Canadian Paediatric Neurology Workforce Survey and Consensus Statement.

Science.gov (United States)

Doja, Asif; Orr, Serena L; McMillan, Hugh J; Kirton, Adam; Brna, Paula; Esser, Michael; Tang-Wai, Richard; Major, Philippe; Poulin, Chantal; Prasad, Narayan; Selby, Kathryn; Weiss, Shelly K; Yeh, E Ann; Callen, David Ja

2016-05-01

Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.

Immune response to H pylori

Science.gov (United States)

Suarez, Giovanni; Reyes, Victor E; Beswick, Ellen J

2006-01-01

The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer, attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium. PMID:17007009

Manipulations of the immune response in the chicken

International Nuclear Information System (INIS)

Bixler, G.S. Jr.

1978-01-01

The chicken with its dissociation of immune responses in cell-mediated immunity, dependent on the thymus, and humoral immunity, dependent on the bursa of Fabricius, provides a unique model for studying the two components of the immune system. While there are methods of obtaining selective, profound deficiency of humoral immunity, in this species, methods for obtaining a consistent, profound selective deficiency of cell-mediated immunity have been lacking. Oxisuran, 2[(methylsulfinyl)acetal] pyridine, has been reported to have the unique ability to differentially suppress cell-mediated immunity in several species of mammals without a concomitant reduction in antibody forming capacity. The effect of this compound on two parameters of cell-mediated immune responses in chickens was investigated. In further attempts to create a deficiency of both cell-mediated and humoral immunity, the effects of a combination of cyclophosphamide treatment and x-irradiation early in life on immune responses were studied

Bounded rationality alters the dynamics of paediatric immunization acceptance

Science.gov (United States)

Oraby, Tamer; Bauch, Chris T.

2015-01-01

Interactions between disease dynamics and vaccinating behavior have been explored in many coupled behavior-disease models. Cognitive effects such as risk perception, framing, and subjective probabilities of adverse events can be important determinants of the vaccinating behaviour, and represent departures from the pure “rational” decision model that are often described as “bounded rationality”. However, the impact of such cognitive effects in the context of paediatric infectious disease vaccines has received relatively little attention. Here, we develop a disease-behavior model that accounts for bounded rationality through prospect theory. We analyze the model and compare its predictions to a reduced model that lacks bounded rationality. We find that, in general, introducing bounded rationality increases the dynamical richness of the model and makes it harder to eliminate a paediatric infectious disease. In contrast, in other cases, a low cost, highly efficacious vaccine can be refused, even when the rational decision model predicts acceptance. Injunctive social norms can prevent vaccine refusal, if vaccine acceptance is sufficiently high in the beginning of the vaccination campaign. Cognitive processes can have major impacts on the predictions of behaviour-disease models, and further study of such processes in the context of vaccination is thus warranted. PMID:26035413

The Immune Response of Maternally Immune Chicks to Vaccination ...

African Journals Online (AJOL)

The Immune Response of Maternally Immune Chicks to Vaccination with Newcastle Disease Virus. ... G A El-Tayeb, M Y El-Ttegani, I E Hajer, M A Mohammed ... This study was conducted to determine the persistence of maternally derived antibodies (MDA) to Newcastle disease virus (NDV) in newly hatched chicks and the ...

Gastrointestinal immune responses in HIV infected subjects

Directory of Open Access Journals (Sweden)

LRR Castello-Branco

1996-06-01

Full Text Available The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

Enhancement of Immune Memory Responses to Respiratory Infection

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-16-1-0360 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Min Chen PhD...5a. CONTRACT NUMBER Enhancement of Immune Memory Responses to Respiratory Infection 5b. GRANT NUMBER W81XWH-16-1-0360 5c. PROGRAM ELEMENT NUMBER...entitled “ENHANCEMENT OF IMMUNE MEMORY RESPONSES TO RESPIRATORY INFECTION: AUTOPHAGY IN MEMORY B-CELLS RESPONSE TO INFLUENZA VACCINE (AMBRIV

Immune Response to Lipoproteins in Atherosclerosis

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Sonia Samson

2012-01-01

Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Cholinergic Modulation of Type 2 Immune Responses

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Goele Bosmans

2017-12-01

Full Text Available In recent years, the bidirectional relationship between the nervous and immune system has become increasingly clear, and its role in both homeostasis and inflammation has been well documented over the years. Since the introduction of the cholinergic anti-inflammatory pathway, there has been an increased interest in parasympathetic regulation of both innate and adaptive immune responses, including T helper 2 responses. Increasing evidence has been emerging suggesting a role for the parasympathetic nervous system in the pathophysiology of allergic diseases, including allergic rhinitis, asthma, food allergy, and atopic dermatitis. In this review, we will highlight the role of cholinergic modulation by both nicotinic and muscarinic receptors in several key aspects of the allergic inflammatory response, including barrier function, innate and adaptive immune responses, and effector cells responses. A better understanding of these cholinergic processes mediating key aspects of type 2 immune disorders might lead to novel therapeutic approaches to treat allergic diseases.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis

DEFF Research Database (Denmark)

Ruperto, Nicolino; Pistorio, Angela; Ravelli, Angelo

2010-01-01

To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables....

Immunomodulator-based enhancement of anti smallpox immune responses.

Directory of Open Access Journals (Sweden)

Osmarie Martínez

Full Text Available The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists, and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

Immunomodulator-based enhancement of anti smallpox immune responses.

Science.gov (United States)

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

Stress proteins and the immune response.

Science.gov (United States)

Moseley, P

2000-07-25

The heat shock or stress response is one of the most highly conserved adaptive responses in nature. In single cell organisms, the stress response confers tolerance to a variety of stresses including hyperthermia, hyperoxia, hypoxia, and other perturbations, which alter protein synthesis. This tolerance phenomenon is also extremely important in the multicellular organism, resulting in not only thermal tolerance, but also resistance to stresses of the whole organism such as ischemia-reperfusion injury. Moreover, recent data indicates that these stress proteins have the ability to modulate the cellular immune response. Although the terms heat shock proteins (HSPs) and stress proteins are often used interchangeably, the term stress proteins includes the HSPs, the glucose-regulated proteins (GRPs) and ubiquitin. The stress proteins may be grouped by molecular weight ranging from the large 110 kDa HSP110 to ubiquitin at 8 kDa. These proteins serve as cellular chaperones, participating in protein synthesis and transport through the various cellular compartments. Because these proteins have unique cellular localizations, the chaperone function of the stress proteins often involves a transfer of peptides between stress proteins as the peptide is moved between cellular compartments. For example, HSP70 is a cytosolic and nuclear chaperone, which is critical for the transfer of cellular peptides in the mitochondrion through a hand-off that involves mitochondrial HSP60 at the inner mitochondrial membrane. Similarly, cytosolic proteins are transferred from HSP70 to gp96 as they move into the endoplasmic reticulum. The central role of the stress proteins in the transfer of peptides through the cell may be responsible for the recently recognized importance of the stress proteins in the modulation of the immune system [Feder, M.E., Hofmann, G.E., 1999. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu. Rev. Physiol. 61

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

Science.gov (United States)

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

2014-06-05

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

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

Science.gov (United States)

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L.; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

Background The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. Methods We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. Results The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. Conclusion These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform. PMID:25875833

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

Directory of Open Access Journals (Sweden)

Heng Liu

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

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

Science.gov (United States)

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

2013-01-01

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

Paediatric Interventional Uroradiology

International Nuclear Information System (INIS)

Barnacle, Alex M.; Wilkinson, A. Graham; Roebuck, Derek J.

2011-01-01

Paediatric interventional uroradiology lies at the intersection of the disciplines of paediatric interventional radiology and paediatric endourology. Interdisciplinary collaboration has led to the development of new techniques and refinement of procedures adopted from adult practice. This article reviews the major procedures used in paediatric interventional uroradiology, with emphasis on nephrostomy, percutaneous nephrolithotomy, balloon-burst pyeloplasty, and antegrade ureteric stenting.

Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

International Nuclear Information System (INIS)

Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas

2011-01-01

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

Energy Technology Data Exchange (ETDEWEB)

Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

2011-11-11

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

Pleurodeles Waltl Humoral Immune Response under Spaceflight Conditions

Science.gov (United States)

Bascove, Matthieu; Touche, Nadege; Frippiat, Jean-Pol

2008-06-01

The immune system is an important regulatory mechanism affected by spaceflights. In a previous work, we performed a first study of the humoral immune response induced by the immunization of Pleurodeles waltl during a 5 months stay onboard the Mir space station. This analysis indicated that heavy-chain variable domains of specific IgM are encoded by genes of the VHII and VHVI families. However, the contributions of these two families to IgM heavy-chains are different in flown animals [1]. To better understand this immune response modification, we have now determined how individual VH genes have been used to build specific IgM binding sites in animals immunized on earth or in space. This new study revealed quantitative and qualitative modifications in VH genes expression. These data confirm that a spaceflight might affect the humoral response.

Pancreaticoduodenectomy in children: optimising outcome of uncommon paediatric procedures.

LENUS (Irish Health Repository)

Yeap, B H

2012-02-01

Contemporary surgical practice is increasingly dominated by subspecialisation in response to improved outcome from high volume centres, though uncertainties persist for uncommon paediatric procedures. Three paediatric pancreaticoduodenectomies performed at Our Lady\\'s Children\\'s Hospital, Dublin, over a period of 9 years were evaluated to substantiate their continuing performance by paediatric rather than adult pancreatic surgeons. With ages ranging from 18 months to 8 years old, the mean operating time was 263 minutes, while the average hospital stay was 12 days. There was no perioperative mortality, although complication rate was 100%. Re-operation was required in 33%. The long term outcome of this small paediatric cohort was comparable to adult series despite the low patient accrual, underscoring the advantages of a multidisciplinary approach afforded by tertiary paediatric institutions for intricate yet infrequent operations in children.

The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models.

Science.gov (United States)

Palsson, Sirus; Hickling, Timothy P; Bradshaw-Pierce, Erica L; Zager, Michael; Jooss, Karin; O'Brien, Peter J; Spilker, Mary E; Palsson, Bernhard O; Vicini, Paolo

2013-09-28

The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but rarely have they been proposed to encompass the overall system complexity. We propose here a framework for integration of subset models, based on a system biology approach. A dynamic simulator, the Fully-integrated Immune Response Model (FIRM), was built in a stepwise fashion by integrating published subset models and adding novel features. The approach used to build the model includes the formulation of the network of interacting species and the subsequent introduction of rate laws to describe each biological process. The resulting model represents a multi-organ structure, comprised of the target organ where the immune response takes place, circulating blood, lymphoid T, and lymphoid B tissue. The cell types accounted for include macrophages, a few T-cell lineages (cytotoxic, regulatory, helper 1, and helper 2), and B-cell activation to plasma cells. Four different cytokines were accounted for: IFN-γ, IL-4, IL-10 and IL-12. In addition, generic inflammatory signals are used to represent the kinetics of IL-1, IL-2, and TGF-β. Cell recruitment, differentiation, replication, apoptosis and migration are described as appropriate for the different cell types. The model is a hybrid structure containing information from several mammalian species. The structure of the network was built to be physiologically and biochemically consistent. Rate laws for all the cellular fate processes, growth factor production rates and half-lives, together with antibody production rates and half-lives, are provided. The

Modulation of the innate immune responses in the striped ...

African Journals Online (AJOL)

Thus, most of the innate non-specific immune responses are inducible though they are constitutive of fish immune system exhibiting a basal level of activity even in the absence of pathogen challenge. Keywords: Aeromonas hydrophila, Experimental challenge, Innate immune response, Striped snakehead murrel ...

Survey on sedation in paediatric dentistry: a global perspective.

Science.gov (United States)

Wilson, Stephen; Alcaino, Eduardo A

2011-09-01

Paediatric dentists receive training in sedation during their advanced education training, but evidence suggests that this training varies widely. The purpose of this study was to survey members of the International Association of Paediatric Dentistry (IAPD) and the European Academy of Paediatric Dentistry (EAPD) on their opinion on pharmacological and other behavioural management techniques and their training related to provision of oral health care of paediatric patients in the dental setting. A request was made for access to the IAPD and EAPD membership email addresses. The responses were recorded anonymously and data uploaded into spss (version 9) and analysed using descriptive analysis and chi-square with and without tabulation processes. A total of 311 respondents of 1973 targeted individuals answered the survey. The response rate was 16%. The majority of the respondents came from the continent of Europe, Asia, and the Americas. The most frequent type of sedation was general anaesthesia (52% of the respondents), followed by nitrous oxide (46%) and then oral sedation (44%). At least 91% of the respondents indicated that they were interested in the development of continuing education on the topic of sedation. Paediatric dentists around the world use relatively few behaviour management techniques, including pharmacological management. There is a definite interest in continuing education in the area of sedation. The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

Adenovirus Vector-Derived VA-RNA-Mediated Innate Immune Responses

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Hiroyuki Mizuguchi

2011-07-01

Full Text Available The major limitation of the clinical use of replication-incompetent adenovirus (Ad vectors is the interference by innate immune responses, including induction of inflammatory cytokines and interferons (IFN, following in vivo application of Ad vectors. Ad vector-induced production of inflammatory cytokines and IFNs also results in severe organ damage and efficient induction of acquired immune responses against Ad proteins and transgene products. Ad vector-induced innate immune responses are triggered by the recognition of Ad components by pattern recognition receptors (PRRs. In order to reduce the side effects by Ad vector-induced innate immune responses and to develop safer Ad vectors, it is crucial to clarify which PRRs and which Ad components are involved in Ad vector-induced innate immune responses. Our group previously demonstrated that myeloid differentiating factor 88 (MyD88 and toll-like receptor 9 (TLR9 play crucial roles in the Ad vector-induced inflammatory cytokine production in mouse bone marrow-derived dendritic cells. Furthermore, our group recently found that virus associated-RNAs (VA-RNAs, which are about 160 nucleotide-long non-coding small RNAs encoded in the Ad genome, are involved in IFN production through the IFN-β promoter stimulator-1 (IPS-1-mediated signaling pathway following Ad vector transduction. The aim of this review is to highlight the Ad vector-induced innate immune responses following transduction, especially VA-RNA-mediated innate immune responses. Our findings on the mechanism of Ad vector-induced innate immune responses should make an important contribution to the development of safer Ad vectors, such as an Ad vector lacking expression of VA-RNAs.

High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura.

Science.gov (United States)

Swain, Trupti Rekha; Jena, Rabindra Kumar; Swain, Kali Prasanna

2016-12-01

Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7 th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP.

Immune response induction in the central nervous system

DEFF Research Database (Denmark)

Owens, Trevor; Babcock, Alicia

2002-01-01

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

Interplay between behavioural thermoregulation and immune response in mealworms.

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Catalán, Tamara P; Niemeyer, Hermann M; Kalergis, Alexis M; Bozinovic, Francisco

2012-11-01

Since the preferential body temperature should positively correlate with physiological performance, behavioural fever should enhance an organism's immune response under an immune challenge. Here we have studied the preferential body temperature (T(p)) and its consequences on immune response performance after an immune challenge in larvae of Tenebrio molitor. We evaluated T(p) and immune responses of larvae following a challenge with various concentrations of lipopolysaccharide (LPS), and we studied the correlation between T(p) and two immune traits, namely antibacterial and phenoloxidase (PO) activities. Larvae that were immune challenged with higher LPS concentrations (C(50) and C(100)) preferred in average, warmer temperatures than did larvae challenged with lower concentrations (C(0) and C(25)). T(p) of C(25)-C(100) (challenged)-mealworms was 2.3°C higher than of C(0) (control) larvae. At lower LPS concentration immune challenge (C(0) and C(25)) antibacterial activity correlated positively with T(p), but at C(50) and C(100) correlation was lose. PO activity was higher at higher LPS concentration, but its magnitude of response did not correlate with T(p) Our data suggest that behavioural fever may have a positive effect on host performance by enhancing antibacterial response under a low pathogen load situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs.

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Pollak, Cora N; Wanke, María Magdalena; Estein, Silvia M; Delpino, M Victoria; Monachesi, Norma E; Comercio, Elida A; Fossati, Carlos A; Baldi, Pablo C

2015-03-01

VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

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Franca Citarella

2013-08-01

Full Text Available Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response.

Innate immune response development in nestling tree swallows

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Stambaugh, T.; Houdek, B.J.; Lombardo, M.P.; Thorpe, P.A.; Caldwell, Hahn D.

2011-01-01

We tracked the development of innate immunity in nestling Tree Swallows (Tachycineta bicolor) and compared it to that of adults using blood drawn from nestlings during days 6, 12, and 18 of the ???20-day nestling period and from adults. Innate immunity was characterized using an in vitro assay of the ability of whole blood to kill Escherichia coli. The ability of whole blood to kill E. coli increased as nestlings matured. Neither this component of innate immunity nor right wing chord length on day18 were as developed as in adults indicating that development of the innate immune system and growth both continued after fledging. Narrow sense heritability analyses suggest that females with strong immune responses produced nestlings with strong immune responses. These data suggest nestling Tree Swallows allocated sufficient energy to support rapid growth to enable fledging by day 18, but that further development of innate immunity occurred post-fledging. ?? 2011 by the Wilson Ornithological Society.

COMPARISON OF AIRWAY RESPONSES, HAEMODYNAMICS AND RECOVERY USING SEVOFLURANE AND DESFLURANE VIA LARYNGEAL MASK AIRWAY IN DAY CARE PAEDIATRIC SURGERIES

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A. Satyanarayana

2017-11-01

Full Text Available BACKGROUND The general observation that children achieve better convalescence in the home environment supports the need for adoption of day care surgeries in them. Advantages of paediatric outpatient anaesthesia include- minimises parental separation, uninterrupted feeding schedule/sleeping patterns, less risk of nosocomial infections, reduced cost of hospitalisation, convenience and improved patient satisfaction. The aim of the study is to compare the airway responses, haemodynamic parameters and recovery using sevoflurane and desflurane via laryngeal mask airway in day care paediatric surgeries. MATERIALS AND METHODS 60 paediatric patients of both gender between the age group of 6 and 14 years with ASA grade 1 and 2 undergoing elective day care surgeries under general anaesthesia with LMA are divided into two groups. (Group S sevoflurane group received sevoflurane 2% to 3% and (group D desflurane group received desflurane 6% to 8% for maintenance of anaesthesia after induction with IV propofol 2 mg/kg. Airway responses, haemodynamics and recovery parameters are recorded. RESULTS Recovery parameters spontaneous eye opening, response to verbal commands, Aldrete score at 5 and 10 mins. showed statistically significant difference between two groups. Recovery is faster in desflurane group compared to sevoflurane group. The airway responses and adverse events were found to be more in desflurane group, but statistically not significant. CONCLUSION Recovery from anaesthesia was faster in patients maintained with desflurane (6% to 8% compared with sevoflurane (2% to 3%.

Long-chain inulin for stimulating an immune response

NARCIS (Netherlands)

de Vos, Paulus; Vogt, Leonie

2017-01-01

The invention relates to a long chain inulin for influencing the immune response against a pathogen. The invention also relates to a combination comprising a long chain inulin and a vaccine for influencing the immune response against a pathogen, wherein the long chain inulin is orally administrated.

Immune Responses Involved in Mycobacterium Tuberculosis Infection

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Roghayeh Teimourpour

2016-09-01

Full Text Available Background and Objectives: Mycobacterium tuberculosis is the causative agent of tuberculosis (TB. Approximately one-third of the world's population is infected with M. tuberculosis. Despite the availability of drug and vaccine, it remains one of the leading causes of death in humans especially in developing countries. Epidemiological studies have indicated that only 10-30% of people exposed to tubercle bacillus are infected with M. tuberculosis, and at least 90% of the infected people finally do not acquire TB. The studies have indicated that the host efficient immune system has essential roles in the control of TB infection such that the highest rate of mortality and morbidity is seen in immunocompromised patients such as people infected with HIV. M. tuberculosis is an obligatory intracellular bacterium. It enters the body mainly through the respiratory tract and alveolar macrophages combat this pathogen most commonly. In addition to alveolar macrophages, various T-cell subpopulations need to be activated to overcome this bacterium's resistance to the host defense systems. CD4+ T cells, through production of several cytokines such as IFN-γ and TNF-α, and CD8+ T cells, through cytotoxic activities and induction of apoptosis in infected cells, play critical roles in inducing appropriate immune responses against M. tuberculosis. Although cell-mediated immunity is the cornerstone of host responses against TB and the recent studies have provided evidence for the importance of humoral and innate immune system in the control of TB, a profound understanding of the immune responses would provide a basis for development of new generations of vaccines and drugs. The present study addresses immune responses involved in M. tuberculosis infection.

FDG PET/CT in initial staging and early response to chemotherapy assessment of paediatric rhabdomyosarcomas

International Nuclear Information System (INIS)

Eugene, T.; Ansquer, C.; Oudoux, A.; Carlier, T.; Kraeber-Bodere, T.; Bodet-Milin, C.; Corradini, N.; Thomas, C.; Dupas, B.

2010-01-01

Purpose: The objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma. Patients and methods: Prior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years). Results: PET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years). Conclusion: This study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment. (authors)

Agouron and immune response to commercialize remune immune-based treatment.

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James, J S

1998-06-19

Agouron Pharmaceuticals agreed in June to collaborate with The Immune Response Corporation on the final development and marketing of an immune-based treatment for HIV. Remune, the vaccine developed by Dr. Jonas Salk, is currently in Phase III randomized trials with 2,500 patients, and the trials are expected to be completed in April 1999. Immune-based treatments have been difficult to test, as there is no surrogate marker, like viral load, to determine if the drug is working. Agouron agreed to participate in the joint venture after reviewing encouraging results from preliminary trials in which remune was taken in combination with highly active antiretroviral drugs.

Reducing dose in paediatric CT: a preliminary study of radiographers' knowledge

International Nuclear Information System (INIS)

Heagney, J.; Lewis, S.; Chaffey, C.; Howlett, G.; Moran, A.; McLean, D.

2003-01-01

The objective of this study is to evaluate the responses of Australian radiographers in comparison with current literature on paediatric protocols and scanning recommendations in order to determine how and if paediatric Computed Tomography (CT) exposure reductions are taking place within Medical Imaging Departments. Subjects and Methods: The method involved a dual format; consisting of surveying 30 CT radiographers, and additionally, interviewing 5 senior CT radiographers. Of the 30 surveys completed, one was completed by a PDY radiographer, 7 by CT Senior radiographers and 22 by CT radiographers. The survey contained a range of questions about appropriate paediatric CT scanning parameters and protocols. Five CT Seniors were interviewed to ascertain the current level and opinion of training in paediatric protocols, in-house educational programs and the implementation of radiation dose saving parameters. Radiographers demonstrated reasonable ability to identify suitable paediatric protocols and believed the in-house CT protocols resident to their medical imaging department to be adequate, despite many utilising exposures higher than those from recommended literature. The interviews revealed that no further training in CT paediatric dose reduction was currently available, however survey responses indicated that further training would be beneficial. This study demonstrates that radiographers are aware of the need to reduce exposure parameters for paediatric CT and tend to follow protocols in place within their workplace, regardless of suitability and patient needs. Copyright (2003) Australian Institute of Radiography

Reducing dose in paediatric CT: a preliminary study of radiographers' Knowledge

International Nuclear Information System (INIS)

Heagney, Jillian; Lewis, Sarah; Chaffey, Clare; Howlett, Genevieve; Moran, Alexander; McLean, Donald

2003-01-01

The objective of this study is to evaluate the responses of Australian radiographers in comparison with current literature on paediatric protocols and scanning recommendations in order to determine how and if paediatric Computed Tomography (CT) exposure reductions are taking place within Medical Imaging Departments. Subjects and Methods: The method involved a dual format; consisting of surveying 30 CT radiographers, and additionally, interviewing 5 senior CT radiographers. Of the 30 surveys completed, one was completed by a PDY radiographer, 7 by CT Senior radiographers and 22 by CT radiographers. The survey contained a range of questions about appropriate paediatric CT scanning parameters and protocols. Five CT Seniors were interviewed to ascertain the current level and opinion of training in paediatric protocols, in-house educational programs and the implementation of radiation dose saving parameters. Radiographers demonstrated reasonable ability to identify suitable paediatric protocols and believed the in-house CT protocols resident to their medical imaging department to be adequate, despite many utilising exposures higher than those from recommended literature. The interviews revealed that no further training in CT paediatric dose reduction was currently available, however survey responses indicated that further training would be beneficial. This study demonstrates that radiographers are aware of the need to reduce exposure parameters for paediatric CT and tend to follow protocols in place within their workplace, regardless of suitability and patient needs Copyright (2003) Australian Institute of Radiography

Modulation of immune responses in stress by Yoga

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Arora Sarika

2008-01-01

Full Text Available Stress is a constant factor in today′s fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

Heterogeneity in cervical spine assessment in paediatric trauma: A survey of physicians' knowledge and application at a paediatric major trauma centre.

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Buckland, Aaron J; Bressan, Silvia; Jowett, Helen; Johnson, Michael B; Teague, Warwick J

2016-10-01

Evidence-based decision-making tools are widely used to guide cervical spine assessment in adult trauma patients. Similar tools validated for use in injured children are lacking. A paediatric-specific approach is appropriate given important differences in cervical spine anatomy, mechanism of spinal injury and concerns over ionising radiation in children. The present study aims to survey physicians' knowledge and application of cervical spine assessment in injured children. A cross-sectional survey of physicians actively engaged in trauma care within a paediatric trauma centre was undertaken. Participation was voluntary and responses de-idenitified. The survey comprised 20 questions regarding initial assessment, imaging, immobilisation and perioperative management. Physicians' responses were compared with available current evidence. Sixty-seven physicians (28% registrars, 17% fellows and 55.2% consultants) participated. Physicians rated altered mental state, intoxication and distracting injury as the most important contraindications to cervical spine clearance in children. Fifty-four per cent considered adequate plain imaging to be 3-view cervical spine radiographs (anterior-posterior, lateral and odontoid), whereas 30% considered CT the most sensitive modality for detecting unstable cervical spine injuries. Physicians' responses reflected marked heterogeneity regarding semi-rigid cervical collars and what constitutes cervical spine 'clearance'. Greater consensus existed for perioperative precautions in this setting. Physicians actively engaged in paediatric trauma care demonstrate marked heterogeneity in their knowledge and application of cervical spine assessment. This is compounded by a lack of paediatric-specific evidence and definitions, involvement of multiple specialties and staff turnover within busy departments. A validated decision-making tool for cervical spine assessment will represent an important advance in paediatric trauma. © 2016 Australasian

Paediatric acute care: Highlights from the Paediatric Acute Care-Advanced Paediatric Life Support Conference, Gold Coast, 2017.

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Teo, Stephen Ss; Rao, Arjun; Acworth, Jason

2018-04-25

The Paediatric Acute Care Conference is an annual conference organised by APLS Australia to advance paediatric acute care topics for clinicians in pre-hospital medicine, EDs, acute paediatrics, intensive care and anaesthesia. The Conference 2017 was held at Surfers Paradise, Queensland. We provide a summary of some of the presentations. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Modulation of immune response by bacterial lipopolysaccharides

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Gustavo Aldapa-Vega

2016-08-01

Full Text Available Lipopolysaccharide (LPS is a molecule that is profusely found on the outer membrane of Gram-negative bacteria and is also a potent stimulator of the immune response. As the main molecule on the bacterial surface, is also the most biologically active. The immune response of the host is activated by the recognition of LPS through Toll-like receptor 4 (TLR4 and this receptor-ligand interaction is closely linked to LPS structure. Microorganisms have evolved systems to control the expression and structure of LPS, producing structural variants that are used for modulating the host immune responses during infection. Examples of this include Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis and Salmonella spp. High concentrations of LPS can cause fever, increased heart rate and lead to septic shock and death. However, at relatively low concentrations some LPS are highly active immunomodulators, which can induce non-specific resistance to invading microorganisms. The elucidation of the molecular and cellular mechanisms involved in the recognition of LPS and its structural variants has been fundamental to understand inflammation and is currently a pivotal field of research to understand the innate immune response, inflammation, the complex host-pathogen relationship and has important implications for the rational development of new immunomodulators and adjuvants.

The immune response to sand fly salivary proteins and its influence on Leishmania immunity

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Regis eGomes

2012-05-01

Full Text Available Leishmaniasis is a vector-borne disease transmitted by bites of phlebotomine sand flies. During Leishmania transmission, sand fly saliva is co-inoculated with parasites into the skin of the mammalian host. Sand fly saliva consists of roughly thirty different salivary proteins, many with known roles linked to blood feeding facilitation. Apart from the anti-hemostatic capacity of saliva, several sand fly salivary proteins have been shown to be immunogenic upon multiple contacts with a mammalian host. Immunization with single immunogenic salivary proteins or exposure to uninfected bites can produce protective immune responses against leishmaniasis. These sand fly salivary proteins induce cellular immune responses and/or antibodies. Antibodies to saliva are not required for protection in a mouse model against leishmaniasis. A strong body of evidence points to the role for saliva-specific T cells producing IFN-γ in the form of a delayed-type hypersensitivity reaction at the bite site as the main protective response. Herein, we review immunity to sand fly salivary proteins in the context of its vector-parasite-host combinations and vaccine potential, as well as some recent advances to shed light on the mechanism of how an immune response to sand fly saliva protects against leishmaniasis.

Modulation of systemic immune responses through commensal gastrointestinal microbiota.

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Kyle M Schachtschneider

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

Sex hormones and the immune response in humans

NARCIS (Netherlands)

Bouman, Annechien; Heineman, Maas Jan; Faas, Marijke M.

2005-01-01

In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more

Bovine immune response to inoculation with Neospora caninum surface antigen SRS2 lipopeptides mimics immune response to infection with live parasites.

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Baszler, Timothy V; Shkap, Varda; Mwangi, Waithaka; Davies, Christopher J; Mathison, Bruce A; Mazuz, Monica; Resnikov, Dror; Fish, Lea; Leibovitch, Benjamin; Staska, Lauren M; Savitsky, Igor

2008-04-01

Infection of cattle with Neospora caninum protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4(+) T-lymphocyte activation and gamma interferon (IFN-gamma) secretion. In the present study, N. caninum SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4(+) cell proliferation and IFN-gamma T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-gamma secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-gamma-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that N. caninum NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-gamma secretion. The findings support the investigation of NcSRS2 immunogens for protection against N. caninum-induced fetal infection and abortion in cattle.

The innate immune response during urinary tract infection and pyelonephritis.

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Spencer, John David; Schwaderer, Andrew L; Becknell, Brian; Watson, Joshua; Hains, David S

2014-07-01

Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides-a ubiquitous component of the innate immune response.

Models for Immune Response and Immune Evasion in MSI Cancer and Lynch Syndrome

OpenAIRE

Özcan, Mine

2017-01-01

Microsatellite-unstable (MSI) cancers occurring in the context of the hereditary Lynch syndrome or as sporadic cancers elicit pronounced tumor-specific immune responses. The pronounced immune response was shown to be closely associated with frameshift peptides (FSP) that are generated as a result of deficiency in DNA mismatch repair system leading to insertion/deletion mutations in coding microsatellites (cMS). FSP neoantigens are long antigenic amino acid stretches that bear m...

Immune and stress responses in oysters with insights on adaptation.

Science.gov (United States)

Guo, Ximing; He, Yan; Zhang, Linlin; Lelong, Christophe; Jouaux, Aude

2015-09-01

Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

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Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

2016-07-15

In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. Copyright © 2016 Elsevier B.V. All rights reserved.

Probiotics, antibiotics and the immune responses to vaccines.

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Praharaj, Ira; John, Sushil M; Bandyopadhyay, Rini; Kang, Gagandeep

2015-06-19

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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

NARCIS (Netherlands)

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

2013-01-01

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

Characterization of host immune responses in Ebola virus infections.

Science.gov (United States)

Wong, Gary; Kobinger, Gary P; Qiu, Xiangguo

2014-06-01

Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.

Initiation of innate immune responses by surveillance of homeostasis perturbations.

Science.gov (United States)

Colaço, Henrique G; Moita, Luis F

2016-07-01

Pathogen recognition, signaling transduction pathways, and effector mechanisms are necessary steps of innate immune responses that play key roles in the early phase of defense and in the stimulation of the later specific response of adaptive immunity. Here, we argue that in addition to the direct recognition of conserved common structural and functional molecular signatures of microorganisms using pattern recognition receptors, hosts can mount an immune response following the sensing of disruption in homeostasis as proximal reporters for infections. Surveillance of disruption of core cellular activities leading to defense responses is a flexible strategy that requires few additional components and that can effectively detect relevant threats. It is likely to be evolutionarily very conserved and ancient because it is operational in organisms that lack pattern recognition triggered immunity. A homeostasis disruption model of immune response initiation and modulation has broad implications for pathophysiology and treatment of disease and might constitute an often overlooked but central component of a comprehensive conceptual framework for innate immunity. © 2016 Federation of European Biochemical Societies.

Respons imun humoral pada pulpitis (Humoral immune response on pulpitis

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Trijoedani Widodo

2005-06-01

Full Text Available Pulpitis is an inflammation process on dental pulp tissue, and usually as the continuous of caries. The microorganism in the caries is a potential immunogenic triggering the immune respons, both humoral and celluler immune responses. The aim of this research is to explain the humoral immune response changes in the dental pulp tissues of pulpitis. This research was done on three group samples: Irreversible pulpitis, Reversible pulpitis and sound teeth as the control group. The result showed that there were three pulpitis immunopathologic patterns: the sound teeth immunopathologic pattern showing a low humoral immune response, in a low level of IgG, IgA and IgM, the reversible pulpitis pattern showing that in a higher humoral immune response, IgG and IgA decreased but IgM increased, the irreversible pulpitis pattern showing that IgG and IgM increased, but it couldn't be repaired although it has highly immunity, and it showed an unusually low level of IgA. This low level of IgA meant that irreversible pulpitis had a low mucosal immunity.

Regulation of immune responses and tolerance: the microRNA perspective

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Chen, Chang-Zheng; Schaffert, Steven; Fragoso, Rita; Loh, Christina

2013-01-01

Summary Much has been learned about the molecular and cellular components critical for the control of immune responses and tolerance. It remains a challenge, however, to control the immune response and tolerance at the system level without causing significant toxicity to normal tissues. Recent studies suggest that microRNA (miRNA) genes, an abundant class of non-coding RNA genes that produce characteristic approximately 22 nucleotides small RNAs, play important roles in immune cells. In this article, we discuss emerging knowledge regarding the functions of miRNA genes in the immune system. We delve into the roles of miRNAs in regulating signaling strength and threshold, homeostasis, and the dynamics of the immune response and tolerance during normal and pathogenic immunological conditions. We also present observations based on analyzes of miR-181 family genes that indicate the potential functions of primary and/ or precursor miRNAs in target recognition and explore the impact of these findings on target identification. Finally, we illustrate that despite the subtle effects of miRNAs on gene expression, miRNAs have the potential to influence the outcomes of normal and pathogenic immune responses by controlling the quantitative and dynamic aspects of immune responses. Tuning miRNA functions in immune cells, through gain- and loss-of-function approaches in mice, may reveal novel approach to restore immune equilibrium from pathogenic conditions, such as autoimmune disease and leukemia, without significant toxicity. PMID:23550642

Regulation of immune responses and tolerance: the microRNA perspective.

Science.gov (United States)

Chen, Chang-Zheng; Schaffert, Steven; Fragoso, Rita; Loh, Christina

2013-05-01

Much has been learned about the molecular and cellular components critical for the control of immune responses and tolerance. It remains a challenge, however, to control the immune response and tolerance at the system level without causing significant toxicity to normal tissues. Recent studies suggest that microRNA (miRNA) genes, an abundant class of non-coding RNA genes that produce characteristic approximately 22 nucleotides small RNAs, play important roles in immune cells. In this article, we discuss emerging knowledge regarding the functions of miRNA genes in the immune system. We delve into the roles of miRNAs in regulating signaling strength and threshold, homeostasis, and the dynamics of the immune response and tolerance during normal and pathogenic immunological conditions. We also present observations based on analyzes of miR-181 family genes that indicate the potential functions of primary and/or precursor miRNAs in target recognition and explore the impact of these findings on target identification. Finally, we illustrate that despite the subtle effects of miRNAs on gene expression, miRNAs have the potential to influence the outcomes of normal and pathogenic immune responses by controlling the quantitative and dynamic aspects of immune responses. Tuning miRNA functions in immune cells, through gain- and loss-of-function approaches in mice, may reveal novel approach to restore immune equilibrium from pathogenic conditions, such as autoimmune disease and leukemia, without significant toxicity. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Chemokine-mediated immune responses in the female genital tract mucosa.

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Deruaz, Maud; Luster, Andrew D

2015-04-01

The genital tract mucosa is the site where sexually transmitted infections gain entry to the host. The immune response at this site is thus critical to provide innate protection against pathogens that are seen for the very first time as well as provide long-term pathogen-specific immunity, which would be required for an effective vaccine against sexually transmitted infection. A finely regulated immune response is therefore required to provide an effective barrier against pathogens without compromising the capacity of the genital tract to allow for successful conception and fetal development. We review recent developments in our understanding of the immune response in the female genital tract to infectious pathogens, using herpes simplex virus-2, human immunodeficiency virus-1 and Chlamydia trachomatis as examples, with a particular focus on the role of chemokines in orchestrating immune cell migration necessary to achieve effective innate and adaptive immune responses in the female genital tract.

Risk factors for discordant immune response among HIV-infected ...

African Journals Online (AJOL)

Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study. ... Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic ...

Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences.

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Roved, Jacob; Westerdahl, Helena; Hasselquist, Dennis

2017-02-01

Males and females differ in both parasite load and the strength of immune responses and these effects have been verified in humans and other vertebrates. Sex hormones act as important modulators of immune responses; the male sex hormone testosterone is generally immunosuppressive while the female sex hormone estrogen tends to be immunoenhancing. Different sets of T-helper cells (Th) have important roles in adaptive immunity, e.g. Th1 cells trigger type 1 responses which are primarily cell-mediated, and Th2 cells trigger type 2 responses which are primarily humoral responses. In our review of the literature, we find that estrogen and progesterone enhance type 2 and suppress type 1 responses in females, whereas testosterone suppresses type 2 responses and shows an inconsistent pattern for type 1 responses in males. When we combine these patterns of generally immunosuppressive and immunoenhancing effects of the sex hormones, our results imply that the sex differences in immune responses should be particularly strong in immune functions associated with type 2 responses, and less pronounced with type 1 responses. In general the hormone-mediated sex differences in immune responses may lead to genetic sexual conflicts on immunity. Thus, we propose the novel hypothesis that sexually antagonistic selection may act on immune genes shared by the sexes, and that the strength of this sexually antagonistic selection should be stronger for type 2- as compared with type 1-associated immune genes. Finally, we put the consequences of sex hormone-induced effects on immune responses into behavioral and ecological contexts, considering social mating system, sexual selection, geographical distribution of hosts, and parasite abundance. Copyright © 2016 Elsevier Inc. All rights reserved.

A simple non-linear model of immune response

International Nuclear Information System (INIS)

Gutnikov, Sergei; Melnikov, Yuri

2003-01-01

It is still unknown why the adaptive immune response in the natural immune system based on clonal proliferation of lymphocytes requires interaction of at least two different cell types with the same antigen. We present a simple mathematical model illustrating that the system with separate types of cells for antigen recognition and patogen destruction provides more robust adaptive immunity than the system where just one cell type is responsible for both recognition and destruction. The model is over-simplified as we did not have an intention of describing the natural immune system. However, our model provides a tool for testing the proposed approach through qualitative analysis of the immune system dynamics in order to construct more sophisticated models of the immune systems that exist in the living nature. It also opens a possibility to explore specific features of highly non-linear dynamics in nature-inspired computational paradigms like artificial immune systems and immunocomputing . We expect this paper to be of interest not only for mathematicians but also for biologists; therefore we made effort to explain mathematics in sufficient detail for readers without professional mathematical background

Systems biology of neutrophil differentiation and immune response

DEFF Research Database (Denmark)

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

2005-01-01

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

A Drosophila immune response against Ras-induced overgrowth

Directory of Open Access Journals (Sweden)

Thomas Hauling

2014-03-01

Full Text Available Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12, both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria, which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity.

Costs of mounting an immune response during pregnancy in a lizard.

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Meylan, Sandrine; Richard, Murielle; Bauer, Sophie; Haussy, Claudy; Miles, Donald

2013-01-01

Immune defenses are of great benefit to hosts, but reducing the impact of infection by mounting an immune response also entails costs. However, the physiological mechanisms that generate the costs of an immune response remain poorly understood. Moreover, the majority of studies investigating the consequences of an immune challenge in vertebrates have been conducted on mammals and birds. The aim of this study is to investigate the physiological costs of mounting an immune response during gestation in an ectothermic species. Indeed, because ectothermic species are unable to internally regulate their body temperature, the apportionment of resources to homeostatic activities in ectothermic species can differ from that in endothermic species. We conducted this study on the common lizard Zootoca vivipara. We investigated the costs of mounting an immune response by injecting females with sheep red blood cells and quantified the consequences to reproductive performance (litter mass and success) and physiological performance (standard metabolic rate, endurance, and phytohemagglutinin response). In addition, we measured basking behavior. Our analyses revealed that mounting an immune response affected litter mass, physiological performance, and basking behavior. Moreover, we demonstrated that the modulation of an immune challenge is impacted by intrinsic factors, such as body size and condition.

Wallerian degeneration: the innate-immune response to traumatic nerve injury

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Rotshenker Shlomo

2011-08-01

Full Text Available Abstract Traumatic injury to peripheral nerves results in the loss of neural functions. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. Innate-immunity is central to Wallerian degeneration since innate-immune cells, functions and molecules that are produced by immune and non-immune cells are involved. The innate-immune response helps to turn the peripheral nerve tissue into an environment that supports regeneration by removing inhibitory myelin and by upregulating neurotrophic properties. The characteristics of an efficient innate-immune response are rapid onset and conclusion, and the orchestrated interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and molecules they produce. Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration.

Multiscale modeling of mucosal immune responses

Science.gov (United States)

2015-01-01

Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut

Multiscale modeling of mucosal immune responses.

Science.gov (United States)

Mei, Yongguo; Abedi, Vida; Carbo, Adria; Zhang, Xiaoying; Lu, Pinyi; Philipson, Casandra; Hontecillas, Raquel; Hoops, Stefan; Liles, Nathan; Bassaganya-Riera, Josep

2015-01-01

Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut inflammation. Our modeling predictions dissect the mechanisms by which effector CD4+ T cell responses contribute to tissue damage in the gut mucosa following immune dysregulation.Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T

Suppressive influences in the immune response to cancer.

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Bronte, Vincenzo; Mocellin, Simone

2009-01-01

Although much evidence has been gathered demonstrating that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells do evade immune surveillance in most cases. Considering that anticancer active specific immunotherapy seems to have reached a plateau of results and that currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted.

Lessons Learned from Protective Immune Responses to Optimize Vaccines against Cryptosporidiosis.

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Lemieux, Maxime W; Sonzogni-Desautels, Karine; Ndao, Momar

2017-12-24

In developing countries, cryptosporidiosis causes moderate-to-severe diarrhea and kills thousands of infants and toddlers annually. Drinking and recreational water contaminated with Cryptosporidium spp. oocysts has led to waterborne outbreaks in developed countries. A competent immune system is necessary to clear this parasitic infection. A better understanding of the immune responses required to prevent or limit infection by this protozoan parasite is the cornerstone of development of an effective vaccine. In this light, lessons learned from previously developed vaccines against Cryptosporidium spp. are at the foundation for development of better next-generation vaccines. In this review, we summarize the immune responses elicited by naturally and experimentally-induced Cryptosporidium spp. infection and by several experimental vaccines in various animal models. Our aim is to increase awareness about the immune responses that underlie protection against cryptosporidiosis and to encourage promotion of these immune responses as a key strategy for vaccine development. Innate and mucosal immunity will be addressed as well as adaptive immunity, with an emphasis on the balance between T H 1/T H 2 immune responses. Development of more effective vaccines against cryptosporidiosis is needed to prevent Cryptosporidium spp.-related deaths in infants and toddlers in developing countries.

Serum anti-glycan antibodies in paediatric-onset Crohn's disease: association with disease phenotype and diagnostic accuracy.

Science.gov (United States)

Sładek, Małgorzata; Wasilewska, Agata; Swiat, Agnieszka; Cmiel, Adam

2014-01-01

Antibodies reacting with various microbial epitopes have been described in inflammatory bowel disease (IBD) and are associated with a specific diagnosis and clinical presentation. To evaluate the profile of new anti-glycan antibodies, their potential association with disease phenotype and diagnostic accuracy in paediatric Crohn's disease (CD). Blood samples from 134 paediatric IBD patients (109 CD, 25 ulcerative colitis (UC)) and 67 controls were blindly analysed for anti-Saccharomyces cerevisiae (ASCA), anti-chitobioside carbohydrate (ACCA), anti-laminaribioside carbohydrate (ALCA), and anti-mannobioside carbohydrate (AMCA) antibodies using commercially available assays. The serological response to glycans was correlated with clinical disease characteristics. At least one of the tested anti-glycan antibodies was present in 75% of CD patients. Despite the high frequency of reactivity to glycan epitopes, a limited overlap of serological markers was observed. In total, 49% of ASCA-negative patients presented with one of the following: ACCA, ALCA, or AMCA. The occurrence of one antibody from the anti-glycan panel was independently associated with complicated disease phenotype and ileocolonic disease location. A higher level of immune response as assessed by the quartile sum scores for ACCA, ALCA, and AMCA was linked with older age at diagnosis (10-17 years) and ileocolonic disease location. The ASCA had the greatest accuracy for diagnosis and differentiation of CD. Qualitative and quantitative serologicalal response to glycan epitopes was associated with distinct clinical presentation in paediatric CD patients. This raises the possibility for the use of these markers to differentiate subgroups of CD patients with more sever clinical presentation. The ASCA was the most accurate serological marker for CD; however, testing for the new anti-glycan antibodies may constitute an adjunctive tool in a specific group of patients to aid in the differentiation of CD with absent

The Role of the Immune Response in Merkel Cell Carcinoma

International Nuclear Information System (INIS)

Triozzi, Pierre L.; Fernandez, Anthony P.

2013-01-01

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

The Role of the Immune Response in Merkel Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Triozzi, Pierre L., E-mail: triozzp@ccf.org [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)

2013-02-28

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

Early-life inflammation, immune response and ageing.

Science.gov (United States)

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Caring for paediatric patient as to broaden radiography spectrum

International Nuclear Information System (INIS)

Atiti, J.S.M.

2006-01-01

The paediatric patient is a special group of patients in the hospital set up. thus their special needs contribute to about 75% of quality imaging services offered. Age, Psychological aspects, parents participation, departmental atmosphere and environmental make them special. this presentation aims at installing into Imaging Technologies a sense of Responsibility for purpose of improving the resultant quality of Imaging services offered to paediatrics

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

NARCIS (Netherlands)

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

2016-01-01

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

Ovine model for studying pulmonary immune responses

International Nuclear Information System (INIS)

Joel, D.D.; Chanana, A.D.

1984-01-01

Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with 125 I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables

Ovine model for studying pulmonary immune responses

Energy Technology Data Exchange (ETDEWEB)

Joel, D.D.; Chanana, A.D.

1984-11-25

Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with /sup 125/I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables.

Future career intentions of higher specialist trainees in general Paediatrics.

Science.gov (United States)

Butler, Grainne; Breatnach, Colm; Harty, Sinead; Gavin, Patrick; O'Donnell, Colm; O'Grady, Michael J

2018-03-27

A survey of paediatric higher specialist trainees was carried out in 2002 assessing career intentions and perception of training. Fourteen years later, with increased numbers of trainees and a national model of care and a tertiary paediatric hospital on the horizon, we re-evaluated the career intentions of the current trainee workforce. To assess the career intentions of the current paediatric higher specialist trainees. A 28-item questionnaire was developed based on a previously validated instrument and distributed online using the Royal College of Physicians of Ireland trainee database. We distributed the questionnaire to 118 eligible trainees and received responses from 92 (78%). Seventy-nine (86%) respondents desire a consultant post in Ireland. Seventy-five (82%) indicated that their preferred consultant post location was in a tertiary paediatric centre. Sixty-two trainees (67%) intend to become subspecialists with 25 (27%) planning a career in general paediatrics. This contrasts with the 2002 survey when 76% wished to work in urban centres and 61% of trainees planned a career in general paediatrics. There appears to be a mismatch between the career goals of the future paediatric consultant workforce and the requirements for staffing paediatric units nationally. This has the potential to complicate the proposed expansion of general paediatricians in regional centres and result in a significant proportion of current trainees failing to secure a post in their desired location.

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

OpenAIRE

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...

Innate Immune Responses in Leprosy

Science.gov (United States)

Pinheiro, Roberta Olmo; Schmitz, Veronica; Silva, Bruno Jorge de Andrade; Dias, André Alves; de Souza, Beatriz Junqueira; de Mattos Barbosa, Mayara Garcia; de Almeida Esquenazi, Danuza; Pessolani, Maria Cristina Vidal; Sarno, Euzenir Nunes

2018-01-01

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management. PMID:29643852

Preexisting Salmonella-specific immunity interferes with the subsequent development of immune responses against the Salmonella strains delivering H9N2 hemagglutinin.

Science.gov (United States)

Hajam, Irshad Ahmed; Lee, John Hwa

2017-06-01

Recombinant Salmonella strains expressing foreign heterologous antigens have been extensively studied as promising live vaccine delivery vehicles. In this study, we constructed attenuated smooth (S-HA) and rough (R-HA) Salmonella strains expressing hemagglutinin (HA) of H9N2, a low pathogenic avian influenza A virus. We then investigated the HA-specific immune responses following oral immunization with either S-HA or R-HA strain in chicken model. We further examined the effects of the preexisting anti-Salmonella immunity on the subsequent elicitation of the HA and the Salmonella ompA specific immune responses. Our results showed that primary immunization with either the S-HA or the R-HA strain elicited comparable HA-specific immune responses and the responses were significantly (pSalmonella vector control. When chickens were pre-immunized with the smooth Salmonella carrier alone and then vaccinated with either S-HA or R-HA strain 3, 6 and 9 weeks later, respectively, significant reductions were seen for HA-specific immune responses at week 6, a point which corresponded to the peak of the primary Salmonella-specific antibody responses. No reductions were seen at week 3 and 9, albeit, the HA-specific immune responses were boosted at week 9, a point which corresponded to the lowest primary Salmonella-specific antibody responses. The ompA recall responses remain refractory at week 3 and 6 following deliberate immunization with the carrier strain, but were significantly (pSalmonella immunity inhibits antigen-specific immune responses and this effect could be avoided by carefully selecting the time point when carrier-specific immune responses are relatively low. Copyright © 2017 Elsevier B.V. All rights reserved.

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

Science.gov (United States)

Marcu, Oana; Lera, Matthew P.; Sanchez, Max E.; Levic, Edina; Higgins, Laura A.; Shmygelska, Alena; Fahlen, Thomas F.; Nichol, Helen; Bhattacharya, Sharmila

2011-01-01

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways. PMID:21264297

Innate immune responses of Drosophila melanogaster are altered by spaceflight.

Directory of Open Access Journals (Sweden)

Oana Marcu

2011-01-01

Full Text Available Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways.

Quantitating cellular immune responses to cancer vaccines.

Science.gov (United States)

Lyerly, H Kim

2003-06-01

While the future of immunotherapy in the treatment of cancer is promising, it is difficult to compare the various approaches because monitoring assays have not been standardized in approach or technique. Common assays for measuring the immune response need to be established so that these assays can one day serve as surrogate markers for clinical response. Assays that accurately detect and quantitate T-cell-mediated, antigen-specific immune responses are particularly desired. However, to date, increases in the number of cytotoxic T cells through immunization have not been correlated with clinical tumor regression. Ideally, then, a T-cell assay not only needs to be sensitive, specific, reliable, reproducible, simple, and quick to perform, it must also demonstrate close correlation with clinical outcome. Assays currently used to measure T-cell response are delayed-type hypersensitivity testing, flow cytometry using peptide major histocompatibility complex tetramers, lymphoproliferation assay, enzyme-linked immunosorbant assay, enzyme-linked immunospot assay, cytokine flow cytometry, direct cytotoxicity assay, measurement of cytokine mRNA by quantitative reverse transcriptase polymerase chain reaction, and limiting dilution analysis. The purpose of this review is to describe the attributes of each test and compare their advantages and disadvantages.

Immune responses in cattle vaccinated with gamma-irradiated Anaplasma marginale

International Nuclear Information System (INIS)

Sharma, S.P.; Bansal, G.C.

1986-01-01

The infectivity and immunogenecity of gamma-irradiated Anaplasma marginale organisms were studied in bovine calves. The severity of Anaplasma infection based on per cent infected red blood cells, haematological values and mortality was more in animals immunized with blood exposed to 60 kR in comparison to those inoculated with blood irradiated at 70, 80 and 90 kR. The immunizing controls demonstrated a significantly high parasitaemia, marked anaemia and more deaths. Marked and prolonged cell-mediated and humoral immune responses detectable in the first 3 weeks of post-immunization may be responsible for conferring of protective immunity. (author)

Lessons Learned from Protective Immune Responses to Optimize Vaccines against Cryptosporidiosis

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Maxime W. Lemieux

2017-12-01

Full Text Available In developing countries, cryptosporidiosis causes moderate-to-severe diarrhea and kills thousands of infants and toddlers annually. Drinking and recreational water contaminated with Cryptosporidium spp. oocysts has led to waterborne outbreaks in developed countries. A competent immune system is necessary to clear this parasitic infection. A better understanding of the immune responses required to prevent or limit infection by this protozoan parasite is the cornerstone of development of an effective vaccine. In this light, lessons learned from previously developed vaccines against Cryptosporidium spp. are at the foundation for development of better next-generation vaccines. In this review, we summarize the immune responses elicited by naturally and experimentally-induced Cryptosporidium spp. infection and by several experimental vaccines in various animal models. Our aim is to increase awareness about the immune responses that underlie protection against cryptosporidiosis and to encourage promotion of these immune responses as a key strategy for vaccine development. Innate and mucosal immunity will be addressed as well as adaptive immunity, with an emphasis on the balance between TH1/TH2 immune responses. Development of more effective vaccines against cryptosporidiosis is needed to prevent Cryptosporidium spp.-related deaths in infants and toddlers in developing countries.

Paediatric talus fracture.

LENUS (Irish Health Repository)

Byrne, Ann-Maria

2012-01-01

Paediatric talus fractures are rare injuries resulting from axial loading of the talus against the anterior tibia with the foot in dorsiflexion. Skeletally immature bone is less brittle, with higher elastic resistance than adult bone, thus the paediatric talus can sustain higher forces before fractures occur. However, displaced paediatric talus fractures and those associated with high-energy trauma have been associated with complications including avascular necrosis, arthrosis, delayed union, neurapraxia and the need for revision surgery. The authors present the rare case of a talar neck fracture in a skeletally immature young girl, initially missed on radiological review. However, clinical suspicion on the part of the emergency physician, repeat examination and further radiographic imaging revealed this rare paediatric injury.

Optimal approximation of linear systems by artificial immune response

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

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

The role of radiotherapy for the induction of antitumor immune responses

International Nuclear Information System (INIS)

Multhoff, G.; Helmholtz-Zentrum Muenchen; Gaipl, U.S.; Niedermann, G.

2012-01-01

Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.

Immune responses to hair dyes containing toluene-2,5-diamine

DEFF Research Database (Denmark)

Schmidt, J D; Johansen, J D; Nielsen, M M

2014-01-01

BACKGROUND: Toluene-2,5-diamine (PTD) is the most frequently used dye in oxidative hair dyes on the Scandinavian market. However, little is known about immune responses to PTD-containing oxidative hair dyes. OBJECTIVES: To study immune responses induced by PTD-containing hair dyes in mice. METHODS......: Immune responses against two different permanent hair dye products containing 1·60% (w/w) and 0·48% (w/w) PTD within the colour gel, and various concentrations of pure PTD were studied. The local inflammatory response was measured by ear swelling and cell infiltration, and T- and B-cell infiltration...... and proliferation was determined in the draining lymph nodes. RESULTS: Concentration-dependent immune responses were seen to PTD both in the skin and draining lymph nodes. The hair dye containing 1·60% PTD induced strong local inflammation and caused T- and B-cell infiltration and proliferation as well...

Trachoma: protective and pathogenic ocular immune responses to Chlamydia trachomatis.

Directory of Open Access Journals (Sweden)

Victor H Hu

Full Text Available Trachoma, caused by Chlamydia trachomatis (Ct, is the leading infectious blinding disease worldwide. Chronic conjunctival inflammation develops in childhood and leads to eyelid scarring and blindness in adulthood. The immune response to Ct provides only partial protection against re-infection, which can be frequent. Moreover, the immune response is central to the development of scarring pathology, leading to loss of vision. Here we review the current literature on both protective and pathological immune responses in trachoma. The resolution of Ct infection in animal models is IFNγ-dependent, involving Th1 cells, but whether this is the case in human ocular infection still needs to be confirmed. An increasing number of studies indicate that innate immune responses arising from the epithelium and other innate immune cells, along with changes in matrix metalloproteinase activity, are important in the development of tissue damage and scarring. Current trachoma control measures, which are centred on repeated mass antibiotic treatment of populations, are logistically challenging and have the potential to drive antimicrobial resistance. A trachoma vaccine would offer significant advantages. However, limited understanding of the mechanisms of both protective immunity and immunopathology to Ct remain barriers to vaccine development.

Ethical dimensions of paediatric nursing: A rapid evidence assessment.

Science.gov (United States)

Bagnasco, Annamaria; Cadorin, Lucia; Barisone, Michela; Bressan, Valentina; Iemmi, Marina; Prandi, Marzia; Timmins, Fiona; Watson, Roger; Sasso, Loredana

2018-02-01

Paediatric nurses often face complex situations requiring decisions that sometimes clash with their own values and beliefs, or with the needs of the children they care for and their families. Paediatric nurses often use new technology that changes the way they provide care, but also reduces their direct interaction with the child. This may generate ethical issues, which nurses should be able to address in the full respect of the child. Research question and objectives: The purpose of this review is to describe the main ethical dimensions of paediatric nursing. Our research question was, 'What are the most common ethical dimensions and competences related to paediatric nursing?' A rapid evidence assessment. According to the principles of the rapid evidence assessment, we searched the PubMed, SCOPUS and CINAHL databases for papers published between January 2001 and March 2015. These papers were then independently read by two researchers and analysed according to the inclusion criteria. Ethical considerations: Since this was a rapid evidence assessment, no approval from the ethics committee was required. Ten papers met our inclusion criteria. Ethical issues in paediatric nursing were grouped into three areas: (a) ethical issues in paediatric care, (b) social responsibility and (c) decision-making process. Few studies investigate the ethical dimensions and aspects of paediatric nursing, and they are mainly qualitative studies conducted in critical care settings based on nurses' perceptions and experiences. Paediatric nurses require specific educational interventions to help them resolve ethical issues, contribute to the decision-making process and fulfil their role as advocates of a vulnerable population (i.e. sick children and their families). Further research is needed to investigate how paediatric nurses can improve the involvement of children and their families in decision-making processes related to their care plan.

Bovine anaplasmosis with emphasis on immune responses and protection

International Nuclear Information System (INIS)

Ristic, M.

1980-01-01

Anaplasmosis is an infectious and transmissible disease manifested by progressive anaemia and the appearance of other characteristic disease symptoms. It is a world-wide tick-borne disease of cattle and some wild ruminants caused by the rickettsia Anaplasma marginale. By drawing on information obtained from studies of plasmodial cell cultures, a method has recently been developed for short-term in vitro cultivation of A. marginale. An attenuated Anaplasma organism capable of growth in both ovine and bovine erythrocytes was used to demonstrate that the in vitro system provided the necessary requirements for active transfer of the organism from cell to cell. Organismal antigens are found in the erythrocytes of infected animals, whereas soluble antigens are derived from their erythrocytes and serum. Serums from convalescing animals interact with these antigens in agglutination, complement fixation, fluorescent antibody and precipitation tests. Passive transfer of sera from immune to susceptible cattle, however, does not seem to confer protection against the infection and development of the disease. Studies that employed various tests for measuring cell-mediated immune (CMI) responses (leukocyte migration inhibition, blast transformation and cytotoxicity), in association with information collected simultaneously on antibody activity, have shown that both humoral and cellular immune responses are needed for the development of protective immunity in anaplasmosis. It was further shown that an active replication of Anaplasma is essential for induction of these two types of immune responses. Consequently, live virulent and attenuated immunogens fulfil requirements for induction of protective immunity. With the virulent agent, however, development of protective immunity is preceded by induction of auto-immune responses apparently associated with pathogenesis of anaemia in anaplasmosis. Inactivated immunogens derived from blood of infected cattle and used in combination with

Peer teaching in paediatrics - medical students as learners and teachers on a paediatric course.

Science.gov (United States)

Schauseil-Zipf, Ulrike; Karay, Yassin; Ehrlich, Roland; Knoop, Kai; Michalk, Dietrich

2010-01-01

Peer assisted learning is known as an effective educational strategy in medical teaching. We established a peer assisted teaching program by student tutors with a focus on clinical competencies for students during their practical training on paediatric wards. It was the purpose of this study to investigate the effects of a clinical skills training by tutors, residents and consultants on students evaluations of the teaching quality and the effects of a peer teaching program on self assessed clinical competencies by the students. Medical student peers in their 6(th) year were trained by an intensive instruction program for teaching clinical skills by paediatric consultants, doctors and psychologists. 109 students in their 5(th) year (study group) participated in a peer assisted teaching program for training clinical skills in paediatrics. The skills training by student peer teachers were supervised by paediatric doctors. 45 students (control group) participated in a conventional paediatric skills training by paediatric doctors and consultants. Students from both groups, which were consecutively investigated, completed a questionnaire with an evaluation of the satisfaction with their practical training and a self assessment of their practical competencies. The paediatric skills training with student peer teachers received significantly better ratings than the conventional skills training by paediatric doctors concerning both the quality of the practical training and the support by the teaching medical staff. Self assessed learning success in practical skills was higher rated in the peer teaching program than in the conventional training. The peer assisted teaching program of paediatric skills training was rated higher by the students regarding their satisfaction with the teaching quality and their self assessment of the acquired skills. Clinical skills training by student peer teachers have to be supervised by paediatric doctors. Paediatric doctors seem to be more

Anopheles gambiae antiviral immune response to systemic O'nyong-nyong infection.

Directory of Open Access Journals (Sweden)

Joanna Waldock

Full Text Available Mosquito-borne viral diseases cause significant burden in much of the developing world. Although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. In contrast to mosquitoes of the Aedes and Culex genera, Anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is O'nyong-nyong virus (ONNV. Here we have investigated the A. gambiae immune response to systemic ONNV infection using forward and reverse genetic approaches.We have used DNA microarrays to profile the transcriptional response of A. gambiae inoculated with ONNV and investigate the antiviral function of candidate genes through RNAi gene silencing assays. Our results demonstrate that A. gambiae responses to systemic viral infection involve genes covering all aspects of innate immunity including pathogen recognition, modulation of immune signalling, complement-mediated lysis/opsonisation and other immune effector mechanisms. Patterns of transcriptional regulation and co-infections of A. gambiae with ONNV and the rodent malaria parasite Plasmodium berghei suggest that hemolymph immune responses to viral infection are diverted away from melanisation. We show that four viral responsive genes encoding two putative recognition receptors, a galectin and an MD2-like receptor, and two effector lysozymes, function in limiting viral load.This study is the first step in elucidating the antiviral mechanisms of A. gambiae mosquitoes, and has revealed interesting differences between A. gambiae and other invertebrates. Our data suggest that mechanisms employed by A. gambiae are distinct from described invertebrate antiviral immunity to date, and involve the complement-like branch of the humoral immune response, supressing the melanisation response that is prominent in anti-parasitic immunity. The antiviral immune response in A. gambiae is thus

Paediatric airway management: basic aspects

DEFF Research Database (Denmark)

Holm-Knudsen, R J; Rasmussen, L S

2009-01-01

Paediatric airway management is a great challenge, especially for anaesthesiologists working in departments with a low number of paediatric surgical procedures. The paediatric airway is substantially different from the adult airway and obstruction leads to rapid desaturation in infants and small...... children. This paper aims at providing the non-paediatric anaesthesiologist with a set of safe and simple principles for basic paediatric airway management. In contrast to adults, most children with difficult airways are recognised before induction of anaesthesia but problems may arise in all children...

Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine

Directory of Open Access Journals (Sweden)

Danylo Sirskyj

2016-07-01

Full Text Available Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future.

Anterior Chamber-Associated Immune Deviation (ACAID: An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?

Directory of Open Access Journals (Sweden)

Robert E. Cone

2009-01-01

Full Text Available The “immune privilege” that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID a is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80 + monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection.

Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination.

Science.gov (United States)

Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

2017-07-18

Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics. In the current study, we sought to determine if measures of antigen-specific or antigen non-specific immunity were present prior to treatment, and associated with subsequent immune response, to identify possible predictive immune biomarkers. Patients who developed persistent PAP-specific, IFNγ-secreting immune responses were defined as immune "responders." The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells were assessed by flow cytometry and clinical laboratory values. PAP-specific immune responses were evaluated by cytokine secretion in vitro, and by antigen-specific suppression of delayed-type hypersensitivity to a recall antigen in an in vivo SCID mouse model. The frequency of peripheral blood cell types did not differ between the immune responder and non-responder groups. Non-responder patients tended to have higher PAP-specific IL-10 production pre-vaccination (p = 0.09). Responder patients had greater preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen (p = 0.016). While our study population was small (n = 38), these results suggest that different measures of antigen-specific tolerance or regulation might help predict immunological outcome from DNA vaccination. These will be prospectively evaluated in an ongoing randomized, phase II trial.

Immobilisation in Australian paediatric medical imaging: A pilot study

International Nuclear Information System (INIS)

Noonan, S.; Spuur, K.; Nielsen, S.

2017-01-01

Aims: The primary aim of this study is to document the use of paediatric immobilisation techniques in medical imaging. Secondary aims are to investigate differences between current practice of paediatric and non-paediatric facilities and radiographer gender and to investigate immobilisation protocols. Methods: A SurveyMonkey link was distributed through the Australian Society of Medical Imaging and Radiation Therapy (ASMIRT) newsletter. Radiographer members of ASMIRT were invited to participate. Frequency percentage analysis was undertaken; as the 'frequency of immobilisation' response was on a Likert scale and the ages categorical, a Fisher's exact test could determine dependency. Results: The use of paediatric immobilisation techniques was determined to be related to age. The most commonly used technique in general X-ray was “other people”; in computed tomography, Velcro, verbal reminders and distraction techniques; and in magnetic resonance imaging, sedation and Velcro. A comparison of immobilisation techniques demonstrated that Velcro use in X-ray was dependent on facility (p = 0.017) with paediatric facilities using it up to 17 years. Immobilisation frequency was dependent in 13–17 years (p = 0.035) with paediatric facilities rarely immobilising and non-paediatric facilities never. No dependencies resulted upon comparing genders. Immobilisation frequency was not dependent between protocols or current practice. Conclusion: The use of paediatric immobilisation technique is related to age with “other people”, sedation, Velcro, verbal reminders and distraction techniques being regularly used. The dependency of Velcro use and immobilisation frequency in 13–17 years is for unknown reasons and further investigation is required. A larger study should be carried out to validate these findings. - Highlights: • Document the use of paediatric immobilisation techniques in medical imaging. • Investigate differences in practice between

Reprogramming Antitumor Immune Responses with microRNAs

Science.gov (United States)

2013-10-01

disease, including cancer etiology (4) and the generation and inhibition of antitumor immune responses (5–9). Biologically active miRNAs bind to MREs...breast, colorectal, lung, pancreatic , and thyroid carcinomas and in liquid tumors including lymphomas and some acute myeloid leukemias (9, 35). The...immunity [9], underscoring the potential of targeting this major microenvironmental compartment. Accumulating evidence suggests that chronic

Heavy metal pollution disturbs immune response in wild ant populations

International Nuclear Information System (INIS)

Sorvari, Jouni; Rantala, Liisa M.; Rantala, Markus J.; Hakkarainen, Harri; Eeva, Tapio

2007-01-01

Concern about the effects of environmental contaminants on immune function in both humans and wildlife is growing and practically nothing is known about this impact on terrestrial invertebrates, even though they are known to easily accumulate pollutants. We studied the effect of industrial heavy metal contamination on immune defense of a free-living wood ant (Formica aquilonia). To find out whether ants show an adapted immune function in a polluted environment, we compared encapsulation responses between local and translocated colonies. Local colonies showed higher heavy metal levels than the translocated ones but the encapsulation response was similar between the two groups, indicating that the immune system of local ants has not adapted to high contamination level. The encapsulation response was elevated in moderate whereas suppressed in high heavy metal levels suggesting higher risk for infections in heavily polluted areas. - Heavy metal pollution affects immune function in ants

Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus.

Science.gov (United States)

Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter; Jensen, Trine Hammer; Jensen, Tove Dannemann; Aasted, Bent; Blixenkrone-Møller, Merete

2009-07-30

The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper is still a problem worldwide. The broad host range of CDV creates a constant viral reservoir among wildlife animals. Our results demonstrated early humoral and cell-mediated immune responses (IFN-gamma) in DNA vaccinated mink compared to mock-vaccinated mink after challenge with a Danish wild-type CDV. The DNA vaccine-induced immunity protected the natural host against disease development.

Safety in paediatric imaging

International Nuclear Information System (INIS)

Carter, D.; Filice, I.; Murray, D.; Thomas, K.

2006-01-01

Those of us working in a dedicated paediatric environment are aware of the important safety issues with regard to paediatrics. Our goal when working with paediatric patients, the goal is to obtain the best quality images while keeping patients safe and their distress to a minimum. This article will discuss some of the issues regarding paediatric safety in a diagnostic imaging department, including radiation doses and the risk to paediatric patients, reducing medication errors, safe sedation practice and environmental safety. Also discussed are some conditions requiring special consideration to maintain patient safety such as epiglottitis and suspected child abuse. Promotion of a patient/family-centered care system will create an environment of trust where parents or guardians will know that their children are being well cared for in a safe, effective environment. (author)

Immune Response to Dengue and Zika.

Science.gov (United States)

Ngono, Annie Elong; Shresta, Sujan

2018-04-26

Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection. As DENV and ZIKV are closely related, knowledge based on DENV studies has been used to prioritize investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV diagnostic, therapeutic, and vaccine design. This review discusses the following topics related to innate and adaptive immune responses to DENV and ZIKV: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell-mediated protection versus original T cell antigenic sin. Understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during DENV and ZIKV infections is critical toward development of safe and effective DENV and ZIKV therapeutics and vaccines.

Skin immunization by microneedle patch overcomes statin-induced suppression of immune responses to influenza vaccine.

Science.gov (United States)

Vassilieva, Elena V; Wang, Shelly; Li, Song; Prausnitz, Mark R; Compans, Richard W

2017-12-19

Recent studies indicated that in elderly individuals, statin therapy is associated with a reduced response to influenza vaccination. The present study was designed to determine effects on the immune response to influenza vaccination induced by statin administration in a mouse model, and investigate potential approaches to improve the outcome of vaccination on the background of statin therapy. We fed middle aged BALB/c mice a high fat "western" diet (WD) alone or supplemented with atorvastatin (AT) for 14 weeks, and control mice were fed with the regular rodent diet. Mice were immunized with a single dose of subunit A/Brisbane/59/07 (H1N1) vaccine, either systemically or with dissolving microneedle patches (MNPs). We observed that a greater age-dependent decline in the hemagglutinin inhibition titers occurred in systemically-immunized mice than in MNP- immunized mice. AT dampened the antibody response in the animals vaccinated by either route of vaccine delivery. However, the MNP-vaccinated AT-treated animals had ~20 times higher total antibody levels to the influenza vaccine than the systemically vaccinated group one month postvaccination. We propose that microneedle vaccination against influenza provides an approach to ameliorate the immunosuppressive effect of statin therapy observed with systemic immunization.

Age at BCG administration during routine immunization.

African Journals Online (AJOL)

Age at BCG administration during routine immunization. R.D. Wammanda , M.J. Gambo and I. Abdulkadir. Department of Paediatrics,. Ahmadu Bello University Teaching Hospital,. Zaria. Correspondence to: Dr.R.D. Wammanda. Email: wammanda@yahoo.com. Summary. In Nigeria, as part of the National Programme on ...

Eosinophils in mucosal immune responses

Science.gov (United States)

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

Functional characterization of Foxp3-specific spontaneous immune responses

DEFF Research Database (Denmark)

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

2013-01-01

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

A multiherbal formulation influencing immune response in vitro.

Science.gov (United States)

Menghini, L; Leporini, L; Scanu, N; Pintore, G; Ferrante, C; Recinella, L; Orlando, G; Vacca, M; Brunetti, L

2012-02-01

Aim of this study was to evaluate the effects of phytocomplexes of Uncaria, Shiitake and Ribes in terms of viability and inflammatory response on immune cell-derived cultures. Standardized extracts of Uncaria, Shitake and Ribes and their commercial formulation were tested on cell lines PBMC, U937 and macrophage. The activity was evaluated in terms of cell viability (MTT test), variations of oxidative marker release (ROS and PGE2) and modulatory effects on immune response (gene expression of IL-6, IL-8 and TNFα, RT-PCR). Cell viability was not affected by extracts, except subtle variations observed only at higher doses (>250 µg/mL). The extract mixture was well tolerated, with no effects on cell viability up to doses of 500 µg/mL. Pre-treatment of macrophages with subtoxic doses of the extracts reduced the basal release of oxidative markers and enhanced the cell response to exogenous oxidant stimulation, as revealed by ROS and PGE2 release reduction. The same treatment on macrophage resulted in a selective modulation of the immune response, as shown by an increase of IL-6 mRNA and, partially, IL-8 mRNA, while a reduction was observed for TNFα mRNA. Data confirm that extracts and their formulations can act as regulator of the immune system with mechanisms involving the oxidative stress and the release of selected proinflammatory cytokines.

DNA Damage Response and Immune Defence: Links and Mechanisms

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Björn Schumacher

2016-08-01

Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

Pathogen recognition in the innate immune response.

Science.gov (United States)

Kumar, Himanshu; Kawai, Taro; Akira, Shizuo

2009-04-28

Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)-like receptors] and NLRs (Nod-like receptors). These receptors recognize pathogens or pathogen-derived products in different cellular compartments, such as the plasma membrane, the endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and instruct pathogen-specific adaptive immune responses. In the present review, we will discuss the recent progress in the study of pathogen recognition by TLRs, RLRs and NLRs and their signalling pathways.

Modulation of the immune response by emotional stress

NARCIS (Netherlands)

Croiset, G; Heijnen, C J; Veldhuis, H D; de Wied, D; Ballieux, R E

1987-01-01

The influence of mild, emotional stress was investigated for its effect on the immune system by subjecting rats to the one-trial-learning passive avoidance test. The reactivity of the immune system was tested by determining the proliferative response after mitogenic stimulation in vitro as well as

The sterile immune response during hepatic ischemia/reperfusion

NARCIS (Netherlands)

van Golen, Rowan F.; van Gulik, Thomas M.; Heger, Michal

2012-01-01

Hepatic ischemia and reperfusion elicits an immune response that lacks a microbial constituent yet poses a potentially lethal threat to the host. In this sterile setting, the immune system is alarmed by endogenous danger signals that are release by stressed and dying liver cells. The detection of

Inflammatory cytokines in the brain: does the CNS shape immune responses?

Science.gov (United States)

Owens, T; Renno, T; Taupin, V; Krakowski, M

1994-12-01

Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

Influence of bedding type on mucosal immune responses.

Science.gov (United States)

Sanford, Amy N; Clark, Stephanie E; Talham, Gwen; Sidelsky, Michael G; Coffin, Susan E

2002-10-01

The mucosal immune system interacts with the external environment. In the study reported here, we found that bedding materials can influence the intestinal immune responses of mice. We observed that mice housed on wood, compared with cotton bedding, had increased numbers of Peyer's patches (PP) visible under a dissecting microscope. In addition, culture of lymphoid organs revealed increased production of total and virus-specific IgA by PP and mesenteric lymph node (MLN) lymphocytes from mice housed on wood, compared with cotton bedding. However, bedding type did not influence serum virus-specific antibody responses. These observations indicate that bedding type influences the intestinal immune system and suggest that this issue should be considered by mucosal immunologists and personnel at animal care facilities.

Adrenaline influence on the immune response. I

International Nuclear Information System (INIS)

Depelchin, A.; Letesson, J.J.

1981-01-01

The intervention of adrenaline in the immunoregulation was investigated through the modification of the anti-SRBC PFC response of mice after its i.p. administration (4 μg) at various intervals before SRBC antigen. When the interval was less than 24 h, adrenaline accelerated the immune kinetics. This modification was apparent on both direct and indirect PFC, as well as on naive and immune mice. However, mice treated from 2 days showed a suppression of the response. The adrenaline affect subsisted on the adoptive response of spleen cells drug-treated either in vivo or in vitro. The mitogenic response after in vitro PHA or LPS stimulation of spleen cells from adrenaline-treated mice indicated that the T-cells were the drug target. The physiological role of the adrenaline and immunological influences of acute stress are discussed in the paper. The stress was provided by gamma irradiation. (Auth.)

Paediatric Anxiety Disorders

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Beena Johnson

2017-07-01

Full Text Available Anxiety disorders are highly prevalent among children and are associated with serious morbidity. Lifetime prevalence of paediatric anxiety disorders is about fifteen percent. Social phobia, generalized anxiety disorder and separation anxiety disorder are included in the triad of paediatric anxiety disorders. Specific phobia, obsessive compulsive disorder and post-traumatic stress disorder are also commonly seen in children. Overprotection by parents, parental death or separation, female sex, low educational status, family history of anxiety disorder, financial stress in family and adverse childhood experiences are risk factors for the development of anxiety disorders. If not diagnosed and managed at the earliest, paediatric anxiety disorders can cause life threatening problems in the future. Hence early and scientific management of anxiety disorders is essential. Cognitive behavioural therapy is the effective evidence based treatment for paediatric anxiety disorders.

Respons imun humoral pada pulpitis (Humoral immune response on pulpitis)

OpenAIRE

Widodo, Trijoedani

2005-01-01

Pulpitis is an inflammation process on dental pulp tissue, and usually as the continuous of caries. The microorganism in the caries is a potential immunogenic triggering the immune respons, both humoral and celluler immune responses. The aim of this research is to explain the humoral immune response changes in the dental pulp tissues of pulpitis. This research was done on three group samples: Irreversible pulpitis, Reversible pulpitis and sound teeth as the control group. The result showed th...

The host immune response to Clostridium difficile infection

Science.gov (United States)

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

The efficacy of an extended scope physiotherapy clinic in paediatric orthopaedics.

LENUS (Irish Health Repository)

O Mir, Marie

2016-04-01

The demand for paediatric orthopaedic care is growing, and providing the service required is an increasingly challenging task. Physiotherapist-led triage clinics are utilised in adult orthopaedics to enable the provision of care to patients who may not require a surgical consult. The Physiotherapy Orthopaedic Triage Clinic (POTC) was established in Our Lady\\'s Children\\'s Hospital Crumlin in response to increasing demands on the paediatric orthopaedic service. The clinic is run by physiotherapists working in an advanced practice role (APP), and is the first paediatric clinic of its type and scale in the Republic of Ireland.

Effect of nutrition support on immunity in paediatric patients with beta-thalassaemia major.

Science.gov (United States)

Tienboon, Prasong

2003-01-01

Nutritional deficiencies have been variably observed in thalassaemia and the aetiology of many of the immune abnormalities in thalassaemic children are poorly defined. Therefore, we tested the hypothesis that certain immune abnormalities have a nutritional basis. Nutritional status, selective quantitative and functional indices of immunity were studied in twelve children (7 females, 5 males; mean age 28 months, SD 5 and range 19.8-35.5), with thalassaemia major before and after a one month period of intensive nutrition support (the study diet consisted of 'Enfapro' liquid formula (Mead Johnson) with added dextrose and corn oil to achieve a caloric density of 1.1 kcal/cc in addition to vitamins and minerals). Each child was provided approximately 150 kcal/day and 4 g of protein/day. Lymphocyte proliferation to Concanavalin A (Con A) (P = 0.008) and Purified Protein Derivative (PPD) (P = 0.002) was depressed upon entry into the study, however the response to Con A attained normal values by the end of the intervention. Compared to baselines, the proliferative response to Con A (P = 0.005) and Phytohemagglutinin A (PHA) (P = 0.031) both improved after the nutrition support. Although there was no general correlation of zinc status with lymphocyte proliferation, normal baseline zinc status was associated with improvement of proliferation. The %CD4 increased (P = 0.036), primarily because of a decrease in total lymphocytes and to lesser extent a decrease in CD8 lymphocytes. Serum immunoglobulin concentrations were found to be elevated on admission but were not significantly affected by the nutrition intervention. C3 concentrations were uniformly depressed on admission but increased by the end of the study protocol (P = 0.037). C4 and CH50 activity were not significantly influenced by the intervention. In conclusion, children with beta thalassaemia have abnormalities of lymphocyte function as well as key complement components that are responsive to nutrition support. In

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

Science.gov (United States)

Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Tumor PDT-associated immune response: relevance of sphingolipids

Science.gov (United States)

Korbelik, Mladen; Merchant, Soroush; Separovic, Duska M.

2010-02-01

Sphingolipids have become recognized as essential effector molecules in signal transduction with involvement in various aspects of cell function and death, immune response and cancer treatment response. Major representatives of sphingolipids family, ceramide, sphingosine and sphingosine-1-phosphate (S1P), have attracted interest in their relevance to tumor response to photodynamic therapy (PDT) because of their roles as enhancers of apoptosis, mediators of cell growth and vasculogenesis, and regulators of immune response. Our recent in vivo studies with mouse tumor models have confirmed that PDT treatment has a pronounced impact on sphingolipid profile in the targeted tumor and that significant advances in therapeutic gain with PDT can be attained by combining this modality with adjuvant treatment with ceramide analog LCL29.

Transgenerational effects enhance specific immune response in a wild passerine

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Juli Broggi

2016-03-01

Full Text Available Vertebrate mothers transfer diverse compounds to developing embryos that can affect their development and final phenotype (i.e., maternal effects. However, the way such effects modulate offspring phenotype, in particular their immunity, remains unclear. To test the impact of maternal effects on offspring development, we treated wild breeding house sparrows (Passer domesticus in Sevilla, SE Spain with Newcastle disease virus (NDV vaccine. Female parents were vaccinated when caring for first broods, eliciting a specific immune response to NDV. The immune response to the same vaccine, and to the PHA inflammatory test were measured in 11-day-old chicks from their following brood. Vaccinated chicks from vaccinated mothers developed a stronger specific response that was related to maternal NDV antibody concentration while rearing their chicks. The chicks’ carotenoid concentration and total antioxidant capacity in blood were negatively related to NDV antibody concentration, whereas no relation with PHA response was found. Specific NDV antibodies could not be detected in 11-day-old control chicks from vaccinated mothers, implying that maternally transmitted antibodies are not directly involved but may promote offspring specific immunity through a priming effect, while other immunity components remain unaffected. Maternally transmitted antibodies in the house sparrow are short-lived, depend on maternal circulation levels and enhance pre-fledging chick specific immunity when exposed to the same pathogens as the mothers.

An interprofessional approach to improving paediatric medication safety

Directory of Open Access Journals (Sweden)

Kennedy Neil

2010-02-01

Full Text Available Abstract Background Safe drug prescribing and administration are essential elements within undergraduate healthcare curricula, but medication errors, especially in paediatric practice, continue to compromise patient safety. In this area of clinical care, collective responsibility, team working and communication between health professionals have been identified as key elements in safe clinical practice. To date, there is limited research evidence as to how best to deliver teaching and learning of these competencies to practitioners of the future. Methods An interprofessional workshop to facilitate learning of knowledge, core competencies, communication and team working skills in paediatric drug prescribing and administration at undergraduate level was developed and evaluated. The practical, ward-based workshop was delivered to 4th year medical and 3rd year nursing students and evaluated using a pre and post workshop questionnaire with open-ended response questions. Results Following the workshop, students reported an increase in their knowledge and awareness of paediatric medication safety and the causes of medication errors (p Conclusion This study has helped bridge the knowledge-skills gap, demonstrating how an interprofessional approach to drug prescribing and administration has the potential to improve quality and safety within healthcare.

A specific primed immune response in Drosophila is dependent on phagocytes.

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Linh N Pham

2007-03-01

Full Text Available Drosophila melanogaster, like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-lethal second challenge of S. pneumoniae. This protective effect exhibits coarse specificity for S. pneumoniae and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by Beauveria bassiana, a natural fly pathogen. To characterize this primed response, we focused on S. pneumoniae-induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.

Paediatrics: messages from Munich

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Fabio Midulla

2015-05-01

Full Text Available The aim of this article is to describe paediatric highlights from the 2014 European Respiratory Society (ERS International Congress in Munich, Germany. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology are presented in the context of the current literature.

ALARA and paediatric imaging in radiation therapy: A survey of Canadian paediatric imaging practice

International Nuclear Information System (INIS)

Rodgerson, Christine

2014-01-01

Purpose: There is little discussion in the literature regarding paediatric imaging dose reduction with respect to conventional imaging carried out in radiotherapy departments. This is in contrast to diagnostic radiography where dose optimization when imaging children is a very current topic. For this reason Canadian radiotherapy clinics were surveyed to look at paediatric imaging practice, knowledge and perspectives with respect to imaging dose reduction. Method: As this was an exploratory study, a questionnaire was developed and sent to radiation therapy clinics across Canada, via email, to assess knowledge of paediatric imaging and dose reduction initiatives. The questionnaire focus was CT simulation and treatment verification imaging of children. Results: Practice and knowledge of paediatric imaging varied across Canada. Forty percent of clinics reported using paediatric specific protocols for CT simulation and 20% of clinics reported using paediatric specific protocols for treatment verification imaging. There was variation in imaging practices among the clinics that reported treating the most children. The survey results show that while some measures are being taken to reduce paediatric imaging dose in radiation therapy, 46.7% of the respondents felt more could be done. Conclusion: The survey demonstrates interest in dose reduction in radiation therapy imaging as well as differences in current practice and knowledge across Canada. Paediatric imaging dose reduction would appear to be an area of practice that would benefit from more study and development of standards of practice

Immune responses of ducks infected with duck Tembusu virus

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Ning eLi

2015-05-01

Full Text Available Duck Tembusu virus (DTMUV can cause serious disease in ducks, characterized by reduced egg production. Although the virus has been isolated and detection methods developed, the host immune responses to DTMUV infection are unclear. Therefore, we systematically examined the expression of immune-related genes and the viral distribution in DTMUV-infected ducks, using quantitative real-time PCR. Our results show that DTMUV replicates quickly in many tissues early in infection, with the highest viral titers in the spleen 1 day after infection. Rig-1, Mda5, and Tlr3 are involved in the host immune response to DTMUV, and the expression of proinflammatory cytokines (Il-1β, -2, -6, Cxcl8 and antiviral proteins (Mx, Oas, etc. are also upregulated early in infection. The expression of Il-6 increased most significantly in the tissues tested. The upregulation of Mhc-I was observed in the brain and spleen, but the expression of Mhc-II was upregulated in the brain and downregulated in the spleen. The expression of the interferons was also upregulated to different degrees in the spleen but that of the brain was various. Our study suggests that DTMUV replicates rapidly in various tissues and that the host immune responses are activated early in infection. However, the overexpression of cytokines may damage the host. These results extend our understanding of the immune responses of ducks to DTMUV infection, and provide insight into the pathogenesis of DTMUV attributable to host factors.

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

Science.gov (United States)

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

2017-12-01

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

Immunizations with hepatitis B viral antigens and a TLR7/8 agonist adjuvant induce antigen-specific immune responses in HBV-transgenic mice

Directory of Open Access Journals (Sweden)

Ying Wang

2014-12-01

Conclusions: Immunization with CL097-conjugated HBV-Ag reversed immune tolerance in HBV-Tg mice and induced antigen-specific immune responses. TLR7/8 agonists appear to be potent adjuvants for the induction of antigen-specific Th1 responses in an immune tolerant state.

CD28 Aptamers as Powerful Immune Response Modulators

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Fernando Pastor

2013-01-01

Full Text Available CD28 is one of the main costimulatory receptors responsible for the proper activation of T lymphocytes. We have isolated two aptamers that bind to the CD28 receptor. As a monomer, one of them interfered with the binding of CD28 to its ligand (B7, precluding the costimulatory signal, whereas the other one was inactive. However, dimerization of any of the anti-CD28 aptamers was sufficient to provide an artificial costimulatory signal. No antibody has featured a dual function (i.e., the ability to work as agonist and antagonist to date. Two different agonistic structures were engineered for each anti-CD28 aptamer. One showed remarkably improved costimulatory properties, surpassing the agonistic effect of an anti-CD28 antibody. Moreover, we showed in vivo that the CD28 agonistic aptamer is capable of enhancing the cellular immune response against a lymphoma idiotype and of prolonging survival of mice which receive the aptamer together with an idiotype vaccine. The CD28 aptamers described in this work could be used to modulate the immune response either blocking the interaction with B7 or enhancing vaccine-induced immune responses in cancer immunotherapy.

Immune Response of Multiparous Hyper-Immunized Sows against Peptides from Non-Structural and Structural Proteins of PRRSV

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Edgar Rascón-Castelo

2015-11-01

Full Text Available The purpose of this study was to evaluate the humoral and cellular responses of commercial multiparous and hyper-immunized sows against peptides from non-structural (nsp and structural proteins of porcine reproductive and respiratory syndrome virus (PRRSV. We selected sows with different numbers of parities from a commercial farm. Management practices on this farm include the use of the MLV commercial vaccine four times per year, plus two vaccinations during the acclimation period. The humoral response was evaluated via the antibody recognition of peptides from nsp and structural proteins, and the cellular response was assessed by measuring the frequency of peptide and PRRSV-specific IFN-gamma-secreting cells (IFNγ-SC. Our results show that sows with six parities have more antibodies against peptides from structural proteins than against peptides from nsp. The analysis of the cellular response revealed that the number of immunizations did not affect the frequency of IFNγ-SC and that the response was stronger against peptides from structural proteins (M protein than against nsp (nsp2. In summary, these results demonstrate that multiparous, hyper-immunized sows have a stronger immune humoral response to PRRSV structural peptides than nsp, but no differences in IFNγ-SC against the same peptides were observed.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

Directory of Open Access Journals (Sweden)

Hong Zhong

2018-01-01

Full Text Available In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

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

Science.gov (United States)

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.

Dosimetry in Diagnostic Radiology for Paediatric Patients

International Nuclear Information System (INIS)

2013-01-01

Concern about the radiation dose to children from diagnostic radiology examinations has recently been popularly expressed, particularly as related to computed tomography (CT) procedures. This involves the observation that children can receive doses far in excess of those delivered to adults, in part due to the digital nature of the image receptors that may give no warning to the operator of the dose to the patient. Concern for CT examinations should be extended to the broad range of paediatric diagnostic radiological procedures responsible for radiation doses in children, especially as factors, such as increased radiosensitivity and the longer life expectancy of children, increase the associated radiation risk. In all cases, owing to the added paediatric radiological examination factor of patient size and its associated impact on equipment selection, clinical examination protocol and dosimetric audit, the determination of paediatric dose requires a distinct approach from adult dosimetry associated with diagnostic radiological examinations. In response to this, there is a need to inform health professionals about standardized methodologies used to determine paediatric dose for all major modalities such as general radiography, fluoroscopy and CT. Methodologies for standardizing the conduct of dose audits and their use for the derivation and application of diagnostic reference levels for patient populations, that vary in size, are also required. In addition, a review is needed of the current knowledge on risks specific to non-adults from radiation, and also an analysis of the management of factors contributing to dose from paediatric radiological examinations. In 2007, the IAEA published a code of practice, Dosimetry in Diagnostic Radiology: An International Code of Practice, as Technical Reports Series No. 457 (TRS 457). TRS 457 recommends procedures for dosimetric measurement and calibration for the attainment of standardized dosimetry, and addresses requirements

The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi

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Paul T. King

2015-01-01

Full Text Available Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management.

Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation

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K Murai

2010-01-01

Full Text Available Although intervertebral disc herniation and associated sciatica is a common disease, its molecular pathogenesis is not well understood. Immune responses are thought to be involved. This study provides direct evidence that even non-degenerated nucleus pulposus (NP cells elicit immune responses. An in vitro colony forming inhibition assay demonstrated the suppressive effects of autologous spleen cells on NP cells and an in vitro cytotoxicity assay showed the positive cytotoxic effects of natural killer (NK cells and macrophages on NP cells. Non-degenerated rat NP tissues transplanted into wild type rats and immune-deficient mice demonstrated a significantly higher NP cell survival rate in immune-deficient mice. Immunohistochemical staining showed the presence of macrophages and NK cells in the transplanted NP tissues. These results suggest that even non-degenerated autologous NP cells are recognized by macrophages and NK cells, which may have an immunological function in the early phase of disc herniation. These findings contribute to understanding resorption and the inflammatory reaction to disc herniation.

African Journal of Paediatric Surgery

African Journals Online (AJOL)

The African Journal of Paediatric Surgery aims to promote research, post- graduate training and further education among Paediatric surgeons, Paediatric Surgical Trainees and paramedical personnel in the surgery of newborn infants and children particularly in Africa and other tropical regions of the world.AJPS welcomes ...

African Journal of Paediatric Nephrology

African Journals Online (AJOL)

African Journal of Paediatric Nephrology is the official Journal of the African Paediatric Nephrology Association (AFPNA). The journal is dedicated to increasing awareness and knowledge of Paediatric nephrology in Africa and beyond. We publish research articles on renal diseases in children, on fluid and electrolyte ...

DMPD: Innate immune responses during infection. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available va Correia J. Vaccine. 2004 Dec 6;22 Suppl 1:S25-30. (.png) (.svg) (.html) (.csml) Show Innate immune responses during infection. Pub...medID 15576198 Title Innate immune responses during infection. Authors Ulevitch RJ,

Gait and Lower Limb Observation of Paediatrics (GALLOP): development of a consensus based paediatric podiatry and physiotherapy standardised recording proforma.

Science.gov (United States)

Cranage, Simone; Banwell, Helen; Williams, Cylie M

2016-01-01

Paediatric gait and lower limb assessments are frequently undertaken in podiatry and physiotherapy clinical practice and this is a growing area of expertise within Australia. No concise paediatric standardised recording proforma exists to assist clinicians in clinical practice. The aim of this study was to develop a gait and lower limb standardised recording proforma guided by the literature and consensus, for assessment of the paediatric foot and lower limb in children aged 0-18 years. Expert Australian podiatrists and physiotherapists were invited to participate in a three round Delphi survey panel using the online Qualtrics(©) survey platform. The first round of the survey consisted of open-ended questions on paediatric gait and lower limb assessment developed from existing templates and a literature search of standardised lower limb assessment methods. Rounds two and three consisted of statements developed from the first round responses. Questions and statements were included in the final proforma if 70 % or more of the participants indicated consensus or agreement with the assessment method and if there was support within the literature for paediatric age-specific normative data with acceptable reliability of outcome measures. There were 17 of the 21 (81 %) participants who completed three rounds of the survey. Consensus was achieved for 41 statements in Round one, 54 statements achieved agreement in two subsequent rounds. Participants agreed on 95 statements relating to birth history, developmental history, hip measurement, rotation of the lower limb, ankle range of motion, foot posture, balance and gait. Assessments with acceptable validity and reliability were included within the final Gait and Lower Limb Observation of Paediatrics (GALLOP) proforma. The GALLOP proforma is a consensus based, systematic and standardised way to collect information and outcome measures in paediatric lower limb assessment. This standardised recording proforma will assist

Paediatric radiopharmaceutical administration

DEFF Research Database (Denmark)

Lassmann, Michael; Treves, S Ted; Borgwardt, Lise

2014-01-01

In 2008 the EANM published their paediatric dosage card. In 2011 the North American consensus guidelines recommended a set of administered activities for paediatric nuclear medicine. During the EANM congress in 2012 a working group of the EANM and the SNMMI met to study the possibility of harmoni...

Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

International Nuclear Information System (INIS)

Guo Lizheng; Lu Xiaoyan; Kang, S.-M.; Chen Changyi; Compans, Richard W.; Yao Qizhi

2003-01-01

To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a T H 1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of T H 1/T H 2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

A model immunization programme to control Japanese encephalitis in Viet Nam.

Science.gov (United States)

Yen, Nguyen Thu; Liu, Wei; Hanh, Hoang Duc; Chang, Na Yoon; Duong, Tran Nhu; Gibbons, Robert V; Marks, Florian; Thu, Nghiem Anh; Hong, Nguyen Minh; Park, Jin Kyung; Tuan, Pham Anh; Nisalak, Ananda; Clemens, John D; Xu, Zhi-Yi

2015-03-01

In Viet Nam, an inactivated, mouse brain-derived vaccine for Japanese encephalitis (JE) has been given exclusively to ≤ 5 years old children in 3 paediatric doses since 1997. However, JE incidence remained high, especially among children aged 5-9 years. We conducted a model JE immunization programme to assess the feasibility and impact of JE vaccine administered to 1-9 year(s) children in 3 standard-dose regimen: paediatric doses for children aged <3 years and adult doses for those aged ≥ 3 years. Of the targeted children, 96.2% were immunized with ≥ 2 doses of the vaccine. Compared to the national immunization programme, JE incidence rate declined sharply in districts with the model programme (11.32 to 0.87 per 100,000 in pre-versus post-vaccination period). The rate of reduction was most significant in the 5-9 years age-group. We recommend a policy change to include 5-9 years old children in the catch-up immunization campaign and administer a 4th dose to those aged 5-9 years, who had received 3 doses of the vaccine during the first 2-3 years of life.

Sex-specific consequences of an induced immune response on reproduction in a moth.

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Barthel, Andrea; Staudacher, Heike; Schmaltz, Antje; Heckel, David G; Groot, Astrid T

2015-12-16

Immune response induction benefits insects in combatting infection by pathogens. However, organisms have a limited amount of resources available and face the dilemma of partitioning resources between immunity and other life-history traits. Since males and females differ in their life histories, sex-specific resource investment strategies to achieve an optimal immune response following an infection can be expected. We investigated immune response induction of females and males of Heliothis virescens in response to the entomopathogenic bacterium Serratia entomophila, and its effects on mating success and the female sexual signal. We found that females had higher expression levels of immune-related genes after bacterial challenge than males. However, males maintained a higher baseline expression of immune-related genes than females. The increased investment in immunity of female moths was negatively correlated with mating success and the female sexual signal. Male mating success was unaffected by bacterial challenge. Our results show that the sexes differed in their investment strategies: females invested in immune defense after a bacterial challenge, indicating facultative immune deployment, whereas males had higher baseline immunity than females, indicating immune maintenance. Interestingly, these differences in investment were reflected in the mate choice assays. As female moths are the sexual signallers, females need to invest resources in their attractiveness. However, female moths appeared to invest in immunity at the cost of reproductive effort.

Perillyl alcohol suppresses antigen-induced immune responses in the lung

International Nuclear Information System (INIS)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko; Dohi, Makoto

2014-01-01

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4 + T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4 + T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects

Inter-donor variation in cell subset specific immune signaling responses in healthy individuals.

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Longo, Diane M; Louie, Brent; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Hawtin, Rachael E; Cesano, Alessandra

2012-01-01

Single cell network profiling (SCNP) is a multi-parameter flow cytometry based approach that allows for the simultaneous interrogation of intracellular signaling pathways in multiple cell subpopulations within heterogeneous tissues, without the need for individual cell subset isolation. Thus, the technology is extremely well-suited for characterizing the multitude of interconnected signaling pathways and immune cell subpopulations that regulate the function of the immune system. Recently, SCNP was applied to generate a functional map of the healthy human immune cell signaling network by profiling immune signaling pathways downstream of 12 immunomodulators in 7 distinct immune cell subsets within peripheral blood mononuclear cells (PBMCs) from 60 healthy donors. In the study reported here, the degree of inter-donor variation in the magnitude of the immune signaling responses was analyzed. The highest inter-donor differences in immune signaling pathway activity occurred following perturbation of the immune signaling network, rather than in basal signaling. When examining the full panel of immune signaling responses, as one may expect, the overall degree of inter-donor variation was positively correlated (r = 0.727) with the magnitude of node response (i.e. a larger median signaling response was associated with greater inter-donor variation). However, when examining the degree of heterogeneity across cell subpopulations for individual signaling nodes, cell subset specificity in the degree of inter-donor variation was observed for several nodes. For such nodes, relatively weak correlations between inter-donor variation and the magnitude of the response were observed. Further, within the phenotypically distinct subpopulations, a fraction of the immune signaling responses had bimodal response profiles in which (a) only a portion of the cells had elevated phospho-protein levels following modulation and (b) the proportion of responsive cells varied by donor. These data

Teleconsultation in paediatric orthopaedics in Djibouti: evaluation of response performance.

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Bertani, A; Launay, F; Candoni, P; Mathieu, L; Rongieras, F; Chauvin, F

2012-11-01

Djibouti has no paediatric orthopaedics department and three options are available for difficult cases: transfer of the patient to another country; overseas mission transfer to Djibouti by a specialised surgical team; and management by a local orthopaedic surgeon receiving guidance from an expert. The extreme poverty of part of the population of Djibouti often precludes the first two options. Telemedecine can allow the local orthopaedic surgeon to receive expert advice. HYPOTHESES AND STUDY DESIGN: We prospectively recorded all the paediatric orthopaedics teleconsultations that occurred between November 2009 and November 2011. Our objective was to assess the performance of the teleconsultations. We hypothetized that this option was influential in decision making. We assessed the influence of the teleconsultation on patient management (i.e., change in the surgical indication and/or procedure). We then used the electronic patient records to compare the actual management to that recommended retrospectively by two independent orthopaedic surgeon consultants who had experience working overseas. Finally, we assessed the clinical outcomes in the patients. Of 48 teleconsultations for 39 patients, 13 dealt with diagnostic problems and 35 with therapeutic problems. The teleconsultation resolved the diagnostic uncertainties in 90% of cases. Advice from the expert modified the management in 37 (77%) teleconsultations; the change was related to the surgical indication in 18 cases, the surgical technique in 13 cases, and both in six cases. Agreement between the advice from the independent consultants and the treatment delivered by the local surgeon was 2.2/3. Clinical outcomes were good or very good in 31 (81%) of the 38 treated patients. This study establishes the feasibility and usefulness of paediatric orthopaedics teleconsultations in Djibouti. The introduction of telemedicine has changed our approach to challenges raised by patients in remote locations or precarious

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

Science.gov (United States)

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.

Behavioral Fever Drives Epigenetic Modulation of the Immune Response in Fish.

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Boltana, Sebastian; Aguilar, Andrea; Sanhueza, Nataly; Donoso, Andrea; Mercado, Luis; Imarai, Monica; Mackenzie, Simon

2018-01-01

Ectotherms choose the best thermal conditions to mount a successful immune response, a phenomenon known as behavioral fever. The cumulative evidence suggests that behavioral fever impacts positively upon lymphocyte proliferation, inflammatory cytokine expression, and other immune functions. In this study, we have explored how thermal choice during infection impacts upon underpinning molecular processes and how temperature increase is coupled to the immune response. Our results show that behavioral fever results in a widespread, plastic imprint on gene regulation, and lymphocyte proliferation. We further explored the possible contribution of histone modification and identified global associations between temperature and histone changes that suggest epigenetic remodeling as a result of behavioral fever. Together, these results highlight the critical importance of thermal choice in mobile ectotherms, particularly in response to an infection, and demonstrate the key role of epigenetic modification to orchestrate the thermocoupling of the immune response during behavioral fever.

Immune responses to influenza virus and its correlation to age and inherited factors

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Azadeh Bahadoran

2016-11-01

Full Text Available Influenza viruses belong to the family Orthomyxoviridae of enveloped viruses and are an important cause of respiratory infections worldwide. The influenza virus is able to infect a wide variety species as diverse as poultry, marine, pigs, horses and humans. Upon infection with influenza virus the innate immunity plays a critical role in efficient and rapid control of viral infections as well as in adaptive immunity initiation. The humoral immune system produces antibodies against different influenza antigens, of which the HA-specific antibody is the most important for neutralization of the virus and thus prevention of illness. Cell mediated immunity including CD4+ helper T cells and CD8+ cytotoxic T cells are the other arms of adaptive immunity induced upon influenza virus infection. The complex inherited factors and age related changes are associated with the host immune responses. Here, we review the different components of immune responses against influenza virus. Additionally, the correlation of the immune response to age and inherited factors has been discussed. These determinations lead to a better understanding of the limitations of immune responses for developing improved vaccines to control influenza virus infection.

Host control of malaria infections: constraints on immune and erythropoeitic response kinetics.

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Philip G McQueen

2008-08-01

Full Text Available The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum, can induce severe anemia and provoke strong, complex immune reactions. Which dynamical behaviors of host immune and erythropoietic responses would foster control of infection, and which would lead to runaway parasitemia and/or severe anemia? To answer these questions, we developed differential equation models of interacting parasite and red blood cell (RBC populations modulated by host immune and erythropoietic responses. The model immune responses incorporate both a rapidly responding innate component and a slower-responding, long-term antibody component, with several parasite developmental stages considered as targets for each type of immune response. We found that simulated infections with the highest parasitemia tended to be those with ineffective innate immunity even if antibodies were present. We also compared infections with dyserythropoiesis (reduced RBC production during infection to those with compensatory erythropoiesis (boosted RBC production or a fixed basal RBC production rate. Dyserythropoiesis tended to reduce parasitemia slightly but at a cost to the host of aggravating anemia. On the other hand, compensatory erythropoiesis tended to reduce the severity of anemia but with enhanced parasitemia if the innate response was ineffective. For both parasite species, sharp transitions between the schizont and the merozoite stages of development (i.e., with standard deviation in intra-RBC development time immune response, though P. vivax attacks a much smaller subset of RBCs. Since most P. vivax infections are nonlethal (if debilitating clinically, this suggests that P

Delicate regulation of the cGAS-MITA-mediated innate immune response.

Science.gov (United States)

Luo, Wei-Wei; Shu, Hong-Bing

2018-02-19

Although it has long been demonstrated that cytosolic DNA is a potent immune stimulant, it is only in recent years that the molecular mechanisms of DNA-stimulated innate immune responses have emerged. Studies have established critical roles for the DNA sensor cyclic GMP-AMP synthase (cGAS) and the adapter protein MITA/STING in the innate immune response to cytosolic DNA or DNA viruses. Although the regulation of cGAS-MITA/STING-mediated signaling remains to be fully investigated, understanding the processes involved may help to explain the mechanisms of innate immune signaling events and perhaps autoinflammatory diseases and to provide potential therapeutic targets for drug intervention. In this review, we summarize recent progress on the regulation of the cGAS-MITA/STING-mediated innate immune response to DNA viruses at the organelle-trafficking, post-translational and transcriptional levels.Cellular & Molecular Immunology advance online publication, 19 February 2018; doi:10.1038/cmi.2016.51.

Modelling the innate immune response against avian influenza virus in chicken

NARCIS (Netherlands)

Hagenaars, T.J.; Fischer, E.A.J.; Jansen, C.A.; Rebel, J.M.J.; Spekreijse, D.; Vervelde, L.; Backer, J.A.; Jong, de M.C.M.; Koets, A.P.

2016-01-01

At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load,

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Science.gov (United States)

Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

2004-03-01

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

Marketing paediatric influenza vaccination: results of a major metropolitan trial

Science.gov (United States)

Van Buynder, Paul G.; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily

2010-01-01

Please cite this paper as: Van Buynder et al. (2010) Marketing paediatric influenza vaccination: results of a major metropolitan trial. Influenza and Other Respiratory Viruses 5(1), 33–38. Objectives  After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Design  Advertising occurred in major statewide newspapers, via public poster displays and static ‘eye‐lite’ displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web‐sites. Parents were subsequently surveyed to assess reasons for vaccination. Main Outcome Results  The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Conclusions  Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community ‘myths’ about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. PMID:21138538

Escaping deleterious immune response in their hosts: lessons from trypanosomatids

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Anne eGeiger

2016-05-01

Full Text Available The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, T. cruzi and Leishmania spp are important human pathogens causing Human African Trypanosomiasis (HAT or Sleeping Sickness, Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs or sandflies and affect millions of people worldwide.In humans, extracellular African trypanosomes (T. brucei evade the hosts’ immune defences, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response.This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and, will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation.

Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

Science.gov (United States)

Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

2016-01-01

The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

Study of the integrated immune response induced by an inactivated EV71 vaccine.

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Longding Liu

Full Text Available Enterovirus 71 (EV71, a major causative agent of hand-foot-and-mouth disease (HFMD, causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs of 30 infants (6 to 11 months immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response.NCT01391494 and NCT01512706.

Modelling the Innate Immune Response against Avian Influenza Virus in Chicken

NARCIS (Netherlands)

Hagenaars, T J; Fischer, E A J; Jansen, C A; Rebel, J M J; Spekreijse, D; Vervelde, L; Backer, J A; de Jong, M.C.M.; Koets, A P

2016-01-01

At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α, -β

Immune response to uv-induced tumors: transplantation immunity and lymphocyte populations exhibiting anti-tumor activity

International Nuclear Information System (INIS)

Streeter, P.R.

1985-01-01

Ultraviolet light-induced murine skin tumors were analyzed for their ability to induce tumor-specific and cross-protective transplantation immunity in immunocompetent syngeneic mice. These studies revealed that progressor UV-tumors, like regressor UV-tumors, possess tumor-specific transplantation antigens. Cross-protective transplantation immunity to UV-tumors, however, was associated with sensitization to the serum used to culture the tumor lines rather than to cross-reactive or common determinants on UV-tumors. An analysis of the cytolytic activity of lymphocytes from the spleens of mice immunized with either regressor or progressor UV-tumors revealed a striking difference between the two immune splenocyte populations. From regressor tumor-immune animals, cytolytic T (Tc) lymphocytes with specificity for the immunizing tumor were found. However, the analysis of splenic lymphocytes from progressor tumor immune animals revealed no such effector cells. To more effectively examine those lymphocytes exhibiting cytolytic activity in vitro, T lymphocyte cloning technology was used as a means of isolating homogeneous lymphocyte populations with the effector activities described above. The mechanisms where NK cells and other nonspecific effector cells could be induced in tumor-immune animals are discussed in the context of class II restricted immune responses

Role of IL-12 and IFN-γ in immune response to toxoplasma gondii infection

International Nuclear Information System (INIS)

Moawad, M.A.F.; ElGawish, M.A.M.

2004-01-01

Interlenkin 12 (IL-12) is a potent immunoregulatory molecule that is critically involved in a wide range of diseases. In several murine models of intracellular infection, endogenous IL-12 has been shown to be crucial for the generation of a protective Th1 response in a primary infection for a intracellular pathogens. Interferon-gamma (IFN-γ) is also an important mediator of cellular immunity against microbial pathogens and tumor cells due to its potent capacity to activate macrophages for enhanced cytotoxicity. The aim of the present study is to evaluate the immune response to toxoplasma gondii after primary inflection (infected groups and secondary infection (re-infected groups for over 19 weeks (the time of the experiment). the evaluation was assessed by measurements of levels of IL-12 and IFN-γ using ELISA technique in the sera of these infected rats. The results demonstrated that the primary immune response induced a fluctuation in the levels of IL-12 in the sera of infected rats, which reached maximum value of 122.6 ±1.4 pg/ml after 15 weeks of primary infection. While, in the challenged groups (secondary immune response, re-infected groups) the levels of IL-12 were generally lower than that of the primary immune response. On the other hand, IFN-γ levels increased significantly in the secondary immune response (re-infected groups) as compared to primary immune response 9 infected groups) In conclusion, the results suggest that IL-12 might have a role in the defense mechanism against intracellular infection with T-gondii especially in primary immune response than in the secondary immune response. This is in contrast to IFN-γ that takes the up-hand in secondary immune response to T-gondii infection

Immune responses accelerate ageing: proof-of-principle in an insect model.

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E Rhiannon Pursall

Full Text Available The pathology of many of the world's most important infectious diseases is caused by the immune response. Additionally age-related disease is often attributed to inflammatory responses. Consequently a reduction in infections and hence inflammation early in life has been hypothesized to explain the rise in lifespan in industrialized societies. Here we demonstrate experimentally for the first time that eliciting an immune response early in life accelerates ageing. We use the beetle Tenebrio molitor as an inflammation model. We provide a proof of principle for the effects of early infection on morbidity late in life and demonstrate a long-lasting cost of immunopathology. Along with presenting a proof-of-principle study, we discuss a mechanism for the apparently counter-adaptive persistence of immunopathology in natural populations. If immunopathology from early immune response only becomes costly later in life, natural selection on reducing self-harm would be relaxed, which could explain the presence of immune self-harm in nature.

Neonatal and Infantile Immune Responses to Encapsulated Bacteria and Conjugate Vaccines

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Peter Klein Klouwenberg

2008-01-01

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

Paediatric Abdominal Surgical Emergencies in a General Surgical ...

African Journals Online (AJOL)

... organized for general surgeons undertaking paediatric surgical emergencies. More paediatric surgeons should be trained and more paediatric surgical units should established in the country. Key Words: Paediatric Abdominal Surgical Emergencies; Paediatric Surgeons, General Surgeons. Journal of College of Medicine ...

Variation in radiographic protocols in paediatric interventional cardiology

International Nuclear Information System (INIS)

McFadden, S L; Hughes, C M; Winder, R J

2013-01-01

The aim of this work is to determine current radiographic protocols in paediatric interventional cardiology (IC) in the UK and Ireland. To do this we investigated which imaging parameters/protocols are commonly used in IC in different hospitals, to identify if a standard technique is used and illustrate any variation in practice. A questionnaire was sent to all hospitals in the UK and Ireland which perform paediatric IC to obtain information on techniques used in each clinical department and on the range of clinical examinations performed. Ethical and research governance approval was sought from the Office for Research Ethics Committees Northern Ireland and the individual trusts. A response rate of 79% was achieved, and a wide variation in technique was found between hospitals. The main differences in technique involved variations in the use of an anti-scatter grid and the use of additional filtration to the radiation beam, frame rates for digital acquisition and pre-programmed projections/paediatric specific programming in the equipment. We conclude that there is no standard protocol for carrying out paediatric IC in the UK or Ireland. Each hospital carries out the IC procedure according to its own local protocols resulting in a wide variation in radiation dose. (paper)

Variation in radiographic protocols in paediatric interventional cardiology.

Science.gov (United States)

McFadden, S L; Hughes, C M; Winder, R J

2013-06-01

The aim of this work is to determine current radiographic protocols in paediatric interventional cardiology (IC) in the UK and Ireland. To do this we investigated which imaging parameters/protocols are commonly used in IC in different hospitals, to identify if a standard technique is used and illustrate any variation in practice. A questionnaire was sent to all hospitals in the UK and Ireland which perform paediatric IC to obtain information on techniques used in each clinical department and on the range of clinical examinations performed. Ethical and research governance approval was sought from the Office for Research Ethics Committees Northern Ireland and the individual trusts. A response rate of 79% was achieved, and a wide variation in technique was found between hospitals. The main differences in technique involved variations in the use of an anti-scatter grid and the use of additional filtration to the radiation beam, frame rates for digital acquisition and pre-programmed projections/paediatric specific programming in the equipment. We conclude that there is no standard protocol for carrying out paediatric IC in the UK or Ireland. Each hospital carries out the IC procedure according to its own local protocols resulting in a wide variation in radiation dose.

Humoral and cellular immune responses to modified hepatitis B ...

African Journals Online (AJOL)

Purpose: To evaluate the immunogenicity and types of immune response of a quality-controlled modified recombinant hepatitis B surface antigen (HBsAg) plasmid encoding HBsAg in mice. Methods: The characterized plasmid DNA was used in the immunization of Balb/c mice. Three groups of mice were intramuscularly ...

Perillyl alcohol suppresses antigen-induced immune responses in the lung

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Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Dohi, Makoto, E-mail: mdohi-tky@umin.ac.jp [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo (Japan)

2014-01-03

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

Mycobacterium tuberculosis co-operonic PE32/PPE65 proteins alter host immune responses by hampering Th1 response

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Mohd eKhubaib

2016-05-01

Full Text Available PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed and co-translated, and play role in modulating host immune responses. Experiments with macrophage cell lines revealed that this protein complex suppresses pro-inflammatory cytokines such as TNF-α and IL-6 whereas also inducing high expression of anti-inflammatory IL-10. Immunization of mice with these recombinant proteins dampens an effective Th1 response as evident from reduced frequency of IFN-g and IL-2 producing CD4+ and CD8+ T cells. IgG sub-typing from serum of immunized mice revealed high levels of IgG1 when compared with IgG2a and IgG2b. Further IgG1/IgG2a ratio clearly demonstrated that the protein complex manipulates the host immune response favourable to the pathogen. Our results demonstrate that the co-transcribed and co-translated PE32 and PPE65 antigens are involved specifically in modulating anti-mycobacterial host immune response by hampering Th1 response.

A modified live canine parvovirus vaccine. II. Immune response.

Science.gov (United States)

Carmichael, L E; Joubert, J C; Pollock, R V

1983-01-01

The safety and efficacy of an attenuated canine parvovirus (A-CPV) vaccine was evaluated in both experimental and in field dogs. After parenteral vaccination, seronegative dogs developed hemagglutination-inhibition (HI) antibody titers as early as postvaccination (PV) day 2. Maximal titers occurred within 1 week. Immunity was associated with the persistence of HI antibody titers (titers greater than 80) that endured at least 2 years. Immune dogs challenged with virulent CPV did not shed virus in their feces. The A-CPV vaccine did not cause illness alone or in combination with living canine distemper (CD) and canine adenovirus type-2 (CAV-2) vaccines, nor did it interfere with the immune response to the other viruses. A high rate (greater than 98%) of immunity was engendered in seronegative pups. In contrast, maternal antibody interfered with the active immune response to the A-CPV. More than 95% of the dogs with HI titers less than 10 responded to the vaccine, but only 50% responded when titers were approximately 20. No animal with a titer greater than 80 at the time of vaccination became actively immunized. Susceptibility to virulent CPV during that period when maternal antibody no longer protects against infection, but still prevents active immunization, is the principal cause of vaccinal failure in breeding kennels where CPV is present. Reduction, but not complete elimination, of CPV disease in large breeding kennels occurred within 1-2 months of instituting an A-CPV vaccination program.

The BRACELET Study: surveys of mortality in UK neonatal and paediatric intensive care trials

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Platt Martin

2010-05-01

Full Text Available Abstract Background The subject of death and bereavement in the context of randomised controlled trials in neonatal or paediatric intensive care is under-researched. The objectives of this phase of the Bereavement and RAndomised ControlLEd Trials (BRACELET Study were to determine trial activity in UK neonatal and paediatric intensive care (2002-06; numbers of deaths before hospital discharge; and variation in mortality across intensive care units and trials and to determine whether bereavement support policies were available within trials. These are essential prerequisites to considering the implications of future policies and practice subsequent to bereavement following a child's enrolment in a trial. Methods The units survey involved neonatal units providing level 2 or 3 care, and paediatric units providing level II care or above; the trials survey involved trials where allocation was randomized and interventions were delivered to intensive care patients, or to parents but designed to affect patient outcomes. Results Information was available from 191/220 (87% neonatal units (149 level 2 or 3 care; and 28/32 (88% paediatric units. 90/177 (51% eligible responding units participated in one or more trial (76 neonatal, 14 paediatric and 54 neonatal units and 6 paediatric units witnessed at least one death. 50 trials were identified (36 neonatal, 14 paediatric. 3,137 babies were enrolled in neonatal trials, 210 children in paediatric trials. Deaths ranged 0-278 (median [IQR interquartile range] 2 [1, 14.5] per neonatal trial, 0-4 (median [IQR] 1 [0, 2.5] per paediatric trial. 534 (16% participants died post-enrolment: 522 (17% in neonatal trials, 12 (6% in paediatric trials. Trial participants ranged 1-236 (median [IQR] 21.5 [8, 39.8] per neonatal unit, 1-53 (median [IQR] 11.5 [2.3, 33.8] per paediatric unit. Deaths ranged 0-37 (median [IQR] 3.5 [0.3, 8.8] per neonatal unit, 0-7 (median [IQR] 0.5 [0, 1.8] per paediatric unit. Three trials had a

Nanotechnology, neuromodulation & the immune response: discourse, materiality & ethics.

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Fins, Joseph J

2015-04-01

Drawing upon the American Pragmatic tradition in philosophy and the more recent work of philosopher Karen Barad, this paper examines how scientific problems are both obscured, and resolved by our use of language describing the natural world. Using the example of the immune response engendered by neural implants inserted in the brain, the author explains how this discourse has been altered by the advent of nanotechnology methods and devices which offer putative remedies that might temper the immune response in the central nervous system. This emergent nanotechnology has altered this problem space and catalyzed one scientific community to acknowledge a material reality that was always present, if not fully acknowledged.

Cell mediated immune response in human antirabies revaccination

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Débora Regina Veiga

1987-04-01

Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

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Longo, Diane M; Louie, Brent; Ptacek, Jason; Friedland, Greg; Evensen, Erik; Putta, Santosh; Atallah, Michelle; Spellmeyer, David; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Schaeffer, Andrea; Lukac, Suzanne; Railkar, Radha; Beals, Chan R; Cesano, Alessandra; Carayannopoulos, Leonidas N; Hawtin, Rachael E

2014-06-21

Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)]. Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies.

Secondary immune response of rainbow trout following repeated immersion vaccination

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Jaafar, R. M.; Al-Jubury, A.; Chettri, J. K.

2017-01-01

Teleosts are able to raise a protective immune response, comprising both innate and adaptive elements, against various pathogens. This is the basis for a widespread use of vaccines, administered as injection or immersion, in the aquaculture industry. It has been described that repeated injection...... vaccination of fish raises a secondary immune response, consisting of rapid, accelerated and increased antibody reaction. This study reports how rainbow trout responds to repeated immersion vaccination against yersiniosis (ERM) caused by the bacterial pathogen Yersinia ruckeri. It was found that rainbow trout...... does not raise a classical secondary response following repeated immersion vaccination. Serum antibody titres were merely slightly increased even after three immunizations, using 30-s immersion into a bacterin consisting of formalin-inactivated Y. ruckeri (serotype O1, biotypes 1 and 2), performed over...

Secondary immune response of rainbow trout following repeated immersion vaccination

DEFF Research Database (Denmark)

Jaafar, R. M.; Al-Jubury, Azmi; Chettri, Jiwan Kumar

2018-01-01

Teleosts are able to raise a protective immune response, comprising both innate and adaptive elements, against various pathogens. This is the basis for a widespread use of vaccines, administered as injection or immersion, in the aquaculture industry. It has been described that repeated injection...... vaccination of fish raises a secondary immune response, consisting of rapid, accelerated and increased antibody reaction. This study reports how rainbow trout responds to repeated immersion vaccination against yersiniosis (ERM) caused by the bacterial pathogen Yersinia ruckeri. It was found that rainbow trout...... does not raise a classical secondary response following repeated immersion vaccination. Serum antibody titres were merely slightly increased even after three immunizations, using 30-s immersion into a bacterin consisting of formalin-inactivated Y. ruckeri (serotype O1, biotypes 1 and 2), performed over...

Nigerian Journal of Paediatrics: Editorial Policies

African Journals Online (AJOL)

Dr. Austine I Omoigberale FWACP (Paed) Professor of Paediatrics, Neonatology & Infectious diseases. Dept of Child Health University of Benin Teaching Hospital Benin City Nigeria isigboge@gmail.com +2348030750641. Dr. Felix Akinbami FWACP (Paed) Professor of Paediatrics & Gastroenterology Dept of Paediatrics

[Comparison of immune response after oral and intranasal immunization with recombinant Lactobacillus casei expressing ETEC F41].

Science.gov (United States)

Liu, Jiankui; Wei, Chunhua; Hou, Xilin; Wang, Guihua; Yu, Liyun

2009-04-01

In order to represent a promising strategy for mucosal vaccination, oral or intranasal immunization of Specific Pathogen Free (SPF) BALB/c mice were performed. The mucosal immunity, systemic immune and protective immune responses were compared after immunization with the recombinant Lactobacillus casei (L. casei) harboring enterotoxigenic Escherichia coli (ETEC) F41. The recombinant fusion proteins were detected by Western blot. Surface localization of the fusion protein was verified by immunofluorescence microscopy and flow cytometry. Six-week-old female SPF BALB/c mice (160 heads) were divided into 4 groups for immunization and control. Oral and intranasal immunization of mice was performed with the recombinant strain L. casei harboring pLA-F41 or pLA. For oral immunization, the mice were inoculated daily on days 0 to 4, 7 to 11, 21 to 25, and 49 to 53. A lighter schedule was used for nasal immunization (days 0 to 2, 7 to 9, 21 and 49). Specific anti-F41 IgG antibody in the serum and specific anti-F41 secret immunoglobulin A (sIgA) antibody in the lung, intestines, vagina fluid and feces of mice were detected by indirect ELISA. The mice orally or intranasally immunized with pLA-F41/L. casei and pLA/IL. casei were challenged with standard-type ETEC F41 (C83919) (2 x 10(3) LD50). Mice immunized with pLA-F41/L. casei could produce remarkable anti-F41 antibody level. More than 90% survived in oral immunization group whereas more than 85% survived in intranasal immunization group after challenged with C83919, all dead in the control group. Ninety percent of the pups survived in oral immunization group whereas 80% survived in intranasal immunization group after challenged with C83919, but only a 5% survival rate for pups that were either immunized with a control pLA vector or unimmunized. Oral or intranasal immunization with recombinant L. casei displaying ETEC F41 antigens on the surface induced effective and similar systemic and mucosal immune responses against the

Induction of the immune response suppression in mice inoculated with Candida albicans.

Science.gov (United States)

Valdez, J C; Mesón, D E; Sirena, A; de Petrino, S F; Eugenia, M; de Jorrat, B B; de Valdex, M G

1986-03-01

There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans. Candidosis would induce sub-populations of suppressor cells in the host cell-immune response. This report tries to show the effect of different doses of C. albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity. The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C. albicans and checking for delayed-type hipersensitivity (D.T.H.). D.T.H. was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells. Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C. albicans. Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead).

Immune system development during early childhood in tropical Latin America: evidence for the age-dependent down regulation of the innate immune response.

Science.gov (United States)

Teran, Rommy; Mitre, Edward; Vaca, Maritza; Erazo, Silvia; Oviedo, Gisela; Hübner, Marc P; Chico, Martha E; Mattapallil, Joseph J; Bickle, Quentin; Rodrigues, Laura C; Cooper, Philip J

2011-03-01

The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5 years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6-9 months, 22-26 months, and 48-60 months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4(+) and CD8(+) T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3(+) T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology. Copyright © 2010 Elsevier Inc. All rights reserved.

Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

Science.gov (United States)

Reyes, L; Hartikka, J; Bozoukova, V; Sukhu, L; Nishioka, W; Singh, G; Ferrari, M; Enas, J; Wheeler, C J; Manthorpe, M; Wloch, M K

2001-06-14

Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

The Internet and the paediatric surgeon.

Science.gov (United States)

Srinivas, M; Inumpudi, A; Mitra, D K

1998-12-01

The Internet, which has truly united the world, is an extensive network of inter-linked computers storing immense bytes of information that can be accessed by anyone, transcending all barriers. The paediatric surgery Internet consists of exponentially growing material that deals with information specifically for paediatric surgeons and patients of the paediatric age group. We reviewed the methods available to take advantage of this network to enable busy paediatric surgeons to accrue the benefits easily and efficiently rather than be lost in the information ocean by surfing individually. By getting connected to the Internet, the paediatric surgeon gains enormous information that can be useful for patient care. The Internet has revolutionised scientific publications by virtue of its fast and accurate transmission of manuscripts. Paediatric surgeons can send manuscripts by this channel and also access journals, obviating the inherent lag period of communication by post.

Innate immune responses to gut microbiota differ between oceanic and freshwater threespine stickleback populations

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Kathryn Milligan-Myhre

2016-02-01

Full Text Available Animal hosts must co-exist with beneficial microbes while simultaneously being able to mount rapid, non-specific, innate immune responses to pathogenic microbes. How this balance is achieved is not fully understood, and disruption of this relationship can lead to disease. Excessive inflammatory responses to resident microbes are characteristic of certain gastrointestinal pathologies such as inflammatory bowel disease (IBD. The immune dysregulation of IBD has complex genetic underpinnings that cannot be fully recapitulated with single-gene-knockout models. A deeper understanding of the genetic regulation of innate immune responses to resident microbes requires the ability to measure immune responses in the presence and absence of the microbiota using vertebrate models with complex genetic variation. Here, we describe a new gnotobiotic vertebrate model to explore the natural genetic variation that contributes to differences in innate immune responses to microbiota. Threespine stickleback, Gasterosteus aculeatus, has been used to study the developmental genetics of complex traits during the repeated evolution from ancestral oceanic to derived freshwater forms. We established methods to rear germ-free stickleback larvae and gnotobiotic animals monoassociated with single bacterial isolates. We characterized the innate immune response of these fish to resident gut microbes by quantifying the neutrophil cells in conventionally reared monoassociated or germ-free stickleback from both oceanic and freshwater populations grown in a common intermediate salinity environment. We found that oceanic and freshwater fish in the wild and in the laboratory share many intestinal microbial community members. However, oceanic fish mount a strong immune response to residential microbiota, whereas freshwater fish frequently do not. A strong innate immune response was uniformly observed across oceanic families, but this response varied among families of freshwater fish

Inhibition of the immune response to experimental fresh osteoarticular allografts

International Nuclear Information System (INIS)

Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. III; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M.

1989-01-01

The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed

Study of the immune response to thyroglobulin through a model of experimental autoimmune thyroiditis

International Nuclear Information System (INIS)

Santos Castro, M. dos.

1981-01-01

The cellular and humoral immune response to thyroglobulin of different species was studied in guinea pigs. The experiments described suggested that the immune system can be activated against self-determinants. Human and pork thyroglobulin were able to induce the experimental thyroiditis as well as some immune responses, such as in vitro proliferative response, delayed hypersensitivity and antibodies. Although guinea pig thyroglobulin was unable to induce specific T-lymphocyte proliferation in vitro, delayed hypersensitivity response and antibodies, it was very efficient in inducing the autoimmune thyroiditis. On the contrary, bovine thyroglobulin did not induce experimental autoimmune thyroiditis despite producing good responses as determined by similar in vitro proliferative response, delayed hypersensitivity and on the humoral level. These results suggest that the assays utilised were not able to evaluate the relevant immune response to genesis of the thyroiditis. The determinant selection mechanisms operating in these immune responses are probably selecting determinants not responsible for self-recognition in vivo. It was suggested that the macrophage could be the cell responsible for the presentation of these determinants to the lymphocyte in an immunogenic form. (Author) [pt

Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine

International Nuclear Information System (INIS)

Yoshikawa, Tomoaki; Imazu, Susumu; Gao Jianqing; Hayashi, Kazuyuki; Tsuda, Yasuhiro; Shimokawa, Mariko; Sugita, Toshiki; Niwa, Takako; Oda, Atushi; Akashi, Mitsuru; Tsutsumi, Yasuo; Mayumi, Tadanori; Nakagawa, Shinsaku

2004-01-01

In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro. Consistent with this observation, an in vitro assay showed that FL-mediated antigen-gene delivery can induce potent presentation of antigen via the MHC class I-dependent pathway. Accordingly, immunization with FL containing the OVA-gene induced potent OVA-specific Th1 and Th2 cytokine production. Additionally, OVA-specific CTL responses and antibody production were also observed in systemic compartments including the spleen, upon immunization with the OVA-gene encapsulating FL. These findings suggest that FL is an effective genetic immunization carrier system for the stimulation of antigen-specific immune responses against its encoding antigen

[Promotion of breast feeding in paediatric outpatient settings].

Science.gov (United States)

Böse-O'Reilly, S; Wermuth, I; Hellmann, J; Siebert, U; Lob-Corzilius, T

2008-03-01

With some data and examples it can be shown that the competence and the knowledge of paediatric doctor's assistants and paediatric nurses can and should be improved. The training courses to become a "prevention assistant" have been very positively accepted by doctor's assistants and paediatric nurses, and it seems an appropriate method to reach these aims. Prevention and especially promotion of breast feeding is possible in paediatric outpatient settings. The immediate contact between infants, parents, paediatric doctor's assistants, paediatric nurses, and doctors offers a unique opportunity to promote the health of children, mainly due to the high acceptance of regular check-ups. So why not introduce the promotion of breast feeding in paediatric outpatient settings with specially trained doctor's assistants and paediatric nurses?

Immune response capacity after human splenic autotransplantation - Restoration of response to individual pneumococcal vaccine subtypes

NARCIS (Netherlands)

Leemans, R; Manson, W; Snijder, JAM; Smit, JW; Klasen, HJ; The, TH; Timens, W

Objective To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. Summary Background Data After splenectomy, patients

Humoral and cell-mediated immune responses in DNA immunized mink challenged with wild-type canine distemper virus

DEFF Research Database (Denmark)

Nielsen, Line; Søgaard, Mette; Karlskov-Mortensen, Peter

2009-01-01

The aim of the study was to investigate the different phases of the immune response after DNA immunization with the hemagglutinin and nucleoprotein genes from canine distemper virus (CDV). Although attenuated live CDV vaccines have effectively reduced the incidence of disease, canine distemper...

Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses

Science.gov (United States)

Feng, Pinghui; Moses, Ashlee; Früh, Klaus

2015-01-01

γ-Herpesviral immune evasion mechanisms are optimized to support the acute, lytic and the longterm, latent phase of infection. During acute infection, specific immune modulatory proteins limit, but also exploit, the antiviral activities of cell intrinsic innate immune responses as well as those of innate and adaptive immune cells. During latent infection, a restricted gene expression program limits immune targeting and cis-acting mechanisms to reduce the antigen presentation as well as antigenicity of latency-associated proteins. Here, we will review recent progress in our understanding of γ-herpesviral immune evasion strategies. PMID:23735334

Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

Science.gov (United States)

Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

2017-02-06

In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

Ageing and the humoral immune response in mice

International Nuclear Information System (INIS)

Blankwater, M.J.

1978-01-01

The study presented in this thesis is concerned with changes in the humoral immune system as a function of age in different inbred mouse strains. Their capacity to develop humoral immune responses to experimentally given thymus-dependent and thymus-independent antigens under various conditions is compared. Furthermore, experiments employing thymus transplantation and thymic humoral factors which are directed at the restoration of the diminished T cell functions in old age are reported. (Auth.)

Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention.

Science.gov (United States)

Marcinkiewicz, Janusz; Bryniarski, Krzysztof; Nazimek, Katarzyna

2014-01-01

Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.

Immune response and biochemistry of calves immunized with rMSP1a ( Anaplasma marginale using carbon nanotubes as carrier molecules

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Bruna Torres Silvestre

2018-05-01

Full Text Available Abstract Vaccination against Anaplasma marginale has been considered an important control strategy for bovine anaplasmosis. Recently, mice immunized with rMSP1 a linked to carbon nanotubes (MWNT showed significant immune responses, generating a new possibility for use of an inactivated vaccine. The objective of this study was to investigate the cellular and humoral responses in calves immunized with MWNT+rMSP1a , associated with inactivated vaccine of A. marginale produced in vitro, and evaluate the toxic effects of the MWNT on renal and hepatic function. rMSP1a was covalently linked to MWNT. Inactivated vaccine (AmUFMG2 was produced by cultivating A. marginale in IDE8 cells. Twenty-four Holstein calves were divided (four groups and immunized subcutaneously with PBS and non-carboxylated MWNT (control, G1, AmUFMG2 (G2, MWNT+rMSP1a (G3, and AmUFMG2 with MWNT+rMSP1a (G4. Blood samples were collected for total leukocyte counts, biochemical profiling and evaluation of the cellular and humoral response. Immunization with MWNT+rMSP1a induced increase in the total number of leukocytes, NK cells, in the lymphocyte populations and higher levels of antibodies compared to calves immunized only with AmUFMG2. Furthermore, MWNT did not induce changes in the biochemical profile. These data indicate that MWNT+rMSP1a were able to induce the immune responses more efficiently than AmUFMG2 alone, without generating toxicity.

Work stress and innate immune response.

Science.gov (United States)

Boscolo, P; Di Gioacchino, M; Reale, M; Muraro, R; Di Giampaolo, L

2011-01-01

Several reports highlight the relationship between blood NK cytotoxic activity and life style. Easy life style, including physical activity, healthy dietary habits as well as good mental health are characterized by an efficient immune response. Life style is related to the type of occupational activity since work has a central part in life either as source of income or contributing to represent the social identity. Not only occupational stress, but also job loss or insecurity are thus considered serious stressful situations, inducing emotional disorders which may affect both neuroendocrine and immune systems; reduced reactivity to mitogens and/or decreased blood NK cytotoxic activity was reported in unemployed workers or in those with a high perception of job insecurity and/or job stress. Although genetic factors have a key role in the pathogenesis of autoimmune disorders, occupational stress (as in night shifts) was reported associated to an increased incidence of autoimmune disorders. Monitoring blood NK response may thus be included in the health programs as an indirect index of stressful job and/or poor lifestyle.

Non specific immune response in the African catfish ...

African Journals Online (AJOL)

Non specific immune response in the African catfish, Heterobranchus longifilis fed diets fortified with ethanolic extracts of selected traditional medicinal plants and disease resistance against Pseudomonas aeruginosa.

Immune Response in Mussels To Environmental Pollution.

Science.gov (United States)

Pryor, Stephen C.; Facher, Evan

1997-01-01

Describes the use of mussels in measuring the extent of chemical contamination and its variation in different coastal regions. Presents an experiment to introduce students to immune response and the effects of environmental pollution on marine organisms. Contains 14 references. (JRH)

Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish

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Arunita Chatterjee

2016-06-01

Full Text Available Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual.

Collaboration between paediatric surgery and other medical specialties in Nigeria

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Philemon E Okoro

2012-01-01

Full Text Available Background: The quality of service and success of patient care and research in most fields of medicine depend on effective collaboration between different specialties. Paediatric surgery is a relatively young specialty in Nigeria and such collaborations are desirable. This survey assesses the nature and extent of collaboration between paediatric surgery and other specialties in Nigeria. Materials and Methods: This is a questionnaire survey carried out in November 2008 among paediatric surgeons and their trainees practising in Nigeria. Questionnaires were distributed and retrieved either by hand or e-mailing. The responses were then collated and analysed using the SPSS 17.0. Results: Forty-seven respondents were included in the survey. Forty-five (95.7% respondents thought that there was inadequate collaboration and that there was a need for an increased collaboration between paediatric surgery and other specialties. Anaesthesia, paediatrics and radiology are among the specialties where collaborations were most required but not adequately received. Collaboration had been required from these specialties in areas of patient care, training and research. Reasons for inadequate collaboration included the paucity of avenues for inter-specialty communication and exchange of ideas 33 (70.3%, lack of awareness of the need for collaboration 32 (68.1%, tendency to apportion blames for bad outcome 13 (27.7%, and mutual suspicion 8 (17%. Conclusion: There is presently inadequate collaboration between paediatric surgery and other specialties in Nigeria. There is a need for more inter-specialty support, communication, and exchange of ideas in order to achieve desirable outcomes.

Enhanced responses to tumor immunization following total body irradiation are time-dependent.

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Adi Diab

Full Text Available The development of successful cancer vaccines is contingent on the ability to induce effective and persistent anti-tumor immunity against self-antigens that do not typically elicit immune responses. In this study, we examine the effects of a non-myeloablative dose of total body irradiation on the ability of tumor-naïve mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation followed by lymphocyte infusion results in a dramatic increase in responsiveness to tumor vaccination, with augmentation of T cell responses to tumor antigens and tumor eradication. In irradiated mice, infused CD8(+ T cells expand in an environment that is relatively depleted in regulatory T cells, and this correlates with improved CD8(+ T cell functionality. We also observe an increase in the frequency of dendritic cells displaying an activated phenotype within lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the relative decrease in regulatory T cells and increase in activated dendritic cells correspond with a brief window of augmented responsiveness to immunization. After this 24 hour window, the numbers of dendritic cells decline, as does the ability of mice to respond to immunizations. When immunizations are initiated within the period of augmented dendritic cell activation, mice develop anti-tumor responses that show increased durability as well as magnitude, and this approach leads to improved survival in experiments with mice bearing established tumors as well as in a spontaneous melanoma model. We conclude that irradiation can produce potent immune adjuvant effects independent of its ability to induce tumor ablation, and that the timing of immunization and lymphocyte infusion in the irradiated host are crucial for generating optimal anti-tumor immunity. Clinical strategies using these approaches must therefore optimize such parameters, as the correct timing of infusion and vaccination may mean the difference

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

International Nuclear Information System (INIS)

Zhao Ping; Cao Jie; Zhao Lanjuan; Qin Zhaolin; Ke Jinshan; Pan Wei; Ren Hao; Yu Jianguo; Qi Zhongtian

2005-01-01

The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5α and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobulins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity (DTH) and CD8 + CTL responses to N protein. The study shows that N protein of SARS-CoV not only is an important B cell immunogen, but also can elicit broad-based cellular immune responses. The results indicate that the N protein may be of potential value in vaccine development for specific prophylaxis and treatment against SARS

Indian Hedgehog Suppresses a Stromal Cell–Driven Intestinal Immune Response

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B. Florien Westendorp

2018-01-01

Conclusions: We show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast-derived CXCL12, and migration of immune cells into the lamina propria.

Memory B-Cell and Antibody Responses Induced by Plasmodium falciparum Sporozoite Immunization

NARCIS (Netherlands)

Nahrendorf, W.; Scholzen, A.; Bijker, E.M.; Teirlinck, A.C.; Bastiaens, G.J.H.; Schats, R.; Hermsen, C.C.; Visser, L.G.; Langhorne, J.; Sauerwein, R.W.

2014-01-01

BACKGROUND: Immunization of healthy volunteers during receipt of chemoprophylaxis with Plasmodium falciparum sporozoites (CPS-immunization) induces sterile protection from malaria. Antibody responses have long been known to contribute to naturally acquired immunity against malaria, but their

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

Science.gov (United States)

Miró, Lluïsa; Garcia-Just, Alba; Amat, Concepció; Polo, Javier; Moretó, Miquel; Pérez-Bosque, Anna

2017-12-11

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

[Current situation of the organisation, resources and activity in paediatric cardiology in Spain].

Science.gov (United States)

Sánchez Ferrer, Francisco; Castro García, Francisco José; Pérez-Lescure Picarzo, Javier; Roses Noguer, Ferrán; Centeno Malfaz, Fernándo; Grima Murcia, María Dolores; Brotons, Dimpna Albert

2018-04-26

The results are presented on the «current situation of the organisation, resources and activity in paediatric cardiology in Spain». It was promoted by the Spanish Society of Paediatric Cardiology and Congenital Heart disease. An analysis was carried out on the results obtained from a specifically designed questionnaire, prepared by the Spanish Society of Paediatric Cardiology and Congenital Heart disease, that was sent to all hospitals around the country that offer the speciality of paediatric cardiology. A total of 86 questionnaires were obtained, including 14 hospitals that perform cardiac surgery on children. A total of 190 paediatric cardiology consultants, 40 cardiac surgeons, and 27 middle grade doctors performing their paediatric residency (MIR program) were identified. All hospitals had adequate equipment to perform an optimal initial evaluation of any child with a possible cardiac abnormality, but only tertiary centres could perform complex diagnostic procedures, interventional cardiology, and cardiac surgery. In almost all units around the country, paediatric cardiology consultants were responsible for outpatient clinics and hospital admissions, whereas foetal cardiology units were still mainly managed by obstetricians. The number of diagnostic and therapeutic procedures was similar to those reported in the first survey, except for a slight decrease in the total number of closed cardiac surgery procedures, and a proportional increase in the number of therapeutic catheterisations. Paediatric Cardiology in Spain is performed by paediatric cardiology consultants that were trained initially as general paediatricians, and then completed a paediatric cardiology training period. Almost all units have adequate means for diagnosis and treatment. Efforts should be directed to create a national registry that would not only allow a prospective quantification of diagnostic and therapeutic procedures, but also focus on their clinical outcomes. Copyright © 2018

Predictors of responses to immune checkpoint blockade in advanced melanoma

DEFF Research Database (Denmark)

Jacquelot, N; Roberti, M P; Enot, D P

2017-01-01

Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs....... Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we...

Effects of alcohol consumption on the allergen-specific immune response in mice

DEFF Research Database (Denmark)

Linneberg, Allan; Roursgaard, Martin; Hersoug, Lars-Georg

2008-01-01

There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization....

Persistence of the immune response induced by BCG vaccination

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Blitz Rose

2008-01-01

Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

[Effect of vitamine A on mice immune response induced by specific periodontal pathogenic bacteria-immunization].

Science.gov (United States)

Lin, Xiao-Ping; Zhou, Xiao-Jia; Liu, Hong-Li; DU, Li-Li; Toshihisa, Kawai

2010-12-01

The aim of this study was to investigate the effect of vitamine-A deficiency on the induction of specific periodontal pathogenic bacteria A. actinomycetetemcomitans(Aa) immunization. BALB/c mice were fed with vitamine A-depleted diet or control regular diet throughout the whole experiment period. After 2 weeks, immunized formalin-killed Aa to build immunized models, 6 weeks later, sacrificed to determine specific antibody-IgG, IgM and sub-class IgG antibody titers in serum, and concentration of IL-10, IFN-γ, TNF-α and RANKL in T cell supernatant were measured by ELISA and T cell proliferation was measured by cintilography. SPSS 11.5 software package was used for statistical analysis. The levels of whole IgG and IgM antibody which were immunized by Aa significantly elevated, non-immune group was unable to produce any antibody. Compared with Aa immunized+RD group, the level of whole IgG in Aa immunized+VAD group was significantly higher (Pvitamin-A diet can increase the immunized mice's susceptibility to periodontal pathogenic bacteria and trigger or aggravate immune inflammatory response. Adequate vitamin A is an important factor in maintaining body health. Supported by Natural Science Foundation of Liaoning Province (Grant No.20092139) and Science and Technology Program of Shenyang Municipality (Grant No.F10-149-9-32).

F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response.

Science.gov (United States)

Luo, Yu; Van Nguyen, Ut; de la Fe Rodriguez, Pedro Y; Devriendt, Bert; Cox, Eric

2015-10-21

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4(+) ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4(+) ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4(+) ETEC infection and could aid in the design of future ETEC vaccines.

Inflammation and Immune Response in COPD: Where Do We Stand?

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Nikoletta Rovina

2013-01-01

Full Text Available Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs, triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs. Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

HIF-mediated innate immune responses: cell signaling and therapeutic implications

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Harris AJ

2014-05-01

Full Text Available Alison J Harris, AA Roger Thompson, Moira KB Whyte, Sarah R Walmsley Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out. Keywords: hypoxia, neutrophils, monocytes, macrophages

Glycan-mediated modification of the immune response

DEFF Research Database (Denmark)

Madsen, Caroline B; Pedersen, Anders E; Wandall, Hans H

2013-01-01

Aberrantly glycosylated tumor antigens represent promising targets for the development of anti-cancer vaccines, yet how glycans influence immune responses is poorly understood. Recent studies have demonstrated that GalNAc-glycosylation enhances antigen uptake by dendritic cells as well as CD4(+) T......-cell and humoral responses, but prevents CD8(+) T-cell activation. Here, we briefly discuss the relevance of glycans as candidate targets for anti-cancer vaccines....

The neurophysiology of paediatric movement disorders.

Science.gov (United States)

McClelland, Verity M

2017-12-01

To demonstrate how neurophysiological tools have advanced our understanding of the pathophysiology of paediatric movement disorders, and of neuroplasticity in the developing brain. Delineation of corticospinal tract connectivity using transcranial magnetic stimulation (TMS) is being investigated as a potential biomarker for response to therapy. TMS measures of cortical excitability and neuroplasticity are also being used to investigate the effects of therapy, demonstrating neuroplastic changes that relate to functional improvements. Analyses of evoked potentials and event-related changes in the electroencephalogaphy spectral activity provide growing evidence for the important role of aberrant sensory processing in the pathophysiology of many different movement disorders. Neurophysiological findings demonstrate that children with clinically similar phenotypes may have differing underlying pathophysiology, which in turn may explain differential response to therapy. Neurophysiological parameters can act as biomarkers, providing a means to stratify individuals, and are well suited to provide biofeedback. They therefore have enormous potential to facilitate improvements to therapy. Although currently a small field, the role of neurophysiology in paediatric movement disorders is poised to expand, both fuelled by and contributing to the rapidly growing fields of neuro-rehabilitation and neuromodulation and the move towards a more individualized therapeutic approach.

Modulation of immune response by alloactivated suppressor T cells

International Nuclear Information System (INIS)

Bernstein, A.; Sopori, M.L.; Gose, J.E.; Sondel, P.M.

1979-01-01

These studies show that there may be several different kinds of suppressor cells, each activated by different pathways and able to suppress different parts of the immune response either specifically or nonspecifically. As such, the physiology of one type of suppressor cell need not necessarily apply to that of another type of suppressor. Thus we emphasize the trap that the suppressor cell option provides: that is, virtually any previously inexplicable in vitro and in vivo immune phenomenon can always be adequately accounted for by evoking a suppressor mechanism, either by suppressing the response or suppressing the suppressor

The role of complement in the acquired immune response

DEFF Research Database (Denmark)

Nielsen, C H; Fischer, E M; Leslie, R G

2000-01-01

Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...

Malnutrition in paediatric oncology patients

African Journals Online (AJOL)

Nutritional status of paediatric cancer patients at diagnosis ... Professor and Executive Head, Department of Paediatrics and Child Health, Stellenbosch University and Tygerberg Hospital, .... can lead to decreased oral intake, weight loss.

Transfusion therapy in paediatric trauma patients

DEFF Research Database (Denmark)

Nystrup, Kristin Brønnum; Stensballe, Jakob; Bøttger, Morten

2015-01-01

Haemorrhage is a leading cause of death in paediatric trauma patients. Predefined massive transfusion protocols (MTP) have the potential to significantly reduce mortality by treating haemorrhagic shock and coagulopathy, in adhering to the principles of haemostatic resuscitation with rapid...... in paediatric trauma patients is challenging, and the optimal blood product ratio that will increase survival in massively bleeding paediatric trauma patients has yet to be determined. To date, only a few small descriptive studies and case reports have investigated the use of predefined MTP in paediatric trauma...... patients.MTP with increased FFP or PLT to RBC ratios combined with viscoelastic haemostatic assay (VHA) guided haemostatic resuscitation have not yet been tested in paediatric populations but based on results from adult trauma patients, this therapeutic approach seems promising.Considering the high...

Babassu aqueous extract (BAE as an adjuvant for T helper (Th1-dependent immune responses in mice of a Th2 immune response-prone strain

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Nascimento Flavia RF

2011-01-01

Full Text Available Abstract Background The aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE exerts a clear immunostimulative activity in vivo. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of Leishmania amazonensis promastigote extract (LE, adsorbed or not to Al(OH3, and in the presence or not of BAE, were used as immunogens. LE and Al(OH3 have been shown to preferentially elicit Th2 immune responses. Results The addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH3, clearly promoted the in vitro production of interferon γ (IFN-γ, a major Th1-dependent cytokine, and not of interleukin (IL-4 (a Th2-dependent cytokine, by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the in vivo formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH3-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH3-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were in vitro stimulated with BAE or which received no specific in vitro stimulus. No differences in IL-10 (an immunoregulatory cytokine levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous ex vivo production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by

Good practice recommendations for paediatric outpatient parenteral antibiotic therapy (p-OPAT) in the UK: a consensus statement.

Science.gov (United States)

Patel, Sanjay; Abrahamson, Ed; Goldring, Stephen; Green, Helen; Wickens, Hayley; Laundy, Matt

2015-02-01

There is compelling evidence to support the rationale for managing children on intravenous antimicrobial therapy at home whenever possible, including parent and patient satisfaction, psychological well-being, return to school/employment, reductions in healthcare-associated infection and cost savings. As a joint collaboration between the BSAC and the British Paediatric Allergy, Immunity and Infection Group, we have developed good practice recommendations to highlight good clinical practice and governance within paediatric outpatient parenteral antibiotic therapy (p-OPAT) services across the UK. These guidelines provide a practical approach for safely delivering a p-OPAT service in both secondary care and tertiary care settings, in terms of the roles and responsibilities of members of the p-OPAT team, the structure required to deliver the service, identifying patients and pathologies that are suitable for p-OPAT, ensuring appropriate vascular access, antimicrobial choice and delivery and the clinical governance aspects of delivering a p-OPAT service. The process of writing a business case to support the introduction of a p-OPAT service is also addressed. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Transcriptomic immune response of Tenebrio molitor pupae to parasitization by Scleroderma guani.

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Jia-Ying Zhu

Full Text Available BACKGROUND: Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26% showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. CONCLUSIONS/SIGNIFICANCE: obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular

Transcriptomic immune response of Tenebrio molitor pupae to parasitization by Scleroderma guani.

Science.gov (United States)

Zhu, Jia-Ying; Yang, Pu; Zhang, Zhong; Wu, Guo-Xing; Yang, Bin

2013-01-01

Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE) analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26%) showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular understanding of the host-parasitoid interaction.

Transcriptomic Immune Response of Tenebrio molitor Pupae to Parasitization by Scleroderma guani

Science.gov (United States)

Zhu, Jia-Ying; Yang, Pu; Zhang, Zhong; Wu, Guo-Xing; Yang, Bin

2013-01-01

Background Host and parasitoid interaction is one of the most fascinating relationships of insects, which is currently receiving an increasing interest. Understanding the mechanisms evolved by the parasitoids to evade or suppress the host immune system is important for dissecting this interaction, while it was still poorly known. In order to gain insight into the immune response of Tenebrio molitor to parasitization by Scleroderma guani, the transcriptome of T. molitor pupae was sequenced with focus on immune-related gene, and the non-parasitized and parasitized T. molitor pupae were analyzed by digital gene expression (DGE) analysis with special emphasis on parasitoid-induced immune-related genes using Illumina sequencing. Methodology/Principal Findings In a single run, 264,698 raw reads were obtained. De novo assembly generated 71,514 unigenes with mean length of 424 bp. Of those unigenes, 37,373 (52.26%) showed similarity to the known proteins in the NCBI nr database. Via analysis of the transcriptome data in depth, 430 unigenes related to immunity were identified. DGE analysis revealed that parasitization by S. guani had considerable impacts on the transcriptome profile of T. molitor pupae, as indicated by the significant up- or down-regulation of 3,431 parasitism-responsive transcripts. The expression of a total of 74 unigenes involved in immune response of T. molitor was significantly altered after parasitization. Conclusions/Significance obtained T. molitor transcriptome, in addition to establishing a fundamental resource for further research on functional genomics, has allowed the discovery of a large group of immune genes that might provide a meaningful framework to better understand the immune response in this species and other beetles. The DGE profiling data provides comprehensive T. molitor immune gene expression information at the transcriptional level following parasitization, and sheds valuable light on the molecular understanding of the host

Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

Science.gov (United States)

Chotirmall, Sanjay H.; Al-Alawi, Mazen; Logan, P. Mark; Greene, Catherine M.; McElvaney, Noel G.

2013-01-01

Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit. PMID:23971044

Tailoring the Immune Response via Customization of Pathogen Gene Expression.

Science.gov (United States)

Runco, Lisa M; Stauft, Charles B; Coleman, J Robert

2014-01-01

The majority of studies focused on the construction and reengineering of bacterial pathogens have mainly relied on the knocking out of virulence factors or deletion/mutation of amino acid residues to then observe the microbe's phenotype and the resulting effect on the host immune response. These knockout bacterial strains have also been proposed as vaccines to combat bacterial disease. Theoretically, knockout strains would be unable to cause disease since their virulence factors have been removed, yet they could induce a protective memory response. While knockout strains have been valuable tools to discern the role of virulence factors in host immunity and bacterial pathogenesis, they have been unable to yield clinically relevant vaccines. The advent of synthetic biology and enhanced user-directed gene customization has altered this binary process of knockout, followed by observation. Recent studies have shown that a researcher can now tailor and customize a given microbe's gene expression to produce a desired immune response. In this commentary, we highlight these studies as a new avenue for controlling the inflammatory response as well as vaccine development.

Genodermatoses in paediatric age group

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Kumar Sunil

1996-01-01

Full Text Available Pattern of genodermatoses in paediatric age group was studied. The relative incidence of genodermatoses in paediatric dermatology out patient department was 0.62%. The commonest genodermatoses observed was ichthyosis.

Paediatric interventional radiology

International Nuclear Information System (INIS)

McLaren, Clare

2014-01-01

Paediatric interventional radiology (PIR) is a rapidly-growing subspecialty, which offers a wide range of procedures applicable to almost all areas of hospital paediatrics. There are many important differences between paediatric and adult practice in interventional radiology, including disease processes and treatment goals, anatomical considerations, periprocedural patient management, radiation exposure optimisation and legal aspects. The use of retrievable or absorbable interventional devices such as stents will probably become more widespread in PIR practice. Recent advances in the technology of imaging equipment have been accompanied by an increase in the complexity of the work done by the radiographer. These developments present challenges and opportunities related to training and maintenance of skills, staffing arrangements, and the potential for advanced practice. It is likely that specialisation in PIR will become a more common role for radiographers in the future

Immune response of T cells during herpes simplex virus type 1 (HSV-1) infection.

Science.gov (United States)

Zhang, Jie; Liu, Huan; Wei, Bin

Herpes simplex virus type 1 (HSV-1), a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine candidates for HSV-1.

The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase

DEFF Research Database (Denmark)

Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels

2009-01-01

BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance...... to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T...... of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals...

Adoptive transfer of natural antibodies to non-immunized chickens affects subsequent antigen-specific humoral and cellular immune responses

NARCIS (Netherlands)

Lammers, A.; Klomp, M.E.V.; Nieuwland, M.G.B.; Savelkoul, H.F.J.; Parmentier, H.K.

2004-01-01

To determine a regulatory function of natural antibodies in the immune response of chickens, pooled plasma obtained from non-immunized (naive) 15 months old hens was subjected to keyhole limpet hemocyanin (KLH) antigen-affinity chromatography. Purified KLH-binding antibodies were adoptively

Polysaccharides isolated from Açaí fruit induce innate immune responses.

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Jeff Holderness

2011-02-01

Full Text Available The Açaí (Acai fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

The Relationship Between Morphological Symmetry and Immune Response in Wild-Caught Adult Bush-Crickets

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Åsa Berggren

2009-09-01

Full Text Available Despite interest in the relationship between fluctuating asymmetry (FA, immune response and ecological factors in insects, little data are available from wild populations. In this study we measured FA and immune response in 370 wild-caught male bush-crickets, Metrioptera roeseli, from 20 experimentally introduced populations in southern-central Sweden. Individuals with more-symmetric wings had a higher immune response as measured by the cellular encapsulation of a surgically-implanted nylon monofilament. However, we found no relationship between measures of FA in other organs (i.e. tibia and maxillary palp and immune response, suggesting that this pattern may reflect differing selection pressures.

Augmenting Plant Immune Responses and Biological Control by Microbial Determinants

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Sang Moo Lee

2015-09-01

Full Text Available Plant have developed sophisticated defence mechanisms against microbial pathogens. The recent accumulated information allow us to understand the nature of plant immune responses followed by recognition of microbial factors/determinants through cutting-edge genomics and multi-omics techniques. However, the practical approaches to sustain plant health using enhancement of plant immunity is yet to be fully appreciated. Here, we overviewed the general concept and representative examples on the plant immunity. The fungal, bacterial, and viral determinants that was previously reported as the triggers of plant immune responses are introduced and described as the potential protocol of biological control. Specifically, the role of chitin, glucan, lipopolysaccharides/extracellular polysaccharides, microbe/pathogen-associated molecular pattern, antibiotics, mimic-phytohormones, N-acyl homoserine lactone, harpin, vitamins, and volatile organic compounds are considered. We hope that this review stimulates scientific community and farmers to broaden their knowledge on the microbial determinant-based biological control and to apply the technology on the integrated pest management program.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice

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Lluïsa Miró

2017-12-01

Full Text Available Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP, which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT in rodents challenged by S. aureus enterotoxin B (SEB, and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8 at different ages (compared to mice resistant to accelerated senescence; SAMR1. Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer’s patches (all, p < 0.05, as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05. With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05. However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

Qualitative and quantitative evaluation of donkeys responses to immunization by rabbits' IgG

International Nuclear Information System (INIS)

Hassan, A. M. E.; Saeed, A. M.

2012-12-01

In this study two apparently healthy donkeys were immunized with highly pure rabbit's 1gG using a revised protocol. Qualitative test using the same immuno gen was done as a primary test to eva lute the immune system response. However, the same 1gG was iodinated with 1 25I using chloramine T method and the labeled 1gG was used to quantitatively study the immune response. The two donkeys showed good response with the younger one having the best response. The obtained donkey anti rabbit sera was used as separating agent for RIA assay for human PRL. (Author)

L-carnitine: a partner between immune response and lipid metabolism ?

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Giuseppe Famularo

1993-01-01

Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

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

Science.gov (United States)

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

2017-09-15

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

Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice

International Nuclear Information System (INIS)

Cai Ping; Koenig, Rolf; Khan, M. Firoze; Kaphalia, Bhupendra S.; Ansari, G.A.S.

2007-01-01

Trichloroethene (TCE) is an industrial degreasing solvent and widespread environmental contaminant. Exposure to TCE is associated with autoimmunity. The mode of action of TCE is via its oxidative metabolism, and most likely, immunotoxicity is mediated via haptenization of macromolecules and subsequent induction of immune responses. To better understand the role of protein haptenization through TCE metabolism, we immunized MRL+/+ mice with albumin adducts of various TCE reactive intermediates. Serum immunoglobulins and cytokine levels were measured to determine immune responses against haptenized albumin. We found antigen-specific IgG responses of the IgG subtypes IgG 1 , IgG 2a , and IgG 2b , with IgG 1 predominating. Serum levels of G-CSF were increased in immunized mice, suggesting macrophage activation. Liver histology revealed lymphocyte infiltration in the lobules and the portal area following immunization with formyl-albumin. Our findings suggest that proteins haptenized by metabolites of TCE may act as neo-antigens that can induce humoral immune responses and T cell-mediated hepatitis

Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials.

Science.gov (United States)

Franz, Sandra; Rammelt, Stefan; Scharnweber, Dieter; Simon, Jan C

2011-10-01

A key for long-term survival and function of biomaterials is that they do not elicit a detrimental immune response. As biomaterials can have profound impacts on the host immune response the concept emerged to design biomaterials that are able to trigger desired immunological outcomes and thus support the healing process. However, engineering such biomaterials requires an in-depth understanding of the host inflammatory and wound healing response to implanted materials. One focus of this review is to outline the up-to-date knowledge on immune responses to biomaterials. Understanding the complex interactions of host response and material implants reveals the need for and also the potential of "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies of triggering appropriate immune responses by functional biomaterials and highlight recent approaches of biomaterials that mimic the physiological extracellular matrix and modify cellular immune responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

A focus on paediatric hypertension

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Pier Paolo Bassareo

2015-04-01

Full Text Available Hypertension can begin early in childhood, as occasional increases in blood pressure or abnormal blood pressure responses to physical or emotional stress. High blood pressure in juvenile age is defined as a blood pressure repeatedly above the 95th percentile of specific nomograms. Its worldwide prevalence ranges from 1% to about 10%. The purpose of this paper is to perform an overview about characteristics, diagnosis, risk factors, therapy, and prognosis of paediatric hypertension.

The nature of immune responses to urinary tract infections

Science.gov (United States)

Abraham, Soman N.; Miao, Yuxuan

2016-01-01

The urinary tract is constantly exposed to microorganisms that inhabit the gastrointestinal tract, but generally the urinary tract resists infection by gut microorganisms. This resistance to infection is mainly ascribed to the versatility of the innate immune defences in the urinary tract as the adaptive immune responses are limited, particularly when only the lower urinary tract is infected. In recent years, as the strengths and weaknesses of the immune system of the urinary tract have emerged and as the virulence attributes of uropathogens are recognized, several potentially effective and unconventional strategies to contain or prevent urinary tract infections have emerged. PMID:26388331

Immune responses of pigs inoculated with a recombinant fowlpox ...

African Journals Online (AJOL)

Yomi

2012-04-03

Apr 3, 2012 ... Key words: PCV2, rFPV, FMDV, immune response, prime-boost. .... After 10 min in the dark at room temperature, the color reaction was terminated with 50 µl of ..... ponses and improve memory and/or effector cell responses ...

Flavobacterium psychrophilum - Experimental challenge and immune response

DEFF Research Database (Denmark)

Henriksen, Maya Maria Mihályi

the immune system of the fry is not fully developed. Theoretically, the infection pressure could be subdued by vaccinating larger fish, but no commercial vaccine is yet available. Diagnostic methods are well described and the disease is treated with antibiotics. To prevent disease outbreaks and subsequent......-time PCR (RT-PCR) was used to examine the immune response in the head kidney during the first eight days after infection, and enzyme-linked immunosorbent assay (ELISA) was used to evaluate the production of antibodies 50 days post-exposure. A pro-inflammatory response was observed in both groups infected...... of edemas, but in both cases the tissue was regenerating after 192 hours. However, when the fish had been exposed to both H2O2 and F. psychrophilum, the damage was still evident at this time point. The relative pathogen load measured as 16S rRNA was highest at the first sampling and decreased steadily...

Interpretation of Chemical Pathology Test Results in Paediatrics ...

African Journals Online (AJOL)

At any time we interprete paediatric chemical pathology test results we must take into consideration a number of factors, which are related with and restricted to paediatric patients. Such factors include the paediatric patient's age that may change from prematurity to above 18 years, and the paediatric patient's body weight ...

Immune responses of poultry to Newcastle disease virus.

Science.gov (United States)

Kapczynski, Darrell R; Afonso, Claudio L; Miller, Patti J

2013-11-01

Newcastle disease (ND) remains a constant threat to poultry producers worldwide, in spite of the availability and global employment of ND vaccinations since the 1950s. Strains of Newcastle disease virus (NDV) belong to the order Mononegavirales, family Paramyxoviridae, and genus Avulavirus, are contained in one serotype and are also known as avian paramyxovirus serotype-1 (APMV-1). They are pleomorphic in shape and are single-stranded, non-segmented, negative sense RNA viruses. The virus has been reported to infect most orders of birds and thus has a wide host range. Isolates are characterized by virulence in chickens and the presence of basic amino acids at the fusion protein cleavage site. Low virulent NDV typically produce subclinical disease with some morbidity, whereas virulent isolates can result in rapid, high mortality of birds. Virulent NDV are listed pathogens that require immediate notification to the Office of International Epizootics and outbreaks typically result in trade embargos. Protection against NDV is through the use of vaccines generated with low virulent NDV strains. Immunity is derived from neutralizing antibodies formed against the viral hemagglutinin and fusion glycoproteins, which are responsible for attachment and spread of the virus. However, new techniques and technologies have also allowed for more in depth analysis of the innate and cell-mediated immunity of poultry to NDV. Gene profiling experiments have led to the discovery of novel host genes modulated immediately after infection. Differences in virus virulence alter host gene response patterns have been demonstrated. Furthermore, the timing and contributions of cell-mediated immune responses appear to decrease disease and transmission potential. In view of recent reports of vaccine failure from many countries on the ability of classical NDV vaccines to stop spread of disease, renewed interest in a more complete understanding of the global immune response of poultry to NDV will be

Immune Response among Patients Exposed to Molds

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Jordan N. Fink

2009-12-01

Full Text Available Macrocyclic trichothecenes, mycotoxins produced by Stachybotrys chartarum, have been implicated in adverse reactions in individuals exposed to mold-contaminated environments. Cellular and humoral immune responses and the presence of trichothecenes were evaluated in patients with mold-related health complaints. Patients underwent history, physical examination, skin prick/puncture tests with mold extracts, immunological evaluations and their sera were analyzed for trichothecenes. T-cell proliferation, macrocyclic trichothecenes, and mold specific IgG and IgA levels were not significantly different than controls; however 70% of the patients had positive skin tests to molds. Thus, IgE mediated or other non-immune mechanisms could be the cause of their symptoms.

Hepatitis B Virus Vaccine immune response in Egyptian children 15 ...

African Journals Online (AJOL)

Egypt J Pediatr Allergy Immunol 2015;13(2):45-48. 45. Hepatitis B Virus Vaccine immune response in Egyptian children 15-17 years after primary immunization; should we provide a booster dose? INTRODUCTION. Hepatitis B virus (HBV) infection is a global public health problem. With approximately 350 million hepatitis B ...

THE IMPACT OF PERSISTENT HERPESVIRUS INFECTION ON IMMUNITY AND VACCINATION RESPONSE

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Volyanskiy AYu

2016-09-01

Full Text Available In this review we summarize current knowledge on the ability of latent herpesviruses to modulate the immunity and response to vaccination. Nearly all humans are latently infected with multiple herpesviruses but little is known about virus-host interactions. Meanwhile, the study of the immune response to Epshtein-Barr virus (EBV and сytomegalovirus (CMV has revealed significant regulatory effects on the immune system. During the primary infection a human cytomegalovirus is predominately found in peripheral blood monocytes and polymorphonuclear leukocytes. However, the virus can not be replicated in these cells. CMV induces the survival and differentiation of infected monocytes into long-lived macrophages capable of supporting viral replication and the release of virions, which infect CD34+ myeloid progenitor cells. CMV latently persists in myeloid progenitor cells and monocytes and reactivates during their differentiation into macrophages. CMV-infected monocytes exhibit a unique reprogramming of their differentiation and secret both pro-inflammatory M1- and anti-inflammatory M2-associated cytokines. But cytomegalovirus induced macrophage phenotype skewed towards pro-inflammatory M1 type. MV has profound effects on the composition and function of both T cells and NK cells. CMV constantly reactivates during differentiation of monocytes into macrophages. Consequently, persons with latent CMV infection have substantially increased numbers and proportions of CD8+ T cells that lead to exhaustion and an early onset of immunosenescence. Also, it has been shown that the latent CMV virus infection markedly increases the proportion of NK cells expressing the activating NKG2C receptor. So, it has been proposed that CMV alters the composition of T cell and NK cell subsets and accelerates immune aging. Given the capacity of CMV to alter a macrophage, as well as NK and T cell responses it is reasonable to hypothesize that latent infection would alter the

Tertiary paediatric emergency department use in children and young people with cerebral palsy.

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Meehan, Elaine; Reid, Susan M; Williams, Katrina; Freed, Gary L; Babl, Franz E; Sewell, Jillian R; Rawicki, Barry; Reddihough, Dinah S

2015-10-01

The aim of this study was to describe the pattern of tertiary paediatric emergency department (ED) use in children and young people with cerebral palsy (CP). A retrospective analysis of ED data routinely collected at the two tertiary paediatric hospitals in Victoria, Australia, cross-matched with the Victorian Cerebral Palsy Register. Data pertaining to the ED presentations of 2183 registered individuals born 1993-2008 were obtained. Between 2008 and 2012, 37% (n = 814) of the CP cohort had 3631 tertiary paediatric ED presentations. Overall, 40% (n = 332) of presenters were residing in inner metropolitan Melbourne; 44% (n = 356) in outer Melbourne; and 13% (n = 108) in regional Victoria. Presenters were more likely than non-presenters to be younger, non-ambulant and have epilepsy. In total, 71% of presentations were triaged as Australasian Triage Scale 1-3 (urgent), and 44% resulted in a hospital admission. Disorders of the respiratory, neurological and gastrointestinal systems, and medical device problems were responsible for 72% of presentations. Many of the tertiary paediatric ED presentations in this group were appropriate based on the high admission rate and the large proportion triaged as urgent. However, there is evidence that some families are bypassing local services and travelling long distances to attend the tertiary paediatric ED, even for less urgent complaints that do not require hospital admission. Alternative pathways of care delivery, and strategies to promote the management of common problems experienced by children and young people with CP in non-paediatric EDs or primary care settings, may go some way towards reducing unnecessary tertiary paediatric ED use in this group. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity

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Eiji Yuba

2017-11-01

Full Text Available (1 Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2 Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3 Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4 Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

Drugs for the paediatric heart

African Journals Online (AJOL)

Head, Paediatric Cardiology Service of the Western Cape, Department of Paediatrics and Child Health, ... His interests also include the care of complex patients ... The pharmacy only has enalapril available – can you substitute this drug for the ...

Ebola Virus Glycoprotein Induces an Innate Immune Response In vivo via TLR4

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Chih-Yun Lai

2017-08-01

Full Text Available Ebola virus (EBOV, a member of the Filoviridae family, causes the most severe form of viral hemorrhagic fever. Although no FDA licensed vaccine or treatment against Ebola virus disease (EVD is currently available, Ebola virus glycoprotein (GP is the major antigen used in all candidate Ebola vaccines. Recent reports of protection as quickly as within 6 days of administration of the rVSV-based vaccine expressing EBOV GP before robust humoral responses were generated suggests that the innate immune responses elicited early after vaccination may contribute to the protection. However, the innate immune responses induced by EBOV GP in the absence of viral vectors or adjuvants have not been fully characterized in vivo. Our recent studies demonstrated that immunization with highly purified recombinant GP in the absence of adjuvants induced a robust IgG response and partial protection against EBOV infection suggesting that GP alone can induce protective immunity. In this study we investigated the early immune response to purified EBOV GP alone in vitro and in vivo. We show that GP was efficiently internalized by antigen presenting cells and subsequently induced production of key inflammatory cytokines. In vivo, immunization of mice with EBOV GP triggered the production of key Th1 and Th2 innate immune cytokines and chemokines, which directly governed the recruitment of CD11b+ macrophages and CD11c+ dendritic cells to the draining lymph nodes (DLNs. Pre-treatment of mice with a TLR4 antagonist inhibited GP-induced cytokine production and recruitment of immune cells to the DLN. EBOV GP also upregulated the expression of costimulatory molecules in bone marrow derived macrophages suggesting its ability to enhance APC stimulatory capacity, which is critical for the induction of effective antigen-specific adaptive immunity. Collectively, these results provide the first in vivo evidence that early innate immune responses to EBOV GP are mediated via the TLR4

Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response

Science.gov (United States)

Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J.; Repasky, Elizabeth A.; Hylander, Bonnie L.

2018-01-01

An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed. Generally, an acute stress response is beneficial but chronic stress is detrimental because it suppresses the activities of effector immune cells while increasing the activities of immunosuppressive cells. In this review, we first discuss the underlying biology of adrenergic signaling in cells of both the innate and adaptive immune system. We then focus on the effects of chronic adrenergic stress in promoting tumor growth, giving examples of effects on tumor cells and immune cells, explaining the methods commonly used to induce stress in preclinical mouse models. We highlight how this relates to our observations that mandated housing conditions impose baseline chronic stress on mouse models, which is sufficient to cause chronic immunosuppression. This problem is not commonly recognized, but it has been shown to impact conclusions of several studies of mouse physiology and mouse models of disease. Moreover, the fact that preclinical mouse models are chronically immunosuppressed has critical ramifications for analysis of any experiments with an immune component. Our group has found that reducing adrenergic stress by housing mice at thermoneutrality or treating mice housed at cooler temperatures with β-blockers reverses immunosuppression and significantly improves responses to checkpoint inhibitor immunotherapy. These observations are clinically relevant because there are numerous retrospective epidemiological studies concluding that cancer patients who were

Paediatric traumatic cardiac arrest: a Delphi study to establish consensus on definition and management.

Science.gov (United States)

Rickard, Annette C; Vassallo, James; Nutbeam, Tim; Lyttle, Mark D; Maconochie, Ian K; Enki, Doyo G; Smith, Jason E

2018-04-28

Paediatric traumatic cardiac arrest (TCA) is associated with low survival and poor outcomes. The mechanisms that underlie TCA are different from medical cardiac arrest; the approach to treatment of TCA may therefore also need to differ to optimise outcomes. The aim of this study was to explore the opinion of subject matter experts regarding the diagnosis and treatment of paediatric TCA, and to reach consensus on how best to manage this group of patients. An online Delphi study was conducted over three rounds, with the aim of achieving consensus (defined as 70% agreement) on statements related to the diagnosis and management of paediatric TCA. Participants were invited from paediatric and adult emergency medicine, paediatric anaesthetics, paediatric ICU and paediatric surgery, as well as Paediatric Major Trauma Centre leads and representatives from the Resuscitation Council UK. Statements were informed by literature reviews and were based on elements of APLS resuscitation algorithms as well as some concepts used in the management of adult TCA; they ranged from confirmation of cardiac arrest to the indications for thoracotomy. 73 experts completed all three rounds between June and November 2016. Consensus was reached on 14 statements regarding the diagnosis and management of paediatric TCA; oxygenation and ventilatory support, along with rapid volume replacement with warmed blood, improve survival. The duration of cardiac arrest and the lack of a response to intervention, along with cardiac standstill on ultrasound, help to guide the decision to terminate resuscitation. This study has given a consensus-based framework to guide protocol development in the management of paediatric TCA, though further work is required in other key areas including its acceptability to clinicians. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Radiation-induced augmentation of the immune response

International Nuclear Information System (INIS)

Anderson, R.E.; Lefkovits, I.; Troup, G.M.

1980-01-01

Radiation-induced augmentation of the immune response has been shown to occur both in vivo and in vitro. Evidence is presented to implicate injury to an extremely radiosensitive T cell in the expression of this phenomenon. Experiments are outlined which could be employed to support or reflect this hypothesis

Platelets in Immune Response to Virus and Immunopathology of Viral Infections

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Eugenio D. Hottz

2018-04-01

Full Text Available Platelets are essential effector cells in hemostasis. Aside from their role in coagulation, platelets are now recognized as major inflammatory cells with key roles in the innate and adaptive arms of the immune system. Activated platelets have key thromboinflammatory functions linking coagulation to immune responses in various infections, including in response to virus. Recent studies have revealed that platelets exhibit several pattern recognition receptors (PRR including those from the toll-like receptor, NOD-like receptor, and C-type lectin receptor family and are first-line sentinels in detecting and responding to pathogens in the vasculature. Here, we review the main mechanisms of platelets interaction with viruses, including their ability to sustain viral infection and replication, their expression of specialized PRR, and activation of thromboinflammatory responses against viruses. Finally, we discuss the role of platelet-derived mediators and platelet interaction with vascular and immune cells in protective and pathophysiologic responses to dengue, influenza, and human immunodeficiency virus 1 infections.

Isotope-based immunological techniques. Their use in assessment of immune competence and the study of immune responses to pathogens

International Nuclear Information System (INIS)

Duffus, W.P.H.

1984-01-01

The influence of isotope-based techniques on both assessment of immune competence and immune response to pathogens is discussed. Immunodeficiencies acquired as a result of factors like malnutrition and concomitant disease can severely affect not only attempts to intensify and improve production but also successful immune response against important vaccines such as rinderpest and foot-and-mouth disease. Isotope-based techniques, with their accuracy, speed and small sample volume, are ideally suited for assessing immunocompetence. One of the main drawbacks remains antigen purity, an area where research should now be concentrated. Lymphocyte transformation is widely used to assess cell-mediated immuno-competence but techniques to assess biological functions such as phagocytosis and cell-mediated cytotoxicity could more usefully reflect immune status. These latter techniques utilize isotopes such as 3 H, 14 C, 32 P and 125 I. Investigation of specific cell-mediated immune response often requires a labelled target. Suitable isotopes such as 51 Cr, 99 Tcsup(m), 75 Se and 3 H are compared for their capacity to label both mammalian and parasite targets. Suggestions are made on a number of areas of research that might usefully be encouraged and supported in order to improve applied veterinary immunology in tropical countries. (author)

DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

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Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

The specificity of targeted vaccines for APC surface molecules influences the immune response phenotype.

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Gunnveig Grødeland

Full Text Available Different diseases require different immune responses for efficient protection. Thus, prophylactic vaccines should prime the immune system for the particular type of response needed for protection against a given infectious agent. We have here tested fusion DNA vaccines which encode proteins that bivalently target influenza hemagglutinins (HA to different surface molecules on antigen presenting cells (APC. We demonstrate that targeting to MHC class II molecules predominantly induced an antibody/Th2 response, whereas targeting to CCR1/3/5 predominantly induced a CD8(+/Th1 T cell response. With respect to antibodies, the polarizing effect was even more pronounced upon intramuscular (i.m delivery as compared to intradermal (i.d. vaccination. Despite these differences in induced immune responses, both vaccines protected against a viral challenge with influenza H1N1. Substitution of HA with ovalbumin (OVA demonstrated that polarization of immune responses, as a consequence of APC targeting specificity, could be extended to other antigens. Taken together, the results demonstrate that vaccination can be tailor-made to induce a particular phenotype of adaptive immune responses by specifically targeting different surface molecules on APCs.

The development of paediatric neuroradiology

International Nuclear Information System (INIS)

Harwood-Nash, D.C.

1978-01-01

The development of paediatric neuroradiology is a specific persuasion within neuroradiology and has increased in scope and significance throughout the last ten years. The emergence of computed tomography has altered the indications for types of neuroradiological procedures in infants and children. The sophistication, accuracy, and safety of standard neuroradiological procedures have been increased by the accuracy and safety of computed tomography, particularly in the premature infant. There is a growing need for education and instruction in paediatric neuroradiological techniques and paediatric neuroradiological diseases within the neuroradiological fraternity as a whole. (orig.) [de

Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

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Sanjay H. Chotirmall

2013-01-01

Full Text Available Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

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Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

2013-11-01

Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

An Organismal Model for Gene Regulatory Networks in the Gut-Associated Immune Response

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Katherine M. Buckley

2017-10-01

Full Text Available The gut epithelium is an ancient site of complex communication between the animal immune system and the microbial world. While elements of self-non-self receptors and effector mechanisms differ greatly among animal phyla, some aspects of recognition, regulation, and response are broadly conserved. A gene regulatory network (GRN approach provides a means to investigate the nature of this conservation and divergence even as more peripheral functional details remain incompletely understood. The sea urchin embryo is an unparalleled experimental model for detangling the GRNs that govern embryonic development. By applying this theoretical framework to the free swimming, feeding larval stage of the purple sea urchin, it is possible to delineate the conserved regulatory circuitry that regulates the gut-associated immune response. This model provides a morphologically simple system in which to efficiently unravel regulatory connections that are phylogenetically relevant to immunity in vertebrates. Here, we review the organism-wide cellular and transcriptional immune response of the sea urchin larva. A large set of transcription factors and signal systems, including epithelial expression of interleukin 17 (IL17, are important mediators in the activation of the early gut-associated response. Many of these have homologs that are active in vertebrate immunity, while others are ancient in animals but absent in vertebrates or specific to echinoderms. This larval model provides a means to experimentally characterize immune function encoded in the sea urchin genome and the regulatory interconnections that control immune response and resolution across the tissues of the organism.

Paediatric fever management: continuing education for clinical nurses.

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Walsh, Anne M; Edwards, Helen E; Courtney, Mary D; Wilson, Jenny E; Monaghan, Sarah J

2006-01-01

This study examined the influence of level of practice, additional paediatric education and length of paediatric and current experience on nurses' knowledge of and beliefs about fever and fever management. Fifty-one nurses from medical wards in an Australian metropolitan paediatric hospital completed a self-report descriptive survey. Knowledge of fever management was mediocre (Mean 12.4, SD 2.18 on 20 items). Nurses practicing at a higher level and those with between one and four years paediatric or current experience were more knowledgeable than novices or more experienced nurses. Negative beliefs that would impact nursing practice were identified. Interestingly, beliefs about fever, antipyretic use in fever management and febrile seizures were similar; they were not influenced by nurses' knowledge, experience, education or level of practice. Paediatric nurses are not expert fever managers. Knowledge deficits and negative attitudes influence their practice irrespective of additional paediatric education, paediatric or current experience or level of practice. Continuing education is therefore needed for all paediatric nurses to ensure the latest clear evidence available in the literature for best practice in fever management is applied.

Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine

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Dai, Zhihong [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); China Institute of Veterinary Drug Control, Beijing 100081 (China); Zhang, Quan [College of Veterinary Medicine, Yangzhou University, Yangzhou 225009 (China); Wang, Zaishi [China Institute of Veterinary Drug Control, Beijing 100081 (China); Zhang, Zhongqiu [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Veterinary Bureau, Ministry of Agriculture of the People' s Republic of China, Beijing 100125 (China); Guo, Pengju [Institute of Veterinary Medicine, Guangdong Academy of Agricultural Sciences, Guangdong 510640 (China); Zhao, Deming, E-mail: zhaodm@cau.edu.cn [State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

2011-11-11

Highlights: Black-Right-Pointing-Pointer We investigated the immunoadjuvant effects of HVJ-E on killed PRRSV vaccine. Black-Right-Pointing-Pointer HVJ-E enhanced the humoral and cellular responses of the piglets to PRRSV. Black-Right-Pointing-Pointer It is suggested that HVJ-E could be developed as a new-type adjuvant for mammals. -- Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-{gamma} production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.

Defective B cell response to T-dependent immunization in lupus-prone mice

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Niu, Haitao; Sobel, Eric S.; Morel, Laurence

2009-01-01

Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209

Prevalence of local immune response against oral infection in a Drosophila/Pseudomonas infection model.

Directory of Open Access Journals (Sweden)

Peter Liehl

2006-06-01

Full Text Available Pathogens have developed multiple strategies that allow them to exploit host resources and resist the immune response. To study how Drosophila flies deal with infectious diseases in a natural context, we investigated the interactions between Drosophila and a newly identified entomopathogen, Pseudomonas entomophila. Flies orally infected with P. entomophila rapidly succumb despite the induction of both local and systemic immune responses, indicating that this bacterium has developed specific strategies to escape the fly immune response. Using a combined genetic approach on both host and pathogen, we showed that P. entomophila virulence is multi-factorial with a clear differentiation between factors that trigger the immune response and those that promote pathogenicity. We demonstrate that AprA, an abundant secreted metalloprotease produced by P. entomophila, is an important virulence factor. Inactivation of aprA attenuated both the capacity to persist in the host and pathogenicity. Interestingly, aprA mutants were able to survive to wild-type levels in immune-deficient Relish flies, indicating that the protease plays an important role in protection against the Drosophila immune response. Our study also reveals that the major contribution to the fly defense against P. entomophila is provided by the local, rather than the systemic immune response. More precisely, our data points to an important role for the antimicrobial peptide Diptericin against orally infectious Gram-negative bacteria, emphasizing the critical role of local antimicrobial peptide expression against food-borne pathogens.

Consultant paediatric outreach clinics--a practical step in integration.

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Spencer, N J

1993-04-01

Ten years' experience of paediatric outreach clinics is reviewed and evaluated. The advantages and disadvantages of paediatric outreach and its possible place in the new era of contracting and more developed community paediatric services are discussed. It is concluded that paediatric outreach increases parental and professional choice and access to paediatric consultant services, increases service flexibility, reduces unnecessary hospital visits, and enables more rational and relevant clinical decision making. Outreach is particularly relevant in areas of deprivation where paediatric needs are greatest.

MECHANISMS OF IMMUNE RESPONSES IN CNIDARIANS

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Iván Darío Ocampo

2015-05-01

Full Text Available The immune system maintains the integrity of the organisms through a complex network of molecules, cells, and tissues that recognize internal or external antigenic substances to neutralized and eliminate them. The mechanisms of immune response have evolved in a modular fashion, where members of a given module interact strongly among them, but weakly with members of other modules, providing robustness and evolvability to the immune system. Ancestral modules are the raw material for the generation of new modules through evolution. Thus, the study of immune systems in basal metazoans such as cnidarians seeks to determine the basic tool kit from which the metazoans started to construct their immune systems. In addition, understanding the immune mechanisms in cnidarians contributes to decipher the etiopathology of coral diseases of infectious nature that are affecting coral reefs worldwide. RESUMEN El sistema inmune mantiene la integridad de los organismos vivos por medio de una red compleja de moléculas, células y tejidos que reconocen sustancias antigénicas internas o externas para neutralizarlas y eliminarlas. Los mecanismos de respuesta inmune han evolucionado de una manera modular, en donde miembros de un módulo dado interactúan fuertemente entre sí, pero débilmente con componentes de otros módulos, otorgando así robustez y potencial evolutivo al sistema inmune. Módulos ancestrales representan el material básico para la generación de nuevos módulos durante el proceso evolutivo. Así, el estudio de sistemas inmunes en metazoarios basales como los cnidarios busca determinar cuales son los módulos ancestrales a partir de los cuales se constituyen los sistemas inmunes de animales derivados. Adicionalmente, el entendimiento de los mecanismos de respuesta inmune en cnidarios eventualmente contribuirá a descifrar la etiopatología de las enfermedades de corales de carácter infeccioso que está afectando los corales en el mundo.

Hypocretin/orexin loss changes the hypothalamic immune response.

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Tanaka, Susumu; Takizawa, Nae; Honda, Yoshiko; Koike, Taro; Oe, Souichi; Toyoda, Hiromi; Kodama, Tohru; Yamada, Hisao

2016-10-01

Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy. Copyright © 2016 Elsevier Inc. All

CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets

DEFF Research Database (Denmark)

Martel, Cyril Jean-Marie; Agger, Else Marie; Poulsen, Julie Juul

2011-01-01

response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different...

Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-16-2-0032 TITLE: Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL INVESTIGATOR...CONTRACT NUMBER Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0032 5c. PROGRAM ELEMENT...cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach. During the first

Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response.

Science.gov (United States)

Westendorp, B Florien; Büller, Nikè V J A; Karpus, Olga N; van Dop, Willemijn A; Koster, Jan; Versteeg, Rogier; Koelink, Pim J; Snel, Clinton Y; Meisner, Sander; Roelofs, Joris J T H; Uhmann, Anja; Ver Loren van Themaat, Emiel; Heijmans, Jarom; Hahn, Heidi; Muncan, Vanesa; Wildenberg, Manon E; van den Brink, Gijs R

2018-01-01

Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation. Hedgehog activity was modulated genetically in both cell type-specific and body-wide models and the resulting animals were analyzed for gene expression profiles and sensitivity for dextran sodium sulfate (DSS) colitis. To characterize the Hedgehog target cell, Gli1-CreERT2-Rosa26-ZsGreen animals were generated, which express ZsGreen in all Hedgehog-responsive cells. These cells were characterized using flow cytometry and immunofluorescence. Loss of Indian Hedgehog from the intestinal epithelium resulted in a rapid increase in expression of inflammation-related genes, accompanied by increased influx of immune cells. Animals with epithelium-specific deletion of Ihh or lacking the Hedgehog receptor Smoothened from Hedgehog target cells were more sensitive to DSS colitis. In contrast, specific deletion of Smoothened in the myeloid compartment did not alter the response to DSS. This suggests that Hedgehog signaling does not repress intestinal immunity through an effect on myeloid cells. Indeed, we found that Hedgehog-responsive cells expressed gp38, smooth muscle actin, and desmin, indicating a fibroblastic nature. Ihh signaling inhibited expression of C-X-C motif chemokine ligand 12 (CXCL12) in fibroblasts in vitro and in vivo, thereby impairing the recruitment of immune cells. We show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast

Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses

OpenAIRE

Holderness, Jeff; Schepetkin, Igor A.; Freedman, Brett; Kirpotina, Liliya N.; Quinn, Mark T.; Hedges, Jodi F.; Jutila, Mark A.

2011-01-01

The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fr...

T cell-derived Lymphotoxin is Essential for anti-HSV-1 Humoral Immune Response.

Science.gov (United States)

Yang, Kaiting; Liang, Yong; Sun, Zhichen; Xue, Diyuan; Xu, Hairong; Zhu, Mingzhao; Fu, Yang-Xin; Peng, Hua

2018-05-09

B cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin-β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute HSV-1 infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells. Using bone marrow chimeric mice and adoptive transplantation, we determined that T cell-derived LT played an indispensable role in the humoral immune response to HSV-1. Up-regulation of IFNγ by the LTβR-Ig blockade impairs the sustainability of Tfh-like cells, thus leading to an impaired humoral immune response. Our findings have identified a novel role of T cell-derived LT in the humoral immune response against HSV-1 infection. IMPORTANCE Immunocompromised people are susceptible for HSV-1 infection and lethal recurrence, which could be inhibited by anti-HSV-1 humoral immune response in the host. This study sought to explore the role of T cell-derived LT in the anti-HSV-1 humoral immune response using LT-LTβR signaling deficient mice and the LTβR-Ig blockade. The data indicate that the T cell-derived LT may play an essential role in sustaining Tfh-like cells and ensure Tfh-like cells' migration into primary or secondary follicles for further maturation. This study provides insights for vaccine development against infectious diseases. Copyright © 2018 American Society for Microbiology.

Effect of produced water on cod (Gadus morhua) immune responses

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Hamoutene, D.; Mabrouk, G.; Samuelson, S.; Mansour, A.; Lee, K. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Maritimes Region, Ocean Sciences Division; Volkoff, H.; Parrish, C. [Memorial Univ. of Newfoundland, St. John' s, NL (Canada); Mathieu, A. [Oceans Ltd., St. John' s, NL (Canada)

2007-07-01

Studies have shown that produced water (PW) discharged from North Sea offshore platforms affects the biota at greater distances from operational platforms than originally presumed. According to PW dispersion simulations, dilution by at least 240 times occurs within 50-100 m, and up to 9000 times by 20 km from the discharge. In this study, the effect of PW on cod immunity was investigated by exposing fish to 0, 100 ppm (x 10,000 dilution) or 200 ppm (x 500) of PW for 76 days. Immune responses were evaluated at the end of the exposure. Fish from the 3 groups were injected with Aeromonas salmonicida lipopolysaccharides (LPS). Blood cell observation and flow cytometry were used to investigate the serum cortisol levels and gill histology along with ratios and respiratory burst (RB) responses of both circulating and head-kidney white blood cells (WBCs). The study revealed that baseline immunity and stress response were not affected by PW, other than an irritant-induced change in gill cells found in treated cod. In all groups, LPS injection resulted in a pronounced decrease in RB of head-kidney cells and an increase in serum cortisol and protein levels. However, the group exposed to 200 ppm of PW exhibited the most significant changes. LPS injection was also shown to influence WBC ratios, but further studies are needed to determine if this impact is stronger in fish exposed to PW. This study suggested an effect of PW on cod immunity after immune challenge with LPS.

Tetranychus urticae mites do not mount an induced immune response against bacteria.

Science.gov (United States)

Santos-Matos, Gonçalo; Wybouw, Nicky; Martins, Nelson E; Zélé, Flore; Riga, Maria; Leitão, Alexandre B; Vontas, John; Grbić, Miodrag; Van Leeuwen, Thomas; Magalhães, Sara; Sucena, Élio

2017-06-14

The genome of the spider mite Tetranychus urticae , a herbivore, is missing important elements of the canonical Drosophila immune pathways necessary to fight bacterial infections. However, it is not known whether spider mites can mount an immune response and survive bacterial infection. In other chelicerates, bacterial infection elicits a response mediated by immune effectors leading to the survival of infected organisms. In T. urticae , infection by either Escherichia coli or Bacillus megaterium did not elicit a response as assessed through genome-wide transcriptomic analysis. In line with this, spider mites died within days even upon injection with low doses of bacteria that are non-pathogenic to Drosophila Moreover, bacterial populations grew exponentially inside the infected spider mites. By contrast, Sancassania berlesei , a litter-dwelling mite, controlled bacterial proliferation and resisted infections with both Gram-negative and Gram-positive bacteria lethal to T. urticae This differential mortality between mite species was absent when mites were infected with heat-killed bacteria. Also, we found that spider mites harbour in their gut 1000-fold less bacteria than S. berlesei We show that T. urticae has lost the capacity to mount an induced immune response against bacteria, in contrast to other mites and chelicerates but similarly to the phloem feeding aphid Acyrthosiphon pisum Hence, our results reinforce the putative evolutionary link between ecological conditions regarding exposure to bacteria and the architecture of the immune response. © 2017 The Authors.

A mixed methods evaluation of paediatric trainee preparedness to manage cardiopulmonary arrests.

Science.gov (United States)

Walsh, Órla; Lydon, Sinéad; O'Connor, Paul

2017-12-01

Paediatric cardiopulmonary arrest (CPA) survival rates are strongly linked to the training of the doctors responding to the event. This study sought to characterise the level of experience in managing CPAs among paediatric trainees and to investigate the nontechnical (NTS) required to effectively lead a paediatric CPA team. A mixed-methods research design was used. For the quantitative phase, a questionnaire was developed to assess training, confidence, and experiences related to CPA management. During the qualitative phase, 17 paediatric trainees participated in a series of critical incident technique (CIT) interviews to explore the NTS used during the management of paediatric CPAs. A total of 56 of 131 (37.1% response rate) trainees responded to the preparedness questionnaire. A total of 48.2% of respondents expressed low confidence in their skill as a team leader during the management of a CPA. The CIT interviews highlighted deficiencies in specific NTS (identifying options, prioritising, and identifying and utilising resources). Our results indicate that there is a desire for more training in CPA management among paediatric trainees, in particular as a team leader, which includes a focus on key NTS. What is Known • Levels of preparedness to be a paediatric cardiopulmonary arrests team member/leader are generally lower than desirable. • The importance of nontechnical skills to the effective performance of adult cardiopulmonary arrests teams has been identified. What is New • Levels of preparedness to be a cardiopulmonary arrests team member were higher than reported in US studies. • There is a need for greater training in cardiopulmonary arrest management which includes a focus on key nontechnical skills to include identifying options, prioritising, identifying and utilising resources.

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

Directory of Open Access Journals (Sweden)

Ruth Pye

2018-02-01

Full Text Available Devil facial tumor disease (DFTD is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33, these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol® and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of

Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

Science.gov (United States)

Pye, Ruth; Patchett, Amanda; McLennan, Elspeth; Thomson, Russell; Carver, Scott; Fox, Samantha; Pemberton, David; Kreiss, Alexandre; Baz Morelli, Adriana; Silva, Anabel; Pearse, Martin J.; Corcoran, Lynn M.; Belov, Katherine; Hogg, Carolyn J.; Woods, Gregory M; Lyons, A. Bruce

2018-01-01

Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti

The effect of doxycycline treatment on the postvaccinal immune response in pigs

International Nuclear Information System (INIS)

Pomorska-Mól, Małgorzata; Kwit, Krzysztof; Markowska-Daniel, Iwona; Pejsak, Zygmunt

2014-01-01

The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n = 10), control vaccinated (CV, n = 20), and experimental — received doxycycline (DOXY, n = 20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day − 1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8 + cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications. - Highlights: • We examine the postvaccinal immune response in pigs treated with doxycycline. • Doxycycline negatively influenced the specific proliferation after recall stimulation. • Doxycycline negatively influenced secretion of IFN-γ after recall stimulation. • The lower number of

The effect of doxycycline treatment on the postvaccinal immune response in pigs

Energy Technology Data Exchange (ETDEWEB)

Pomorska-Mól, Małgorzata, E-mail: mpomorska@piwet.pulawy.pl; Kwit, Krzysztof; Markowska-Daniel, Iwona; Pejsak, Zygmunt

2014-07-01

The effect of a seven-day antibiotic therapy with doxycycline was investigated on the postvaccinal humoral and cellular immune response in pigs. The selected parameters of non-specific immunity were also studied. Fifty pigs were used (control not vaccinated (C, n = 10), control vaccinated (CV, n = 20), and experimental — received doxycycline (DOXY, n = 20)). For vaccination live-attenuated vaccine against pseudorabies (PR) was used. From day − 1 to day 5 pigs from DOXY group received doxycycline orally with drinking water, at the recommended dose. Pigs from DOXY and CV groups were vaccinated at 8 and 10 weeks of age. The results of the present study showed that cell-mediated postvaccinal immune response can be modulated by oral treatment with doxycycline. Significantly lower values of stimulation index were observed after PRV restimulation in doxycycline-treated pigs. Moreover, in the DOXY group a significant decrease in IFN-γ production after PRV restimulation was noted. The significantly lower number of CD4+CD8 + cells was also observed in doxy-treated, vaccinated pigs, 2 weeks after final vaccination. Simultaneously, specific humoral response was not disturbed. This study demonstrated the importance of defining the immune modulatory activity of doxycycline because it may alter the immune responses to vaccines. The exact mechanism of T-cell response suppression by doxycycline remains to be elucidated, however the influence of doxycycline on the secretion of various cytokines, including IFN-γ, may be considered as a possible cause. The present observations should prompt further studies on the practical significance of such phenomena in terms of clinical implications. - Highlights: • We examine the postvaccinal immune response in pigs treated with doxycycline. • Doxycycline negatively influenced the specific proliferation after recall stimulation. • Doxycycline negatively influenced secretion of IFN-γ after recall stimulation. • The lower number of

Maternal nutritional status during pregnancy and infant immune response to routine childhood vaccinations.

Science.gov (United States)

Obanewa, Olayinka; Newell, Marie-Louise

2017-09-01

To systematically review the association between maternal nutritional status in pregnancy and infant immune response to childhood vaccines. We reviewed literature on maternal nutrition during pregnancy, fetal immune system and vaccines and possible relationships. Thereafter, we undertook a systematic review of the literature of maternal nutritional status and infant vaccine response, extracted relevant information, assessed quality of the nine papers identified and present findings in a narrative format. From limited evidence of average quality, intrauterine nutrition deficiency could lead to functional deficit in the infant's immune function; child vaccine response may thus be negatively affected by maternal malnutrition. Response to childhood vaccination may be associated with fetal and early life environment; evaluation of programs should take this into account.

A Mathematical Model of Skeletal Muscle Disease and Immune Response in the mdx Mouse

Directory of Open Access Journals (Sweden)

Abdul Salam Jarrah

2014-01-01

Full Text Available Duchenne muscular dystrophy (DMD is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.

Metabolic and adaptive immune responses induced in mice infected ...

African Journals Online (AJOL)

This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

Marketing paediatric influenza vaccination: results of a major metropolitan trial.

Science.gov (United States)

Van Buynder, Paul G; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily

2011-01-01

After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Advertising occurred in major statewide newspapers, via public poster displays and static 'eye-lite' displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web-sites. Parents were subsequently surveyed to assess reasons for vaccination. The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community 'myths' about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. © 2010 Blackwell Publishing Ltd.

Aberrant cellular immune responses in humans infected persistently with parvovirus B19

DEFF Research Database (Denmark)

Isa, Adiba; Norbeck, Oscar; Hirbod, Taha

2006-01-01

A subset of parvovirus B19 (B19) infected patients retains the infection for years, as defined by detection of B19 DNA in bone marrow. Thus far, analysis of B19-specific humoral immune responses and viral genome variations has not revealed a mechanism for the absent viral clearance. In this study......, ex-vivo cellular immune responses were assessed by enzyme linked immunospot assay mounted against the majority of the translated viral genome. Compared to seropositive healthy individuals, individuals with B19 persistence (2-8 years) showed larger number of responses to the structural proteins (P = 0.......0022), whereas responses to the non-structural protein were of lower magnitude (P = 0.012). These observations provide the first findings of immunological discrepancies between individuals with B19 persistence and healthy individuals, findings that may reflect both failed immunity and antigenic exhaustion....

Anaesthesia for paediatric patients: Minimising the risk

African Journals Online (AJOL)

to paediatric patients need to be offset against the need for optimal utilisation of national ... Risk stratification of paediatric patients for specific procedures in ... support colleagues in smaller district hospitals by means of telephonic advice, the ... techniques that can minimise risk in the paediatric surgical population. S Afr Med ...

The immune response against Candida spp. and Sporothrix schenckii.

Science.gov (United States)

Martínez-Álvarez, José A; Pérez-García, Luis A; Flores-Carreón, Arturo; Mora-Montes, Héctor M

2014-01-01

Candida albicans is the main causative agent of systemic candidiasis, a condition with high mortality rates. The study of the interaction between C. albicans and immune system components has been thoroughly studied and nowadays there is a model for the anti-C. albicans immune response; however, little is known about the sensing of other pathogenic species of the Candida genus. Sporothrix schenckii is the causative agent of sporotrichosis, a subcutaneous mycosis, and thus far there is limited information about its interaction with the immune system. In this paper, we review the most recent information about the immune sensing of species from genus Candida and S. schenckii. Thoroughly searches in scientific journal databases were performed, looking for papers addressing either Candida- or Sporothrix-immune system interactions. There is a significant advance in the knowledge of non-C. albicans species of Candida and Sporothrix immune sensing; however, there are still relevant points to address, such as the specific contribution of pathogen-associated molecular patterns (PAMPs) for sensing by different immune cells and the immune receptors involved in such interactions. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles.

Science.gov (United States)

Goujon, Catherine; Gougeon, Marie-Lise; Tondeur, Laura; Poirier, Béatrice; Seffer, Valérie; Desprès, Philippe; Consigny, Paul-Henri; Vray, Muriel

2017-10-27

For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area. A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-27days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27days between receiving the measles vaccine and yellow fever vaccine. The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample. One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1. The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27

FEATURES OF THE IMMUNE RESPONSE DURING INFECTION AND PROSPECTS FOR THE VACCINES CREATION

Directory of Open Access Journals (Sweden)

Davidova T.V.

2015-12-01

Full Text Available The influenza virus belongs to the family Orthomyxoviridae and is a major cause of respiratory infections in humans. Each year, influenza viruses cause, according to experts, 3-5 million severe course of the disease and 250 000-500 000 deaths. Influenza A viruses are divided into serotypes based on their surface glycoproteins - known currently 17 subtypes of HA and NA subtypes ten. Upon infection with an influenza virus, both innate and adaptive immune responses are inducing. In recent years the annual seasonal epidemics were causing strains of the virus A (H1N1 and H3N2 and virus B. This may be due to their ability to be unrecognizable virus specific antibodies due to antigenic drift (Figure 1. Seasonal flu vaccine, to be effective, must be updated almost annually, according to new epidemic strains. In this work will discuss various strategies used by influenza viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells.The primary targets for influenza viruses are the epithelial cells that line the respiratory tract and which initiate an antiviral immune response upon detection of the virus. The first line of defense is formed by the innate immune system, which is quick but lacks specificity and memory. Innate immunity is formed by physical barriers and innate cellular immune responses. Here, we outline several of the innate defense mechanisms directed against influenza infections. During homeostasis, alveolar macrophages exhibit a relatively quiescent state, producing only low levels of cytokines, and suppress the induction of innate and adaptive immunity. Activated macrophages enhance their pro-inflammatory cytokine response, including IL-6 and TNF-α. Alveolar macrophages have a direct role in limiting viral spread by phagocytosis of apoptotic infected cells and by phagocyte

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Institutional review boards' attitudes towards remuneration in paediatric research

DEFF Research Database (Denmark)

Flege, Marius M; Thomsen, Simon F

2017-01-01

Remuneration in paediatric research poses an ethical dilemma. Too large a sum might cause parents to enrol their children in research projects with no benefit for the child, whereas too modest a sum might hamper recruitment. The institutional review boards have the responsibility to only approve ...

The paediatric acute scrotum: are we still managing correctly ...

African Journals Online (AJOL)

Summary background Diagnosis and management of the paediatric acute scrotum remains an elusive and often challenging area of urology. In response to this, the urology team developed local guidelines to aid the management and treatment of this potentially life-changing condition. Patients and methods We reviewed ...

Provision of general paediatric surgical services in a regional hospital.

LENUS (Irish Health Repository)

Zgraj, O

2012-01-31

BACKGROUND: In Ireland, specialist paediatric surgery is carried out in paediatric hospitals in Dublin. General surgeons\\/consultants in other surgical specialities provide paediatric surgical care in regional centres. There has been a failure to train general surgeons with paediatric skills to replace these surgeons upon retirement. AIM: To assess paediatric surgical workload in one regional centre to focus the debate regarding the future provision of general paediatric surgery in Ireland. METHODS: Hospital in-patient enquiry (HIPE) system was used to identify total number of paediatric surgical admissions and procedures. Cases assessed requiring hospital transfer. RESULTS: Of 17,478 surgical patients treated, 2,584 (14.8%) were under 14 years. A total of 2,154 procedures were performed. CONCLUSION: Regional centres without dedicated paediatric surgeons deliver care to large numbers of paediatric patients. The demand for care highlights the need for formal paediatric services\\/appropriate surgical training for general surgical trainees.

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

Science.gov (United States)

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

2016-01-01

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. PMID:27192936

The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections

Science.gov (United States)

García-Patiño, María Guadalupe; García-Contreras, Rodolfo; Licona-Limón, Paula

2017-01-01

Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial infections, including pneumonia, bacteremia, and skin infections. Over the last 45 years, an alarming increase in the antibiotic resistance of this opportunistic microorganism has been reported, a situation that hinders effective treatments. In order to develop effective therapies against A. baumannii it is crucial to understand the basis of host–bacterium interactions, especially those concerning the immune response of the host. Different innate immune cells such as monocytes, macrophages, dendritic cells, and natural killer cells have been identified as important effectors in the defense against A. baumannii; among them, neutrophils represent a key immune cell indispensable for the control of the infection. Several immune strategies to combat A. baumannii have been identified such as recognition of the bacteria by immune cells through pattern recognition receptors, specifically toll-like receptors, which trigger bactericidal mechanisms including oxidative burst and cytokine and chemokine production to amplify the immune response against the pathogen. However, a complete picture of the protective immune strategies activated by this bacteria and its potential therapeutic use remains to be determined and explored. PMID:28446911

The Abscopal Effect Associated With a Systemic Anti-melanoma Immune Response

International Nuclear Information System (INIS)

Stamell, Emily F.; Wolchok, Jedd D.; Gnjatic, Sacha; Lee, Nancy Y.; Brownell, Isaac

2013-01-01

The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effect and a systemic antitumor immune response. A brain recurrence was then treated with a combination of stereotactic radiosurgery and immunotherapy with ipilimumab. The patient experienced a complete remission that included resolution of nodal metastases, with a concomitant increase in MAGEA3 titers and a new response to the cancer antigen PASD1. This case supports the immune hypothesis for the abscopal effect, and illustrates the potential of combining radiotherapy and immunotherapy in the treatment of melanoma.

The Abscopal Effect Associated With a Systemic Anti-melanoma Immune Response

Energy Technology Data Exchange (ETDEWEB)

Stamell, Emily F. [Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York (United States); Wolchok, Jedd D. [Melanoma and Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York, New York (United States); Gnjatic, Sacha [Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lee, Nancy Y. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brownell, Isaac, E-mail: Isaac.brownell@nih.gov [Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Dermatology Branch, National Cancer Institute, Bethesda, Maryland (United States)

2013-02-01

The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effect and a systemic antitumor immune response. A brain recurrence was then treated with a combination of stereotactic radiosurgery and immunotherapy with ipilimumab. The patient experienced a complete remission that included resolution of nodal metastases, with a concomitant increase in MAGEA3 titers and a new response to the cancer antigen PASD1. This case supports the immune hypothesis for the abscopal effect, and illustrates the potential of combining radiotherapy and immunotherapy in the treatment of melanoma.

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

Science.gov (United States)

Muyanja, Enoch; Ssemaganda, Aloysius; Ngauv, Pearline; Cubas, Rafael; Perrin, Helene; Srinivasan, Divya; Canderan, Glenda; Lawson, Benton; Kopycinski, Jakub; Graham, Amanda S; Rowe, Dawne K; Smith, Michaela J; Isern, Sharon; Michael, Scott; Silvestri, Guido; Vanderford, Thomas H; Castro, Erika; Pantaleo, Giuseppe; Singer, Joel; Gillmour, Jill; Kiwanuka, Noah; Nanvubya, Annet; Schmidt, Claudia; Birungi, Josephine; Cox, Josephine; Haddad, Elias K; Kaleebu, Pontiano; Fast, Patricia; Sekaly, Rafick-Pierre; Trautmann, Lydie; Gaucher, Denis

2014-07-01

Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Registration is not required for observational studies. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases

Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans

Directory of Open Access Journals (Sweden)

Line Larry L

2010-03-01

Full Text Available Abstract Background Astaxanthin modulates immune response, inhibits cancer cell growth, reduces bacterial load and gastric inflammation, and protects against UVA-induced oxidative stress in in vitro and rodent models. Similar clinical studies in humans are unavailable. Our objective is to study the action of dietary astaxanthin in modulating immune response, oxidative status and inflammation in young healthy adult female human subjects. Methods Participants (averaged 21.5 yr received 0, 2, or 8 mg astaxanthin (n = 14/diet daily for 8 wk in a randomized double-blind, placebo-controlled study. Immune response was assessed on wk 0, 4 and 8, and tuberculin test performed on wk 8. Results Plasma astaxanthin increased (P helper, Tcytotoxic or natural killer cells. A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8. Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects. There was no difference in TNF and IL-2 concentrations, but plasma IFN-γ and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin. Conclusion Therefore, dietary astaxanthin decreases a DNA damage biomarker and acute phase protein, and enhances immune response in young healthy females.

Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

Directory of Open Access Journals (Sweden)

Susu eDuan

2016-02-01

Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

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Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: estefaniabio@yahoo.com.br, e-mail: antero@cdtn.br; Resende, Maria Aparecida de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: maresend@mono.icb.ufmg.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia], e-mail: goes@mono.icb.ufmg.br, e-mail: brsgarbi@mono.icb.ufmg.br

2009-07-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - {gamma}, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-{gamma} production was maintained indicating that a Th1 pattern was

Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

International Nuclear Information System (INIS)

Martins, Estefania M.N.; Andrade, Antero S.R.; Resende, Maria Aparecida de; Reis, Bernardo S.; Goes, Alfredo M.

2009-01-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - γ, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-γ production was maintained indicating that a Th1 pattern was dominant. For

The serological response to heartwater immunization in cattle is an indicator of protective immunity

DEFF Research Database (Denmark)

Lawrence, J A; Tjørnehøj, Kirsten; Whiteland, A P

1995-01-01

A significant correlation was demonstrated in Friesian-cross steers between the serological response to previous vaccination with the Ball 3 strain of Cowdria ruminantium and the development of protective immunity against the Kalota isolate from Malawi. Of 10 animals which seroconverted after vac...

Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

Science.gov (United States)

Biswas, Sumi; Choudhary, Prateek; Elias, Sean C; Miura, Kazutoyo; Milne, Kathryn H; de Cassan, Simone C; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Osier, Faith H; Hodgson, Susanne H; Duncan, Christopher J A; O'Hara, Geraldine A; Long, Carole A; Hill, Adrian V S; Draper, Simon J

2014-01-01

The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases

Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

Directory of Open Access Journals (Sweden)

Sumi Biswas

Full Text Available The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i ChAd63-MVA immunization, ii immunization and CHMI, and iii primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i total IgG responses before and after CHMI, ii responses to allelic variants of MSP1 and AMA1, iii functional growth inhibitory activity (GIA, iv IgG avidity, and v isotype responses (IgG1-4, IgA and IgM. These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

Effects of inhaled insoluble 239PuO2 on immune responses following lung immunization

International Nuclear Information System (INIS)

Bice, D.E.; Harris, D.L.; Brooks, A.L.; Mewhinney, J.A.

1978-01-01

To determine if inhaled 239 PuO 2 suppresses immunity in lung-associated lymph nodes, Chinese hamsters were exposed to a polydisperse aerosol of 239 PuO 2 produced at 1150 0 C. The mean lung burden of these animals was estimated to be 10 nCi at 8 days after exposure. At 128, 256 and 400 days after exposure, sham exposed controls and experimental animals were immunized by intratracheal instillation of 1 x 10 8 sheep red blood cells (SRBC). Six days later, they were sacrificed and the number of antibody forming cells (AFC) in lung-associated lymph nodes, spleen and cervical lymph nodes was evaluated. Results of these studies indicated that the number of AFC in lung-associated lymph modes was significantly lower in animals exposed to 239 PuO 2 . Only a few AFC were found in spleen and cervical lymph nodes after intratracheal immunization and the number in exposed animals was not significantly different than in the controls. These data indicate that even though the 239 PuO 2 exposure had suppressed immune responses in lung-associated lymph nodes, their filtering capacity was unaffected and antigen did not translocate to the spleen. We conclude that, at the sacrifice intervals evaluated, the immune function of lung-associated lymph nodes was suppressed and that distant lymphoid tissue (e.g., spleen and cervical lymph nodes) did not replace the immune function of the lung-associated lymph nodes

The relevance of the Goudge inquiry to the practice of child protection/forensic paediatrics.

Science.gov (United States)

Skellern, Catherine; Donald, Terence

2014-10-01

In 2008 Ontario, Canada the Goudge Inquiry arose following increasing concerns about practices surrounding forensic pathology and the investigation of paediatric deaths. Some of the considerations and recommendations have relevance to child protection/forensic paediatricians, particularly in relation to their responsibilities in opinion formulation and as expert witnesses. By examining the Inquiry recommendations, this paper applies them in relation to child protection/forensic paediatrics by discussing forensic medicine and its legal context, how interpretation of published reports and data should be used in opinion formulation; issues of 'diagnosis' versus 'opinion'; issues specific to child protection paediatrics; quality control; aspects of report writing and terminological considerations. It concludes with an adaptation of key recommendations directly from those of Goudge, applied to the context of paediatric forensic medicine undertaken in child protection assessments. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-Protein Signaling in Epithelial Cells

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Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A.; Hodgkin, Jonathan; McMullan, Rachel

2013-01-01

The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food. PMID:24348250

Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review

Directory of Open Access Journals (Sweden)

Renata Maronna Praça Longhi

Full Text Available We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1-or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-a, IL-12p40 and IFN-I production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease.

Behavioural fever is a synergic signal amplifying the innate immune response.

Science.gov (United States)

Boltaña, Sebastian; Rey, Sonia; Roher, Nerea; Vargas, Reynaldo; Huerta, Mario; Huntingford, Felicity Anne; Goetz, Frederick William; Moore, Janice; Garcia-Valtanen, Pablo; Estepa, Amparo; Mackenzie, S

2013-09-07

Behavioural fever, defined as an acute change in thermal preference driven by pathogen recognition, has been reported in a variety of invertebrates and ectothermic vertebrates. It has been suggested, but so far not confirmed, that such changes in thermal regime favour the immune response and thus promote survival. Here, we show that zebrafish display behavioural fever that acts to promote extensive and highly specific temperature-dependent changes in the brain transcriptome. The observed coupling of the immune response to fever acts at the gene-environment level to promote a robust, highly specific time-dependent anti-viral response that, under viral infection, increases survival. Fish that are not offered a choice of temperatures and that therefore cannot express behavioural fever show decreased survival under viral challenge. This phenomenon provides an underlying explanation for the varied functional responses observed during systemic fever. Given the effects of behavioural fever on survival and the fact that it exists across considerable phylogenetic space, such immunity-environment interactions are likely to be under strong positive selection.

Spore load and immune response of honey bees naturally infected by Nosema ceranae.

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Li, Wenfeng; Evans, Jay D; Li, Jianghong; Su, Songkun; Hamilton, Michele; Chen, Yanping

2017-12-01

Nosema ceranae causes widespread infection in adult workers of European honey bees, Apis mellifera, and has often been linked to honey bee colony losses worldwide. Previous investigations of honey bee immune response to N. ceranae infection were largely based on laboratory experiment, however, little is known about the immune response of honey bees that are naturally infected by N. ceranae. Here, we compared the infection levels of N. ceranae in three different categories of adult bees (emergent bees, nurses, and foragers) and detected the host immune response to the N. ceranae infection under natural conditions. Our studies showed that the Nosema spore load and infection prevalence varied among the different types of adult workers, and both of them increased as honey bees aged: No infection was detected in emergent bees, nurses had a medium spore load and prevalence, while foragers were with the highest Nosema infection level and prevalence. Quantification of the mRNA levels of antimicrobial peptides (abaecin, apidaecin, defensin-1, defensin-2, and hymenoptaecin) and microbial recognition proteins (PGRP-S1, PGRP-S2, PGRP-S3, PGRP-LC, GNBP1-1, and GNBP1-2) confirmed the involvement of the Toll and/or Imd immune pathways in the host response to N. ceranae infection, and revealed an activation of host immune response by N. ceranae infection under natural conditions. Additionally, the levels of immune response were positively correlated with the Nosema spore loads in the infected bees. The information gained from this study will be relevant to the predictive modeling of honey bee disease dynamics for Nosema disease prevention and management.

ENDOCANNABINOIDS AND EICOSAMOIDS: BIOSYNTHESIS AND INTERACTIONS WITH IMMUNE RESPONSE

Directory of Open Access Journals (Sweden)

Yu. K. Karaman

2013-01-01

Full Text Available The review is dedicated to modern concepts of arachidonic acid metabolites, i.e., endocannabinoids and eicosanoids, their biosynthetic pathways, cross-talk mechanisms and participation in immune response. New information from literature and own results include data concerning overlapping enzymatic pathways controlling biosynthesis of endocannabinoids and eicosanoids. Impact of synthetic cannabinoid receptor ligands upon production rates of proinflammatory cytokines and eicosanoids is discussed, as like as relationships among immune system reactivity and expression levels of cannabinoid receptors.

Paediatric Malignancies | Joseph | African Journal of Paediatric ...

African Journals Online (AJOL)

malignancies. Other common malignancies included sarcomas 10(14.71%), neurofibromatosis 9(13.24%), nephroblastoma 8(11.77%), acute lymphoblastic leukaemia 5(7.35%) and retinoblastoma 4(5.88%). The less common paediatric malignancies were melanoma, invasive lobular breast carcinoma and squamous cell ...

Role of Activin A in Immune Response to Breast Cancer

Science.gov (United States)

2016-12-01

strategies are needed in order to eradicate metastatic breast cancer. In this respect, the activation of the immune system to elicit anti-tumor immune...responses represents one of the most promising approaches that have recently demonstrated some success in other diseases. However, clinically apparent...content/76/14_Supplement/4986 Advertisement Advanced Search search ! Clinical Research (Excluding Clinical Trials) Abstract 4986: Regulation of radiation

Anti-TNF therapy for paediatric IBD: the Scottish national experience.

Science.gov (United States)

Cameron, F L; Wilson, M L; Basheer, N; Jamison, A; McGrogan, P; Bisset, W M; Gillett, P M; Russell, R K; Wilson, D C

2015-04-01

Biological agents are being increasingly used in the UK for paediatric-onset inflammatory bowel disease (PIBD) despite limited evidence and safety concerns. We evaluated effectiveness and safety in the clinical setting, highlighting drug cost pressures, using our national Scottish PIBD biological registry. Complete usage of the biological agents, infliximab (IFX) and adalimumab (ADA) for treatment of PIBD (in those aged Scottish Paediatric Gastroenterology, Hepatology and Nutrition (PGHAN) national managed service network (all regional PGHAN centres and paediatric units within their associated district general hospitals). 132 children had biological therapy; 24 required both agents; 114 had Crohn's disease (CD), 16 had ulcerative colitis (UC) and 2 had IBD Unclassified (IBDU). 127 children received IFX to induce remission; 61 entered remission, 49 had partial response and 17 had no response. 72 were given maintenance IFX and 23 required dose escalation. 18 had infusion reactions and 27 had adverse events (infections/other adverse events). 29 had ADA to induce remission (28 CD and 1 UC), 24 after IFX; 10 entered remission, 12 had partial response and 7 had no response. All had maintenance; 19 required dose escalation. 12 children overall required hospitalisation due to drug toxicity. No deaths occurred with either IFX or ADA. Complete accrual of the Scottish nationwide 'real-life' experience demonstrates moderate effectiveness of anti tumour necrosis factor agents in severe PIBD but duration of effect is limited; significant financial issues (drug cost-need for dose escalation and/or multiple biological usage) and safety issues exist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The ESSKA paediatric anterior cruciate ligament monitoring initiative.

Science.gov (United States)

Moksnes, Håvard; Engebretsen, Lars; Seil, Romain

2016-03-01

To survey and describe the treatment of paediatric anterior cruciate ligament (ACL) injuries performed by orthopaedic surgeons affiliated with the European Society for Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA). A closed e-survey was submitted to all registered members and affiliates of ESSKA in July 2013. All recipients were invited to participate in the survey by answering 34 questions online. The list of potential respondents was extracted from the ESSKA office database. Invitation was sent to 2236 ESSKA members and affiliates, and received 491 (22%) unique responses. Among the respondents, 445 (91%) were orthopaedic surgeons, with 354 (72%) stating that they were involved in treatment of paediatric ACL injuries. The main findings were that there are substantial differences with regard to preferred treatment algorithms, surgical techniques and long-term follow-up procedures. The summed estimate of skeletally immature children with ACL injury seen by the responders in 2012 was minimum 1923 individuals, and a minimum of 102 clinically relevant post-operative growth disturbances were registered. The present survey documents that the incidences of paediatric ACL injuries and idiopathic growth disturbances may be higher than previously estimated. Treatment algorithms and surgical techniques are highly diverse, and consensus could not be identified. It is worrying that only half the surgeons reported to follow-up children until skeletal maturity after surgical treatment. The results of this survey highlight the importance of international multicentre studies on paediatric ACL treatment and the development of an outcome registry to enable prospective data collections. IV.

Late effects of atomic bomb radiation on human immune responses, (10); Results on studies of immune responses to EB-virus

Energy Technology Data Exchange (ETDEWEB)

Kusunoki, Yoichiro; Kyoizumi, Seishi; Ozaki, Kyoko; Saito, Mayumi; Cologne, J.B.; Akiyama, Mitoshi (Radiation Effects Research Foundation, Hiroshima (Japan))

1992-12-01

Anti-Epstein-Barr (EV) virus antibody titers were measured in age- and sex-matched three groups of each 124 A-bomb survivors who had exposed to <0.01 Gy, 0.01-1 Gy, or >1 Gy. These serum samples showed positive antibodies against viral capsid antigens (VCA). Antibody titers to anti-VCA-IgM or anti-EA-IgG were significantly higher in the groups of 0.01-1 Gy and >1 Gy than in the group of <0.01 Gy, reflecting decreased immune response ability for EV virus. When precursor frequency of cytotoxic cells against autologous EB virus LCL was determined in 68 other A-bomb survivors, no definitive influence of A-bombing was observed. However, serological study revealed that there was inverse correlation between precursor frequency and anti-EA-IgG antibody titer. These findings suggest that the immune response ability for EB virus may have been damaged and that biological reactivity of EB virus may occur frequently in A-bomb survivors. (N.K.).

Leptin, immune responses and autoimmune disease. Perspectives on the use of leptin antagonists.

Science.gov (United States)

Peelman, F; Iserentant, H; Eyckerman, S; Zabeau, L; Tavernier, J

2005-01-01

The pivotal role of leptin in regulating body weight and energy homeostasis is very well established. More recently, leptin also emerged as an important regulator of T-cell-dependent immunity. Reduced leptin levels, as observed during periods of starvation, correlate with an impaired cellular immune response, whereby especially the T(H)1 pro-inflammatory immune response appears to be affected. Physiologically, this could reflect the high energy demand of such processes, which are suppressed in animals or people with nutrient shortage. Several autoimmune diseases are T(H)1 T-cell dependent. In line with a pro-inflammatory role for leptin, animal models of leptin deficiency are markedly resistant to a variety of T-cell dependent autoimmune diseases. Here, we review the role of leptin in immune responses, with emphasis on autoimmune diseases. The design and potential use of leptin antagonists is also discussed.

Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

Science.gov (United States)

Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

2014-01-01

Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

A paediatric cardiopulmonary resuscitation training project in Honduras.

Science.gov (United States)

Urbano, Javier; Matamoros, Martha M; López-Herce, Jesús; Carrillo, Angel P; Ordóñez, Flora; Moral, Ramón; Mencía, Santiago

2010-04-01

It is possible that the exportation of North American and European models has hindered the creation of a structured cardiopulmonary resuscitation (CPR) training programme in developing countries. The objective of this paper is to describe the design and present the results of a European paediatric and neonatal CPR training programme adapted to Honduras. A paediatric CPR training project was set up in Honduras with the instructional and scientific support of the Spanish Group for Paediatric and Neonatal CPR. The programme was divided into four phases: CPR training and preparation of instructors; training for instructors; supervised teaching; and independent teaching. During the first phase, 24 Honduran doctors from paediatric intensive care, paediatric emergency and anaesthesiology departments attended the paediatric CPR course and 16 of them the course for preparation as instructors. The Honduran Paediatric and Neonatal CPR Group was formed. In the second phase, workshops were given by Honduran instructors and four of them attended a CPR course in Spain as trainee instructors. In the third phase, a CPR course was given in Honduras by the Honduran instructors, supervised by the Spanish team. In the final phase of independent teaching, eight courses were given, providing 177 students with training in CPR. The training of independent paediatric CPR groups with the collaboration and scientific assessment of an expert group could be a suitable model on which to base paediatric CPR training in Latin American developing countries. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

Science.gov (United States)

Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

2010-01-29

The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

Efficacy of multiple anticancer therapies may depend on host immune response

Directory of Open Access Journals (Sweden)

Kritika Karri

2017-06-01

Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

Aetiological patterns and management outcome of paediatric head trauma: one-year prospective study.

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Emejulu, J K C; Shokunbi, M T

2010-09-01

Trauma is the most common cause ofpaediatric deaths. In 75% ofpaediatric trauma deaths, head injury is responsible, and most are from falls. Recent reports from Nigeria, however, appear to indicate a predominance of road traffic accidents, instead of falls. To evaluate the aetiology of paediatric head trauma, management protocols and outcome from our Centre, in order to acquire a baseline data base and recommend measures to reduce childhood trauma. A prospective study of all paediatric head trauma cases presenting to Nnamdi Azikiwe University Teaching Hospital, Nnewi, for 12months from April 21, 2006 to April 20, 2007, was done and collated data subsequently analyzed. The paediatric age group was taken as = 15 years, and grading of head injury was with the Glasgow Coma Scale (3-15) and the modified scale for non-verbal children; while outcome was measured with the Glasgow Outcome Scale (1-5). Out of 334 patients treated within the period of study, 210 were head trauma cases. Of these, 52 were paediatric head trauma, representing 24.8% of all head trauma cases; and 19.2% (10 of 52) of them were aged 0-2 years. About 62% (32 of 52) were males. Falls and RTA were each responsible in 25 (48.1%) cases. Mild head injury occurred in 31 (59.6%), and 49 (94.2%) patients were evaluated by plain radiography. Treatment was conservative in 39 (75%) cases; with satisfactory outcome in 36 (69.2%), and a mortality rate of 15.4%. Road traffic injury, mostly from motorcycles, has become the major cause of morbidity and mortality amongst the paediatric age group, especially the male gender, and outcome from management is mostly satisfactory.

An Immune-inspired Adaptive Automated Intrusion Response System Model

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Ling-xi Peng

2012-09-01

Full Text Available An immune-inspired adaptive automated intrusion response system model, named as , is proposed. The descriptions of self, non-self, immunocyte, memory detector, mature detector and immature detector of the network transactions, and the realtime network danger evaluation equations are given. Then, the automated response polices are adaptively performed or adjusted according to the realtime network danger. Thus, not only accurately evaluates the network attacks, but also greatly reduces the response times and response costs.

Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

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Gavin Churchyard

Full Text Available The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM, SAAVI MVA-C (2.9 x 109 pfu IM and Novartis V2-deleted subtype C gp140 (100 mcg with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa.Participants at three South African sites were randomized (1:1:1:1 to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P; concurrent MVA/gp140 (MP/MP; DNA prime, sequential MVA boost (D/D/M/M; DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP or placebo. Peak HIV specific humoral and cellular responses were measured.184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens.The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen.ClinicalTrials.gov NCT01418235.

Practical application of natriuretic peptides in paediatric cardiology

DEFF Research Database (Denmark)

Smith, Julie; Goetze, Jens Peter; B. Andersen, Claus

2010-01-01

It is still uncertain if cardiac natriuretic peptides are useful biomarkers in paediatric cardiology. In this review we identify four clinical scenarios in paediatric cardiology, where clinical decision-making can be difficult, and where we feel the paediatric cardiologists need additional...

Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity.

Science.gov (United States)

Zak, Daniel E; Andersen-Nissen, Erica; Peterson, Eric R; Sato, Alicia; Hamilton, M Kristina; Borgerding, Joleen; Krishnamurty, Akshay T; Chang, Joanne T; Adams, Devin J; Hensley, Tiffany R; Salter, Alexander I; Morgan, Cecilia A; Duerr, Ann C; De Rosa, Stephen C; Aderem, Alan; McElrath, M Juliana

2012-12-11

To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8(+) T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.

Humoral Immune Response Kinetics in Philander opossum and Didelphis marsupialis Infected and Immunized by Trypanosoma cruzi Employing an Immunofluorescence Antibody Test

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Ana Paula Legey

1999-05-01

Full Text Available Philander opossum and Didelphis marsupialis considered the most ancient mammals and an evolutionary success, maintain parasitism by Trypanosoma cruzi without developing any apparent disease or important tissue lesion. In order to elucidate this well-balanced interaction, we decided to compare the humoral immune response kinetics of the two didelphids naturally and experimentally infected with T. cruzi and immunized by different schedules of parasite antigens, employing an indirect fluorescence antibody test (IFAT. Both didelphids responded with high serological titers to different immunization routes, while the earliest response occurred with the intradermic route. Serological titers of naturally infected P. opossum showed a significant individual variation, while those of D. marsupialis remained stable during the entire follow-up period. The serological titers of the experimentally infected animals varied according to the inoculated strain. Our data suggest that (1 IFAT was sensitive for follow-up of P. opossum in natural and experimental T. cruzi infections; (2 both P. opossum and D. marsupialis are able to mount an efficient humoral immune response as compared to placental mammals; (3 experimentally infected P. opossum and D. marsupialis present distinct patterns of infection, depending on the subpopulation of T. cruzi, (4 the differences observed in the humoral immune responses between P. opossum and D. marsupialis, probably, reflect distinct strategies selected by these animals during their coevolution with T. cruzi.

A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

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Murphy, Sean C.; Kas, Arnold; Stone, Brad C.; Bevan, Michael J.

2013-01-01

Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins. PMID:23530242

The intracellular cholesterol landscape: dynamic integrator of the immune response

Science.gov (United States)

Fessler, Michael B.

2016-01-01

Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, ‘professional’ role for sterols and oxysterols in macrophage and T cell immunity. Host defense may have been the original selection pressure behind the development of mechanisms for intracellular cholesterol homeostasis. Functional coupling between sterol metabolism and immunity has fundamental implications for health and disease. PMID:27692616

Regular in-situ simulation training of paediatric Medical Emergency Team leads to sustained improvements in hospital response to deteriorating patients, improved outcomes in intensive care and financial savings.

Science.gov (United States)

Theilen, Ulf; Fraser, Laura; Jones, Patricia; Leonard, Paul; Simpson, Dave

2017-06-01

The introduction of a paediatric Medical Emergency Team (pMET) was accompanied by weekly in-situ simulation team training. Key ward staff participated in team training, focusing on recognition of the deteriorating child, teamwork and early involvement of senior staff. Following an earlier study [1], this investigation aimed to evaluate the long-term impact of ongoing regular team training on hospital response to deteriorating ward patients, patient outcome and financial implications. Prospective cohort study of all deteriorating in-patients in a tertiary paediatric hospital requiring admission to paediatric intensive care (PICU) the year before, 1year after and 3 years after the introduction of pMET and team training. Deteriorating patients were recognised more promptly (before/1year after/3years after pMET; median time 4/1.5/0.5h, pIntroduction of pMET coincided with significantly reduced hospital mortality (p<0.001). These results indicate that lessons learnt by ward staff during team training led to sustained improvements in the hospital response to critically deteriorating in-patients, significantly improved patient outcomes and substantial savings. Integration of regular in-situ simulation training of medical emergency teams, including key ward staff, in routine clinical care has potential application in all acute specialties. Copyright © 2017. Published by Elsevier B.V.

Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

Science.gov (United States)

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.

Science.gov (United States)

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.

Mathematical modeling provides kinetic details of the human immune response to vaccination

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Dustin eLe

2015-01-01

Full Text Available With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combine mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response is determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increases slowly, the slow increase can still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model describes well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization are derived from the population of circulating antibody-secreting cells. Taken together, our analysis provides novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlight challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

Mathematical modeling provides kinetic details of the human immune response to vaccination.

Science.gov (United States)

Le, Dustin; Miller, Joseph D; Ganusov, Vitaly V

2014-01-01

With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

Genetic variations in non-specific immune response to ...

African Journals Online (AJOL)

Non-specific immune response in three strains of Heterobranchus bidorsalis challenged with the bacterium Aeromonas hydrophilia was evaluated. The study was undertaken in three strains of H. bidorsalis from different ecological zones in Nigeria and the percentage cumulative mortality was lowest and significantly ...

A novel method of modifying immune responses by vaccination with lipiodol-siRNA mixtures

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Yijian Li

2006-01-01

Full Text Available Abstract The dendritic cell (DC possesses the ability to stimulate both T helper 1 (Th1 and Th2 responses depending on activation stimuli. Although it is known that chemically or genetically modified DC can be used therapeutically to steer immune responses towards either Th1 or Th2, cellular therapy with ex vivo manipulated DC is clinically difficult. Here we demonstrate a novel method of switching immune responses from Th1 to Th2 through in vivo immune modulation by administration of siRNA. We demonstrate that siRNA targeting of the IL-12p35 gene leads to a Th2 bias in vitro through an IL-10 dependent mechanism. In vivo administration of siRNA admixed with the oil-based contrast agent lipiodol in the presence of antigen and adjuvant induced a deviation in recall response to reduced production of IFN-γ and augmented IL-4 response using either KLH or ovalbumin. This simple method of in vivo modification of immune response possesses therapeutic potential in Th1-mediated diseases such as multiple sclerosis and autoimmune diabetes.

Optimization of paediatric radiation doses with CR systems

International Nuclear Information System (INIS)

Zatelli, Giovanna; Mazzocchi, S.; Ciccarone, A.; Fonda, C.; De Otto, G.

2008-01-01

Full text: Radiation protection of paediatric patients is a primary objective in paediatric radiology due the higher life expectance of the little patients undergoing radiology examinations and due to the higher radiosensitivity of tissues. Aim of this work is the study of the optimization process in paediatric doses needed after the recent installation of a new Computed Radiography System in the Radiology of the Meyer paediatric Hospital, in Florence, Italy. This process involves both the use of new dedicated digitizer (Agfa DX-S) and elaboration software (Agfa NX2.0). The choice of the DX-S systems has been performed in consideration of high resolution (Scanhead technology - DirectriX detector), image sharpness and portability of the cassettes that make DX-S ideal in paediatric applications as neonatal intensive care. The NX software for image processing has been installed with the 'Paediatric' licence that optimizes paediatric images especially for exposures of premature newborns. Paediatric NX automatically selects the paediatric age group, depending on the patient's birth date. Each age group contains enhanced algorithms and settings adapted to age group, for optimized visibility of fine details. All the CR system has been accepted by mean of quality control acceptance tool AGFA AutoQC2, and all the automatic exposure control devices installed on radiographic devices were previously calibrated in accordance to literature with signal to noise vs dose considerations [S. Mazzocchi et al. 'AEC set-up optimization with computed radiography imaging' Radiat. Prot. Dosim. 117, 169-173 2005]. Paediatric patients were then divided into age-weight categories and the Entrance Surface Doses (ESD) were calculated by output x-rays measurements. ESD for thorax examinations were correlated to the image evaluations performed by experienced radiologists following European Guidelines on quality criteria for diagnostic radiographic images in paediatrics (EUR 16261, European

The Impact of Ultraviolet Radiation on Immune Responses (invited paper)

International Nuclear Information System (INIS)

Norval, M.

2000-01-01

In addition to its genotoxic and mutagenic effects, UV has the capacity to suppress immune responses. The mechanism involved is complex, beginning with chromophores located in the skin which absorb UV, this leading in turn to changes in the production of a range of immune mediators locally and systemically which then induce phenotypic and functional alterations in antigen presentation. The cascade ends with the promotion of a subset of T-cells downregulating cell-mediated immunity. The possible consequences of this immunomodulation for the control of tumours and infectious diseases require careful evaluation from laboratory and human studies. (author)

Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies

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Andrea Farini

2014-01-01

Full Text Available Muscular dystrophies (MDs are a heterogeneous group of diseases, caused by mutations in different components of sarcolemma, extracellular matrix, or enzymes. Inflammation and innate or adaptive immune response activation are prominent features of MDs. Various therapies under development are directed toward rescuing the dystrophic muscle damage using gene transfer or cell therapy. Here we discussed current knowledge about involvement of immune system responses to experimental therapies in MDs.

Effect of glucocorticoids on melatonin receptor expression under T-cell activated immune response

International Nuclear Information System (INIS)

Tauschanova, P.; Georgiev, G.; Manchev, S.; Konakchieva, R.

2007-01-01

The present study was aimed to explore the stress response in rats under conditions of T-cell antigen-activated immune function and to investigate the specific melatonin (MEL) receptor binding in primary and secondary immune tissue of rats employing 2-( 125 I)-iodo melatonin autoradiography and in vitro ligand binding assay. The study revealed that melatonin receptor binding was specifically expressed in discrete areas of the lymphoid sheath of the spleen and in a network of interdigitating cells of the experimental rats. Demonstration of the modulation of MEL receptor binding in the course of a primary immune response under hypercorticalemic conditions indicate that the pineal hormone might interfere in the processes of glucocorticoid-dependent immune competency. (authors)

Teaching ethics to paediatrics residents: the centrality of the therapeutic alliance.

Science.gov (United States)

Taylor, Holly A; McDonald, Erin L; Moon, Margaret; Hughes, Mark T; Carrese, Joseph A

2009-10-01

Previous research on ethical issues encountered by medical professionals in training and practice have presented the thematic content of the cases they encounter rather than the activities in which clinicians engage and in which they most often encounter ethical issues. We conducted a direct observation study of paediatrics residents and their preceptors seeing patients in an out-patient general paediatrics clinic. Our objectives were to describe the everyday ethics-related issues paediatrics residents encounter as they interact with patients. Our ultimate goal is to use this knowledge to enhance current efforts to teach ethics to paediatrics residents. The study team directly observed paediatrics residents discussing patients with their faculty preceptors (19 half-day sessions, 76 hours) in an out-patient general paediatrics clinic located in an urban academic medical centre. Each interaction between resident and preceptor about a single patient was considered a case for further analysis. A total of 247 cases were recorded. Forty-one of the cases were coded as having ethics-related content. A constant comparative method of qualitative data analysis revealed that residents were most likely to encounter ethical issues when engaged in the following activities: (i) maintaining a therapeutic alliance with the caregiver (e.g. the parent); (ii) prioritising patient or family needs; (iii) adjusting to the power embodied by the role of doctors, and (iv) distinguishing suboptimal care from abuse or neglect. In addition, our findings indicate that it is through their efforts to maintain the therapeutic alliance with the caregivers of their patients that residents engage in and integrate three processes: developing their medical knowledge; adhering to professional norms, and balancing the power inherent in the doctor's role with their responsibility to serve the patient's interests. Medical faculty tasked with teaching ethics to paediatrics residents can utilise the results

Plasma EBV microRNAs in paediatric renal transplant recipients.

Science.gov (United States)

Hassan, Jaythoon; Dean, Jonathan; De Gascun, Cillian F; Riordan, Michael; Sweeney, Clodagh; Connell, Jeff; Awan, Atif

2018-06-01

Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To date, 44 mature miRNAs are encoded for within the EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant recipients. In this study, we investigated circulating EBV miRNA profiles as novel biomarkers in paediatric renal transplant patients. Forty-two microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined in renal transplant recipients who resolved EBV infection (REI) or maintained chronic high viral loads (CHL), and in non-transplant patients with acute infectious mononucleosis (IM). Plasma EBV-miR-BART2-5p was present in higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12) patients. A trend was observed between the numbers of plasma EBV miRNAs expressed and EBV viral load (p < 0.07). Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p and 3-3p were detected in IM and CHL patients only. The lytic EBV-miRs, BHRF1-2-3p and 1-1, indicating active viral replication, were detected in IM patients only. One CHL patient developed post-transplant lymphoproliferative disease (PTLD) after several years and analysis of 10 samples over a 30-month period showed an average 24-fold higher change in plasma EBV-miR-BART2-5p compared to the CHL group and 110-fold higher change compared to the REI group. Our results suggest that EBV-miR-BART2-5p, which targets the stress-induced immune ligand MICB to escape recognition and elimination by NK cells, may have a role in sustaining high EBV viral loads in CHL paediatric kidney transplant recipients.

Paediatric multidetector CT optimisation training: a survey of common scanning procedures and the resultant dose reduction associated with paediatric MDCT investigations in Australia

International Nuclear Information System (INIS)

Wallace, Anthony; Sibelle, Kimberly; Stanley, Martin; Budd, Ray; Goergen, Stacey; Heggie, John

2008-01-01

The growing recognition of the increased risk of stochastic injury to paediatric patients from multidetector CT (MDCT) investigations prompted a survey sponsored by Royal Australian and New Zealand College of Radiology (RANZCR), Austin Health and Monash University to initiate a national paediatric dosimetry review for some of the most common investigations undertaken in MDCT paediatric practice. The survey forms included a data sheet requiring acquisition protocol parameters and a phantom graphic sheet requiring the marking of the inferior and superior acquisition margins. Survey forms were supplied for each of 13 common MDCT acquisitions to be tested. Response data was input into CT-Expo Version 1.5.1., a CT dosimetry calculation engine, to determine dose length product (DLP (mGy.cm)) and effective dose (ED (mSv)). Initial survey data was collected, calculated, blinded and collated into various presentations that were given at a MDCT optimisation seminar in November, 2006. All sites were re-surveyed in May 2007 and doses calculated. Initial survey data showed a range of dose efficiencies spread across the surveyed sites. A measure of the initial spread of DLP values per procedure ranged from a minimum of less than 2 for a head-trauma acquisition (372 - 520 mGy.cm) to 14 for a chest-trauma acquisition (28 - 388 mGy.cm). Results of the 2nd survey strongly indicate that the application of optimisation training to paediatric MDCT scanning can produce significant dose savings by the application of simple dose saving strategies. Many protocols demonstrated dose reductions of greater than 50% with significant reductions in both the maximum and minimum values of calculated DLP and ED. The development of a survey-training-resurvey model of MDCT optimisation has proven to be a successful strategy for paediatric MDCT dose reduction in Australia. (author)

Immune Response to Electromagnetic Fields through Cybernetic Modeling

International Nuclear Information System (INIS)

Godina-Nava, J. J.; Segura, M. A. Rodriguez; Cadena, S. Reyes; Sierra, L. C. Gaitan

2008-01-01

We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen

Immune Response to Electromagnetic Fields through Cybernetic Modeling

Science.gov (United States)

Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

2008-08-01

We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

Evaluation of the immune response in Shitou geese (Anser anser domesticus) following immunization with GPV-VP1 DNA-based and live attenuated vaccines.

Science.gov (United States)

Deng, Shu-xuan; Cai, Ming-sheng; Cui, Wei; Huang, Jin-lu; Li, Mei-li

2014-01-01

Goose parvovirus (GPV) is a highly contagious and deadly disease for goslings and Muscovy ducklings. To compare the differences in immune response of geese immunized with GPV-VP1 DNA-based and live attenuated vaccines. Shitou geese were immunized once with either 20 μg pcDNA-GPV-VP1 DNA gene vaccine by gene gun bombardment via intramuscular injection, or 300 μg by i.m. injection, or 300 μL live attenuated vaccine by i.m. injection, whereas 300 μg pcDNA3.1 (+) i.m. or 300 μL saline i.m. were used as positive and negative controls, respectively. Each group comprised 28 animals. Peripheral blood samples were collected from 2-210 days after immunization and the proliferation of T lymphocytes, the number of CD4(+) and CD8(+) T cells and the level of IgG assessed. Statistical analysis was performed using a one-way analysis of variance with group multiple comparisons via Tukey's test. The pcDNA-GPV-VP1 DNA and attenuated vaccine induced cellular and humoral responses, and there were no differences between the 20 and 300 μg group in the responses of proliferation of T lymphocyte and the CD8(+) T-cell. However, as to CD4(+) T-cell response and humoral immunity, the 20 μg group performed better than the 300 μg group, which induced better cellular and humoral immunity than live attenuated vaccine. This study showed that it is possible to induce both cellular and humoral response using DNA-based vaccines and that the pcDNA-GPV-VP1 DNA gene vaccine induced better cellular and humoral immunity than live attenuated vaccine.

Influences of large sets of environmental exposures on immune responses in healthy adult men.

Science.gov (United States)

Yi, Buqing; Rykova, Marina; Jäger, Gundula; Feuerecker, Matthias; Hörl, Marion; Matzel, Sandra; Ponomarev, Sergey; Vassilieva, Galina; Nichiporuk, Igor; Choukèr, Alexander

2015-08-26

Environmental factors have long been known to influence immune responses. In particular, clinical studies about the association between migration and increased risk of atopy/asthma have provided important information on the role of migration associated large sets of environmental exposures in the development of allergic diseases. However, investigations about environmental effects on immune responses are mostly limited in candidate environmental exposures, such as air pollution. The influences of large sets of environmental exposures on immune responses are still largely unknown. A simulated 520-d Mars mission provided an opportunity to investigate this topic. Six healthy males lived in a closed habitat simulating a spacecraft for 520 days. When they exited their "spacecraft" after the mission, the scenario was similar to that of migration, involving exposure to a new set of environmental pollutants and allergens. We measured multiple immune parameters with blood samples at chosen time points after the mission. At the early adaptation stage, highly enhanced cytokine responses were observed upon ex vivo antigen stimulations. For cell population frequencies, we found the subjects displayed increased neutrophils. These results may presumably represent the immune changes occurred in healthy humans when migrating, indicating that large sets of environmental exposures may trigger aberrant immune activity.

Vaccine platforms combining circumsporozoite protein and potent immune modulators, rEA or EAT-2, paradoxically result in opposing immune responses.

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Nathaniel J Schuldt

Full Text Available Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA or SLAM receptors adaptor protein (EAT-2. Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly

Effective doses in paediatric radiology

International Nuclear Information System (INIS)

Iacob, Olga; Diaconescu, Cornelia; Roca, Antoaneta

2001-01-01

Because of their longer life expectancy, the risk of late manifestations of detrimental radiation effects is greater in children than in adults and, consequently, paediatric radiology gives ground for more concern regarding radiation protection than radiology of adults. The purpose of our study is to assess in terms of effective doses the magnitude of paediatric patient exposure during conventional X-ray examinations, selected for their high frequency or their relatively high doses to the patient. Effective doses have been derived from measurements of dose-area product (DAP) carried out on over 900 patients undergoing X-ray examinations, in five paediatric units. The conversion coefficients for estimating effective doses are those calculated by the NRPB using Monte-Carlo technique on a series of 5 mathematical phantoms representing 0, 1, 5, 10 and 15 year old children. The annual frequency of X-ray examinations necessary for collective dose calculation are those reported in our last national study on medical exposure, conducted in 1995. The annual effective doses from all medical examinations for the average paediatric patient are as follows: 1.05 mSv for 0 year old, 0.98 mSv for 1 year old, 0.53 mSv for 5 year old, 0.65 mSv for 10 year old and 0.70 mSv for 15 year old. The resulting annual collective effective dose was evaluated at 625 man Sv with the largest contribution of pelvis and hip examinations (34%). The annual collective effective associated with paediatric radiology in Romania represent 5% of the annual value resulting from all diagnostic radiology. Examination of the chest is by far the most frequent procedure for children, accounting for about 60 per cent of all annually performed X-ray conventional examinations. Knowledge of real level of patient dose is an essential component of quality assurance programs in paediatric radiology. (authors)

The metabolic cost of mounting an immune response in male brown anoles (Anolis sagrei).

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Cox, Christian L; Peaden, Robert T; Cox, Robert M

2015-09-09

The tradeoff between reproduction and survival is central to life-history theory and is thought to reflect underlying energetic tradeoffs between reproduction and self-maintenance. Immune responses to parasites and pathogens are important components of self-maintenance in many species, but whether these defenses impose significant energetic costs has only been tested in a handful of organisms. We tested for a metabolic cost of mounting an immune response in the male brown anole (Anolis sagrei), a lizard in which we have previously shown that reproduction causes a marked reduction in immune response to the novel antigen phytohaemagglutinin (PHA). We treated captive male anoles with a subcutaneous injection of either PHA, which induces an immune response that manifests as localized swelling, or saline vehicle as a control. Prior to injection and at 24, 48, and 72 hr post-injection, we measured swelling at the site of injection and whole-animal resting metabolic rate (RMR) using stop-flow respirometry. Although we detected a robust swelling response to PHA at 24, 48, and 72 hr post-injection, mean RMR did not differ between treatments at any of these time points. However, within the PHA treatment group, RMR increased with the extent of swelling, suggesting a variable metabolic cost that scales with the magnitude of the induced immune response. Although individual anoles varied considerably in the extent to which they responded to PHA challenge, our results suggest that an immune response can impose a substantial metabolic cost (potentially as much as 63% above baseline RMR) for individuals that do respond maximally. J. Exp. Zool. 9999A:XX-XX, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma

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