controls, whereas IgG and IgM production rates showed no remarkable differences. In addition, the sera of treated mice revealed higher antigen-specific IgA titers but not increased IgM and IgG levels. We conclude that priming the gut-associated lymphoid tissue with bacterial antigens of pneumotropic microorganisms can elicit an enhanced IgA response in a distant mucosal effector site, such as the respiratory tract, according to the concept of a common mucosa-associated immune system. PMID:7496936

Immune response in the lungs following oral immunization with bacterial lysates of respiratory pathogens.

PubMed

Ruedl, C; Frühwirth, M; Wick, G; Wolf, H

1994-03-01

We have investigated the local immune response of the BALB/c mouse respiratory tract after oral immunization with a bacterial lysate of seven common respiratory pathogens. After two immunization on five consecutive days, we examined the immunoglobulin (immunoglobulin G [IgG], IgM, and IgA) secretion rates of cells isolated from the lungs and compared them with those of spleen cells of orally immunized and nonimmunized animals by using a new test system based on time-resolved fluorescence. The procedure followed the principle of the classical ELISPOT test with nitrocellulose-bottomed microtiter plates, but europium (Eu3+)-linked streptavidin rather than enzyme-conjugated streptavidin was used, with the advantage of quantifying secreted immunoglobulins instead of detecting single antibody-secreting cells. Lymphocytes isolated from the lungs of treated animals revealed significant increases in total and antigen-specific IgA synthesis compared with the rates of the controls, whereas IgG and IgM production rates showed no remarkable differences. In addition, the sera of treated mice revealed higher antigen-specific IgA titers but not increased IgM and IgG levels. We conclude that priming the gut-associated lymphoid tissue with bacterial antigens of pneumotropic microorganisms can elicit an enhanced IgA response in a distant mucosal effector site, such as the respiratory tract, according to the concept of a common mucosa-associated immune system.

TLR9-based immunotherapy for the treatment of allergic diseases.

PubMed

Farrokhi, Shokrollah; Abbasirad, Narjes; Movahed, Ali; Khazaei, Hossein Ali; Pishjoo, Masoud; Rezaei, Nima

2017-03-01

Toll-like receptors (TLRs), a family of pattern recognition receptors expressed on many cell types of innate immunity, recognize the pathogen-associated molecular patterns of microbes. The hygiene hypothesis suggests that a reduced microbial exposure in early childhood increases the susceptibility to allergic diseases due to deviation in development of the immune system. TLRs are key roles in the right and healthy direction of adaptive immunity with the induction of T-helper 2 toward Th1 immune responses and regulatory T cells. TLR ligand CpG-ODN-based immunomodulation is independent of allergen and it mainly affects innate immune system. While, CpG-oligodeoxynucleotide-based vaccination is allergen specific and induces adaptive immune system. The use of agonists of TLR9 in two distinct strategies of immunotherapy, immunomodulation and vaccination, could be presented as the curative method for the treatment of allergic diseases.

Behavioral Immunity in Insects

PubMed Central

de Roode, Jacobus C.; Lefèvre, Thierry

2012-01-01

Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied. PMID:26466629

Donor lymphocyte infusions to leukemic bone lesions are therapeutically effective in a Ph+ ALL patient with post-HSCT relapse.

PubMed

Lange, Andrzej; Dlubek, Dorota; Zdziarski, Robert; Chodorowska, Anna; Mordak-Domagala, Monika; Klimczak, Aleksandra; Lange, Janusz; Jaskula, Emilia

2014-10-01

A Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) case was maintained in remission with the use of chemo-immunotherapy. The latter involved sibling bone marrow transplant (BMT) (three procedures) followed by intravenous (IV) donor lymphocyte infusion (DLI). The third relapse responded to routine chemotherapy and again DLI was employed. During hematological and molecular remission verified at the level of iliac crest aspiration, extra-medullary relapse in the bones was apparent. A novel procedure of donor lymphocyte injection to the bone leukemic lesions was developed and employed. A dose of 10(6) donor lymphocytes/kg body weight (BW) of the recipient were each time injected to the plane of the right and left tibia, the head of the humerus, and the calcaneus, which resulted in healing of the destructive process. In consequence of this novel approach, in addition to the healing of bone lesions, an accumulation of cytotoxic activated T-cells in the marrow was documented, which was mirrored by an increase in the number of transcripts for interferon (IFN)-γ, interleukin (IL)-17, as well as RORγt. The local administration of DLI directly to the leukemic lesions requires a lower dose that diminishes the toxicity due to the general immune system activation.

HIV-DNA priming alters T-cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable1

PubMed Central

De Rosa, Stephen C.; Thomas, Evan P.; Bui, John; Huang, Yunda; deCamp, Allan; Morgan, Cecilia; Kalams, Spyros; Tomaras, Georgia D.; Akondy, Rama; Ahmed, Rafi; Lau, Chuen-Yen; Graham, Barney S.; Nabel, Gary J.; McElrath, M. Juliana

2011-01-01

Many candidate HIV vaccines are designed to primarily elicit T-cell responses. Although repeated immunization with the same vaccine boosts antibody responses, the benefit for T-cell responses is ill-defined. We compared two immunization regimens that include the same recombinant adenoviral serotype 5 (rAd5) boost. Repeated homologous rAd5 immunization fails to increase T-cell responses, but increases gp140 antibody responses ten-fold. DNA prime, as compared with rAd5 prime, directs long-term memory CD8+ T cells toward a terminally differentiated effector memory phenotype with cytotoxic potential. Based on the kinetics of activated cells measured directly ex vivo, the DNA vaccination primes for both CD4+ and CD8+ T cells, despite the lack of detection of the latter until after the boost. These results suggest that heterologous prime-boost combinations have distinct immunological advantages over homologous prime-boosts, and suggest that the effect of DNA on subsequent boosting may not be easily detectable directly after the DNA vaccination. PMID:21844392

ENGINEERING NANO- AND MICRO-PARTICLES TO TUNE IMMUNITY

PubMed Central

Moon, James J.; Irvine, Darrell J.; Huang, Bonnie

2013-01-01

The immune system can be a cure or cause of disease, fulfilling a protective role in attacking cancer or pathogenic microbes but also causing tissue destruction in autoimmune disorders. Thus, therapies aimed to amplify or suppress immune reactions are of great interest. However, the complex regulation of the immune system, coupled with the potential systemic side effects associated with traditional systemic drug therapies, has presented a major hurdle for the development of successful immunotherapies,. Recent progress in the design of synthetic micro- and nano-particles that can target drugs, deliver imaging agents, or stimulate immune cells directly through their physical and chemical properties is leading to new approaches to deliver vaccines, promote immune responses against tumors, and suppress autoimmunity. In addition, novel strategies, such as the use of particle-laden immune cells as living targeting agents for drugs, are providing exciting new approaches for immunotherapy. This progress report describes recent advances in the design of micro- and nano-particles in immunotherapies and diagnostics. PMID:22641380

Complex Immune Correlates of Protection in HIV-1 Vaccine Efficacy Trials

PubMed Central

Tomaras, Georgia D.; Plotkin, Stanley A.

2016-01-01

Summary Development of an efficacious HIV-1 vaccine is a major priority for improving human health worldwide. Vaccine mediated protection against human pathogens can be achieved through elicitation of protective innate, humoral, and cellular responses. Identification of specific immune responses responsible for pathogen protection enables vaccine development and provides insights into host defenses against pathogens and the immunological mechanisms that most effectively fight infection. Defining immunological correlates of transmission risk in preclinical and clinical HIV-1 vaccine trials has moved the HIV-1 vaccine development field forward and directed new candidate vaccine development. Immune correlate studies are providing novel hypotheses about immunological mechanisms that may be responsible for preventing HIV-1 acquisition. Recent results from HIV-1 immune correlates work has demonstrated that there are multiple types of immune responses that together, comprise an immune correlate—thus implicating polyfunctional immune control of HIV-1 transmission. An in depth understanding of these complex immunological mechanisms of protection against HIV-1 will accelerate the development of an efficacious HIV-1 vaccine. PMID:28133811

Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine

PubMed Central

Woodruff, Matthew C.; Heesters, Balthasar A.; Herndon, Caroline N.; Groom, Joanna R.; Thomas, Paul G.; Luster, Andrew D.; Turley, Shannon J.

2014-01-01

Dendritic cells (DCs) are well established as potent antigen-presenting cells critical to adaptive immunity. In vaccination approaches, appropriately stimulating lymph node–resident DCs (LNDCs) is highly relevant to effective immunization. Although LNDCs have been implicated in immune response, their ability to directly drive effective immunity to lymph-borne antigen remains unclear. Using an inactive influenza vaccine model and whole node imaging approaches, we observed surprising responsiveness of LNDC populations to vaccine arrival resulting in a transnodal repositioning into specific antigen collection sites within minutes after immunization. Once there, LNDCs acquired viral antigen and initiated activation of viral specific CD4+ T cells, resulting in germinal center formation and B cell memory in the absence of skin migratory DCs. Together, these results demonstrate an unexpected stimulatory role for LNDCs where they are capable of rapidly locating viral antigen, driving early activation of T cell populations, and independently establishing functional immune response. PMID:25049334

Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis

PubMed Central

Gibson, Josie F.; Johnston, Simon A.

2015-01-01

The vast majority of infection with cryptococcal species occurs with Cryptococcus neoformans in the severely immunocompromised. A significant exception to this is the infections of those with apparently normal immune systems by Cryptococcus gattii. Susceptibility to cryptococcosis can be broadly categorised as a defect in adaptive immune responses, especially in T cell immunity. However, innate immune cells such as macrophages play a key role and are likely the primary effector cell in the killing and ultimate clearance of cryptococcal infection. In this review we discuss the current state of our understanding of how the immune system responds to cryptococcal infection in health and disease, with reference to the work communicated at the 9th International Conference on Cryptococcus and Cryptococcosis (ICCC9). We have focussed on cell mediated responses, particularly early in infection, but with the aim of presenting a broad overview of our understanding of immunity to cryptococcal infection, highlighting some recent advances and offering some perspectives on future directions. PMID:25498576

Bruton's Tyrosine Kinase: An Emerging Key Player in Innate Immunity.

PubMed

Weber, Alexander N R; Bittner, Zsofia; Liu, Xiao; Dang, Truong-Minh; Radsak, Markus Philipp; Brunner, Cornelia

2017-01-01

Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thorough basic understanding of the human innate immune system but also as a target to therapeutically modulate innate immunity. We here review the latest developments on the role of BTK in mononuclear innate immune cells in mouse versus man, with specific emphasis on the sensing of infectious agents and the induction of inflammation. Therapeutic implications for modulating innate immunity and critical open questions are also discussed.

Pathogen effectors target Arabidopsis EDS1 and alter its interactions with immune regulators.

PubMed

Bhattacharjee, Saikat; Halane, Morgan K; Kim, Sang Hee; Gassmann, Walter

2011-12-09

Plant resistance proteins detect the presence of specific pathogen effectors and initiate effector-triggered immunity. Few immune regulators downstream of resistance proteins have been identified, none of which are known virulence targets of effectors. We show that Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), a positive regulator of basal resistance and of effector-triggered immunity specifically mediated by Toll-interleukin-1 receptor-nucleotide binding-leucine-rich repeat (TIR-NB-LRR) resistance proteins, forms protein complexes with the TIR-NB-LRR disease resistance proteins RPS4 and RPS6 and with the negative immune regulator SRFR1 at a cytoplasmic membrane. Further, the cognate bacterial effectors AvrRps4 and HopA1 disrupt these EDS1 complexes. Tight association of EDS1 with TIR-NB-LRR-mediated immunity may therefore derive mainly from being guarded by TIR-NB-LRR proteins, and activation of this branch of effector-triggered immunity may directly connect to the basal resistance signaling pathway via EDS1.

The effects of early life adversity on the immune system.

PubMed

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.

An automated diagnosis system of liver disease using artificial immune and genetic algorithms.

PubMed

Liang, Chunlin; Peng, Lingxi

2013-04-01

The rise of health care cost is one of the world's most important problems. Disease prediction is also a vibrant research area. Researchers have approached this problem using various techniques such as support vector machine, artificial neural network, etc. This study typically exploits the immune system's characteristics of learning and memory to solve the problem of liver disease diagnosis. The proposed system applies a combination of two methods of artificial immune and genetic algorithm to diagnose the liver disease. The system architecture is based on artificial immune system. The learning procedure of system adopts genetic algorithm to interfere the evolution of antibody population. The experiments use two benchmark datasets in our study, which are acquired from the famous UCI machine learning repository. The obtained diagnosis accuracies are very promising with regard to the other diagnosis system in the literatures. These results suggest that this system may be a useful automatic diagnosis tool for liver disease.

Protective immunity of a modified-live cyprinid herpesvirus 3 vaccine in koi (Cyprinus carpio koi) 13 months after vaccination.

PubMed

O'Connor, Matthew R; Farver, Thomas B; Malm, Kirsten V; Yun, Susan C; Marty, Gary D; Salonius, Kira; Dishon, Arnon; Weber, E P Scott

2014-10-01

To evaluate the long-term protective immunity of a cyprinid herpesvirus 3 (CyHV3) vaccine in naïve koi (Cyprinus carpio koi). 72 koi. Procedures-Vaccinated koi (n = 36) and unvaccinated control koi (36) were challenge exposed to a wild-type CyHV3 strain (KHVp8 F98-50) 13 months after vaccination. The CyHV3 vaccine provided substantial protective immunity against challenge exposure. The proportional mortality rate was less in vaccinated koi (13/36 [36%]) than in unvaccinated koi (36/36 [100%]). For koi that died during the experiment, mean survival time was significantly greater in vaccinated than in unvaccinated fish (17 vs 10 days). The CyHV3 vaccine provided substantial protective immunity against challenge exposure with CyHV3 13 months after vaccination. This provided evidence that koi can be vaccinated annually with the CyHV3 vaccine to significantly reduce mortality and morbidity rates associated with CyHV3 infection.

The effect of combined stimulation of external cold and vibration during immunization on pain and anxiety levels in children.

PubMed

Canbulat Şahiner, Nejla; İnal, Sevil; Sevim Akbay, Ayşe

2015-06-01

Procedures involving needles are the most common and major sources of pain in children. External cold and vibration via Buzzy (MMJ Labs, Atlanta, GA) is a method that combines cooling and vibration. This study investigated the effect of the combined stimulation of skin with external cold and vibration via Buzzy on the pain and anxiety levels in children during immunization. This study was a prospective, randomized controlled trial. Children were randomized into two groups: experimental (external cold and Buzzy) and control (no intervention). The pain and anxiety levels of the children were assessed using the Wong-Baker FACES scale and Children Fear Scale. The experimental group showed significantly lower pain and anxiety levels than the control group during immunization. The combined stimulation of skin with external cold and vibration can be used to reduce pain and anxiety during pediatric immunization. Copyright © 2015 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy.

PubMed

Gaipl, Udo S; Multhoff, Gabriele; Scheithauer, Heike; Lauber, Kirsten; Hehlgans, Stefanie; Frey, Benjamin; Rödel, Franz

2014-01-01

Besides the direct, targeted effects of ionizing irradiation (x-ray) on cancer cells, namely DNA damage and cell death induction, indirect, nontargeted ones exist, which are mediated in large part by the immune system. Immunogenic forms of tumor cell death induced by x-ray, including immune modulating danger signals like the heat shock protein 70, adenosine triphosphate, and high-mobility group box 1 protein are presented. Further, antitumor effects exerted by cells of the innate (natural killer cells) as well as adaptive immune system (T cells activated by dendritic cells) are outlined. Tumor cell death inhibiting molecules such as survivin are introduced as suitable target for molecularly tailored therapies in combination with x-ray. Finally, reasonable combinations of immune therapies with radiotherapy are discussed.

Targeting myeloid-derived suppressor cells for cancer immunotherapy.

PubMed

Liu, Yijun; Wei, Guowei; Cheng, Wesley A; Dong, Zhenyuan; Sun, Han; Lee, Vincent Y; Cha, Soung-Chul; Smith, D Lynne; Kwak, Larry W; Qin, Hong

2018-05-31

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with an immune suppressive phenotype. They represent a critical component of the immune suppressive niche described in cancer, where they support immune escape and tumor progression through direct effects on both the innate and adaptive immune responses, largely by contributing to maintenance of a high oxidative stress environment. The number of MDSCs positively correlates with protumoral activity, and often diminishes the effectiveness of immunotherapies, which is particularly problematic with the emergence of personalized medicine. Approaches targeting MDSCs showed promising results in preclinical studies and are under active investigation in clinical trials in combination with various immune checkpoint inhibitors. In this review, we discuss MDSC targets and therapeutic approaches targeting MDSC that have the aim of enhancing the existing tumor therapies.

Macrobiota - helminths as active participants and partners of the microbiota in host intestinal homeostasis.

PubMed

Gause, William C; Maizels, Rick M

2016-08-01

Important insights have recently been gained in our understanding of the intricate relationship in the intestinal milieu between the vertebrate host mucosal immune response, commensal bacteria, and helminths. Helminths are metazoan worms (macrobiota) and trigger immune responses that include potent regulatory components capable of controlling harmful inflammation, protecting barrier function and mitigating tissue damage. They can secrete a variety of products that directly affect immune regulatory function but they also have the capacity to influence the composition of microbiota, which can also then impact immune function. Conversely, changes in microbiota can affect susceptibility to helminth infection, indicating that crosstalk between these two disparate groups of endobiota can play an essential role in host intestinal immune function and homeostasis. Copyright © 2016. Published by Elsevier Ltd.

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

PubMed

Kim, Ye-Ram; Yang, Chul-Su

2017-09-28

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

Exploiting Uptake of Nanoparticles by Phagocytes for Cancer Treatment.

PubMed

Sheen, Mee Rie; Fiering, Steven

2017-01-01

Many cancers including ovarian, pancreatic, colon, liver, and stomach cancers are largely confined to the peritoneal cavity. Peritoneal tumors are directly accessible by intraperitoneal injections. Previously we demonstrated that intraperitoneal injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes can be used to either directly impact tumors or stimulate antitumor immune responses. Here we outline methods to specifically utilize iron oxide nanoparticles with the ID8-Defb29/Vegf-A murine ovarian cancer model and discuss the tendency of phagocytes to ingest nanoparticles and the potential of phagocytes to carry nanoparticles to tumors resulting in direct killing of tumor cells or stimulate antitumor immune responses in peritoneal cancers. This basic approach can be modified as needed for different types of tumors and nanoparticles.

14 CFR 11.13 - What is a direct final rule?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false What is a direct final rule? 11.13 Section 11.13 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES GENERAL RULEMAKING PROCEDURES Rulemaking Procedures Definition of Terms § 11.13 What is a direct...

How complete are immunization registries? The Philadelphia story.

PubMed

Kolasa, Maureen S; Chilkatowsky, Andrew P; Clarke, Kevin R; Lutz, James P

2006-01-01

To assess accuracy and completeness of Philadelphia, Pa, registry data among children served by providers in areas at risk for underimmunization. Philadelphia's Department of Public Health selected a simple random sample of 45 children age 19-35 months (or all children age 19-35 months if there were <45 children in the practice) from each of 30 private practices receiving government-funded vaccine and located in zip codes where children are at risk for underimmunization. Chart and registry data were compared with determine the proportion of children missing from the registry and assess differences in immunization coverage. Of 620 children reviewed, 567 (92%) were in the registry. Significant differences (P < .05) were observed in immunization coverage for 4 diphtheria-tetanus-acellular pertussis vaccinations, 3 polio vaccinations, 1 measles-mumps-rubella vaccination, and 3 Haemophilus influenzae type b vaccinations between the chart (80% coverage) and registry (62% coverage). Providers submitting electronic medical records or directly transferring electronic data to the registry had significantly more children in the registry and higher registry-reported immunization coverage than those whose data were entered from billing records or log forms. All practice types experienced difficulties in transferring complete data to the registry. Although 92% of study children were in the registry, immunization coverage was significantly lower when registry data were compared with chart data. Because electronic medical records and direct electronic data transfer resulted in more complete registry data, these methods should be encouraged in linking providers with immunization registries.

Targeted Immune Therapy of Ovarian Cancer

PubMed Central

Knutson, Keith L.; Karyampudi, Lavakumar; Lamichhane, Purushottam; Preston, Claudia

2014-01-01

Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies. PMID:25544369

Ultrasound induced cancer immunotherapy.

PubMed

Unga, Johan; Hashida, Mitsuru

2014-06-01

Recently, the use of ultrasound (US) has been shown to have potential in cancer immunotherapy. High intensity focused US destruction of tumors may lead to immunity forming in situ in the body by immune cells being exposed to the tumor debris and immune stimulatory substances that are present in the tumor remains. Another way of achieving anti-cancer immune responses is by using US in combination with microbubbles and nanobubbles to deliver genes and antigens into cells. US leads to bubble destruction and the forces released to direct delivery of the substances into the cytoplasm of the cells thus circumventing the natural barriers. In this way tumor antigens and antigen-encoding genes can be delivered to immune cells and immune response stimulating genes can be delivered to cancer cells thus enhancing immune responses. Combination of bubbles with cell-targeting ligands and US provides an even more sophisticated delivery system whereby the therapy is not only site specific but also cell specific. In this review we describe how US has been used to achieve immunity and discuss the potential and possible obstacles in future development. Copyright © 2014 Elsevier B.V. All rights reserved.

Immune challenges and visual signalling in tree frogs

NASA Astrophysics Data System (ADS)

Desprat, Julia L.; Lengagne, Thierry; Mondy, Nathalie

2017-04-01

In animals, mate-choice is often based on sexual signals that carry information and help the receiver make the best choice to improve the receiver's fitness. Orange visual sexual signals have been hypothesised to carry immune information because they are often due to carotenoid pigments which are also involved in immunity response. Although many studies have focused on the direct relationships between coloration and immunocompetence, few studies have simultaneously studied immunocompetent response and coloration variation after an immune challenge. We tested this hypothesis on starved and ad libitum-fed males of the European tree frog Hyla arborea. Our results show that male coloration is not a reliable indicator of its immune response capacity in this species. However, after an immune challenge induced by a PHA ( Phaseolus vulgaris phytohaemagglutinin) injection, starved males presented a significant coloration loss and this alteration was related to the immune response intensity. Taken together, these results suggest that the brighter (lighter) coloration may be used as a cue by female to exclude males with a recent immune challenge, due to diseases or parasites for example.

A plant effector-triggered immunity signaling sector is inhibited by pattern-triggered immunity.

PubMed

Hatsugai, Noriyuki; Igarashi, Daisuke; Mase, Keisuke; Lu, You; Tsuda, Yayoi; Chakravarthy, Suma; Wei, Hai-Lei; Foley, Joseph W; Collmer, Alan; Glazebrook, Jane; Katagiri, Fumiaki

2017-09-15

Since signaling machineries for two modes of plant-induced immunity, pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), extensively overlap, PTI and ETI signaling likely interact. In an Arabidopsis quadruple mutant, in which four major sectors of the signaling network, jasmonate, ethylene, PAD4, and salicylate, are disabled, the hypersensitive response (HR) typical of ETI is abolished when the Pseudomonas syringae effector AvrRpt2 is bacterially delivered but is intact when AvrRpt2 is directly expressed in planta These observations led us to discovery of a network-buffered signaling mechanism that mediates HR signaling and is strongly inhibited by PTI signaling. We named this mechanism the ETI-Mediating and PTI-Inhibited Sector (EMPIS). The signaling kinetics of EMPIS explain apparently different plant genetic requirements for ETI triggered by different effectors without postulating different signaling machineries. The properties of EMPIS suggest that information about efficacy of the early immune response is fed back to the immune signaling network, modulating its activity and limiting the fitness cost of unnecessary immune responses. © 2017 The Authors.

The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC.

PubMed

Frantz, Stefan; Falcao-Pires, Ines; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Ciccarelli, Michele; Dawson, Dana; de Windt, Leon J; Giacca, Mauro; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Hirsch, Emilio; Leite-Moreira, Adelino; Mayr, Manuel; Thum, Thomas; Tocchetti, Carlo G; van der Velden, Jolanda; Varricchi, Gilda; Heymans, Stephane

2018-03-01

Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. © 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Mindfulness meditation and the immune system: a systematic review of randomized controlled trials

PubMed Central

Black, David S.; Slavich, George M.

2015-01-01

Mindfulness meditation represents a mental training framework for cultivating the state of mindful awareness in daily life. Recently, there has been a surge of interest in how mindfulness meditation improves human health and well-being. Although studies have shown that mindfulness meditation can improve self-reported measures of disease symptomatology, the effect that mindfulness meditation has on biological mechanisms underlying human aging and disease is less clear. To address this issue, we conducted the first comprehensive review of randomized controlled trials examining the effects of mindfulness meditation on immune system parameters, with a specific focus on five outcomes: (1) circulating and stimulated inflammatory proteins, (2) cellular transcription factors and gene expression, (3) immune cell count, (4) immune cell aging, and (5) antibody response. This analysis revealed substantial heterogeneity across studies with respect to patient population, study design, and assay procedures. The findings suggest possible effects of mindfulness meditation on specific markers of inflammation, cell-mediated immunity, and biological aging, but these results are tentative and require further replication. On the basis of this analysis, we describe the limitations of existing work and suggest possible avenues for future research. Mindfulness mediation may be salutogenic for immune system dynamics, but additional work is needed to examine these effects. PMID:26799456

Mindfulness meditation and the immune system: a systematic review of randomized controlled trials.

PubMed

Black, David S; Slavich, George M

2016-06-01

Mindfulness meditation represents a mental training framework for cultivating the state of mindful awareness in daily life. Recently, there has been a surge of interest in how mindfulness meditation improves human health and well-being. Although studies have shown that mindfulness meditation can improve self-reported measures of disease symptomatology, the effect that mindfulness meditation has on biological mechanisms underlying human aging and disease is less clear. To address this issue, we conducted the first comprehensive review of randomized controlled trials examining the effects of mindfulness meditation on immune system parameters, with a specific focus on five outcomes: (1) circulating and stimulated inflammatory proteins, (2) cellular transcription factors and gene expression, (3) immune cell count, (4) immune cell aging, and (5) antibody response. This analysis revealed substantial heterogeneity across studies with respect to patient population, study design, and assay procedures. The findings suggest possible effects of mindfulness meditation on specific markers of inflammation, cell-mediated immunity, and biological aging, but these results are tentative and require further replication. On the basis of this analysis, we describe the limitations of existing work and suggest possible avenues for future research. Mindfulness meditation may be salutogenic for immune system dynamics, but additional work is needed to examine these effects. © 2016 New York Academy of Sciences.

Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

PubMed Central

Pan, Li; Zhang, Zhongwang; Lv, Jianliang; Zhou, Peng; Hu, Wenfa; Fang, Yuzhen; Chen, Haotai; Liu, Xinsheng; Shao, Junjun; Zhao, Furong; Ding, Yaozhong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Zhang, Yongguang; Wang, Yonglu

2014-01-01

The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD). In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1) chitosan-coated poly(lactic-co-glycolic acid) (PLGA) loaded with plasmid DNA (Chi-PLGA-DNA) and (2) chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV) (Chi-Tre-Inactivated). Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (Ig)A (sIgA) antibodies in nasal washes were initially detected at 4 days postvaccination (dpv) with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles (P<0.05). FMDV-specific IgA antibodies in serum showed a similar pattern. All animals immunized by intranasal route developed low levels of detectable IgG in serum at 10 dpv. Following stimulation with FMDV, the highest levels of proliferation were observed in splenocytes harvested from Chi-PLGA-DNA-immunized animals, followed by proliferation of cells harvested from Chi-Tre-Inactivated nanoparticle-immunized animals (P<0.05). Higher protection rates were associated with the highest sIgA antibody responses induced in the Chi-PLGA-DNA nanoparticle-immunized group. Only one animal was clinically affected with mild signs after 7 days of contact challenge, after a delay of 2–3 days compared with the clinically affected negative-control group. Of the five animals directly challenged that were vaccinated by intranasal route with a double dose of Chi-Tre-Inactivated, four were clinically infected; however, the degree of severity of disease in this group was lower than in control cattle. The number of viral RNA copies in nasal swabs from the vaccinated, severely infected group was significantly higher than in swabs from the vaccinated, clinically protected group. These data suggested that intranasal delivery of Chi-PLGA-DNA nanoparticles resulted in higher levels of mucosal, systemic, and cell-mediated immunity than did of Chi-Tre-Inactivated nanoparticles. In conclusion, although intranasal delivery with FMDV antigen mediated by nanoparticles did not provide complete clinical protection, it reduced disease severity and virus excretion and delayed clinical symptoms. Chi-PLGA-DNA nanoparticle vaccines have potential as a nasal delivery system for vaccines. PMID:25506214

Nomenclature for secreted regulatory proteins of the immune system (interleukins). WHO-IUIS Nomenclature Subcommittee on Interleukin Designation.

PubMed Central

1991-01-01

The recommended procedures and criteria for interleukin designations are described. The officially adopted designations are, in sequence, from interleukin-1 to interleukin-10, including interleukin-1 alpha and interleukin-1 beta. PMID:1934243

How-to-Do-It: Infection Control Guidelines for Blood Typing & Blood Smear Labs.

ERIC Educational Resources Information Center

Vetter, Edwin A.

1989-01-01

Provides a set of guidelines for infection control of the Acquired Immune Deficiency Syndrome and the serum hepatitis viruses during blood typing procedures. Emphasizes that disposal of blood contaminated materials should comply with local health department recommendations. (RT)

The most common friend first immunization

NASA Astrophysics Data System (ADS)

Nian, Fu-Zhong; Hu, Cha-Sheng

2016-12-01

In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts-Strogatz (WS) small-world network model and the Barabsi-Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. Project supported by the National Natural Science Foundation of China (Grant No. 61263019), the Program for International Science and Technology Cooperation Projects of Gansu Province, China (Grant No. 144WCGA166), and the Program for Longyuan Young Innovation Talents and the Doctoral Foundation of Lanzhou University of Technology, China.

Construction of a medicinal leech transcriptome database and its application to the identification of leech homologs of neural and innate immune genes.

PubMed

Macagno, Eduardo R; Gaasterland, Terry; Edsall, Lee; Bafna, Vineet; Soares, Marcelo B; Scheetz, Todd; Casavant, Thomas; Da Silva, Corinne; Wincker, Patrick; Tasiemski, Aurélie; Salzet, Michel

2010-06-25

The medicinal leech, Hirudo medicinalis, is an important model system for the study of nervous system structure, function, development, regeneration and repair. It is also a unique species in being presently approved for use in medical procedures, such as clearing of pooled blood following certain surgical procedures. It is a current, and potentially also future, source of medically useful molecular factors, such as anticoagulants and antibacterial peptides, which may have evolved as a result of its parasitizing large mammals, including humans. Despite the broad focus of research on this system, little has been done at the genomic or transcriptomic levels and there is a paucity of openly available sequence data. To begin to address this problem, we constructed whole embryo and adult central nervous system (CNS) EST libraries and created a clustered sequence database of the Hirudo transcriptome that is available to the scientific community. A total of approximately 133,000 EST clones from two directionally-cloned cDNA libraries, one constructed from mRNA derived from whole embryos at several developmental stages and the other from adult CNS cords, were sequenced in one or both directions by three different groups: Genoscope (French National Sequencing Center), the University of Iowa Sequencing Facility and the DOE Joint Genome Institute. These were assembled using the phrap software package into 31,232 unique contigs and singletons, with an average length of 827 nt. The assembled transcripts were then translated in all six frames and compared to proteins in NCBI's non-redundant (NR) and to the Gene Ontology (GO) protein sequence databases, resulting in 15,565 matches to 11,236 proteins in NR and 13,935 matches to 8,073 proteins in GO. Searching the database for transcripts of genes homologous to those thought to be involved in the innate immune responses of vertebrates and other invertebrates yielded a set of nearly one hundred evolutionarily conserved sequences, representing all known pathways involved in these important functions. The sequences obtained for Hirudo transcripts represent the first major database of genes expressed in this important model system. Comparison of translated open reading frames (ORFs) with the other openly available leech datasets, the genome and transcriptome of Helobdella robusta, shows an average identity at the amino acid level of 58% in matched sequences. Interestingly, comparison with other available Lophotrochozoans shows similar high levels of amino acid identity, where sequences match, for example, 64% with Capitella capitata (a polychaete) and 56% with Aplysia californica (a mollusk), as well as 58% with Schistosoma mansoni (a platyhelminth). Phylogenetic comparisons of putative Hirudo innate immune response genes present within the Hirudo transcriptome database herein described show a strong resemblance to the corresponding mammalian genes, indicating that this important physiological response may have older origins than what has been previously proposed.

Attenuated Shigella as a DNA Delivery Vehicle for DNA-Mediated Immunization

NASA Astrophysics Data System (ADS)

Sizemore, Donata R.; Branstrom, Arthur A.; Sadoff, Jerald C.

1995-10-01

Direct inoculation of DNA, in the form of purified bacterial plasmids that are unable to replicate in mammalian cells but are able to direct cell synthesis of foreign proteins, is being explored as an approach to vaccine development. Here, a highly attenuated Shigella vector invaded mammalian cells and delivered such plasmids into the cytoplasm of cells, and subsequent production of functional foreign protein was measured. Because this Shigella vector was designed to deliver DNA to colonic mucosa, the method is a potential basis for oral and other mucosal DNA immunization and gene therapy strategies.

Trade-offs between acquired and innate immune defenses in humans

PubMed Central

McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

2016-01-01

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

The role of immune dysfunction in the pathophysiology of autism

PubMed Central

Onore, Charity; Careaga, Milo; Ashwood, Paul

2012-01-01

Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors. Although a link between altered immune responses and ASD was first recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted relationship between immune dysfunction and behavior in ASD. Neurobiological research in ASD has highlighted pathways involved in neural development, synapse plasticity, structural brain abnormalities, cognition and behavior. At the same time, several lines of evidence point to altered immune dysfunction in ASD that directly impacts some or all these neurological processes. Extensive alterations in immune function have now been described in both children and adults with ASD, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the CSF and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Furthermore, these dysfunctional immune responses are associated with increased impairments in behaviors characteristic of core features of ASD, in particular, deficits in social interactions and communication. This accumulating evidence suggests that immune processes play a key role in the pathophysiology of ASD. This review will discuss the current state of our knowledge of immune dysfunction in ASD, how these findings may impact on underlying neuro-immune mechanisms and implicate potential areas where the manipulation of the immune response could have an impact on behavior and immunity in ASD. PMID:21906670

Changes in Nutritional Status Impact Immune Cell Metabolism and Function.

PubMed

Alwarawrah, Yazan; Kiernan, Kaitlin; MacIver, Nancie J

2018-01-01

Immune cell function and metabolism are closely linked. Many studies have now clearly demonstrated that alterations in cellular metabolism influence immune cell function and that, conversely, immune cell function determines the cellular metabolic state. Less well understood, however, are the effects of systemic metabolism or whole organism nutritional status on immune cell function and metabolism. Several studies have demonstrated that undernutrition is associated with immunosuppression, which leads to both increased susceptibility to infection and protection against several types of autoimmune disease, whereas overnutrition is associated with low-grade, chronic inflammation that increases the risk of metabolic and cardiovascular disease, promotes autoreactivity, and disrupts protective immunity. Here, we review the effects of nutritional status on immunity and highlight the effects of nutrition on circulating cytokines and immune cell populations in both human studies and mouse models. As T cells are critical members of the immune system, which direct overall immune response, we will focus this review on the influence of systemic nutritional status on T cell metabolism and function. Several cytokines and hormones have been identified which mediate the effects of nutrition on T cell metabolism and function through the expression and action of key regulatory signaling proteins. Understanding how T cells are sensitive to both inadequate and overabundant nutrients may enhance our ability to target immune cell metabolism and alter immunity in both malnutrition and obesity.

Immune Checkpoint Blockade for Breast Cancer.

PubMed

Swoboda, April; Nanda, Rita

An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors. Programmed death receptor-1 (PD-1) is an inhibitory transmembrane protein expressed on T cells, B cells, and NK cells. The interaction between PD-1 and its ligands (PD-L1/L2) functions as an immune checkpoint against unrestrained cytotoxic T effector cell activity-it promotes peripheral T effector cell exhaustion and conversion of T effector cells to immunosuppressive T regulatory (Treg) cells. Immune checkpoint inhibitors, which block the PD-1/PD-L1 axis and reactivate cytotoxic T effector cell function, are actively being investigated for the treatment of breast cancer.

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

PubMed

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

2004-02-07

Good genes models of sexual selection assume that sexual advertisement is costly and thus the level of advertisement honestly reveals heritable viability. Recently it has been suggested that an important cost of sexual advertisement might be impairment of the functioning of the immune system. In this field experiment we investigated the possible trade-offs between immune function and sexual advertisement by manipulating both mating effort and activity of immune defence in male pied flycatchers. Mating effort was increased in a non-arbitrary manner by removing females from mated males during nest building. Widowed males sustained higher haematocrit levels than control males and showed higher expression of forehead patch height, suggesting that manipulation succeeded in increasing mating effort. Males that were experimentally forced to increase mating effort had reduced humoral immune responsiveness compared with control males. In addition, experimental activation of immune defence by vaccination with novel antigens reduced the expression of male ornament dimensions. To conclude, our results indicate that causality behind the trade-off between immune function and sexual advertisement may work in both directions: sexual activity suppresses immune function but immune challenge also reduces sexual advertisement.

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

PubMed Central

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

2004-01-01

Good genes models of sexual selection assume that sexual advertisement is costly and thus the level of advertisement honestly reveals heritable viability. Recently it has been suggested that an important cost of sexual advertisement might be impairment of the functioning of the immune system. In this field experiment we investigated the possible trade-offs between immune function and sexual advertisement by manipulating both mating effort and activity of immune defence in male pied flycatchers. Mating effort was increased in a non-arbitrary manner by removing females from mated males during nest building. Widowed males sustained higher haematocrit levels than control males and showed higher expression of forehead patch height, suggesting that manipulation succeeded in increasing mating effort. Males that were experimentally forced to increase mating effort had reduced humoral immune responsiveness compared with control males. In addition, experimental activation of immune defence by vaccination with novel antigens reduced the expression of male ornament dimensions. To conclude, our results indicate that causality behind the trade-off between immune function and sexual advertisement may work in both directions: sexual activity suppresses immune function but immune challenge also reduces sexual advertisement. PMID:15058434

Characterization of Vaccination Policies for Attendance and Employment at Day/Summer Camps in New York State.

PubMed

Prescott, William A; Violanti, Kelsey C; Fusco, Nicholas M

2018-01-01

New York state requires day/summer camps to keep immunization records for all enrolled campers and strongly recommends requiring vaccination for all campers and staff. The objective of this study was to characterize immunization requirements/recommendations for children/adolescents enrolled in and staff employed at day/summer camps in New York state. An electronic hyperlink to a 9-question survey instrument was distributed via e-mail to 178 day/summer camps located in New York state cities with a population size greater than 100 000 people. A follow-up telephone survey was offered to nonresponders. The survey instrument included questions pertaining to vaccination documentation policies for campers/staff and the specific vaccines that the camp required/recommended. Fisher's exact and Chi-square tests were used to analyze categorical data. Sixty-five day/summer camps responded to the survey (36.5% response rate): 48 (73.8%) and 23 (41.8%) camps indicated having a policy/procedure for documenting vaccinations for campers and staff, respectively. Camps that had a policy/procedure for campers were more likely to have a policy/procedure for staff ( P = .0007). Age-appropriate vaccinations that were required/recommended for campers by at least 80% of camps included: measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), hepatitis B, inactivated/oral poliovirus (IPV/OPV), Haemophilus influenzae type b (Hib), and varicella. Age-appropriate vaccinations that were required/recommended for staff by at least 80% of camps included: DTaP, hepatitis B, IPV/OPV, MMR, meningococcus, varicella, Hib, and tetanus, diphtheria, and pertussis (Tdap). Vaccination policies at day/summer camps in New York state appear to be suboptimal. Educational outreach may encourage camps to strengthen their immunization policies, which may reduce the transmission of vaccine-preventable diseases.

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

PubMed Central

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

2009-01-01

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

Nanoparticles and direct immunosuppression

PubMed Central

Ngobili, Terrika A

2016-01-01

Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

Impact of the CDC’s Section 317 Immunization Grants Program Funding on Childhood Vaccination Coverage

PubMed Central

Rein, David B.; Honeycutt, Amanda A.; Rojas-Smith, Lucia; Hersey, James C.

2006-01-01

The Centers for Disease Control and Prevention’s Section 317 Grants Program is the main source of funding for state and jurisdictional immunization programs, yet no study has evaluated its direct impact on vaccination coverage rates. Therefore, we used a fixed-effects model and data collected from 56 US jurisdictions to estimate the impact of Section 317 financial assistance immunization grants on childhood vaccination coverage rates from 1997 to 2003. Our results showed that increases in Section 317 funding were significantly and meaningfully associated with higher rates of vaccination coverage; a $10 increase in per capita funding corresponded with a 1.6-percentage-point increase in vaccination coverage. Policymakers charged with funding public health programs should consider this study’s findings, which indicate that money allocated to vaccine activities translates directly into higher vaccine coverage rates. PMID:16873738

Pathogens and host immunity in the ancient human oral cavity

PubMed Central

Warinner, Christina; Matias Rodrigues, João F.; Vyas, Rounak; Trachsel, Christian; Shved, Natallia; Grossmann, Jonas; Radini, Anita; Hancock, Y.; Tito, Raul Y.; Fiddyment, Sarah; Speller, Camilla; Hendy, Jessica; Charlton, Sophy; Luder, Hans Ulrich; Salazar-García, Domingo C.; Eppler, Elisabeth; Seiler, Roger; Hansen, Lars; Samaniego Castruita, José Alfredo; Barkow-Oesterreicher, Simon; Teoh, Kai Yik; Kelstrup, Christian; Olsen, Jesper V.; Nanni, Paolo; Kawai, Toshihisa; Willerslev, Eske; von Mering, Christian; Lewis, Cecil M.; Collins, Matthew J.; Gilbert, M. Thomas P.; Rühli, Frank; Cappellini, Enrico

2014-01-01

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize: (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) the first evidence of ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, “red-complex” pathogens, and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity, and diet, thereby extending the direct investigation of common diseases into the human evolutionary past. PMID:24562188

Basic science for the clinician 53: mast cells.

PubMed

Sigal, Leonard H

2011-10-01

Mast cells stand at the interface between the innate immune system and the acquired (adaptive) immune response, serving as sentinels detecting invaders and directing a concerted and coordinated response. Mast cells reside immediately under body surfaces and within lymph nodes, near blood vessels and nerves, perfectly situated to for early detection and defense. They secrete a wide array of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers of a variety of immune and inflammatory functions and bear surface markers suggesting broad functions, including as antigen-presenting cells. Although usually not given their due in medical school lectures, there is great likelihood that mast cells will be implicated in the pathogenesis of rheumatoid arthritis, scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into mast cell functions and mast cell-derived effector molecules should command our attention as we move forward in better understanding disease immunopathogenesis and directed intelligent therapeutics development.

Abundance of the Organic Anion-transporting Polypeptide OATP4A1 in Early-Stage Colorectal Cancer Patients: Association With Disease Relapse.

PubMed

Buxhofer-Ausch, Veronika; Sheikh, Maidah; Ausch, Christoph; Zotter, Simone; Bauer, Heike; Mollik, Marina; Reiner, Angelika; Gleiss, Andreas; Jäger, Walter; Sebesta, Christian; Kriwanek, Stephan; Thalhammer, Theresia

2018-05-03

The abundance of OATP4A1 in colorectal cancer (CRC) might be related to tumor progression. This was studied by immunohistochemistry on paraffin-embedded samples obtained from 178 patients (43 patients with a relapse within 5 y) with early-stage CRC. Positivity for OATP4A1 in tumor cells and noncancerous mucosal cells was proved by double-immunofluorescence staining with antibodies against OATP4A1 and keratin 8, whereas antibodies against appropriate CD markers were used to identify immune cells. Automated microscopic image analysis was used to measure the percentage of OATP4A1-positive cells and OATP4A1 staining intensity in tumor, immune, and adjacent normal-looking mucosal cells separately, as well as in the mucosal and immune cells of 14 nonmalignant tissue samples. In CRC the percentage of OATP4A1-positive cells, but not staining intensity, was significantly higher in tumor and mucosal cells adjacent to the tumor compared to the mucosa of nonmalignant samples (P<0.001 each). No difference was registered between immune cells in malignant and nonmalignant samples. Importantly, high levels of OATP4A1 in immune (odds ratio, 0.73; confidence interval, 0.63-0.85; P<0.001), and tumor cells (odds ratio, 0.79; confidence interval, 0.69-0.91; P<0.001) are significantly associated with a low risk of recurrence and also significantly enhance the discriminative power of other clinical parameters [such as International Union Against Cancer (UICC), adjuvant therapy, localization of the primary tumor] of the risk of relapse (receiver operating characteristics analysis; P=0.002). Using an advanced digital microscopic quantification procedure, we showed that OATP4A1 abundance is negatively associated with tumor recurrence in early-stage CRC. This digital scoring procedure may serve as a novel tool for the assessment of potential prognostic markers in early-stage CRC.

Bovine colostrum supplementation's lack of effect on immune variables during short-term intense exercise in well-trained athletes.

PubMed

Carol, Arnoud; Witkamp, Renger F; Wichers, Harry J; Mensink, Marco

2011-04-01

The purpose of this study was to investigate the potential of bovine colostrum to attenuate postexercise decline in immune function. The authors evaluated the time course of a number of immune variables after short-term intense exercise in 9 male athletes after 10 d of supplementation with either colostrum or skim-milk powder. To increase the stress on the immune system subjects performed a glycogen-depletion trial the evening before the endurance trial (90 min at 50% Wmax). Blood samples were taken before the glycogen-depletion trial, before and after the endurance trial, and the next morning, ~22 hr after cessation of the exercise. Plasma cortisol levels increased over time, reaching the highest level directly after exercise, and were still elevated ~22 hr after exercise compared with baseline values (p < .001). Neutrophil cell count was increased after exercise and dropped below starting values 22 hr after exercise (time effect p < .001). Circulating immunoglobulins did not change over time. A significant time effect was seen for interleukin (IL)-6, IL-10, IL-1-receptor agonist, and C-reactive protein, with levels being higher directly after exercise (p < .05). Other cytokines (interferon-γ, IL-1a, IL-8, tumor necrosis factor-a) did not show a time effect. No differences were seen between colostrum and skim-milk powder in any of the investigated variables. Our results are consistent with the hypothesis that intense exercise affects several variables of the immune system. Colostrum did not alter any of the postexercise immune variables compared with skim-milk powder, suggesting no role for bovine colostrum supplementation in preventing postexercise immune suppression after short-term intense exercise.

New insights into innate immune control of systemic candidiasis

PubMed Central

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

Harnessing dendritic cells in inflammatory skin diseases

PubMed Central

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O.

2011-01-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. PMID:21295490

PRENATAL INFECTION, MATERNAL IMMUNE ACTIVATION, AND RISK FOR SCHIZOPHRENIA.

PubMed

Canetta, Sarah E; Brown, Alan S

2012-12-01

A body of epidemiological literature has suggested an association between prenatal infection, subsequent maternal immune activation (MIA), and later risk of schizophrenia. These epidemiological studies have inspired preclinical research using rodent and primate models of prenatal infection and MIA. The findings from these preclinical studies indicate that severe infection and immune activation during pregnancy can negatively impact offspring brain development and impair adult behavior. This review aims to summarize the major epidemiological and preclinical findings addressing the connection between prenatal infection and immune activation and later risk of developing schizophrenia, as well as the more limited literature addressing the mechanisms by which this gestational insult might affect offspring neurodevelopment. Finally, directions for future research will be discussed.

Contribution of Vaccine-Induced Immunity toward either the HA or the NA Component of Influenza Viruses Limits Secondary Bacterial Complications▿

PubMed Central

Huber, Victor C.; Peltola, Ville; Iverson, Amy R.; McCullers, Jonathan A.

2010-01-01

Secondary bacterial infections contribute to morbidity and mortality from influenza. Vaccine effectiveness is typically assessed using prevention of influenza, not secondary infections, as an endpoint. We vaccinated mice with formalin-inactivated influenza virus vaccine preparations containing disparate HA and NA proteins and demonstrated an ability to induce the appropriate anti-HA and anti-NA immune profiles. Protection from both primary viral and secondary bacterial infection was demonstrated with vaccine-induced immunity directed toward either the HA or the NA. This finding suggests that immunity toward the NA component of the virion is desirable and should be considered in generation of influenza vaccines. PMID:20130054

Receptor-like cytoplasmic kinases are pivotal components in pattern recognition receptor-mediated signaling in plant immunity.

PubMed

Yamaguchi, Koji; Yamada, Kenta; Kawasaki, Tsutomu

2013-10-01

Innate immunity is generally initiated with recognition of conserved pathogen-associated molecular patterns (PAMPs). PAMPs are perceived by pattern recognition receptors (PRRs), leading to activation of a series of immune responses, including the expression of defense genes, ROS production and activation of MAP kinase. Recent progress has indicated that receptor-like cytoplasmic kinases (RLCKs) are directly activated by ligand-activated PRRs and initiate pattern-triggered immunity (PTI) in both Arabidopsis and rice. To suppress PTI, pathogens inhibit the RLCKs by many types of effectors, including AvrAC, AvrPphB and Xoo1488. In this review, we summarize recent advances in RLCK-mediated PTI in plants.

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

PubMed

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedorka, K. M.; Copeland, E. K.; Winterhalter, W. E.

To improve thermoregulation in colder environments, insects are expected to darken their cuticles with melanin via the phenoloxidase cascade, a phenomenon predicted by the thermal melanin hypothesis. However, the phenoloxidase cascade also plays a significant role in insect immunity, leading to the additional hypothesis that the thermal environment indirectly shapes immune function via direct selection on cuticle color. Support for the latter hypothesis comes from the cricket Allonemobius socius, where cuticle darkness and immune-related phenoloxidase activity increase with latitude. However, thermal environments vary seasonally as well as geographically, suggesting that seasonal plasticity in immunity may also exist. Although seasonal fluctuationsmore » in vertebrate immune function are common (because of flux in breeding or resource abundance), seasonality in invertebrate immunity has not been widely explored. We addressed this possibility by rearing crickets in simulated summer and fall environments and assayed their cuticle color and immune function. Prior to estimating immunity, crickets were placed in a common environment to minimize metabolic rate differences. Individuals reared under fall-like conditions exhibited darker cuticles, greater phenoloxidase activity and greater resistance to the bacteria Serratia marcescens. These data support the hypothesis that changes in the thermal environment modify cuticle color, which indirectly shapes immune investment through pleiotropy. This hypothesis may represent a widespread mechanism governing immunity in numerous systems, considering that most insects operate in seasonally and geographically variable thermal environments.« less

Intravital imaging of cutaneous immune responses.

PubMed

Nakamizo, Satoshi; Egawa, Gyohei; Bing, Jasmine Tan Kah; Kabashima, Kenji

2018-05-25

Various immune cells are present in the skin and modulate the cutaneous immune response. In order to capture such dynamic phenomena, intravital imaging is an important technique and there is a possibility to provide substantial information that is not available using conventional histological analysis. Multiphoton microscope enable direct, three-dimensional, minimally invasive imaging of biological samples with high spatiotemporal resolution, and now become the main method for intravital imaging studies. Here, we will introduce the latest knowledge obtained by intravital imaging of the skin. Copyright © 2018 Elsevier Inc. All rights reserved.

The journey from discoveries in fundamental immunology to cancer immunotherapy.

PubMed

Miller, Jacques F A P; Sadelain, Michel

2015-04-13

Recent advances in cancer immunotherapy have directly built on 50 years of fundamental and technological advances that made checkpoint blockade and T cell engineering possible. In this review, we intend to show that research, not specifically designed to bring relief or cure to any particular disease, can, when creatively exploited, lead to spectacular results in the management of cancer. The discovery of thymus immune function, T cells, and immune surveillance bore the seeds for today's targeted immune interventions and chimeric antigen receptors. Copyright © 2015 Elsevier Inc. All rights reserved.

The application of the haemagglutination test to a study of the immunity to malaria in protected and unprotected population groups in Australian New Guinea*

PubMed Central

Desowitz, R. S.; Saave, J. J.

1965-01-01

The formolized tanned sheep erythrocyte haemagglutination test has been applied to an immuno-malariometric study in Australian New Guinea to determine whether the haemagglutination titre reflects a subject's immune state and to measure the effect of malaria control operations on a population's immunity. Two population groups were studied—one (unprotected) living in holoendemic malaria conditions, the other (protected) living in an area subject to malaria control measures for four years. An increase in both serological positivity rates and geometric mean titres among the unprotected group with increasing age suggests that the test does serve to assess the state of immunity; the corresponding rates were much lower in the protected population, particularly among the children. The authors foresee the possible use of the haemagglutination test as a supplement to other procedures in assessing the progress of a malaria campaign. They, note, however, that more immuno-malariometric studies on populations subject to different degrees of malaria endemicity will need to be carried out before the relationship between the immune state and serological results can be clearly established. PMID:14310901

Oral innate immunity in HIV infection in HAART era

PubMed Central

Nittayananta, Wipawee; Tao, Renchuan; Jiang, Lanlan; Peng, Yuanyuan; Huang, Yuxiao

2015-01-01

Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces provide not only a physical barrier but also produce different antimicrobial peptides, including human β-defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co-infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection contributed to a global reduction of HIV-associated oral lesions. However, prolonged treatment by HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: 1) What are the roles of oral innate immunity in health and disease?, 2) What are the effects of HIV infection on oral innate immunity?, 3) What are the roles of oral innate immunity against other co-infections?, 4) What are the effects of HAART on oral innate immunity?, and 5) Is oral innate immunity enhanced by HAART? PMID:25639844

Microbiota regulate the development and function of the immune cells.

PubMed

Yu, Qing; Jia, Anna; Li, Yan; Bi, Yujing; Liu, Guangwei

2018-03-04

Microbiota is a group of microbes coexisting and co-evolving with the immune system in the host body for millions of years. There are mutual interaction between microbiota and the immune system. Immune cells can shape the populations of microbiota in the gut of animals and humans, and the presence of microbiota and the microbial products can regulate the development and function of the immune cells in the host. Although microbiota resides mainly at the mucosa, the effect of microbiota on the immune system can be both local at the mucosa and systemic through the whole body. At the mucosal sites, the presences of microbiota and microbial products have a direct effect on the immune cells. Microbiota induces production of effectors from immune cells, such as cytokines and inflammatory factors, influencing the further development and function of the immune cells. Experimental data have shown that microbial products can influence the activity of some key factors in signaling pathways. At the nonmucosal sites, such as the bone marrow, peripheral lymph nodes, and spleen, microbiota can also regulate the development and function of the immune cells via several mechanisms in mice, such as introduction of chromatin-level changes through histone acetylation and DNA methylation. Given the important effect of microbiota on the immune system, many immunotherapies that are mediated by immune system rely on gut microbiota. Thus, the study of how microbiota influences immune system bring a potential therapy prospect in preventing and treating diseases.

[Platelet transfusion role in neonatal immune thrombocytopenia].

PubMed

Petermann, R

2016-11-01

Neonatal immune thrombocytopenia represent less than 5% of cases of early thrombocytopenia (early-onset<72hours post-delivery). As in adults, thrombocytopenia in neonates is defined as a platelet count less than 150G/L. They are either auto- or allo-immune. Thrombocytopenia resulting from transplacental passage of maternal antibodies directed to platelet membrane glycoproteins can be severe. The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial haemorrhage and neurologic sequelea following. However, auto- and allo-immune thrombocytopenia have very different characteristics including the treatment management. In fact, this treatment is based on platelet transfusion associated or not to intravenous immunoglobulin administration. The purpose of this article is to remind platelet transfusion's place in neonatal immune thrombocytopenia in terms of recently published French guidelines and international practices. Copyright © 2016. Published by Elsevier SAS.

From blood coagulation to innate and adaptive immunity: the role of platelets in the physiology and pathology of autoimmune disorders.

PubMed

Łukasik, Zuzanna Małgorzata; Makowski, Marcin; Makowska, Joanna Samanta

2018-02-28

Thrombosis and cardiovascular complications are common manifestations of a variety of pathological conditions, including infections and chronic inflammatory diseases. Hence, there is great interest in determining the hitherto unforeseen immune role of the main blood coagulation executor-the platelet. Platelets store and release a plethora of immunoactive molecules, generate microparticles, and interact with cells classically belonging to the immune system. The observed effects of platelet involvement in immune processes, especially in autoimmune diseases, are conflicting-from inciting inflammation to mediating its resolution. An in-depth understanding of the role of platelets in inflammation and immunity could open new therapeutic pathways for patients with autoimmune disorders. This review aims to summarize the current knowledge on the role of platelets in the patomechanisms of autoimmune disorders and suggests directions for future research.

[Bone marrow stromal damage mediated by immune response activity].

PubMed

Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

1994-01-01

The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

Feasibilty of in utero DNA vaccination following naked gene transfer into pig fetal muscle: transgene expression, immunity and safety.

PubMed

Rinaldi, Monica; Signori, Emanuela; Rosati, Paolo; Cannelli, Giorgio; Parrella, Paola; Iannace, Enrico; Monego, Giovanni; Ciafrè, Silvia Anna; Farace, Maria Giulia; Iurescia, Sandra; Fioretti, Daniela; Rasi, Guido; Fazio, Vito Michele

2006-05-22

The high toll of death among first-week infants is due to infections occurring at the end of pregnancy, during birth or by breastfeeding. This problem significantly concerns industrialized countries also. To prevent the typical "first-week infections", a vaccine would be protective as early as at the birth. In utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. We have already published results of a 2-year follow-up showing long-term safety, protective antibody titers at birth and long-term immune memory, following intramuscular in utero anti-HBV DNA immunization in 90-days pig fetuses. We have now analyzed further parameters of short-term safety. Two different reporter genes were injected in the thigh muscles of 90-days fetuses. At 8 days following DNA injection, we found high-level of transgenes expression in all injected fetuses. A step gradient of expression from the area of injection was observed with both reporter genes. CMV promoter/enhancer produced higher levels of expression compared to SV40 promoter/enhancer. Moreover, no evidence of local or systemic flogistic alterations or fetal malformations, mortality or haemorrhage following intramuscular injection were observed. A single anti-HBV s-antigen DNA immunization in 90-days fetuses supported protective antibody levels in all immunized newborns, lasting at least up to 4 months after birth. Our report further sustains safety and efficacy of intramuscular in utero naked gene transfer and immunization. This approach may support therapeutic or prophylactic procedure in many early life-threatening pathologic conditions.

The influence of immune system stimulation on encapsulated islet graft survival.

PubMed

Orłowski, Tadeusz M; Godlewska, Ewa; Tarchalska, Magda; Kinasiewicz, Joanna; Antosiak, Magda; Sabat, Marek

2005-01-01

The aim of this study was to determine the influence activating of the recipient immune system on the function of microencapsulated islet xenografts. The skin of WAG or Fisher rats and WAG free or encapsulated (APA) Langerhans islets were transplanted to healthy or to streptozotocin diabetic BALB/c mice. Skin grafts were performed following the method of Billingham and Medawar. Rat islets were isolated from pancreas by the Lacy and Kostianovsy method and encapsulated with calcium alginate-poly-L-lysine-alginate according to the 3-step coating method of Sun. The transplantation of encapsulated WAG islets, despite activation of the host immune system, restored euglycemia for over 180 +/-100 days. A subsequent skin graft taken from the same donor was rejected in the second set mode, but euglycemia persisted. In diabetic recipients, impaired immune response was corrected by successful encapsulated islet transplantation. In diabetic mice, strong stimulation with 2-fold skin transplantation induced primary non-function of grafted islets despite their encapsulation. The survival of an islet xenograft depends on the level of activation of the recipient immune system. The immune response of diabetic mice was impaired, but increased after post-transplant restitution of euglycemia. Microencapsulation sufficiently protected grafted islets, and remission of diabetes was preserved. However, after strong specific or non-specific stimulation of the host immune system, non-function of xenografted islets developed despite their encapsulation. Therefore, islet graft recipients should avoid procedures which could stimulate their immune systems. If absolutely necessary, the graft should be protected by exogenous insulin therapy at that time.

Immune function and the decision to deploy weapons during fights in the beadlet anemone, Actinia equina.

PubMed

Lane, Sarah M; Briffa, Mark

2018-02-20

The ability to mitigate the costs of engaging in a fight will depend on an individual's physiological state. However, the experience of fighting itself may, in turn, affect an individual's state, especially if the fight results in injury. Previous studies have found a correlation between immune state and fighting success, but the causal direction of this relationship remains unclear. Does immune state determine fighting success? Or does fighting itself influence subsequent immune state? Using the beadlet anemone, Actinia equina , we disentangled the cause and effect of this relationship, measuring immune response once pre-fight and twice post-fight. Contrary to previous findings, pre-fight immune response did not predict fighting success, but rather predicted whether an individual used its weapons during the fight. Furthermore, weapon use and contest outcome significantly affected post-fight immune response. Individuals that used their weapons maintained a stable immune response following the fight, whereas those that fought non-injuriously did not. Furthermore, although winners suffered a reduction in immune response similar to that of losers immediately post-fight, winners began to recover pre-fight levels within 24 h. Our findings indicate that immune state can influence strategic fighting decisions and, moreover, that fight outcome and the agonistic behaviours expressed can significantly affect subsequent immunity. © 2018. Published by The Company of Biologists Ltd.

Mucosal immunology of HIV infection.

PubMed

Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S

2013-07-01

Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection, but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of 'symbiotic' intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high-level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4(+) T-cell responses, binding anti-bodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Furthermore, immune therapies specifically directed toward boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mucosal Immunology of HIV Infection

PubMed Central

Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

2013-01-01

Summary Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4+ T-cell responses, binding antibodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Further, immune therapies specifically directed towards boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients. PMID:23772612

The misleading nature of in vitro and ex vivo findings in studying the impact of stress hormones on NK cell cytotoxicity.

PubMed

Gotlieb, Neta; Rosenne, Ella; Matzner, Pini; Shaashua, Lee; Sorski, Liat; Ben-Eliyahu, Shamgar

2015-03-01

In vitro and ex vivo studies assessing the impact of stress hormones on immune competence commonly replace the natural milieu of leukocytes with an artificial medium, excluding plasma factors, hormones, and cytokines. Given prevalent inconsistencies between in vitro, ex vivo, and in vivo findings, we studied whether such procedures could yield misleading outcomes regarding the impact of stress hormones on NK cell cytotoxicity (NKCC), using fresh human whole blood samples. We found that in the presence of plasma 10-30-fold higher concentrations of cortisol, epinephrine, and prostaglandin-E2 (PGE2) were required to reach suppression levels evident in the context of artificial medium. Importantly, whereas the NK suppressive effects of PGE2 occurred immediately and remained stable upon prolonged exposure, the suppressive effects of cortisol slowly increased over time. Last, to simulate the exclusion of stress factors in the ex vivo approach, we subjected whole blood to stress hormones (as occurs in vivo), and abruptly removed them. We found that the effects of epinephrine and PGE2 quickly disappeared, while the effects of cortisol persisted. Overall, these findings demonstrate the potential misleading nature of in vitro and ex vivo procedures, and specifically suggest that (i) the common in vitro findings of profound suppression of NKCC by stress hormones are overestimation of their direct effects expected in vivo; and (ii) the common ex vivo approach cannot reflect the direct in vivo suppressive effects of epinephrine and PGE2 on NKCC, while inflating the effects of glucocorticoids. Some of these fallacies may be circumvented by using non-delayed whole blood NKCC assays in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of immunization with natural and recombinant lysine decarboxylase on canine gingivitis development.

PubMed

Peters, Jennifer L; DeMars, Paul L; Collins, Lindsay M; Stoner, Julie A; Matsumoto, Hiroyuki; Komori, Naoka; Singh, Anil; Feasley, Christa L; Haddock, James A; Levine, Martin

2012-10-19

Periodontal disease, gingival inflammation (gingivitis) and periodontal attachment loss (periodontitis), causes tooth loss and susceptibility to chronic inflammation. Professionally scaling and cleaning the teeth regularly controls the disease, but is expensive in companion animals. Eikenella corrodens is common in canine oral cavities where it is a source of lysine decarboxylase (LDC). In human dental biofilms (plaques), LDC converts lysine to cadaverine and impairs the gingival epithelial barrier to bacteria. LDC vaccination may therefore retard gingivitis development. Year-old beagle dogs provided blood samples, and had weight and clinical measurements (biofilm and gingivitis) recorded. After scaling and cleaning, two dogs were immunized subcutaneously with 0.2mg native LDC from E. corrodens and 2 sets of four dogs with 0.2mg recombinant LDC purified from Escherichia coli. A third set of 4 dogs was immunized intranasally. Rehydragel(®), Emulsigen(®), Polygen™ or Carbigen™ were used as adjuvant. Four additional pairs of dogs were sham-immunized with each adjuvant alone (controls). Immunizations were repeated twice, 3 weeks apart, and clinical measurements were obtained after another 2 weeks, when the teeth were scaled and cleaned again. Tooth brushing was then stopped and the diet was changed from hard to soft chow. Clinical measurements were repeated after 1, 2, 3, 4, 6 and 8 weeks. Compared with sham-immunized dogs, gingivitis was reduced over all 8 weeks of soft diet after subcutaneous immunization with native LDC, or after intranasal immunization with recombinant LDC in Carbigen™, but for only 6 of the 8 weeks after subcutaneous immunization with recombinant LDC in Emulsigen(®) (repeated measures ANOVA). Subcutaneous vaccination induced a strong serum IgG antibody response that decreased during the soft diet period, whereas intranasal immunization induced a weak serum IgA antibody response that did not decrease. Immunization with recombinant LDC may provide protection from gingivitis if procedures are optimized. Copyright © 2012 Elsevier Ltd. All rights reserved.

Approaches Mediating Oxytocin Regulation of the Immune System.

PubMed

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.

Perturbation of gut bacteria induces a coordinated cellular immune response in the purple sea urchin larva.

PubMed

Ch Ho, Eric; Buckley, Katherine M; Schrankel, Catherine S; Schuh, Nicholas W; Hibino, Taku; Solek, Cynthia M; Bae, Koeun; Wang, Guizhi; Rast, Jonathan P

2016-10-01

The purple sea urchin (Strongylocentrotus purpuratus) genome sequence contains a complex repertoire of genes encoding innate immune recognition proteins and homologs of important vertebrate immune regulatory factors. To characterize how this immune system is deployed within an experimentally tractable, intact animal, we investigate the immune capability of the larval stage. Sea urchin embryos and larvae are morphologically simple and transparent, providing an organism-wide model to view immune response at cellular resolution. Here we present evidence for immune function in five mesenchymal cell types based on morphology, behavior and gene expression. Two cell types are phagocytic; the others interact at sites of microbial detection or injury. We characterize immune-associated gene markers for three cell types, including a perforin-like molecule, a scavenger receptor, a complement-like thioester-containing protein and the echinoderm-specific immune response factor 185/333. We elicit larval immune responses by (1) bacterial injection into the blastocoel and (2) seawater exposure to the marine bacterium Vibrio diazotrophicus to perturb immune state in the gut. Exposure at the epithelium induces a strong response in which pigment cells (one type of immune cell) migrate from the ectoderm to interact with the gut epithelium. Bacteria that accumulate in the gut later invade the blastocoel, where they are cleared by phagocytic and granular immune cells. The complexity of this coordinated, dynamic inflammatory program within the simple larval morphology provides a system in which to characterize processes that direct both aspects of the echinoderm-specific immune response as well as those that are shared with other deuterostomes, including vertebrates.

The ecology of immune state in a wild mammal, Mus musculus domesticus.

PubMed

Abolins, Stephen; Lazarou, Luke; Weldon, Laura; Hughes, Louise; King, Elizabeth C; Drescher, Paul; Pocock, Michael J O; Hafalla, Julius C R; Riley, Eleanor M; Viney, Mark

2018-04-01

The immune state of wild animals is largely unknown. Knowing this and what affects it is important in understanding how infection and disease affects wild animals. The immune state of wild animals is also important in understanding the biology of their pathogens, which is directly relevant to explaining pathogen spillover among species, including to humans. The paucity of knowledge about wild animals' immune state is in stark contrast to our exquisitely detailed understanding of the immunobiology of laboratory animals. Making an immune response is costly, and many factors (such as age, sex, infection status, and body condition) have individually been shown to constrain or promote immune responses. But, whether or not these factors affect immune responses and immune state in wild animals, their relative importance, and how they interact (or do not) are unknown. Here, we have investigated the immune ecology of wild house mice-the same species as the laboratory mouse-as an example of a wild mammal, characterising their adaptive humoral, adaptive cellular, and innate immune state. Firstly, we show how immune variation is structured among mouse populations, finding that there can be extensive immune discordance among neighbouring populations. Secondly, we identify the principal factors that underlie the immunological differences among mice, showing that body condition promotes and age constrains individuals' immune state, while factors such as microparasite infection and season are comparatively unimportant. By applying a multifactorial analysis to an immune system-wide analysis, our results bring a new and unified understanding of the immunobiology of a wild mammal.

Effect of space flight on cytokine production

NASA Astrophysics Data System (ADS)

Sonnenfeld, Gerald

Space flight has been shown to alter many immunological responses. Among those affected are the production of cytokines, Cytokines are the messengers of the immune system that facilitate communication among cells that allow the interaction among cells leading to the development of immune responses. Included among the cytokines are the interferons, interleukins, and colony stimulating factors. Cytokines also facilitate communication between the immune system and other body systems, such as the neuroendocrine and musculoskeletal systems. Some cytokines also have direct protective effects on the host, such as interferon, which can inhibit the replication of viruses. Studies in both humans and animals indicate that models of space flight as well as actual space flight alter the production and action of cytokines. Included among these changes are altered interferon production, altered responsiveness of bone marrow cells to granulocyte/monocyte-colony stimulating factor, but no alteration in the production of interleukin-3. This suggests that there are selective effects of space flight on immune responses, i.e. not all cytokines are affected in the same fashion by space flight. Tissue culture studies also suggest that there may be direct effects of space flight on the cells responsible for cytokine production and action. The results of the above study indicate that the effects of space flight on cytokines may be a fundamental mechanism by which space flight not only affects immune responses, but also other biological systems of the human.

Modeled Microgravity Inhibits Apoptosis in Peripheral Blood Lymphocytes

NASA Technical Reports Server (NTRS)

Risin, Diana; Pellis, Neal R.

1999-01-01

Impairment of the immunity in astronauts and cosmonauts even in short term flights is a recognized risk. Long term orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Impairment of the immunity in space may be due tonumerous physiological changes caused by space-related factors, which in turn affect the immune system, or alternatively, it may be due to direct effects of different factors encountered in space on lymphoid cells and their interactions. Indeed, in modeled microgravity (MMG) experiments on Earth we and others showed that microgravity directly affects multiple lymphocyte functions. It interferes with expression of cell surface molecules, causes inhibition of lymphocyte locomotion, suppresses polyclopal and antigen-specific lymphocyte activation, selectively inhibits protein kinase C (PKC) isoforms. Some of these effects were also confirmed in cell culture experiments in real space conditions during Spacelab, Biokosmos and Shuttle Missions. The results of these studies, taken together, strongly indicated that microgravity interferes with fundamental biological processes associated with functional and structural changes in cell surface membranes, cell surface molecules and in their interaction. Based on the data and on their interpretation, we hypothesized that microgravity in addition to observed functional changes affects programmed cell death (PCD) in lymphocyte populations and that this mechanism could contribute to the impairment of the immunity.

Short-term direct contact with soil and plant materials leads to an immediate increase in diversity of skin microbiota.

PubMed

Grönroos, Mira; Parajuli, Anirudra; Laitinen, Olli H; Roslund, Marja I; Vari, Heli K; Hyöty, Heikki; Puhakka, Riikka; Sinkkonen, Aki

2018-05-29

Immune-mediated diseases have increased during the last decades in urban environments. The hygiene hypothesis suggests that increased hygiene level and reduced contacts with natural biodiversity are related to the increase in immune-mediated diseases. We tested whether short-time contact with microbiologically diverse nature-based materials immediately change bacterial diversity on human skin. We tested direct skin contact, as two volunteers rubbed their hands with sixteen soil and plant based materials, and an exposure via fabric packets filled with moss material. Skin swabs were taken before and after both exposures. Next-generation sequencing showed that exposures increased, at least temporarily, the total diversity of skin microbiota and the diversity of Acidobacteria, Actinobacteria, Bacteroidetes, Proteobacteria and Alpha-, Beta- and Gammaproteobacteria suggesting that contact with nature-based materials modify skin microbiome and increase skin microbial diversity. Until now, approaches to cure or prevent immune system disorders using microbe-based treatments have been limited to use of a few microbial species. We propose that nature-based materials with high natural diversity, such as the materials tested here, might be more effective in modifying human skin microbiome, and eventually, in reducing immune system disorders. Future studies should investigate how long-term changes in skin microbiota are achieved and if the exposure induces beneficial changes in the immune system markers. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Innate lymphoid cells in tissue homeostasis and diseases

PubMed Central

Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

2017-01-01

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver. PMID:28878863

Serological profiles in nursery piglets colonized with Staphylococcus aureus

PubMed Central

2013-01-01

At present, the immune response of pigs in relation to Staphylococcus aureus carriage is poorly understood. This study was aimed at investigating the dynamics of the anti-staphylococcal humoral immune response in methicillin-susceptible S. aureus (MSSA)-positive piglets and at assessing the effect of the experimental introduction of a methicillin-resistant S. aureus (MRSA) Sequence Type (ST) 398 strain. Therefore, serum samples were collected at different times from 31 weaned piglets originating from four different sows. Twenty-four out of the 31 piglets were challenged with MRSA ST398. The serum samples were analyzed for IgG antibodies to 39 S. aureus antigens, using a multiplex bead-based assay (xMAP technology, Luminex Corporation). Though antibody responses showed broad inter-individual variability, serological results appeared to be clustered by litter of origin. For most antigens, an age-related response was observed with an apparent increase in antibody titers directed against staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMM), which have been shown to play a role in S. aureus colonization. In most animals, antibody titers directed against staphylococcal toxins or immune-modulating proteins decreased with age, possibly reflecting the absence of bacterial invasion. The introduction of MRSA ST398 did not elicit a significant humoral immune reaction. This study describes, for the first time, the humoral immune response in weaned pigs colonized with S. aureus. PMID:23339425

High agreement between the new Mongolian electronic immunization register and written immunization records: a health centre based audit

PubMed Central

Mungun, Tuya; Dorj, Narangerel; Volody, Baigal; Chuluundorj, Uranjargal; Munkhbat, Enkhtuya; Danzan, Gerelmaa; Nguyen, Cattram D; La Vincente, Sophie; Russell, Fiona

2017-01-01

Introduction Monitoring of vaccination coverage is vital for the prevention and control of vaccine-preventable diseases. Electronic immunization registers have been increasingly adopted to assist with the monitoring of vaccine coverage; however, there is limited literature about the use of electronic registers in low- and middle-income countries such as Mongolia. We aimed to determine the accuracy and completeness of the newly introduced electronic immunization register for calculating vaccination coverage and determining vaccine effectiveness within two districts in Mongolia in comparison to written health provider records. Methods We conducted a cross-sectional record review among children 2–23 months of age vaccinated at immunization clinics within the two districts. We linked data from written records with the electronic immunization register using the national identification number to determine the completeness and accuracy of the electronic register. Results Both completeness (90.9%; 95% CI: 88.4–93.4) and accuracy (93.3%; 95% CI: 84.1–97.4) of the electronic immunization register were high when compared to written records. The increase in completeness over time indicated a delay in data entry. Conclusion Through this audit, we have demonstrated concordance between a newly introduced electronic register and health provider records in a middle-income country setting. Based on this experience, we recommend that electronic registers be accompanied by routine quality assurance procedures for the monitoring of vaccination programmes in such settings. PMID:29051836

Insect parents improve the anti-parasitic and anti-bacterial defence of their offspring by priming the expression of immune-relevant genes.

PubMed

Trauer-Kizilelma, Ute; Hilker, Monika

2015-09-01

Insect parents that experienced an immune challenge are known to prepare (prime) the immune activity of their offspring for improved defence. This phenomenon has intensively been studied by analysing especially immunity-related proteins. However, it is unknown how transgenerational immune priming affects transcript levels of immune-relevant genes of the offspring upon an actual threat. Here, we investigated how an immune challenge of Manduca sexta parents affects the expression of immune-related genes in their eggs that are attacked by parasitoids. Furthermore, we addressed the question whether the transgenerational immune priming of expression of genes in the eggs is still traceable in adult offspring. Our study revealed that a parental immune challenge did not affect the expression of immune-related genes in unparasitised eggs. However, immune-related genes in parasitised eggs of immune-challenged parents were upregulated to a higher level than those in parasitised eggs of unchallenged parents. Hence, this transgenerational immune priming of the eggs was detected only "on demand", i.e. upon parasitoid attack. The priming effects were also traceable in adult female progeny of immune-challenged parents which showed higher transcript levels of several immune-related genes in their ovaries than non-primed progeny. Some of the primed genes showed enhanced expression even when the progeny was left unchallenged, whereas other genes were upregulated to a greater extent in primed female progeny than non-primed ones only when the progeny itself was immune-challenged. Thus, the detection of transgenerational immune priming strongly depends on the analysed genes and the presence or absence of an actual threat for the offspring. We suggest that M. sexta eggs laid by immune-challenged parents "afford" to upregulate the transcription of immunity-related genes only upon attack, because they have the chance to be endowed by parentally directly transferred protective proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Law of Higher Education and the Courts: 1994 in Review.

ERIC Educational Resources Information Center

Robinson, John H.; Pieronek, Catherine

1996-01-01

The review of 1994 judicial pronouncements on the law of higher education reports on and discusses cases addressing the First Amendment, invasion of privacy, tort liability, immunities, civil procedure, access to records and meetings, funding, employment, disciplinary decision, discrimination against students, intercollegiate athletics, and…

Report of the Task Force on AIDS and Dental Education.

ERIC Educational Resources Information Center

Molinari, John; Gray, Carolyn F.

1988-01-01

The American Association of Dental Schools' task force on acquired immune deficiency syndrome and dental education recommends that educational strategies stress the necessity for routine infection control procedures in treatment, enhancing the health professionals' knowledge, attitudes, and behaviors concerning all aspects of disease prevention.…

Program on immunization and cold chain monitoring: the status in eight health districts in Cameroon.

PubMed

Ateudjieu, Jérôme; Kenfack, Bruno; Nkontchou, Blaise Wakam; Demanou, Maurice

2013-03-16

Cold chain monitoring is a precondition to ensure immunization quality, efficacy and safety. In Cameroon, the Expanded Program on Immunization (EPI) has National Standard Operating Procedure (SOP) that describes the vaccines, the cold chain system and equipment, its use and recommended procedures to control and monitor the temperatures and the cold chain. This study was conducted to assess the status of cold chain in eight health districts in Cameroon. The study was carried out in eight health districts out of fifty with poor immunization coverage rate. Data were collected using a validated form by observation and consultation of related documents. District Health Services (DHS) and four Integrated. Health Centers (IHC) randomly selected were targeted per health district. Forty health facilities were included. Twenty eight (70.0%) had at least one functional refrigerator for EPI activities. The power supply was reported to be permanent in 7 (20.6%) out of 34. (85.0%) health facilities with access to power supply. The temperature monitoring chart was pasted on 27 (96.4%) of the cold chain equipment. On 16 (59.3%) of these charts, the temperature was recorded twice daily as recommended. Seven (25.9%) of 27 refrigerators assessed had temperature out of the recommended range of 2 to 8°C. Almost 23.30% of health centers did not received any supervision on cold chain monitoring during a vaccination campaign. This study documents failure of the cold chain maintenance and questions the efficacy and safety of vaccines administered during EPI activities in Cameroun. These findings indicate that appropriate actions are needed to ensure monitoring of EPI cold chain in the country.

Program on immunization and cold chain monitoring: the status in eight health districts in Cameroon

PubMed Central

2013-01-01

Background Cold chain monitoring is a precondition to ensure immunization quality, efficacy and safety. In Cameroon, the Expanded Program on Immunization (EPI) has National Standard Operating Procedure (SOP) that describes the vaccines, the cold chain system and equipment, its use and recommended procedures to control and monitor the temperatures and the cold chain. This study was conducted to assess the status of cold chain in eight health districts in Cameroon. Findings The study was carried out in eight health districts out of fifty with poor immunization coverage rate. Data were collected using a validated form by observation and consultation of related documents. District Health Services (DHS) and four Integrated. Health Centers (IHC) randomly selected were targeted per health district. Forty health facilities were included. Twenty eight (70.0%) had at least one functional refrigerator for EPI activities. The power supply was reported to be permanent in 7 (20.6%) out of 34. (85.0%) health facilities with access to power supply. The temperature monitoring chart was pasted on 27 (96.4%) of the cold chain equipment. On 16 (59.3%) of these charts, the temperature was recorded twice daily as recommended. Seven (25.9%) of 27 refrigerators assessed had temperature out of the recommended range of 2 to 8°C. Almost 23.30% of health centers did not received any supervision on cold chain monitoring during a vaccination campaign. Conclusion This study documents failure of the cold chain maintenance and questions the efficacy and safety of vaccines administered during EPI activities in Cameroun. These findings indicate that appropriate actions are needed to ensure monitoring of EPI cold chain in the country. PMID:23497720

Physician and patient gender concordance and the delivery of comprehensive clinical preventive services.

PubMed

Flocke, Susan A; Gilchrist, Valerie

2005-05-01

Understanding the role of patient- and physician-gender on delivery of preventive services has important implications for identifying strategies to increase preventive service delivery. We attempt to overcome methodological limitations of previous studies in examining the association of the patient-physician gender interaction on the delivery of preventive screening, counseling, and immunization services. In this cross-sectional study, research nurses directly observed 3256 consecutive adult patient visits to 138 family physicians. Delivery of gender neutral US Preventive Services Task Force (USPSTF) recommended screening, health behavior counseling, and immunization services was assessed by direct observation and medical record review. Multilevel regression analyses were used to test the interaction effect of physician and patient gender with preventive service delivery, controlling for patient age, insurance type, number of office visits in the past 2 years and physician age. The interaction effect of physician and patient gender was not significantly associated with delivery of gender neutral screening, counseling, or immunizations. Patients of female physicians were more up-to-date on counseling services (P < 0.01) and immunizations (P < 0.05) than patients of male physicians. Male patients, independent of physician gender, were more up-to-date on counseling and immunizations (P < 0.01). Physician-patient gender concordance is not associated with delivery of more preventive services. Rather, female physicians provide more counseling and immunization services to all of their patients. Previous research showing higher rates of gender-specific screening achieved by women physicians may have been an indication of an overall greater prevention orientation among women physicians rather than a specific benefit of gender concordance.

The expression and genetic immunization of chimeric fragment of Hantaan virus M and S segments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Fanglin; Wu Xingan; Luo Wen

2007-03-23

Hemorrhagic fever with renal syndrome (HFRS), which is characterized by severe symptoms and high mortality, is caused by hantavirus. There are still no effective prophylactic vaccines directed to HFRS until now. In this research, we fused expressed G2 fragment of M segment and 0.7 kb fragment of S segment. We expect it could be a candidate vaccine. Chimeric gene G2S0.7 was first expressed in prokaryotic expression system pGEX-4T. After inducing expressed fusion proteins, GST-G2S0.7 was induced and its molecular weight was about 100 kDa. Meanwhile, the fusion protein kept the activity of its parental proteins. Further, BALB/c mice were vaccinatedmore » by the chimeric gene. ELISA, cell microculture neutralization test in vitro were used to detect the humoral immune response in immunized BALB/c mice. Lymphocyte proliferation assay was used to detect the cellular immune response. The results showed that the chimeric gene could simultaneously evoke specific antibody against nucleocapsid protein (NP) and glycoprotein (GP). And the immunized mice of every group elicited neutralizing antibodies with different titers. But the titers were low. Lymphocyte proliferation assay results showed that the stimulation indexes of splenocytes of chimeric gene to NP and GP were significantly higher than that of control. It suggested that the chimeric gene of Hantaan virus containing G2 fragment of M segment and 0.7 kb fragment of S segment could directly elicit specific anti-Hantaan virus humoral and cellular immune response in BALB/c mice.« less

A paramyxovirus-vectored intranasal vaccine against Ebola virus is immunogenic in vector-immune animals.

PubMed

Yang, Lijuan; Sanchez, Anthony; Ward, Jerrold M; Murphy, Brian R; Collins, Peter L; Bukreyev, Alexander

2008-08-01

Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans. The virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. Because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (HPIV3) expressing EBOV glycoprotein GP (HPIV3/EboGP) and showed that it is immunogenic and protective against a high dose parenteral EBOV challenge. However, because the adult human population has considerable immunity to HPIV3, which is a common human pathogen, replication and immunogenicity of the vaccine in this population might be greatly restricted. Indeed, in the present study, replication of the vaccine in the respiratory tract of HPIV3-immune guinea pigs was found to be restricted to undetectable levels. This restriction appeared to be based on both neutralizing antibodies and cellular or other components of the immunity to HPIV3. Surprisingly, even though replication of HPIV3/EboGP was highly restricted in HPIV3-immune animals, it induced a high level of EBOV-specific antibodies that nearly equaled that obtained in HPIV3-naive animals. We also show that the previously demonstrated presence of functional GP in the vector particle was not associated with increased replication in the respiratory tract nor with spread beyond the respiratory tract of HPIV3-naive guinea pigs, indicating that expression and functional incorporation of the attachment/penetration glycoprotein of this systemic virus did not mediate a change in tissue tropism.

The kinase inhibitors sunitinib and sorafenib differentially affect NK cell antitumor reactivity in vitro.

PubMed

Krusch, Matthias; Salih, Julia; Schlicke, Manuela; Baessler, Tina; Kampa, Kerstin Maria; Mayer, Frank; Salih, Helmut Rainer

2009-12-15

Sunitinib and Sorafenib are protein kinase inhibitors (PKI) approved for treatment of patients with advanced renal cell cancer (RCC). However, long-term remissions of advanced RCC have only been observed after IL-2 treatment, which underlines the importance of antitumor immune responses in RCC patients. Because PKI, besides affecting tumor cells, also may inhibit signaling in immune effector cells, we determined how Sunitinib and Sorafenib influence antitumor immunity. We found that cytotoxicity and cytokine production of resting and IL-2-activated PBMC are inhibited by pharmacological concentrations of Sorafenib but not Sunitinib. Analysis of granule-mobilization within PBMC revealed that this was due to impaired reactivity of NK cells, which substantially contribute to antitumor immunity by directly killing target cells and shaping adaptive immune responses by secreting cytokines like IFN-gamma. Analyses with resting and IL-2-activated NK cells revealed that both PKI concentration dependently inhibit cytotoxicity and IFN-gamma production of NK cells in response to tumor targets. This was due to impaired PI3K and ERK phosphorylation which directly controls NK cell reactivity. However, while Sorafenib inhibited NK cell effector functions and signaling at levels achieved upon recommended dosing, pharmacological concentrations of Sunitinib had no effect, and this was observed upon stimulation of NK cell reactivity by tumor target cells and upon IL-2 treatment. In light of the important role of NK cells in antitumor immunity, and because multiple approaches presently aim to combine PKI treatment with immunotherapeutic strategies, our data demonstrate that choice and dosing of the most suitable PKI in cancer treatment requires careful consideration.

Atypical E2F transcriptional repressor DEL1 acts at the intersection of plant growth and immunity by controlling the hormone salicylic acid.

PubMed

Chandran, Divya; Rickert, Joshua; Huang, Yingxiang; Steinwand, Michael A; Marr, Sharon K; Wildermuth, Mary C

2014-04-09

In plants, the activation of immunity is often inversely correlated with growth. Mechanisms that control plant growth in the context of pathogen challenge and immunity are unclear. Investigating Arabidopsis infection with the powdery mildew fungus, we find that the Arabidopsis atypical E2F DEL1, a transcriptional repressor known to promote cell proliferation, represses accumulation of the hormone salicylic acid (SA), an established regulator of plant immunity. DEL1-deficient plants are more resistant to pathogens and slightly smaller than wild-type. The resistance and size phenotypes of DEL1-deficient plants are due to the induction of SA and activation of immunity in the absence of pathogen challenge. Moreover, Enhanced Disease Susceptibility 5 (EDS5), a SA transporter required for elevated SA and immunity, is a direct repressed target of DEL1. Together, these findings indicate that DEL1 control of SA levels contributes to regulating the balance between growth and immunity in developing leaves. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia

PubMed Central

Volk, David W.

2017-01-01

Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia. PMID:28007586

Immune Interventions to Eliminate the HIV Reservoir.

PubMed

Hsu, Denise C; Ananworanich, Jintanat

2017-10-26

Inducing HIV remission is a monumental challenge. A potential strategy is the "kick and kill" approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV. Specific strategies include increasing the magnitude and breadth of T cell responses through therapeutic vaccinations, reversing the effects of T cell exhaustion using immune checkpoint inhibition, employing bispecific T cell targeting immunomodulatory proteins or dual-affinity re-targeting molecules to direct cytotoxic T lymphocytes to virus-expressing cells and broadly neutralizing antibody infusions. Methods to steer immune responses to tissue sites where latently infected cells are located need to be further explored. Ultimately, strategies to induce HIV remission must be tolerable, safe, and scalable in order to make a global impact.

Suppression of antigen-specific lymphocyte activation in modeled microgravity

NASA Technical Reports Server (NTRS)

Cooper, D.; Pride, M. W.; Brown, E. L.; Risin, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

2001-01-01

Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

The Neuromodulation of the Intestinal Immune System and Its Relevance in Inflammatory Bowel Disease.

PubMed

Di Giovangiulio, Martina; Verheijden, Simon; Bosmans, Goele; Stakenborg, Nathalie; Boeckxstaens, Guy E; Matteoli, Gianluca

2015-01-01

One of the main tasks of the immune system is to discriminate and appropriately react to "danger" or "non-danger" signals. This is crucial in the gastrointestinal tract, where the immune system is confronted with a myriad of food antigens and symbiotic microflora that are in constant contact with the mucosa, in addition to any potential pathogens. This large number of antigens and commensal microflora, which are essential for providing vital nutrients, must be tolerated by the intestinal immune system to prevent aberrant inflammation. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homeostasis and to prevent immune activation indiscriminately against all luminal antigens. Loss of this delicate equilibrium can lead to chronic activation of the intestinal immune response resulting in intestinal disorders, such as inflammatory bowel diseases (IBD). In order to maintain homeostasis, the immune system has evolved diverse regulatory strategies including additional non-immunological actors able to control the immune response. Accumulating evidence strongly indicates a bidirectional link between the two systems in which the brain modulates the immune response via the detection of circulating cytokines and via direct afferent input from sensory fibers and from enteric neurons. In the current review, we will highlight the most recent findings regarding the cross-talk between the nervous system and the mucosal immune system and will discuss the potential use of these neuronal circuits and neuromediators as novel therapeutic tools to reestablish immune tolerance and treat intestinal chronic inflammation.

Hepatitis B immunity in United States military recruits.

PubMed

Scott, Paul T; Niebuhr, David W; McGready, John B; Gaydos, Joel C

2005-06-01

In 2002, the US Department of Defense (DoD) mandated hepatitis B immunization for military recruits. A DoD study reported that screening for immunity with selective immunization would be cost-effective at a prevalence of immunity of >12%. The prevalence of hepatitis B immunity in the military recruit population was unknown. We studied a random sample of Army, Navy, and Marine Corps new recruits (2400 men and women from all 50 states, Puerto Rico, and US territories). Banked serum samples collected in 2001 were tested for antibody to hepatitis B surface antigen (anti-HBs) by AUSAB enzyme-linked immunoassay (EIA). Results were evaluated by military service branch, age, sex, race, level of education, geographic region of origin, and presence of state immunization laws. The overall prevalence of anti-HBs seropositivity, adjusted to the age distribution of the recruit population in 2001, was 31.5% (95% confidence interval [CI], 29.6%-33.4%). The prevalence of anti-HBs seropositivity, directly adjusted to the 18-35-year-old US population in 2000, was 23.0% (95% CI, 20.7%-25.3%). Anti-HBs seropositivity prevalence was highest among the young, decreased with increasing age, and was higher in women, recruits from the Northeast and West, and recruits from states with laws mandating hepatitis B immunization before entry into elementary and middle school. Screening new recruits for evidence of immunity before hepatitis B immunization is indicated. The prevalence of immunity increased with successive birth cohorts and may reflect the success of childhood immunization programs.

Interaction of Bacteriophages with the Immune System: Induction of Bacteriophage-Specific Antibodies.

PubMed

Dąbrowska, Krystyna

2018-01-01

In all cases when a bacteriophage makes direct contact with a mammalian organism, it may challenge the mammalian immunological system. Its major consequence is production of antibodies specific to the bacteriophage. Here we present protocols applicable in studies of bacteriophage ability to induce specific antibodies. The protocols have been divided into three parts: purification, immunization, and detection (ELISA).

48 CFR 29.303 - Application of State and local taxes to Government contractors and subcontractors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... claiming immunity from State or local sales or use taxes. Before any activity contends that a contractor is an agent of the Government, the matter shall be referred to the agency head for review. The referral... transaction from a sales or use tax may not rest on the Government's immunity from direct taxation by States...

High-resolution definition of humoral immune response correlates of effective immunity against HIV.

PubMed

Alter, Galit; Dowell, Karen G; Brown, Eric P; Suscovich, Todd J; Mikhailova, Anastassia; Mahan, Alison E; Walker, Bruce D; Nimmerjahn, Falk; Bailey-Kellogg, Chris; Ackerman, Margaret E

2018-03-26

Defining correlates of immunity by comprehensively interrogating the extensive biological diversity in naturally or experimentally protected subjects may provide insights critical for guiding the development of effective vaccines and antibody-based therapies. We report advances in a humoral immunoprofiling approach and its application to elucidate hallmarks of effective HIV-1 viral control. Systematic serological analysis for a cohort of HIV-infected subjects with varying viral control was conducted using both a high-resolution, high-throughput biophysical antibody profiling approach, providing unbiased dissection of the humoral response, along with functional antibody assays, characterizing antibody-directed effector functions such as complement fixation and phagocytosis that are central to protective immunity. Profiles of subjects with varying viral control were computationally analyzed and modeled in order to deconvolute relationships among IgG Fab properties, Fc characteristics, and effector functions and to identify humoral correlates of potent antiviral antibody-directed effector activity and effective viral suppression. The resulting models reveal multifaceted and coordinated contributions of polyclonal antibodies to diverse antiviral responses, and suggest key biophysical features predictive of viral control. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

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

PubMed Central

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

2006-01-01

Alveolar macrophages (AM) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses. Although several factors contribute to inhalational anthrax, we hypothesized that unimpeded infection of Bacillus anthracis is directly linked to disabling the innate immune functions contributed by AM. Here, we investigated the effects of lethal toxin (LT), one of the binary complex virulence factors produced by B. anthracis, on freshly isolated nonhuman primate AM. Exposure of AM to doses of LT that killed susceptible macrophages had no effect on the viability of AM, despite complete MEK1 cleavage. Intoxicated AM remained fully capable of B. anthracis spore phagocytosis. However, pretreatment of AM with LT resulted in a significant decrease in the clearance of both the Sterne strain and the fully virulent Ames strain of B. anthracis, which may have been a result of impaired AM secretion of proinflammatory cytokines. Our data imply that cytolysis does not correlate with MEK1 cleavage, and this is the first report of LT-mediated impairment of nonhuman primate AM bactericidal activity against B. anthracis. PMID:16926394

Antimicrobial Peptides as Mediators of Innate Immunity in Teleosts

PubMed Central

Katzenback, Barbara A.

2015-01-01

Antimicrobial peptides (AMPs) have been identified throughout the metazoa suggesting their evolutionarily conserved nature and their presence in teleosts is no exception. AMPs are short (18–46 amino acids), usually cationic, amphipathic peptides. While AMPs are diverse in amino acid sequence, with no two AMPs being identical, they collectively appear to have conserved functions in the innate immunity of animals towards the pathogens they encounter in their environment. Fish AMPs are upregulated in response to pathogens and appear to have direct broad-spectrum antimicrobial activity towards both human and fish pathogens. However, an emerging role for AMPs as immunomodulatory molecules has become apparent—the ability of AMPs to activate the innate immune system sheds light onto the multifaceted capacity of these small peptides to combat pathogens through direct and indirect means. Herein, this review focuses on the role of teleost AMPs as modulators of the innate immune system and their regulation in response to pathogens or other exogenous molecules. The capacity to regulate AMP expression by exogenous factors may prove useful in modulating AMP expression in fish to prevent disease, particularly in aquaculture settings where crowded conditions and environmental stress pre-dispose these fish to infection. PMID:26426065

Influences of Plant Traits on Immune Responses of Specialist and Generalist Herbivores

PubMed Central

Lampert, Evan

2012-01-01

Specialist and generalist insect herbivore species often differ in how they respond to host plant traits, particularly defensive traits, and these responses can include weakened or strengthened immune responses to pathogens and parasites. Accurate methods to measure immune response in the presence and absence of pathogens and parasites are necessary to determine whether susceptibility to these natural enemies is reduced or increased by host plant traits. Plant chemical traits are particularly important in that host plant metabolites may function as antioxidants beneficial to the immune response, or interfere with the immune response of both specialist and generalist herbivores. Specialist herbivores that are adapted to process and sometimes accumulate specific plant compounds may experience high metabolic demands that may decrease immune response, whereas the metabolic demands of generalist species differ due to more broad-substrate enzyme systems. However, the direct deleterious effects of plant compounds on generalist herbivores may weaken their immune responses. Further research in this area is important given that the ecological relevance of plant traits to herbivore immune responses is equally important in natural systems and agroecosystems, due to potential incompatibility of some host plant species and cultivars with biological control agents of herbivorous pests. PMID:26466545

Immune activity elevates energy expenditure of house sparrows: a link between direct and indirect costs?

PubMed Central

Martin, Lynn B; Scheuerlein, Alex; Wikelski, Martin

2003-01-01

The activation of an immune response is beneficial for organisms but may also have costs that affect fitness. Documented immune costs include those associated with acquisition of special nutrients, as well as immunopathology or autoimmunity. Here, we test whether an experimental induction of the immune system with a non-pathological stimulant can elevate energy turnover in passerine birds. We injected phytohaemagglutinin (PHA), a commonly used mitogen that activates the cell-mediated immune response, into the wing web of house sparrows, Passer domesticus. We then examined energetic costs resulting from this immune activity and related those costs to other physiological activities. We found that PHA injection significantly elevated resting metabolic rate (RMR) of challenged sparrows relative to saline controls. We calculated the total cost of this immune activity to be ca. 4.20 kJ per day (29% RMR), which is equivalent to the cost of production of half of an egg (8.23 kJ egg(-1)) in this species. We suggest that immune activity in wild passerines increases energy expenditure, which in turn may influence important life-history characteristics such as clutch size, timing of breeding or the scheduling of moult. PMID:12590753

Functions of Calcium-Dependent Protein Kinases in Plant Innate Immunity

PubMed Central

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

2014-01-01

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

Innate immunity is sufficient for the clearance of Chlamydia trachomatis from the female mouse genital tract.

PubMed

Sturdevant, Gail L; Caldwell, Harlan D

2014-10-01

Chlamydia muridarum and Chlamydia trachomatis, mouse and human strains, respectively, have been used to study immunity in a murine model of female genital tract infection. Despite evidence that unique genes of these otherwise genomically similar strains could play a role in innate immune evasion in their respective mouse and human hosts, there have been no animal model findings to directly support this conclusion. Here, we infected C57BL/6 and adaptive immune-deficient Rag1(-/-) female mice with these strains and evaluated their ability to spontaneously resolve genital infection. Predictably, C57BL/6 mice spontaneously cleared infection caused by both chlamydial strains. In contrast, Rag1(-/-) mice which lack mature T and B cell immunity but maintain functional innate immune effectors were incapable of resolving C. muridarum infection but spontaneously cleared C. trachomatis infection. This distinct dichotomy in adaptive and innate immune-mediated clearance between mouse and human strains has important cautionary implications for the study of natural immunity and vaccine development in the mouse model. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

CELL SURFACE SIGNALING MOLECULES IN THE CONTROL OF IMMUNE RESPONSES: A TIDE MODEL

PubMed Central

Zhu, Yuwen; Yao, Sheng; Chen, Lieping

2011-01-01

Summary A large numbers of cell surface signaling molecules (CSSMs) have been molecularly identified and functionally characterized in recent years and, via these studies, our knowledge in the control of immune response has increased exponentially. Two major lines of evidence emerge. First, the majority of immune cells rely on one or few CSSMs to deliver a primary triggering signal to sense their environment, leading to initiation of an immune response. Second, both costimulatory CSSMs that promote the response, and coinhibitory CSSMs that inhibit the response, are required to control direction and magnitude of a given immune response. With such tight feedback, immune responses are tuned and returned to baseline. These findings extend well beyond our previous observation in the requirement for lymphocyte activation and argue a revisit of the traditional “two-signal model” for activation and tolerance of lymphocytes. Here we propose a “tide” model to accommodate and interpret current experimental findings. PMID:21511182

Innate Immunity and Saliva in Candida albicans–mediated Oral Diseases

PubMed Central

Salvatori, O.; Puri, S.; Tati, S.; Edgerton, M.

2016-01-01

The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals. PMID:26747422

Mathematical modeling of diphtheria transmission in Thailand.

PubMed

Sornbundit, Kan; Triampo, Wannapong; Modchang, Charin

2017-08-01

In this work, a mathematical model for describing diphtheria transmission in Thailand is proposed. Based on the course of diphtheria infection, the population is divided into 8 epidemiological classes, namely, susceptible, symptomatic infectious, asymptomatic infectious, carrier with full natural-acquired immunity, carrier with partial natural-acquired immunity, individual with full vaccine-induced immunity, and individual with partial vaccine-induced immunity. Parameter values in the model were either directly obtained from the literature, estimated from available data, or estimated by means of sensitivity analysis. Numerical solutions show that our model can correctly describe the decreasing trend of diphtheria cases in Thailand during the years 1977-2014. Furthermore, despite Thailand having high DTP vaccine coverage, our model predicts that there will be diphtheria outbreaks after the year 2014 due to waning immunity. Our model also suggests that providing booster doses to some susceptible individuals and those with partial immunity every 10 years is a potential way to inhibit future diphtheria outbreaks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Opioids and the immune system: what is their mechanism of action?

PubMed Central

Eisenstein, Toby K

2011-01-01

There is a significant amount of literature showing that morphine and other opioids modulate immune responses. The findings support many mechanisms by which this may occur. In vitro experiments provide evidence for direct actions of opioids on immune cells using a variety of functional end points. When these drugs are given in vivo, a plethora of immune parameters are also altered. The paper in this issue of the journal by Zhang et al. provides new information on morphine alteration of immune cell subsets in the spleen and thymus of mice and the potential role of glucocorticoids in these observed phenomena. This Commentary reviews the in vitro activities of morphine on leucocytes, as well as other documented mechanisms by which morphine can alter immune function in vivo. LINKED ARTICLE This article is a commentary on Zhang et al., pp. 1829–1844 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01475.x PMID:21627636

Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.

PubMed

Heler, Robert; Wright, Addison V; Vucelja, Marija; Bikard, David; Doudna, Jennifer A; Marraffini, Luciano A

2017-01-05

CRISPR loci and their associated (Cas) proteins encode a prokaryotic immune system that protects against viruses and plasmids. Upon infection, a low fraction of cells acquire short DNA sequences from the invader. These sequences (spacers) are integrated in between the repeats of the CRISPR locus and immunize the host against the matching invader. Spacers specify the targets of the CRISPR immune response through transcription into short RNA guides that direct Cas nucleases to the invading DNA molecules. Here we performed random mutagenesis of the RNA-guided Cas9 nuclease to look for variants that provide enhanced immunity against viral infection. We identified a mutation, I473F, that increases the rate of spacer acquisition by more than two orders of magnitude. Our results highlight the role of Cas9 during CRISPR immunization and provide a useful tool to study this rare process and develop it as a biotechnological application. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms for eco-immunity in a changing enviroment: how does the coral innate immune system contend with climate change?

NASA Astrophysics Data System (ADS)

Traylor-Knowles, N. G.

2016-02-01

Innate immunity plays a central role in maintaining homeostasis, and within the context of impending climate change scenarios, understanding how this system works is critical. However, the actual mechanisms involved in the evolution of the innate immune system are largely unknown. Cnidaria (including corals, sea anemones and jellyfish) are well suited for studying the fundamental functions of innate immunity because they share a common ancestor with bilaterians. This study will highlight the transcriptomic changes during a heat shock in the coral Acropora hyacinthus of American Samoa, examining the temporal changes, every half an hour for 5 hours. We hypothesize that genes involved in innate immunity, and extracellular matrix maintenance will be key components to the heat stress response. This presentation will highlight the novel role of the tumor necrosis factor receptor gene family as a responder to heat stress and present future directions for this developing field in coral reef research.

Exosomes carrying immunoinhibitory proteins and their role in cancer.

PubMed

Whiteside, T L

2017-09-01

Recent emergence of exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Multi-directional cross-talk mediated by exosomes carrying proteins, lipids and nucleic acids between normal cells, cells harbouring a pathogen or cancer and immune cells has been instrumental in determining outcomes of physiological as well as pathological conditions. Exosomes play a key role in the broad spectrum of human diseases. In cancer, tumour-derived exosomes carry multiple immunoinhibitory signals, disable anti-tumour immune effector cells and promote tumour escape from immune control. Exosomes delivering negative signals to immune cells in cancer, viral infections, autoimmune or other diseases may interfere with therapy and influence outcome. Exosomes can activate tissue cells to produce inhibitory factors and thus can suppress the host immune responses indirectly. Exosomes also promise to be non-invasive disease biomarkers with a dual capability to provide insights into immune dysfunction as well as disease progression and outcome. © 2017 British Society for Immunology.

Human adaptive immune system Rag2-/-gamma(c)-/- mice.

PubMed

Chicha, Laurie; Tussiwand, Roxane; Traggiai, Elisabetta; Mazzucchelli, Luca; Bronz, Lucio; Piffaretti, Jean-Claude; Lanzavecchia, Antonio; Manz, Markus G

2005-06-01

Although many biologic principles are conserved in mice and humans, species-specific differences exist, for example, in susceptibility and response to pathogens, that often do not allow direct implementation of findings in experimental mice to humans. Research in humans, however, for ethical and practical reasons, is largely restricted to in vitro assays that lack components and the complexity of a living organism. To nevertheless study the human hematopoietic and immune system in vivo, xenotransplantation assays have been developed that substitute human components to small animals. Here, we summarize our recent findings that transplantation of human cord blood CD34(+) cells to newborn Rag2(-/-)gamma(c)(-/-) mice leads to de novo development of major functional components of the human adaptive immune system. These human adaptive immune system Rag2(-/-)gamma(c)(-/-) (huAIS-RG) mice can now be used as a technically straightforward preclinical model to evaluate in vivo human adaptive immune system development as well as immune responses, for example, to vaccines or live infectious pathogens.

Of worms, mice and man: an overview of experimental and clinical helminth-based therapy for inflammatory bowel disease.

PubMed

Heylen, Marthe; Ruyssers, Nathalie E; Gielis, Els M; Vanhomwegen, Els; Pelckmans, Paul A; Moreels, Tom G; De Man, Joris G; De Winter, Benedicte Y

2014-08-01

The incidence of inflammatory and autoimmune disorders is highest in well-developed countries which is directly related to their higher hygienic standards: it is suggested that the lack of exposure to helminths contributes to the susceptibility for immune-related diseases. Epidemiological, experimental and clinical data support the idea that helminths provide protection against immune-mediated diseases such as inflammatory bowel disease (IBD). The most likely mechanism for the suppression of immune responses by helminths is the release of helminth-derived immunomodulatory molecules. This article reviews the experimental and clinical studies investigating the therapeutic potential of helminth-based therapy in IBD and also focuses on the current knowledge of its immunomodulatory mechanisms of action highlighting innate as well as adaptive immune mechanisms. Identifying the mechanisms by which these helminths and helminth-derived molecules modulate the immune system will help in creating novel drugs for the treatment of IBD and other disorders that result from an overactive immune response. Copyright © 2014 Elsevier Inc. All rights reserved.

Solid-Phase Radioimmunoassay of Total and Influenza-Specific Immunoglobulin G

PubMed Central

Daugharty, Harry; Warfield, Donna T.; Davis, Marianne L.

1972-01-01

An antigen-antibody system of polystyrene tubes coated with immunoglobulin antibody was used for quantitating immunoglobulins. A similar radioimmunoassay method was adapted for a viral antigen-antibody system. The viral system can be used for quantitating viruses and for measuring virus-specific antibodies by reacting with 125iodine-labeled anti-immunoglobulin G (IgG). Optimal conditions for coating the solid phase, specificity of the immune reaction, and other kinetics and sensitivities of the assay method were investigated. Comparison of direct and indirect methods of assaying for immunoglobulins or viral antibody indicates that the indirect method is more sensitive and can quantitate a minimum of 0.037 μg of IgG per ml. Results of solid-phase radioimmunoassay for influenza antibody correlate well with hemagglutinin antibody titers but not with complement-fixing antibody titers. Radioimmunoassay results for influenza antibody by solid phase are likewise in agreement with results by the carrier precipitate radioimmunoassay method. The simplicity, reproducibility, and versatility of the solid-phase procedure make it diagnostically useful. PMID:5062884

Space-time Considerations for Hematopoietic Stem Cell Transplantation

PubMed Central

Bhattacharya, Deepta; Ehrlich, Lauren I. Richie; Weissman, Irving L.

2009-01-01

Summary The mammalian blood system contains a multitude of distinct mature cell lineages adapted to serve diverse functional roles. Mutations that abrogate the development or function of one or more of these lineages can lead to profound adverse consequences, such as immunodeficiency, autoimmunity, or anemia. Replacement of hematopoietic stem cells (HSCs) that carry such mutations with HSCs from a healthy donor can reverse such disorders, but because the risks associated with the procedure are often more serious than the blood disorders themselves, bone marrow transplantation is generally not used to treat a number of relatively common inherited blood diseases. Aside from a number of other problems, risks associated with cytoreductive treatments that create "space" for donor HSCs, and the slow kinetics with which immune competence is restored following transplantation hamper progress. This review will focus on how recent studies using experimental model systems may direct future efforts to implement routine use of HSC transplantation to cure inherited blood disorders. PMID:18651698

KAPOSI’S SARCOMA–ASSOCIATED HERPESVIRUS IMMUNOEVASION AND TUMORIGENESIS: TWO SIDES OF THE SAME COIN?

PubMed Central

Moore, Patrick S.; Chang, Yuan

2013-01-01

Kaposi’s sarcoma–associated herpesvirus (KSHV) [or human herpesvirus 8 (HHV-8)] is the most frequent cause of malignancy among AIDS patients. KSHV and related herpesviruses have extensively pirated cellular cDNAs from the host genome, providing a unique opportunity to examine the range of viral mechanisms for controlling cell proliferation. Many of the viral regulatory homologs encode proteins that directly inhibit host adaptive and innate immunity. Other viral proteins target retinoblastoma protein and p53 control of tumor suppressor pathways, which also play key effector roles in intracellular immune responses. The immune evasion strategies employed by KSHV, by targeting tumor suppressor pathways activated during immune system signaling, may lead to inadvertent cell proliferation and tumorigenesis in susceptible hosts. PMID:14527293

Effects of microgravity on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald; Taylor, Gerald R.

1991-01-01

Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

Harnessing dendritic cells in inflammatory skin diseases.

PubMed

Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

2011-02-01

The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

The race between infection and immunity - how do pathogens set the pace?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribiero, Ruy M

2009-01-01

Infection is often referred to as a race between pathogen and immune response. This metaphor suggests that slower growing pathogens should be more easily controlled. However, a growing body ofevidence shows that many chronic infections are caused by failure to control slow growing pathogens. The slow growth of pathogens appears to directly affect the kinetics of the immune response. Compared with the response to fast growing pathogens, the T cell response to slow pathogens is delayed in its initiation, lymphocyte expansion is slow and the response often fails to clear the pathogen, leading to chronic infection. Understanding the 'rules ofthemore » race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections.« less

PRENATAL INFECTION, MATERNAL IMMUNE ACTIVATION, AND RISK FOR SCHIZOPHRENIA

PubMed Central

Canetta, Sarah E.; Brown, Alan S.

2013-01-01

A body of epidemiological literature has suggested an association between prenatal infection, subsequent maternal immune activation (MIA), and later risk of schizophrenia. These epidemiological studies have inspired preclinical research using rodent and primate models of prenatal infection and MIA. The findings from these preclinical studies indicate that severe infection and immune activation during pregnancy can negatively impact offspring brain development and impair adult behavior. This review aims to summarize the major epidemiological and preclinical findings addressing the connection between prenatal infection and immune activation and later risk of developing schizophrenia, as well as the more limited literature addressing the mechanisms by which this gestational insult might affect offspring neurodevelopment. Finally, directions for future research will be discussed. PMID:23956839

Immunomodulation as a neuroprotective and therapeutic strategy for Parkinson's disease.

PubMed

Olson, Katherine E; Gendelman, Howard E

2016-02-01

While immune control is associated with nigrostriatal neuroprotection for Parkinson's disease, direct cause and effect relationships have not yet been realized, and modulating the immune system for therapeutic gain has been openly debated. Here, we review how innate and adaptive immunity affect disease pathobiology, and how each could be harnessed for treatment. The overarching idea is to employ immunopharmacologics as neuroprotective strategies for disease. The aim of the current work is to review disease-modifying treatments that are currently being developed as neuroprotective strategies for PD in experimental animal models and for human disease translation. The long-term goal of this research is to effectively harness the immune system to slow or prevent PD pathobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Hippo Pathway: Immunity and Cancer.

PubMed

Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

2018-03-28

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

Innate Lymphoid Cells: a new paradigm in immunology

PubMed Central

Eberl, Gérard; Colonna, Marco; Di Santo, James P.; McKenzie, Andrew N.J.

2016-01-01

Summary Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not express acquired antigen receptors or undergo clonal selection and expansion when stimulated. Instead, ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins termed cytokines that direct the developing immune response into one that is adapted to the original insult. The complex crosstalk between microenvironment, ILCs and adaptive immunity remains to be fully deciphered. Only by understanding these complex regulatory networks can the power of ILCs be controlled or unleashed to regulate or enhance immune responses in disease prevention and therapy. PMID:25999512

Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

PubMed

Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

Immunopathology of highly virulent pathogens: insights from Ebola virus.

PubMed

Zampieri, Carisa A; Sullivan, Nancy J; Nabel, Gary J

2007-11-01

Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic shock. We summarize the mechanisms of immune dysregulation and virus-mediated cell damage in Ebola virus-infected patients. Future approaches to prevention and treatment of infection will be guided by answers to unresolved questions about interspecies transmission, molecular mechanisms of pathogenesis, and protective adaptive and innate immune responses to Ebola virus.

An XA21-Associated Kinase (OsSERK2) Regulates Immunity Mediated by the XA21 and XA3 Immune Receptors

PubMed Central

Chen, Xuewei; Zuo, Shimin; Schwessinger, Benjamin; Chern, Mawsheng; Canlas, Patrick E.; Ruan, Deling; Zhou, Xiaogang; Wang, Jing; Daudi, Arsalan; Petzold, Christopher J.; Heazlewood, Joshua L.; Ronald, Pamela C.

2014-01-01

The rice XA21 immune receptor kinase and the structurally related XA3 receptor confer immunity to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced for OsSerk2 display altered morphology and reduced sensitivity to the hormone brassinolide. OsSERK2 interacts with the intracellular domains of each immune receptor in the yeast two-hybrid system in a kinase activity-dependent manner. OsSERK2 undergoes bidirectional transphosphorylation with XA21 in vitro and forms a constitutive complex with XA21 in vivo. These results demonstrate an essential role for OsSERK2 in the function of three rice immune receptors and suggest that direct interaction with the rice immune receptors is critical for their function. Taken together, our findings suggest that the mechanism of OsSERK2-meditated regulation of rice XA21, XA3, and FLS2 differs from that of AtSERK3/BAK1-mediated regulation of Arabidopsis FLS2 and EFR. PMID:24482436

The intersection of cancer, cancer stem cells, and the immune system: therapeutic opportunities.

PubMed

Silver, Daniel J; Sinyuk, Maksim; Vogelbaum, Michael A; Ahluwalia, Manmeet S; Lathia, Justin D

2016-02-01

During brain neoplasia, malignant cells subjugate the immune system to provide an environment that favors tumor growth. These mechanisms capitalize on tumor-promoting functions of various immune cell types and typically result in suppression of tumor immune rejection. Immunotherapy efforts are underway to disrupt these mechanisms and turn the immune system against developing tumors. While many of these therapies are already in early-stage clinical trials, understanding how these therapies impact various tumor cell populations, including self-renewing cancer stem cells, may help to predict their efficacy and clarify their mechanisms of action. Moreover, interrogating the biology of glioma cell, cancer stem cell, and immune cell interactions may provide additional therapeutic targets to leverage against disease progression. In this review, we begin by highlighting a series of investigations into immune cell-mediated tumor promotion that do not parse the tumor into stem and non-stem components. We then take a closer look at the immune-suppressive mechanisms derived specifically from cancer stem cell interactions with the immune system and end with an update on immunotherapy and cancer stem cell-directed clinical trials in glioblastoma. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Surface-Micromachined Microfiltration Membranes for Efficient Isolation and Functional Immunophenotyping of Subpopulations of Immune Cells

PubMed Central

Oh, Boram; Lam, Raymond H. W.; Fan, Rong; Cornell, Timothy T.; Shanley, Thomas P.; Kurabayashi, Katsuo; Fu, Jianping

2015-01-01

An accurate measurement of the immune status in patients with immune system disorders is critical in evaluating the stage of diseases and tailoring drug treatments. The functional cellular immunity test is a promising method to establish the diagnosis of immune dysfunctions. The conventional functional cellular immunity test involves measurements of the capacity of peripheral blood mononuclear cells to produce pro-inflammatory cytokines when stimulated ex vivo. However, this “bulk” assay measures the overall reactivity of a population of lymphocytes and monocytes, making it difficult to pinpoint the phenotype or real identity of the reactive immune cells involved. In this research, we develop a large surface micromachined polydimethylsiloxane (PDMS) microfiltration membrane (PMM) with high porosity, which is integrated in a microfluidic microfiltration platform. Using the PMM with functionalized microbeads conjugated with antibodies against specific cell surface proteins, we demonstrated rapid, efficient and high-throughput on-chip isolation, enrichment, and stimulation of subpopulations of immune cells from blood specimens. Furthermore, the PMM-integrated microfiltration platform, coupled with a no-wash homogeneous chemiluminescence assay (“AlphaLISA”), enables us to demonstrate rapid and sensitive on-chip immunophenotyping assays for subpopulations of immune cells isolated directly from minute quantities of blood samples. PMID:23335389

Regulation of cancer immune escape: The roles of miRNAs in immune checkpoint proteins.

PubMed

Yang, Qin; Cao, Wenjie; Wang, Zi; Zhang, Bin; Liu, Jing

2018-09-01

Immune checkpoint proteins (ICPs) are regulators of immune system. The ICP dysregulation silences the host immune response to cancer-specific antigens, contributing to the occurrence and progress of various cancers. MiRNAs are regulatory molecules and function in mRNA silencing and post-transcriptional regulation of gene expression. MiRNAs that modulate the immunity via ICPs have received increasing attention. Many studies have shown that the expressions of ICPs are directly or indirectly repressed by miRNAs in multiple types of cancers. MiRNAs are also subject to regulation by ICPs. In this review, recent studies of the relationship between miRNAs and ICPs (including the PD-1, PD-L1, CTLA-4, ICOS, B7-1, B7-2, B7-H2, B7-H3, CD27, CD70, CD40, and CD40L) in cancer immune escape are comprehensively discussed, which provide critical detailed mechanistic insights into the functions of the miRNA-ICP axes and their effects on immune escape, and will be beneficial for the potential applications of immune checkpoint therapy and miRNA-based guidance for personalized medicine as well as for predicting the prognosis. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of community pharmacy-based vaccination in the USA: current practice and future directions

PubMed Central

Bach, Albert T; Goad, Jeffery A

2015-01-01

Community pharmacy-based provision of immunizations in the USA has become commonplace in the last few decades, with success in increasing rates of immunizations. Community pharmacy-based vaccination services are provided by pharmacists educated in the practice of immunization delivery and provide a convenient and accessible option for receiving immunizations. The pharmacist’s role in immunization practice has been described as serving in the roles of educator, facilitator, and immunizer. With a majority of pharmacist-provided vaccinations occurring in the community pharmacy setting, there are many examples of community pharmacists serving in these immunization roles with successful outcomes. Different community pharmacies employ a number of different models and workflow practices that usually consist of a year-round in-house service staffed by their own immunizing pharmacist. Challenges that currently exist in this setting are variability in scopes of immunization practice for pharmacists across states, inconsistent reimbursement mechanisms, and barriers in technology. Many of these challenges can be alleviated by continual education; working with legislators, state boards of pharmacy, stakeholders, and payers to standardize laws; and reimbursement design. Other challenges that may need to be addressed are improvements in communication and continuity of care between community pharmacists and the patient centered medical home. PMID:29354521

Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes.

PubMed

Hanon, E; Hall, S; Taylor, G P; Saito, M; Davis, R; Tanaka, Y; Usuku, K; Osame, M; Weber, J N; Bangham, C R

2000-02-15

The role of the cellular immune response in human T-cell leukemia virus type I (HTLV-I) infection is not fully understood. A persistently activated cytotoxic T lymphocyte (CTL) response to HTLV-I is found in the majority of infected individuals. However, it remains unclear whether this CTL response is protective or causes tissue damage. In addition, several observations paradoxically suggest that HTLV-I is transcriptionally silent in most infected cells and, therefore, not detectable by virus-specific CTLs. With the use of a new flow cytometric procedure, we show here that a high proportion of naturally infected CD4+ peripheral blood mononuclear cells (PBMC) (between 10% and 80%) are capable of expressing Tax, the immunodominant target antigen recognized by virus-specific CTLs. Furthermore, we provide direct evidence that autologous CD8+ T cells rapidly kill CD4+ cells naturally infected with HTLV-I and expressing Tax in vitro by a perforin-dependent mechanism. Consistent with these observations, we observed a significant negative correlation between the frequency of Tax(11-19)-specific CD8+ T cells and the percentage of CD4+ T cells in peripheral blood of patients infected with HTLV-I. Those results are in accordance with the view that virus-specific CTLs participate in a highly efficient immune surveillance mechanism that persistently destroys Tax-expressing HTLV-I-infected CD4+ T cells in vivo. (Blood. 2000;95:1386-1392)

Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

NASA Astrophysics Data System (ADS)

Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

2001-03-01

Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.

Immunization with excreted-secreted antigens reduces tissue cyst formation in pigs.

PubMed

Wang, Yanhua; Zhang, Delin; Wang, Guangxiang; Yin, Hong; Wang, Meng

2013-11-01

It has been demonstrated that tachyzoite-pooled excreted-secreted antigens (ESAs) of Toxoplasma gondii are highly immunogenic and can be used in vaccine development. However, most of the information regarding protective immunity induced by immunization with ESAs is derived from studies using mouse model systems. These results cannot be extrapolated to pigs due to important differences in the susceptibility and immune response mechanisms between pigs and mice. We show that the immunization of pigs with ESAs emulsified in Freund's adjuvant induced not only a humoral immune response but also a cellular response. The cellular immune response was associated with the production of IFN-γ and IL-4. The humoral immune response was mainly directed against the antigens with molecular masses between 34 and 116 kDa. After intraperitoneal challenge with 10(7) T. gondii of the Gansu Jingtai strain (GJS) of tachyzoites, the immunized pigs remained clinically normal except for a brief low-grade fever (≤40.5 °C), while the control pigs developed clinical signs of toxoplasmosis (cough, anorexia, prostration, and high fever). At necropsy, visible lesions were found at multiple locations (enlarged mesenteric lymph nodes, an enlarged spleen with focal necrosis, and enlarged lungs with miliary or focal necrosis and off-white lesions) in all of the control pigs but not in the pigs that had been immunized. We also found that immunization with ESAs reduced tissue cyst formation in the muscle (P < 0.01). Our data demonstrate that immunization with ESAs can trigger a strong immune response against T. gondii infection in pigs.

Oral innate immunity in HIV infection in HAART era.

PubMed

Nittayananta, Wipawee; Tao, Renchuan; Jiang, Lanlan; Peng, Yuanyuan; Huang, Yuxiao

2016-01-01

Oral innate immunity, an important component in host defense and immune surveillance in the oral cavity, plays a crucial role in the regulation of oral health. As part of the innate immune system, epithelial cells lining oral mucosal surfaces not only provide a physical barrier but also produce different antimicrobial peptides, including human β-defensins (hBDs), secretory leukocyte protease inhibitor (SLPI), and various cytokines. These innate immune mediators help in maintaining oral homeostasis. When they are impaired either by local or systemic causes, various oral infections and malignancies may be developed. Human immunodeficiency virus (HIV) infection and other co-infections appear to have both direct and indirect effects on systemic and local innate immunity leading to the development of oral opportunistic infections and malignancies. Highly active antiretroviral therapy (HAART), the standard treatment of HIV infection, contributed to a global reduction of HIV-associated oral lesions. However, prolonged use of HAART may lead to adverse effects on the oral innate immunity resulting in the relapse of oral lesions. This review article focused on the roles of oral innate immunity in HIV infection in HAART era. The following five key questions were addressed: (i) What are the roles of oral innate immunity in health and disease?, (ii) What are the effects of HIV infection on oral innate immunity?, (iii) What are the roles of oral innate immunity against other co-infections?, (iv) What are the effects of HAART on oral innate immunity?, and (v) Is oral innate immunity enhanced by HAART? © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Estrogen, Angiogenesis, Immunity and Cell Metabolism: Solving the Puzzle.

PubMed

Trenti, Annalisa; Tedesco, Serena; Boscaro, Carlotta; Trevisi, Lucia; Bolego, Chiara; Cignarella, Andrea

2018-03-15

Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ERα and ERβ, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17β-estradiol can influence the cardiovascular and immune systems.

A cross-immunization model for the extinction of old influenza strains.

PubMed

Uekermann, Florian; Sneppen, Kim

2016-05-13

Given the frequent mutation of antigenic features, the constancy of genetic and antigenic diversity of influenza within a subtype is surprising. While the emergence of new strains and antigenic features is commonly attributed to selection by the human immune system, the mechanism that ensures the extinction of older strains remains controversial. To replicate this dynamics of replacement current models utilize mechanisms such as short-lived strain-transcending immunity, a direct competition for hosts, stochastic extinction or constrained antigenic evolution. Building on the idea of short-lived immunity we introduce a minimal model that exhibits the aforementioned dynamics of replacement. Our model relies only on competition due to an antigen specific immune-response in an unconstrained antigenic space. Furthermore the model explains the size of typical influenza epidemics as well as the tendency that new epidemics are associated with mutations of old antigens.

GABAergic neurons in cerebellar interposed nucleus modulate cellular and humoral immunity via hypothalamic and sympathetic pathways.

PubMed

Lu, Jian-Hua; Wang, Xiao-Qin; Huang, Yan; Qiu, Yi-Hua; Peng, Yu-Ping

2015-06-15

Our previous work has shown that cerebellar interposed nucleus (IN) modulates immune function. Herein, we reveal mechanism underlying the immunomodulation. Treatment of bilateral cerebellar IN of rats with 3-mercaptopropionic acid (3-MP), a glutamic acid decarboxylase antagonist that reduces γ-aminobutyric acid (GABA) synthesis, enhanced cellular and humoral immune responses to bovine serum albumin, whereas injection of vigabatrin, a GABA-transaminase inhibitor that inhibits GABA degradation, in bilateral cerebellar IN attenuated the immune responses. The 3-MP or vigabatrin administrations in the cerebellar IN decreased or increased hypothalamic GABA content and lymphoid tissues' norepinephrine content, respectively, but did not alter adrenocortical or thyroid hormone levels in serum. In addition, a direct GABAergic projection from cerebellar IN to hypothalamus was found. These findings suggest that GABAergic neurons in cerebellar IN regulate immune system via hypothalamic and sympathetic pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunization Equity.

PubMed

Hinman, Alan R; McKinlay, Mark A

2015-12-01

Health inequities are the unjust differences in health among different social groups. Unfortunately, inequities are the norm, both in terms of health status and access to, and use of, health services. Childhood immunizations reduce the incidence of vaccine-preventable diseases and represent a cost-effective way to foster health equity. This paper reflects a 2015 review of data from surveys conducted in developing countries from 2005 to 2011 that show significant inequities in immunization coverage and discusses several initiatives currently underway (including Gavi, the Vaccine Alliance) that are directed at increasing childhood immunizations or reducing or abolishing overall health inequities. These initiatives have already had a significant impact on disease burden and childhood mortality and give rise to optimism that health disparities may further be reduced and health equity achieved as a result of investments made in immunization. Copyright © 2015 2015 by American Journal of Preventive Medicine and Els. Published by Elsevier Inc. All rights reserved.

Epilepsy and the immune system: is there a link?

PubMed

Billiau, An D; Wouters, Carine H; Lagae, Lieven G

2005-01-01

The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed more than 20 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients, on the observation of favourable responses of refractory epilepsy syndromes to immunomodulatory treatment, and on the association of certain well-known immune-mediated disease states with epilepsy. This review comprehensively recapitulates the currently available evidence supporting or arguing against the possible involvement of the immune system in the pathogenesis of certain types of epilepsy. It is concluded that an abundance of facts is in support of this concept and that further studies should be directed at substantiating the pathogenic significance of (auto)immune responses in certain types of epilepsy. Current progress in the functional and molecular immunological research techniques will indisputably contribute to the elucidation of this link.

Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

NASA Technical Reports Server (NTRS)

Crucian, Brian; Sams, Clarence F.

2013-01-01

The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in- and post-flight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deep-space exploration missions.

Countermeasure for space flight effects on immune system: nutritional nucleotides

NASA Technical Reports Server (NTRS)

Kulkarni, A. D.; Yamauchi, K.; Sundaresan, A.; Ramesh, G. T.; Pellis, N. R.

2005-01-01

Microgravity and its environment have adverse effects on the immune system. Abnormal immune responses observed in microgravity may pose serious consequences, especially for the recent directions of NASA for long-term space missions to Moon, Mars and deep Space exploration. The study of space flight immunology is limited due to relative inaccessibility, difficulty of performing experiments in space, and inadequate provisions in this area in the United States and Russian space programs (Taylor 1993). Microgravity and stress experienced during space flights results in immune system aberration (Taylor 1993). In ground-based mouse models for some of the microgravity effects on the human body, hindlimb unloading (HU) has been reported to cause abnormal cell proliferation and cytokine production (Armstrong et al., 1993, Chapes et al. 1993). In this report, we document that a nutritional nucleotide supplementation as studied in ground-based microgravity analogs, has potential to serve as a countermeasure for the immune dysfunction observed in space travel.

Kidney dendritic cells in acute and chronic renal disease.

PubMed

Hochheiser, Katharina; Tittel, André; Kurts, Christian

2011-06-01

Dendritic cells are not only the master regulators of adaptive immunity, but also participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney, and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. Here we summarize the current knowledge on the role of kidney dendritic cells that has been obtained from the study of murine models of renal disease. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes

NASA Astrophysics Data System (ADS)

St. John, Ashley L.; Chan, Cheryl Y.; Staats, Herman F.; Leong, Kam W.; Abraham, Soman N.

2012-03-01

Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic particles, which consist of a carbohydrate backbone with encapsulated inflammatory mediators such as tumour necrosis factor, replicate attributes of MCs in vivo including the targeting of draining lymph nodes and the timed release of the encapsulated mediators. When used as an adjuvant during vaccination of mice with haemagglutinin from the influenza virus, the particles enhanced adaptive immune responses and increased survival of mice on lethal challenge. Furthermore, differential loading of the particles with the cytokine IL-12 directed the character of the response towards Th1 lymphocytes. The synthetic MC adjuvants replicate and enhance the functions of MCs during vaccination, and can be extended to polarize the resulting immunity.

A simple method for determining polymeric IgA-containing immune complexes.

PubMed

Sancho, J; Egido, J; González, E

1983-06-10

A simplified assay to measure polymeric IgA-immune complexes in biological fluids is described. The assay is based upon the specific binding of a secretory component for polymeric IgA. In the first step, multimeric IgA (monomeric and polymeric) immune complexes are determined by the standard Raji cell assay. Secondly, labeled secretory component added to the assay is bound to polymeric IgA-immune complexes previously fixed to Raji cells, but not to monomeric IgA immune complexes. To avoid false positives due to possible complement-fixing IgM immune complexes, prior IgM immunoadsorption is performed. Using anti-IgM antiserum coupled to CNBr-activated Sepharose 4B this step is not time-consuming. Polymeric IgA has a low affinity constant and binds weakly to Raji cells, as Scatchard analysis of the data shows. Thus, polymeric IgA immune complexes do not bind to Raji cells directly through Fc receptors, but through complement breakdown products, as with IgG-immune complexes. Using this method, we have been successful in detecting specific polymeric-IgA immune complexes in patients with IgA nephropathy (Berger's disease) and alcoholic liver disease, as well as in normal subjects after meals of high protein content. This new, simple, rapid and reproducible assay might help to study the physiopathological role of polymeric IgA immune complexes in humans and animals.

Parental vaccine concerns, information source, and choice of alternative immunization schedules.

PubMed

Wheeler, Marissa; Buttenheim, Alison M

2013-08-01

Alternative immunization schedules increase the time a child is unvaccinated and require greater resources from providers. Understanding what drives interest in alternative immunization schedules can potentially inform the design of effective, targeted messages that help to reduce time spent counseling and decrease requests for alternative immunization schedules. This study used the Theory of Planned Behavior to explore associations between sources of vaccine information, parental vaccine concerns, peer norms for vaccine behavior and intentions to follow an alternative immunization schedule. We performed logistic regression using medical record data from a private pediatric practice in a large northeastern city. Routine data were recorded in the EMR by the pediatrician during an initial vaccine counseling conversation with the parent(s). Parents who received vaccine information from doctors were less likely to have immunization concerns while parents who got vaccine information from friends and family or from books were more likely to report specific vaccine concerns. Our multivariate analysis shows that number of reported vaccine concerns and concerns about the utility or necessity of vaccines are strongly associated with alternative immunization intentions. We also find a direct relationship between sources of information about vaccines and alternative immunization intentions. Our results suggest that vaccine concerns and non-physician information sources play an important role in alternative immunization intentions while communication from physicians may play an important role in addressing vaccine concerns and promoting adherence to the ACIP immunization schedule.

Nepotism: A Policy of Convenience?

ERIC Educational Resources Information Center

Ruder, Robert

2010-01-01

Nepotism is one of those words that makes people cringe. The hint of such behavior within an organization immediately raises suspicions of unethical behavior despite well-written, comprehensive policies and procedures. School districts are not immune to the damage that can be done to even the most highly regarded and well-respected organizations.…

AIDS on Campus: Emerging Issues for College and University Administrators.

ERIC Educational Resources Information Center

Steinbach, Sheldon Elliot

Legal information concerning Acquired Immune Deficiency Syndrome (AIDS) that college presidents may find helpful in establishing policies and procedures is provided in a paper by the general counsel of the American Council on Education. Sources of medical information, including the American College Health Association, hotlines, and federal…

Developments in the Law--Section 1981.

ERIC Educational Resources Information Center

Aguilar, Javier; And Others

1980-01-01

Reviews the history and current state of the law under Section 1981 of the Civil Rights Act of 1866. Suggests how it may be interpreted to maintain its vitality as a guarantee of racial equality. Considers actionable discrimination claims, protected interests, prima facie evidence, constitutional defenses, immunities, and procedural issues.…

Class Action Aspects of Federal Employment Discrimination Litigation

ERIC Educational Resources Information Center

Bickel, Robert D.; Vandercreek, William

1974-01-01

Overviews Rule 23 (Federal Rules of Civil Procedure) governing class actions in the federal courts and analyzes the issues raised in class determinations for employment discrimination suits under Title VII (Civil Rights Act 1964). Discusses damage claim immunity for public institutions and limitations on evidence offered to prove discrimination.…

Psychosocial Factors and AIDS-Related Behavior of Homosexual Men: Measurement and Associations.

ERIC Educational Resources Information Center

Zapka, Jane G.; And Others

1990-01-01

Measurement and data-reduction procedures were conducted for psychosocial scales used in behavioral research on the acquired immune deficiency syndrome (AIDS). Associations of the scales for other personal and health services/information factors with one selected AIDS protective behavior among 281 asymptomatic homosexual/bisexual men were…

Innate Immune Responses to Cryptococcus.

PubMed

Heung, Lena J

2017-09-01

Cryptococcus species are encapsulated fungi found in the environment that predominantly cause disease in immunocompromised hosts after inhalation into the lungs. Even with contemporary antifungal regimens, patients with cryptococcosis continue to have high morbidity and mortality rates. The development of more effective therapies may depend on our understanding of the cellular and molecular mechanisms by which the host promotes sterilizing immunity against the fungus. This review will highlight our current knowledge of how Cryptococcus , primarily the species C. neoformans , is sensed by the mammalian host and how subsequent signaling pathways direct the anti-cryptococcal response by effector cells of the innate immune system.

Systems immunology: just getting started.

PubMed

Davis, Mark M; Tato, Cristina M; Furman, David

2017-06-20

Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated.

Systems immunology: just getting started

PubMed Central

Davis, Mark M; Tato, Cristina M; Furman, David

2018-01-01

Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated. PMID:28632713

Atypical presentation of systemic lupus erythematosus: parotitis and secondary Sjogren's syndrome. Case report.

PubMed

Criscov, Geanina Irina; Rugină, Aurica; Stana, A B; Azoicăi, Alice Nicoleta; Moraru, Eovelina

2014-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by auto antibodies directed against self-antigens, immune complex formation and immune deregulations and may affect joints, skin, kidneys, heart, lungs, nervous system, and immune system. The onset can be variable and the symptoms can occur for many years. Parotitis as the initial manifestation of systemic lupus erythematosus (SLE) is a rare condition and can be associated with Sjogren's syndrome. In this article we present the case of a young patient who was diagnosed with Sjogren's syndrome retrospectively, after she met the criteria for SLE.

Innate Immune Responses to Cryptococcus

PubMed Central

Heung, Lena J.

2017-01-01

Cryptococcus species are encapsulated fungi found in the environment that predominantly cause disease in immunocompromised hosts after inhalation into the lungs. Even with contemporary antifungal regimens, patients with cryptococcosis continue to have high morbidity and mortality rates. The development of more effective therapies may depend on our understanding of the cellular and molecular mechanisms by which the host promotes sterilizing immunity against the fungus. This review will highlight our current knowledge of how Cryptococcus, primarily the species C. neoformans, is sensed by the mammalian host and how subsequent signaling pathways direct the anti-cryptococcal response by effector cells of the innate immune system. PMID:28936464

Live Music Therapy as an Active Focus of Attention for Pain and Behavioral Symptoms of Distress During Pediatric Immunization.

PubMed

Sundar, Sumathy; Ramesh, Bhuvaneswari; Dixit, Priyanka B; Venkatesh, Soma; Das, Prarthana; Gunasekaran, Dhandapany

2016-07-01

A total of 100 children coming for routine immunization to pediatric outpatient department were included and were divided into experiment (n = 50) and control (n = 50) groups. Experiment group received live music therapy during immunization procedure. Control group received no intervention. The Modified Behavior Pain Scale (MBPS), 10-point pain levels, and 10-point distress levels were documented by parents. Duration of crying was recorded by investigators. Pre- and postimmunization blood pressures and heart rates of parents holding the children were also measured and recorded by investigators. Independent and paired t tests were used for analysis. All 3 domains of the Modified Behavior Pain Scale and duration of crying showed significant improvement (P < .05) in the experiment group. Pain and distress levels also showed statistically nonsignificant improvement in experiment group. Blood pressure and heart rate of parents showed no difference. Music therapy could be helpful to children, parents, and health care providers by reducing discomfort of the child during pediatric immunization. © The Author(s) 2015.

Vaccinomics, adversomics, and the immune response network theory: Individualized vaccinology in the 21st century

PubMed Central

Poland, Gregory A.; Kennedy, Richard B.; McKinney, Brett A.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Jacobson, Robert M.; Oberg, Ann L.

2013-01-01

Vaccines, like drugs and medical procedures, are increasingly amenable to individualization or personalization, often based on novel data resulting from high throughput “omics” technologies. As a result of these technologies, 21st century vaccinology will increasingly see the abandonment of a “one size fits all” approach to vaccine dosing and delivery, as well as the abandonment of the empiric “isolate–inactivate–inject” paradigm for vaccine development. In this review, we discuss the immune response network theory and its application to the new field of vaccinomics and adversomics, and illustrate how vaccinomics can lead to new vaccine candidates, new understandings of how vaccines stimulate immune responses, new biomarkers for vaccine response, and facilitate the understanding of what genetic and other factors might be responsible for rare side effects due to vaccines. Perhaps most exciting will be the ability, at a systems biology level, to integrate increasingly complex high throughput data into descriptive and predictive equations for immune responses to vaccines. Herein, we discuss the above with a view toward the future of vaccinology. PMID:23755893

Immunization of sockeye salmon (Oncorhynchus nerka) against vibriosis using the hyperosmotic infiltration technique

USGS Publications Warehouse

Croy, Thomas R.; Amend, Donald F.

1977-01-01

Various procedures of hyperosmotic infiltration (HI) and intraperitoneal injection were used to vaccinate sockeye salmon (Oncorhynchus nerka) with killed Vibrio anguillarum. Excellent protection was evident against experimentally induced vibriosis in the groups immunized by HI with 10 × Hanks' balanced salt solution (HBSS), 1 × HBSS with 8.0% NaCl and 5.3% NaCl, as well as in the injected groups. Comparisons were made among the various immunization methods by vaccinating fish with ten-fold serial dilutions of bacterin, then challenging them by the water contact method after 6 or 9 weeks. Protection was somewhat better with 10 × HBSS than with 5.3% NaCl, and 1 × HBSS containing 8.0% NaCl was markedly superior to the vaccination of fish without hyperosmotic treatment. Agglutinin titers did not exceed 1 : 8 in any group.

Development of an active boring bar for increased chatter immunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redmond, J.; Barney, P.; Smith, D.

The development and initial evaluation of a prototype boring bar featuring active vibration control for increased chatter immunity is described. The significance of active damping both normal and tangential to the workpiece surface is evaluated, indicating the need for two axis control to ensure adequate performance over expected variations in tool mounting procedures. The prototype tool features a commercially available boring bar modified to accommodate four PZT stack actuators for two axis bending control. Measured closed-loop dynamics are combined with a computer model of the boring process to simulate increased metal removal rate and improved workpiece surface finish through activemore » control.« less

New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells

PubMed Central

Gupta, Nancy; Kumar, Rakesh; Agrawal, Babita

2018-01-01

Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally. Efforts to control and eradicate TB are hampered by the rapid emergence of drug resistance and limited efficacy of the only available vaccine, BCG. Immunological events in the airways and lungs are of major importance in determining whether exposure to Mycobacterium tuberculosis (Mtb) results in successful infection or protective immunity. Several studies have demonstrated that the host microbiota is in constant contact with the immune system, and thus continually directs the nature of immune responses occurring during new infections. However, little is known about its role in the eventual outcome of the mycobacterial infection. In this review, we highlight the changes in microbial composition in the respiratory tract and gut that have been linked to the alteration of immune responses, and to the risk, prevention, and treatment of TB. In addition, we summarize our current understanding of alveolar epithelial cells and the innate immune system, and their interaction with Mtb during early infection. Extensive studies are warranted to fully understand the all-inclusive role of the lung microbiota, its interaction with epithelium and innate immune responses and resulting adaptive immune responses, and in the pathogenesis and/or protection from Mtb infection. Novel interventions aimed at influencing the microbiota, the alveolar immune system and innate immunity will shape future strategies of prevention and treatment for TB. PMID:29692778

New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells.

PubMed

Gupta, Nancy; Kumar, Rakesh; Agrawal, Babita

2018-01-01

Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally. Efforts to control and eradicate TB are hampered by the rapid emergence of drug resistance and limited efficacy of the only available vaccine, BCG. Immunological events in the airways and lungs are of major importance in determining whether exposure to Mycobacterium tuberculosis ( Mtb ) results in successful infection or protective immunity. Several studies have demonstrated that the host microbiota is in constant contact with the immune system, and thus continually directs the nature of immune responses occurring during new infections. However, little is known about its role in the eventual outcome of the mycobacterial infection. In this review, we highlight the changes in microbial composition in the respiratory tract and gut that have been linked to the alteration of immune responses, and to the risk, prevention, and treatment of TB. In addition, we summarize our current understanding of alveolar epithelial cells and the innate immune system, and their interaction with Mtb during early infection. Extensive studies are warranted to fully understand the all-inclusive role of the lung microbiota, its interaction with epithelium and innate immune responses and resulting adaptive immune responses, and in the pathogenesis and/or protection from Mtb infection. Novel interventions aimed at influencing the microbiota, the alveolar immune system and innate immunity will shape future strategies of prevention and treatment for TB.

Interferometric Imaging Directly with Closure Phases and Closure Amplitudes

NASA Astrophysics Data System (ADS)

Chael, Andrew A.; Johnson, Michael D.; Bouman, Katherine L.; Blackburn, Lindy L.; Akiyama, Kazunori; Narayan, Ramesh

2018-04-01

Interferometric imaging now achieves angular resolutions as fine as ∼10 μas, probing scales that are inaccessible to single telescopes. Traditional synthesis imaging methods require calibrated visibilities; however, interferometric calibration is challenging, especially at high frequencies. Nevertheless, most studies present only a single image of their data after a process of “self-calibration,” an iterative procedure where the initial image and calibration assumptions can significantly influence the final image. We present a method for efficient interferometric imaging directly using only closure amplitudes and closure phases, which are immune to station-based calibration errors. Closure-only imaging provides results that are as noncommittal as possible and allows for reconstructing an image independently from separate amplitude and phase self-calibration. While closure-only imaging eliminates some image information (e.g., the total image flux density and the image centroid), this information can be recovered through a small number of additional constraints. We demonstrate that closure-only imaging can produce high-fidelity results, even for sparse arrays such as the Event Horizon Telescope, and that the resulting images are independent of the level of systematic amplitude error. We apply closure imaging to VLBA and ALMA data and show that it is capable of matching or exceeding the performance of traditional self-calibration and CLEAN for these data sets.

Direct effect of plasma permeability factors from patients with idiopatic FSGS on nephrin and podocin expression in human podocytes.

PubMed

Doublier, Sophie; Musante, Luca; Lupia, Enrico; Candiano, Giovanni; Spatola, Tiziana; Caridi, Gianluca; Zennaro, Cristina; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni

2005-07-01

The presence of circulating plasma factors (PF) altering renal permeability to proteins has been previously described in patients with focal segmental glomerulosclerosis (FSGS). Since these patients show reduced nephrin and podocin expression at renal biopsy, we evaluated the effect of serum and PF from patients with FSGS on nephrin and podocin expression in human podocytes. We studied 7 sera from patients with steroid-resistant FSGS, 3 from patients with nephrotic syndrome caused by non-immune disease, and 6 from healthy subjects. PF was prepared from plasmapheresis eluates of 2 patients with post-transplant recurrence of FSGS. Purification procedure was based on protein A Sepharose chromatography and differential precipitation in ammonium sulphate. Nephrin and podocin expression was semi-quantitatively evaluated by immunofluorescence. We found that serum and PF from FSGS patients rapidly induced redistribution and loss of nephrin in podocytes. This effect was associated with cytoskeleton redistribution and inhibited by cytochalasin B and sodium azide. On the contrary, podocin expression was unchanged after incubation with serum and PF from FSGS patients for short periods, but markedly reduced at 24 h. Our results demonstrate that serum and PF from FSGS patients may directly affect nephrin and podocin in human podocytes, thus providing new insights into the mechanisms causing proteinuria in FSGS.

Neuro-Immune Mechanisms in Response to Venezuelan equine encephalitis Virus Infection

DTIC Science & Technology

2000-05-01

horses . They were subsequently shown to be previously unrecognized viral agents of severe equine encephalitis (Smith et al., 1997). One member of...iii ABSTRACT NEURO-IMMUNE MECHANISMS IN RESPONSE TO VENEZUELAN EQUINE ENCEPHALITIS VIRUS INFECTION Major Bruce A. Schoneboom directed by Franziska B...Grieder, DVM, Ph.D., Assistant Professor of Microbiology and Immunology, Molecular and Cellular Biology, and Neuroscience Venezuelan equine

Immunotoxicity of a standardized citrus polymethoxylated flavone extract.

PubMed

Delaney, B; Phillips, K; Buswell, D; Mowry, B; Nickels, D; Cox, D; Wang, H B; Manthey, J

2001-11-01

Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and other pro-inflammatory cytokines. As TNF-alpha also modulates NK cell activity, the current studies were conducted to assess the potential for a standardized citrus PMF mixture to suppress humoral and innate immune functions. PMFs were isolated from orange peel oil using a procedure that obtained a consistent mixture of PMFs both in identity and proportion. The mixture consisted of nobiletin (30.7%), 3,3',4',5,6,7,8-heptamethoxyflavone (27.9%), trimethylscutellarein (14.5%), tangeretin (10.4%), sinensetin (5.8%), 5-demethyl-nobiletin (2.0%), hexa-O-methylquercetagetin (1.3%), 5-demethyl-tetramethylscutellarein (0.6%), and other flavonoids (2.7%). To assess the effect of the PMF mixture on humoral immune responses, female B(6)C(3)F(1) mice (n=8) were exposed to the PMF by gavage at 5, 50, 150 and 500 mg/kg/day for 28 days. On day 25, mice were sensitized to sRBC by tail vein injection and AFC response determined 4 days later. Humoral immunity was insensitive to suppression following exposure to all concentrations of the PMF mixture. Suppression of NK cell activity was observed only following 500 mg/kg/day for 28 days. Body weights were not affected by exposure to any concentration of the PMF mixture in sRBC immunized or non-immunized mice. However, in sRBC-immunized mice, higher concentrations of PMF were associated with a statistically insignificant increase in spleen weight (P>0.05). No change in spleen weight was observed in non-immunized mice. As anticipated, based on previously published in vitro observations, long-term, high-dose exposure to a standardized mixture of citrus PMFs caused a mild suppression of NK cell activity; however, humoral immunity was not sensitive to suppression at the same exposure levels.

Transduction of a Foreign Histocompatibility Gene into the Arterial Wall Induces Vasculitis

NASA Astrophysics Data System (ADS)

Nabel, Elizabeth G.; Plautz, Gregory; Nabel, Gary J.

1992-06-01

Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.

Role of natural killer cells in antibacterial immunity.

PubMed

Schmidt, Stanislaw; Ullrich, Evelyn; Bochennek, Konrad; Zimmermann, Stefanie-Yvonne; Lehrnbecher, Thomas

2016-12-01

Bacteria are a significant cause of infectious complications, in particular in immunocompromised patients. There is an increasing understanding that Natural Killer (NK) cells not only exhibit direct activity against bacteria, but also exert indirect antibacterial activity through interaction with other immune cells via cytokines and interferons. Areas covered: This review seeks to give a global overview of in vitro and in vivo data how NK cells interact with bacteria. In this regard, the review describes how NK cells directly damage and kill bacteria by soluble factors such as perforin, the impact of NK cells on other arms of the immune system, as well as how bacteria may inhibit NK cell activities. Expert commentary: A better characterization of the antibacterial effects of NK cells is urgently needed. With a better understanding of the interaction of NK cells and bacteria, NK cells may become a promising tool to prevent or to combat bacterial infections, e.g. by adoptively transferring NK cells to immunocompromised patients.

Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.

PubMed

Li, Zhi; Hodgkinson, Tom; Gothard, Elizabeth J; Boroumand, Soulmaz; Lamb, Rebecca; Cummins, Ian; Narang, Priyanka; Sawtell, Amy; Coles, Jenny; Leonov, German; Reboldi, Andrea; Buckley, Christopher D; Cupedo, Tom; Siebel, Christian; Bayat, Ardeshir; Coles, Mark C; Ambler, Carrie A

2016-04-21

Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ(+) ILC3s into wounded dermis; RORγ(+) ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ(+) ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair.

National Differences in Requirements for Ethical and Competent Authority Approval for a Multinational Vaccine Trial under the EU Directive 2001/20/EC

PubMed Central

van Doorn, Eva; Hak, Eelko; Wilffert, Bob

2015-01-01

Obtaining approval for a multinational vaccine trial from an ethics committee and the national competent authority of different Member States of the European Union (EU) is challenging under clinical trial Directive 2001/20/EC because of the differences in the implementation of the directive in national laws of Member States. In this review the national differences in requirements for ethical and competent authority approval are illustrated. The national ethical and competent authority review procedures in Finland, Hungary, The Netherlands, Norway and Slovenia are described under the EU trial directive after discussing the provisions of the trial directive related to both review procedures. The review illustrates the differences between the countries in the documents that have to be submitted for the review procedures, the submission procedures and the language requirements of the documents, the organization of the ethics committees and the role of the competent authority in the approval procedure. PMID:26343188

National Differences in Requirements for Ethical and Competent Authority Approval for a Multinational Vaccine Trial under the EU Directive 2001/20/EC.

PubMed

van Doorn, Eva; Hak, Eelko; Wilffert, Bob

2015-04-14

Obtaining approval for a multinational vaccine trial from an ethics committee and the national competent authority of different Member States of the European Union (EU) is challenging under clinical trial Directive 2001/20/EC because of the differences in the implementation of the directive in national laws of Member States. In this review the national differences in requirements for ethical and competent authority approval are illustrated. The national ethical and competent authority review procedures in Finland, Hungary, The Netherlands, Norway and Slovenia are described under the EU trial directive after discussing the provisions of the trial directive related to both review procedures. The review illustrates the differences between the countries in the documents that have to be submitted for the review procedures, the submission procedures and the language requirements of the documents, the organization of the ethics committees and the role of the competent authority in the approval procedure.

Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

PubMed

Nystrand, M; Dowling, D K

2014-05-01

Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

A Normalized Direct Approach for Estimating the Parameters of the Normal Ogive Three-Parameter Model for Ability Tests.

ERIC Educational Resources Information Center

Gugel, John F.

A new method for estimating the parameters of the normal ogive three-parameter model for multiple-choice test items--the normalized direct (NDIR) procedure--is examined. The procedure is compared to a more commonly used estimation procedure, Lord's LOGIST, using computer simulations. The NDIR procedure uses the normalized (mid-percentile)…

Aluminum hydroxide colloid vaccine encapsulated in yeast shells with enhanced humoral and cellular immune responses.

PubMed

Liu, Hui; Jia, Zhenghu; Yang, Chengmao; Song, Mei; Jing, Zhe; Zhao, Yapu; Wu, Zhenzhou; Zhao, Liqing; Wei, Dongsheng; Yin, Zhinan; Hong, Zhangyong

2018-06-01

Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity. Here, we encapsulated an Alum colloid inside β-glucan particles (GPs), which are a type of natural particles derived from the yeast glucan shells, to prepare hybrid GP-Alum (GP-Al) adjuvant particles with a very uniform size of 2-4 μm. These hybrid particles can be used to load antigen proteins through a simple mixing procedure, and can be highly specifically targeted to antigen-presenting cells (APCs) and strongly activate dendritic cells (DCs) maturation and cytokine secretion. In an animal model, they elicit a strong Th1-biased immune response and extremely high antibody titer, and cause marked prophylactic and therapeutic effects against tumors. As Alum has been proven to be a safe adjuvant to induce strong humoral responses and β-glucans are safe for human use, this very uniform hybrid Alum particulate system could have important application as a vaccine carrier to stimulate humoral and cellular immune responses at the same time. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro immunomodulatory effects of herbal products.

PubMed

Wilasrusmee, Chumpon; Siddiqui, Josephine; Bruch, David; Wilasrusmee, Skuntala; Kittur, Smita; Kittur, Dilip S

2002-10-01

Immunosuppressive drugs have been developed from natural products such as soil and fungi, which are also the sources of some commonly used herbal products. However, the effect of herbal products on immune response has not been investigated. Because these products can affect the host immune system they can induce either rejection or tolerance after a transplant procedure. To investigate the effects of ten commonly used herbal products on transplant-related immune function we performed in vitro lymphocyte proliferation tests using phytohemagglutinin, mixed lymphocyte culture (MLC) assay, and interleukin (IL)-2 and IL-10 production from MLC. Dong quai, ginseng, and milk thistle had nonspecific immunostimulatory effects on lymphocyte proliferation, whereas ginger and green tea had immunosuppressive effects. Dong quai and milk thistle increased alloresponsiveness in MLC, whereas ginger and tea decreased these responses. The immunostimulatory effects of dong quai and milk thistle were consistently seen in both cell-mediated immune response and nonspecific lymphoproliferation, whereas that of ginseng was not. The immunosuppressive effect of green tea and ginger were mediated through a decrease in IL-2 production, but the immunostimulatory effects of dong quai and milk thistle were not. We conclude that green tea, dong quai, ginseng, milk thistle, and ginger have effects on in vitro immune assays that may be relevant in transplantation in humans.

Direct versus indirect revascularization procedures for moyamoya disease: a comparative effectiveness study.

PubMed

Macyszyn, Luke; Attiah, Mark; Ma, Tracy S; Ali, Zarina; Faught, Ryan; Hossain, Alisha; Man, Karen; Patel, Hiren; Sobota, Rosanna; Zager, Eric L; Stein, Sherman C

2017-05-01

OBJECTIVE Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to devastating neurological outcomes. Surgical intervention is the definitive treatment, with direct, indirect, and combined revascularization procedures currently employed by surgeons. The optimal surgical approach, however, remains unclear. In this decision analysis, the authors compared the effectiveness of revascularization procedures in both adult and pediatric patients with MMD. METHODS A comprehensive literature search was performed for studies of MMD. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment using a direct and indirect revascularization technique. Utility values for the various outcomes and complications were extracted from the literature examining preferences in similar clinical conditions. Sensitivity analysis was performed. RESULTS A structured literature search yielded 33 studies involving 4197 cases. Cases were divided into adult and pediatric populations. These were further subdivided into 3 different treatment groups: indirect, direct, and combined revascularization procedures. In the pediatric population at 5- and 10-year follow-up, there was no significant difference between indirect and combination procedures, but both were superior to direct revascularization. In adults at 4-year follow-up, indirect was superior to direct revascularization. CONCLUSIONS In the absence of factors that dictate a specific approach, the present decision analysis suggests that direct revascularization procedures are inferior in terms of quality-adjusted life years in both adults at 4 years and children at 5 and 10 years postoperatively, respectively. These findings were statistically significant (p < 0.001 in all cases), suggesting that indirect and combination procedures may offer optimal results at long-term follow-up.

Vascular CD39/ENTPD1 Directly Promotes Tumor Cell Growth by Scavenging Extracellular Adenosine Triphosphate12

PubMed Central

Feng, Lili; Sun, Xiaofeng; Csizmadia, Eva; Han, Lihui; Bian, Shu; Murakami, Takashi; Wang, Xin; Robson, Simon C; Wu, Yan

2011-01-01

Extracellular adenosine triphosphate (ATP) is known to boost immune responses in the tumor microenvironment but might also contribute directly to cancer cell death. CD39/ENTPD1 is the dominant ectonucleotidase expressed by endothelial cells and regulatory T cells and catalyzes the sequential hydrolysis of ATP to AMP that is further degraded to adenosine by CD73/ecto-5′-nucleotidase. We have previously shown that deletion of Cd39 results in decreased growth of transplanted tumors in mice, as a result of both defective angiogenesis and heightened innate immune responses (secondary to loss of adenosinergic immune suppression). Whether alterations in local extracellular ATP and adenosine levels as a result of CD39 bioactivity directly affect tumor growth and cytotoxicity has not been investigated to date. We show here that extracellular ATP exerts antitumor activity by directly inhibiting cell proliferation and promoting cancer cell death. ATP-induced antiproliferative effects and cell death are, in large part, mediated through P2X7 receptor signaling. Tumors in Cd39 null mice exhibit increased necrosis in association with P2X7 expression. We further demonstrate that exogenous soluble NTPDase, or CD39 expression by cocultured liver sinusoidal endothelial cells, stimulates tumor cell proliferation and limits cell death triggered by extracellular ATP. Collectively, our findings indicate that local expression of CD39 directly promotes tumor cell growth by scavenging extracellular ATP. Pharmacological or targeted inhibition of CD39 enzymatic activity may find utility as an adjunct therapy in cancer management. PMID:21390184

The Role of Childhood Infections and Immunizations on Childhood Rhabdomyosarcoma: A Report from the Children's Oncology Group

PubMed Central

Sankaran, Hari; Danysh, Heather E.; Scheurer, Michael E.; Okcu, M. Fatih; Skapek, Stephen X.; Hawkins, Douglas S.; Spector, Logan G.; Erhardt, Erik B.; Grufferman, Seymour; Lupo, Philip J.

2016-01-01

Background Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy Procedure RMS cases (n=322) were enrolled from the third trial coordinated by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n=322) were pair matched to cases on race, sex, and age. The following immunizations were assessed: diphtheria-pertussis-tetanus (DPT), measles-mumps-rubella (MMR), and oral polio vaccine (OPV). We also evaluated if immunizations were complete vs. incomplete. We examined selected infections including chickenpox, mumps, pneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis, and lung infections. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for maternal education and total annual income Results Incomplete immunization schedules (OR=5.30, 95% CI: 2.47-11.33) and incomplete DPT immunization (OR=1.56, 95% CI: 1.06-2.29) were positively associated with childhood RMS. However, infections did not appear to be associated with childhood RMS. Conclusions This is the largest study of RMS to date demonstrating a possible protective effect of immunizations against development of childhood RMS. Further studies are needed to validate our findings. Our findings add to the growing body of literature suggesting a protective role of routine vaccinations in childhood cancer and specifically in childhood RMS. PMID:27198935

Oral Vaccination of Fish – Antigen Preparations, Uptake, and Immune Induction

PubMed Central

Mutoloki, Stephen; Munang’andu, Hetron Mweemba; Evensen, Øystein

2015-01-01

The oral route offers the most attractive approach of immunization of fish for a number of reasons: the ease of administration of antigens, it is less stressful than parenteral delivery and in principle, it is applicable to small and large sized fish; it also provides a procedure for oral boosting during grow-out periods in cages or ponds. There are, however, not many commercial vaccines available at the moment due to lack of efficacy and challenges associated with production of large quantities of antigens. These are required to stimulate an effective immune response locally and systemically, and need to be protected against degradation before they reach the sites where immune induction occurs. The hostile stomach environment is believed to be particularly important with regard to degradation of antigens in certain species. There is also a poor understanding about the requirements for proper immune induction following oral administration on one side, and the potential for induction of tolerance on the other. To what extent primary immunization via the oral route will elicit both local and systemic responses is not understood in detail. Furthermore, to what extent parenteral delivery will protect mucosal/gut surfaces and vice-versa is also not fully understood. We review the work that has been done on the subject and discuss it in light of recent advances that include mass production of antigens, including the use of plant systems. Different encapsulation techniques that have been developed in the quest to protect antigens against digestive degradation, as well as to target them for appropriate immune induction are also highlighted. PMID:26539192

Role of Maternal Dietary Peanut Exposure in Development of Food Allergy and Oral Tolerance.

PubMed

Järvinen, Kirsi M; Westfall, Jennifer; De Jesus, Magdia; Mantis, Nicholas J; Carroll, Jessica A; Metzger, Dennis W; Sampson, Hugh A; Berin, M Cecilia

2015-01-01

The impact of maternal ingestion of peanut during pregnancy and lactation on an offspring's risk for peanut allergy is under debate. To investigate the influence of maternal dietary peanut exposure and breast milk on an offspring's allergy risk. Preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation. The offsprings' responses to peanut sensitization or oral tolerance induction by feeding antigen prior to immunization were assessed. We also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning. For antigen uptake studies, mice were gavaged with fluorescent peanut in the presence or absence of immune murine milk; Peyer's patches were harvested for immunostaining. Preconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. When offspring were fed peanut directly, dose-dependent tolerance induction, unaltered by maternal feeding of peanut, was seen. Although peanut uptake into the gut-associated lymphoid tissues was enhanced by immune milk as compared to naïve milk, tolerance induction was not affected by the co-administration of immune milk either pre- or post-weaning. Maternal peanut exposure during pregnancy and lactation has no impact on the development of peanut allergy in the offspring. Tolerance to peanut can be induced early, even pre-weaning, by giving moderate amounts of peanut directly to the infant, and this is neither enhanced nor impaired by concurrent exposure to immune milk.

Combination of PDT and a DNA demethylating agent produces anti-tumor immune response in a mouse tumor model

NASA Astrophysics Data System (ADS)

Mroz, Pawel; Hamblin, Michael R.

2009-06-01

Epigenetic mechanisms, which involve DNA methylation and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. However, these changes must be actively maintained after each cell division rendering them a promising target for pharmacologic inhibition. DNA methyltransferase inhibitors like 5-aza-deoxycytidine (5-aza-dC) induce and/or up-regulate the expression of MAGE-type antigens in human and mice cancer cells. Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of stimulating tumor-directed immune response. We studied the effects of a new therapy that combined the demethylating agent 5-aza-dC with PDT in the breast cancer model 4T1 syngenic to immunocompetent BALB/c mice. PDT was used as a locally ablating tumor treatment that is capable of eliciting strong and tumor directed immune response while 5-aza-dC pretreatment was used promote de novo induction of the expression of P1A.protein. This is the mouse homolog of human MAGE family antigens and is reported to function as a tumor rejection antigen in certain mouse tumors. This strategy led to an increase in PDT-mediated immune response and better treatment outcome. These results strongly suggest that the MAGE family antigens are important target for PDT mediated immune response but that their expression can be silenced by epigenetic mechanisms. Therefore the possibility that PDT can be combined with epigenetic strategies to elicit anti-tumor immunity in MAGE-positive tumor models is highly clinically significant and should be studied in detail.

Immune mechanisms in polymyositis and dermatomyositis and potential targets for therapy.

PubMed

Venalis, Paulius; Lundberg, Ingrid E

2014-03-01

PM and DM are characterized clinically by weakness and low endurance of skeletal muscle. Other organs are frequently involved, suggesting that idiopathic inflammatory myopathies (IIMs) are systemic inflammatory diseases. Involvement of immune mechanisms in IIMs is supported by the presence of T cells, macrophages and dendritic cells in muscle tissue, by the presence of autoantibodies and by HLA-DR being a strong genetic risk factor. T cells may have direct and indirect toxic effects on muscle fibres, causing muscle fibre necrosis and muscle weakness, but the target of the immune reaction is not known. A newly identified T cell subset, CD28(null) T cells, may have cytotoxic effects in the CD4(+) and CD8(+) T cell phenotype. These cells are apoptosis resistant and may contribute to treatment resistance. Several myositis-specific autoantibodies have been identified, but they are all directed against ubiquitously expressed autoantigens and the specificity of the T cell reactivity is not known. These autoantibodies are associated with distinct clinical phenotypes and some with distinct molecular pathways; e.g. sera from patients with anti-Jo-1 autoantibodies may activate the type I IFN system and these sera also contain high levels of B cell activating factor compared with other IIM subsets. The characterization of patients into subgroups based on autoantibody profiles seems to be a promising way to learn more about the specificities of the immune reactions. Careful phenotyping of infiltrating immune cells in muscle tissue before and after specific therapies and relating the molecular findings to clinical outcome measures may be another way to improve knowledge on specific immune mechanism in IIMs. Such information will be important for the development of new therapies.

The Hippo Pathway: Immunity and Cancer

PubMed Central

J. Janse van Rensburg, Helena

2018-01-01

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work. PMID:29597279

Prokaryotic ancestry of eukaryotic protein networks mediating innate immunity and apoptosis.

PubMed

Dunin-Horkawicz, Stanislaw; Kopec, Klaus O; Lupas, Andrei N

2014-04-03

Protein domains characteristic of eukaryotic innate immunity and apoptosis have many prokaryotic counterparts of unknown function. By reconstructing interactomes computationally, we found that bacterial proteins containing these domains are part of a network that also includes other domains not hitherto associated with immunity. This network is connected to the network of prokaryotic signal transduction proteins, such as histidine kinases and chemoreceptors. The network varies considerably in domain composition and degree of paralogy, even between strains of the same species, and its repetitive domains are often amplified recently, with individual repeats sharing up to 100% sequence identity. Both phenomena are evidence of considerable evolutionary pressure and thus compatible with a role in the "arms race" between host and pathogen. In order to investigate the relationship of this network to its eukaryotic counterparts, we performed a cluster analysis of organisms based on a census of its constituent domains across all fully sequenced genomes. We obtained a large central cluster of mainly unicellular organisms, from which multicellular organisms radiate out in two main directions. One is taken by multicellular bacteria, primarily cyanobacteria and actinomycetes, and plants form an extension of this direction, connected via the basal, unicellular cyanobacteria. The second main direction is taken by animals and fungi, which form separate branches with a common root in the α-proteobacteria of the central cluster. This analysis supports the notion that the innate immunity networks of eukaryotes originated from their endosymbionts and that increases in the complexity of these networks accompanied the emergence of multicellularity. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The roles of the immune system in women's reproduction: evolutionary constraints and life history trade-offs.

PubMed

Abrams, Elizabeth T; Miller, Elizabeth M

2011-01-01

Life history theory posits that, as long as survival is assured, finite resources are available for reproduction, maintenance, and growth/storage. To maximize lifetime reproductive success, resources are subject to trade-offs both within individuals and between current and future investment. For women, reproducing is costly and time-consuming; the bulk of available resources must be allocated to reproduction at the expense of more flexible systems like immune function. When reproducing women contract infectious diseases, the resources required for immune activation can fundamentally shift the patterns of resource allocation. Adding to the complexity of the reproductive-immune trade-offs in women are the pleiotropic effects of many immune factors, which were modified to serve key roles in mammalian reproduction. In this review, we explore the complex intersections between immune function and female reproduction to situate proximate immunological processes within a life history framework. After a brief overview of the immune system, we discuss some important physiological roles of immune factors in women's reproduction and the conflicts that may arise when these factors must play dual roles. We then discuss the influence of reproductive-immune trade-offs on the patterning of lifetime reproductive success: (1) the effect of immune activation/infectious disease on the timing of life history events; (2) the role of the immune system, immune activation, and infectious disease on resource allocation within individual reproductive events, particularly pregnancy; and (3) the role of the immune system in shaping the offspring's patterns of future life history trade-offs. We close with a discussion of future directions in reproductive immunology for anthropologists. Copyright © 2011 Wiley Periodicals, Inc.

Fallen Angels or Risen Apes? A Tale of the Intricate Complexities of Imbalanced Immune Responses in the Pathogenesis and Progression of Immune-Mediated and Viral Cancers

PubMed Central

Ondondo, Beatrice Omusiro

2014-01-01

Excessive immune responses directed against foreign pathogens, self-antigens, or commensal microflora can cause cancer establishment and progression if the execution of tight immuno-regulatory mechanisms fails. On the other hand, induction of potent tumor antigen-specific immune responses together with stimulation of the innate immune system is a pre-requisite for effective anti-tumor immunity, and if suppressed by the strong immuno-regulatory mechanisms can lead to cancer progression. Therefore, it is crucial that the inevitable co-existence of these fundamental, yet conflicting roles of immune-regulatory cells is carefully streamlined as imbalances can be detrimental to the host. Infection with chronic persistent viruses is characterized by severe immune dysfunction resulting in T cell exhaustion and sometimes deletion of antigen-specific T cells. More often, this is due to increased immuno-regulatory processes, which are triggered to down-regulate immune responses and limit immunopathology. However, such heightened levels of immune disruption cause a concomitant loss of tumor immune-surveillance and create a permissive microenvironment for cancer establishment and progression, as demonstrated by increased incidences of cancer in immunosuppressed hosts. Paradoxically, while some cancers arise as a consequence of increased immuno-regulatory mechanisms that inhibit protective immune responses and impinge on tumor surveillance, other cancers arise due to impaired immuno-regulatory mechanisms and failure to limit pathogenic inflammatory responses. This intricate complexity, where immuno-regulatory cells can be beneficial in certain immune settings but detrimental in other settings underscores the need for carefully formulated interventions to equilibrate the balance between immuno-stimulatory and immuno-regulatory processes. PMID:24639678

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

PubMed

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

2014-07-01

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

Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia.

PubMed

Nakatsuka, Yoshinari; Vandenbon, Alexis; Mino, Takashi; Yoshinaga, Masanori; Uehata, Takuya; Cui, Xiaotong; Sato, Ayuko; Tsujimura, Tohru; Suzuki, Yutaka; Sato, Atsuyasu; Handa, Tomohiro; Chin, Kazuo; Sawa, Teiji; Hirai, Toyohiro; Takeuchi, Osamu

2018-04-25

Inhaled pathogens including Pseudomonas aeruginosa initially encounter airway epithelial cells (AECs), which are poised to evoke cell-intrinsic innate defense, affecting second tier of hematopoietic cell-mediated immune reaction. However, it is largely unknown how pulmonary immune responses mediated by a variety of immune cells are coordinated. Here we show that Regnase-1, an endoribonuclease expressed in AECs and immune cells, plays an essential role in coordinating innate responses and adaptive immunity against P. aeruginosa infection. Intratracheal treatment of mice with heat-killed P. aeruginosa resulted in prolonged disappearance of Regnase-1 consistent with sustained expression of Regnase-1 target inflammatory genes, whereas the transcription factor NF-κB was only transiently activated. AEC-specific deletion of Regnase-1 not only augmented innate defenses against P. aeruginosa but also enhanced secretion of Pseudomonas-specific IgA and Th17 accumulation in the lung, culminating in conferring significant resistance against P. aeruginosa re-infection in vivo. Although Regnase-1 directly controls distinct sets of genes in each of AECs and T cells, degradation of Regnase-1 in both cell types is beneficial for maximizing acquired immune responses. Collectively, these results demonstrate that Regnase-1 orchestrates AEC-mediated and immune cell-mediated host defense against pulmonary bacterial infection.

Current immunotherapeutic strategies in pancreatic cancer.

PubMed

Plate, Janet M D

2007-10-01

The immune systems of patients with newly diagnosed pancreatic cancers are functional, with T-cell responses capable of responding to tumor antigen presentation. Pancreatic tumors have been demonstrated to express tumor antigens as mutated, altered, underglycosylated and/or inappropriately overexpressed proteins. Considering these two facts, it should be possible for patients' bodies to recognize their tumors as foreign and to reject them. A number of clinical trials have been initiated to exploit this immune activation to eradicate or stabilize tumor growth. Immunotherapeutic trials include the specific testing of a variety of tumor vaccines, of cytokines as adjuvants or directed cytotoxicity, and of monoclonal antibodies to target specific molecules. This article reviews evidence for immune-cell activation and function in patients with pancreatic cancer, and evidence that pancreatic tumor cells express tumor antigens, or mutated (or altered) proteins. Nevertheless, tumors survive immune attacks by producing products that help them to circumvent effector T cells. The article thus examines complications of immune evasion by cancer cells, as well as the challenges of trying to exploit the immune system in solid tumors where tumor cell products can turn off invading immune T cells set to kill them. Finally, the article discusses the choices of a variety of clinical trials using immune modulation for patients with pancreatic cancer.

Biomarkers for immune-related toxicities of checkpoint inhibitors: current progress and the road ahead.

PubMed

Patil, Pradnya D; Burotto, Mauricio; Velcheti, Vamsidhar

2018-03-01

Immune checkpoint pathways are key immune regulatory pathways that play a physiologic role in maintaining immune-homeostasis and are often co-opted by cancer cells to evade the host immune system. Recent developments in cancer immunotherapy, mainly drugs blocking the immune checkpoint pathways, have revolutionized the treatment paradigm for many solid tumors. A wide spectrum of immune-related adverse events (irAEs) have been described with the use of these agents which necessitate treatment with immunosuppression, lead to disruption of therapy and can on occasion be life-threatening. There are currently no clinically validated biomarkers to predict the risk of irAEs. Areas covered: In this review, the authors describe the current progress in identifying biomarkers for irAEs and potential future directions. Literature search was conducted using PubMed-MEDLINE, Embase and Scopus. In addition, abstracts from major conference proceedings were reviewed for relevant content. Expert commentary: The discovery of biomarkers for irAEs is currently in its infancy, however there are a lot of promising candidate biomarkers that are currently being investigated. Biomarkers that can identify patients at a higher risk of developing irAEs or lead to early detection of autoimmune toxicities are crucial to optimize patient selection for immune-oncology agents and to minimize toxicity with their use.

Mucosal immunization: a review of strategies and challenges.

PubMed

Patel, Hinal; Yewale, Chetan; Rathi, Mohan N; Misra, Ambikanandan

2014-01-01

The vast majority of pathogens enter the human body via the mucosal surfaces of the gastrointestinal, respiratory, and urogenital tracts, where they initiate mucosal infections that lead to systemic infections. Despite strong evidence that a good mucosal immune response can effectively prevent systemic infection too, only a few mucosal vaccines are available due to their low efficiency. Most current immunization techniques involve systemic injection, but they are ineffective to induce immunization at a mucosal site. It is a great challenge to target a mucosal compartment that can induce protective immunity at mucosal sites as well as systemic sites. A better understanding of cellular and molecular factors involved in the regulation of mucosal immunity will aid in the design of safer mucosal vaccines that elicit the desired protective immunity against infectious diseases such as HIV. The development of mucosal vaccines, whether for prevention of infectious diseases or for immunotherapy, requires antigen delivery and adjuvant systems that can effectively present vaccine or immunotherapeutic antigens to the mucosal sites. In this review, we examine the mechanism of mucosal protection, induction of mucosal immune response, types of vaccines, current status of marketed vaccines, and novel strategies for protection against infections and for treatment of inflammatory disorders. Additionally, we offer perspectives on future challenges and research directions.

Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases.

PubMed

Meirow, Yaron; Baniyash, Michal

2017-08-01

Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complications can only be detected upon their appearance. This review focuses on the necessity for such immune status biomarkers, which could predict complications prior to their appearance. Herein we bring examples for the use of cellular and molecular biomarkers in diagnosis, prognosis and follow-up of patients suffering from various cancers, for prediction of response to immune-based anti-cancer therapy and for prediction of cardiovascular disease in type 2 diabetes patients. Monitoring such biomarkers is expected to have a major clinical impact in addition to unraveling of the entangled complexity underlying dysregulated immunity in chronic inflammation. Thus, newly discovered biomarkers and those that are under investigation are projected to open a new era towards combating the silent damage induced by chronic inflammation.

Is performance of influenza vaccination in the elderly related to treating physician's self immunization and other physician characteristics?

PubMed

Abramson, Zvi Howard; Levi, Orit

2008-11-01

Studies have demonstrated associations between physicians' characteristics, specifically personal health behavior, and their reported prevention counseling behavior. This study, performed in 2007, examines associations between patients getting immunized against influenza and characteristics of their primary care physicians, including whether they themselves were immunized. Computerized data were extracted on 29,447 patients aged 65 years and over registered in the largest health maintenance organization (HMO) in the Jerusalem area and on their primary care physicians. Further physician data were collected from a questionnaire distributed to a large sample of physicians. Logistic regression was performed with patient immunization as the dependent variable. Patients were more likely to get vaccinated if their physician was vaccinated and if the physician was female or a specialist or had studied in West Europe or America. Patients of physicians who reported exercising regularly and of physicians who knew that the vaccine can't cause influenza were also more likely to get immunized. These associations of physician factors with patient immunization, though statistically significant, were weaker than those previously reported with physician influenza vaccination counseling. Physician's beliefs and medical education and personal health behavior are of importance in determining patient vaccination. An increase in population immunization rates may possibly be achieved by programs directed at enhancing physician knowledge and self immunization.

Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?

PubMed

Schuiveling, Mark; Vazirpanah, Nadia; Radstake, Timothy R D J; Zimmermann, Maili; Broen, Jasper C A

2018-01-01

Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its anti-inflammatory properties. To provide a critical and comprehensive review of the available literature describing the effects of metformin on the immune system and on auto-inflammatory diseases. Based on the available scientific literature, metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production. Among key immune events, this results in inhibited monocyte to macrophage differentiation and restrained inflammatory capacity of activated macrophages. In addition, metformin treatment increases differentiation of T cells into both regulatory and memory T cells, as well as decreasing the capacity of neutrophils to commence in NETosis. Due to its inhibitory effect on the proinflammatory phenotype of immune cells, metformin seems to reduce auto-immune disease burden not only in several animal models, but has also shown beneficial results in some human trials. Based on its immunomodulatory properties and high tolerability as a drug, metformin is an interesting add-on drug for future trials in treatment of immune mediated inflammatory diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of gender and sex hormones on immune responses following shock.

PubMed

Angele, M K; Schwacha, M G; Ayala, A; Chaudry, I H

2000-08-01

Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

The Immune System’s Role in the Biology of Autism

PubMed Central

Goines, Paula; Van de Water, Judy

2010-01-01

PURPOSE OF REVIEW The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism. This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism. RECENT FINDINGS The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers. In particular, circulating maternal autoantibodies directed towards fetal brain proteins are highly specific for autism. This finding has great potential as a biomarker for disease risk, and may provide an avenue for future therapeutics and prevention. Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems. While studies to explore this hypothesis are ongoing, there is great interest in the commonalities between the neural and immune systems and their extensive interactions. SUMMARY In summary, there is exciting research regarding the role of the immune system in autism spectrum disorders that may have profound implications for diagnosis and treatment of this devastating disease. PMID:20160651

Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

PubMed

Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

2017-06-01

Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

The role of innate immunity in acute allograft rejection after lung transplantation.

PubMed

Palmer, Scott M; Burch, Lauranell H; Davis, R Duane; Herczyk, Walter F; Howell, David N; Reinsmoen, Nancy L; Schwartz, David A

2003-09-15

Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft rejection, we assessed the impact of two functional polymorphisms in the toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness on the development of acute rejection after human lung transplantation. Patients and donors were screened for the TLR4 Asp299Gly and Thr399Ile polymorphisms by polymerase chain reaction using sequence-specific primers. The rate of acute rejection at 6 months was significantly reduced in recipients, but not in donors, with the Asp299Gly or Thr399Ile alleles as compared with wild type (29 vs. 56%, respectively, p = 0.05). This association was confirmed in Cox proportional hazards and multivariate logistic regression models. Our results suggest activation of innate immunity in lung transplant recipients through TLR4 contributes to the development acute rejection after lung transplantation. Therapies directed at inhibition of innate immune responses mediated by TLR4 may represent a novel and effective means to prevent acute rejection after lung transplantation.

Virus-like nanostructures for tuning immune response

NASA Astrophysics Data System (ADS)

Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

2015-11-01

Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.

Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents.

PubMed

Tschirren, B; Råberg, L; Westerdahl, H

2011-06-01

Patterns of selection acting on immune defence genes have recently been the focus of considerable interest. Yet, when it comes to vertebrates, studies have mainly focused on the acquired branch of the immune system. Consequently, the direction and strength of selection acting on genes of the vertebrate innate immune defence remain poorly understood. Here, we present a molecular analysis of selection on an important receptor of the innate immune system of vertebrates, the Toll-like receptor 2 (TLR2), across 17 rodent species. Although purifying selection was the prevalent evolutionary force acting on most parts of the rodent TLR2, we found that codons in close proximity to pathogen-binding and TLR2-TLR1 heterodimerization sites have been subject to positive selection. This indicates that parasite-mediated selection is not restricted to acquired immune system genes like the major histocompatibility complex, but also affects innate defence genes. To obtain a comprehensive understanding of evolutionary processes in host-parasite systems, both innate and acquired immunity thus need to be considered. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Carotenoids, immune response and the expression of sexual ornaments in male greenfinches ( Carduelis chloris)

NASA Astrophysics Data System (ADS)

Aguilera, Eduardo; Amat, Juan A.

2007-11-01

Allocation trade-offs of carotenoids between their use in the immune system and production of sexual ornaments have been suggested as a proximate mechanism maintaining honesty of sexual signals. To test this idea, we experimentally examined whether carotenoid availability in the diet was related to variation in antibody response to novel antigens in male greenfinches ( Carduelis chloris aurantiiventris), a species with extensive carotenoid-dependent plumage colouration. We also measured the cost of mounting a humoral response in terms of circulating carotenoids. Finally, we examined the relationship between plumage colour, immune response and circulating carotenoids. We found that males with carotenoid-supplemented diets showed stronger antibody response than non-supplemented birds. We also found that activation of the immune system significantly reduced circulating carotenoids (24.9% lower in immune-challenged birds than in control birds). Finally, intensity (chroma) of ventral plumage colouration of males, a character directly related to concentration of total carotenoids in feathers, was negatively correlated with the immune response and circulating carotenoids in winter. These results support the idea that carotenoids are a limiting resource and that males trade ornamental colouration against immune response.

Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

PubMed Central

Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

2016-01-01

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

PubMed

Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

2016-01-01

Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

Activation of colo-rectal high-threshold afferent nerves by Interleukin-2 is tetrodotoxin-sensitive and upregulated in a mouse model of chronic visceral hypersensitivity.

PubMed

Campaniello, M A; Harrington, A M; Martin, C M; Ashley Blackshaw, L; Brierley, S M; Hughes, P A

2016-01-01

Chronic visceral pain is a defining feature of irritable bowel syndrome (IBS). IBS patients often show alterations in innate and adaptive immune function which may contribute to symptoms. Immune mediators are known to modulate the activity of viscero-sensory afferent nerves, but the focus has been on the innate immune system. Interleukin-2 (IL-2) is primarily associated with adaptive immune responses but its effects on colo-rectal afferent function in health or disease are unknown. Myeloperoxidase (MPO) activity determined the extent of inflammation in health, acute trinitrobenzene-sulfonic acid (TNBS) colitis, and in our post-TNBS colitis model of chronic visceral hypersensitivity (CVH). The functional effects of IL-2 on high-threshold colo-rectal afferents and the expression of IL-2R and NaV 1.7 mRNA in colo-rectal dorsal root ganglia (DRG) neurons were compared between healthy and CVH mice. MPO activity was increased during acute colitis, but subsided to levels comparable to health in CVH mice. IL-2 caused direct excitation of colo-rectal afferents that was blocked by tetrodotoxin. IL-2 did not affect afferent mechanosensitivity in health or CVH. However, an increased proportion of afferents responded directly to IL-2 in CVH mice compared with controls (73% vs 33%; p < 0.05), and the abundance of IL-2R and NaV 1.7 mRNA was increased 3.5- and 2-fold (p < 0.001 for both) in colo-rectal DRG neurons. IL-2, an immune mediator from the adaptive arm of the immune response, affects colo-rectal afferent function, indicating these effects are not restricted to innate immune mediators. Colo-rectal afferent sensitivity to IL-2 is increased long after healing from inflammation. © 2015 John Wiley & Sons Ltd.

A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk.

PubMed

Baltar, Valéria Troncoso; Xun, Wei W; Johansson, Mattias; Ferrari, Pietro; Chuang, Shu-Chun; Relton, Caroline; Ueland, Per Magne; Midttun, Øivind; Slimani, Nadia; Jenab, Mazda; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Kaaks, Rudolf; Rohrmann, Sabine; Boeing, Heiner; Weikert, Cornelia; Bueno-de-Mesquita, Bas; Boshuizen, Hendriek; van Gils, Carla H; Onland-Moret, N Charlotte; Agudo, Antonio; Barricarte, Aurelio; Navarro, Carmen; Rodríguez, Laudina; Castaño, José Maria Huerta; Larrañaga, Nerea; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E; Crowe, Francesca; Gallo, Valentina; Norat, Teresa; Krogh, Vittorio; Masala, Giovanna; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Rasmuson, Torgny; Hallmans, Göran; Roswall, Nina; Tjønneland, Anne; Riboli, Elio; Brennan, Paul; Vineis, Paolo

2013-08-01

The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.

The catalytic A1 domains of cholera toxin and heat-labile enterotoxin are potent DNA adjuvants that evoke mixed Th1/Th17 cellular immune responses

PubMed Central

Bagley, Kenneth; Xu, Rong; Ota-Setlik, Ayuko; Egan, Michael; Schwartz, Jennifer; Fouts, Timothy

2015-01-01

DNA encoded adjuvants are well known for increasing the magnitude of cellular and/or humoral immune responses directed against vaccine antigens. DNA adjuvants can also tune immune responses directed against vaccine antigens to better protect against infection of the target organism. Two potent DNA adjuvants that have unique abilities to tune immune responses are the catalytic A1 domains of Cholera Toxin (CTA1) and Heat-Labile Enterotoxin (LTA1). Here, we have characterized the adjuvant activities of CTA1 and LTA1 using HIV and SIV genes as model antigens. Both of these adjuvants enhanced the magnitude of antigen-specific cellular immune responses on par with those induced by the well-characterized cytokine adjuvants IL-12 and GM-CSF. CTA1 and LTA1 preferentially enhanced cellular responses to the intracellular antigen SIVmac239-gag over those for the secreted HIVBaL-gp120 antigen. IL-12, GM-CSF and electroporation did the opposite suggesting differences in the mechanisms of actions of these diverse adjuvants. Combinations of CTA1 or LTA1 with IL-12 or GM-CSF generated additive and better balanced cellular responses to both of these antigens. Consistent with observations made with the holotoxin and the CTA1-DD adjuvant, CTA1 and LTA1 evoked mixed Th1/Th17 cellular immune responses. Together, these results show that CTA1 and LTA1 are potent DNA vaccine adjuvants that favor the intracellular antigen gag over the secreted antigen gp120 and evoke mixed Th1/Th17 responses against both of these antigens. The results also indicate that achieving a balanced immune response to multiple intracellular and extracellular antigens delivered via DNA vaccination may require combining adjuvants that have different and complementary mechanisms of action. PMID:26042527

Invited essay: Cognitive influences on the psychological immune system.

PubMed

Rachman, S J

2016-12-01

The construct of the psychological immune system is described and analysed. The direct and indirect cognitive influences on the system are discussed, and the implications of adding a cognitive construal to the influential model of a behavioural immune system are considered. The psychological immune system has two main properties: defensive and healing. It encompasses a good amount of health-related phenomena that is outside the scope of the behavioural model or the biological immune system. Evidence pertaining to the psychological immune system includes meta-analyses of the associations between psychological variables such as positive affect/wellbeing and diseases and mortality, and associations between wellbeing and positive health. The results of long-term prospective studies are consistent with the conclusions drawn from the meta-analyses. Laboratory investigations of the effects of psychological variables on the biological immune system show that negative affect can slow wound-healing, and positive affect can enhance resistance to infections, for example in experiments involving the introduction of the rhinovirus and the influenza A virus. A number of problems concerning the assessment of the functioning of the psychological immune system are considered, and the need to develop techniques for determining when the system is active or not, is emphasized. This problem is particularly challenging when trying to assess the effects of the psychological immune system during a prolonged psychological intervention, such as a course of resilience training. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental evolution of insect immune memory versus pathogen resistance.

PubMed

Khan, Imroze; Prakash, Arun; Agashe, Deepa

2017-12-20

Under strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory (immune priming), whereby sublethal exposure to a pathogen enhances survival after secondary infection. Theory predicts that immune memory should evolve when the pathogen is highly virulent, or when pathogen exposure is relatively rare. However, there are no empirical tests of these hypotheses, and the adaptive benefits of immune memory relative to direct resistance against a pathogen are poorly understood. To determine the selective pressures and ecological conditions that shape immune evolution, we imposed strong pathogen selection on flour beetle ( Tribolium castaneum ) populations, infecting them with Bacillus thuringiensis (Bt) for 11 generations. Populations injected first with heat-killed and then live Bt evolved high basal resistance against multiple Bt strains. By contrast, populations injected only with a high dose of live Bt evolved a less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Intriguingly, one replicate population first evolved priming and subsequently evolved basal resistance, suggesting the potential for dynamic evolution of different immune strategies. Our work is the first report showing that pathogens can select for rapid modulation of insect priming ability, allowing hosts to evolve divergent immune strategies (generalized resistance versus specific immune memory) with potentially distinct mechanisms. © 2017 The Author(s).