CD147 stimulates hepatoma cells escaping from immune surveillance of T cells by interaction with Cyclophilin A.

Science.gov (United States)

Ren, Yi-Xin; Wang, Shu-Jing; Fan, Jian-Hui; Sun, Shi-Jie; Li, Xia; Padhiar, Arshad Ahmed; Zhang, Jia-Ning

2016-05-01

T cells play an important role in tumor immune surveillance. CD147 is a member of immunoglobulin superfamily present on the surface of many tumor cells and mediates malignant cell behaviors. Cyclophilin A (CypA) is an intracellular protein promoting inflammation when released from cells. CypA is a natural ligand for CD147. In this study, CD147 specific short hairpin RNAs (shRNA) were transfected into murine hepatocellular carcinoma Hepa1-6 cells to assess the effects of CD147 on hepatoma cells escaping from immune surveillance of T cells. We found extracellular CypA stimulated cell proliferation through CD147 by activating ERK1/2 signaling pathway. Downregulation of CD147 expression on Hepa1-6 cells significantly suppressed tumor progression in vivo, and decreased cell viability when co-cultured with T cells in vitro. Importantly, knockdown of CD147 on Hepa1-6 cells resulted in significantly increased T cells chemotaxis induced by CypA both in vivo and in vitro. These findings provide novel mechanisms how tumor cells escaping from immune surveillance of T cells. We provide a potential therapy for hepatocellular carcinoma by targeting CD147 or CD147-CypA interactions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Enhancing Immune Checkpoint Inhibitor Therapy in Kidney Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...SUBTITLE Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER...immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or enhance the abscopal in a kidney cancer

MHC class I dowregulation, tumour escape from immune surveillance and design of therapeutic strategies

Czech Academy of Sciences Publication Activity Database

Bubeník, Jan

2005-01-01

Roč. 51, č. 1 (2005), s. 1-2 ISSN 0015-5500 R&D Projects: GA ČR GA301/04/0492; GA MZd NR7807 Institutional research plan: CEZ:AV0Z50520514 Keywords : MHC class I * immune surveillance * immunotherapy Subject RIV: EC - Immunology Impact factor: 0.719, year: 2005

Enhancing disease surveillance reporting using public transport in ...

African Journals Online (AJOL)

Enhancing disease surveillance reporting using public transport in Dodoma District, Central Tanzania. ... LEG Mboera, SF Rumisha, EJ Mwanemile, E Mziwanda, PK Mmbuji ... Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

Outcomes of an Enhanced Surveillance Program for Carbapenem-Resistant Enterobacteriaceae

OpenAIRE

Fitzpatrick, Margaret; Zembower, Teresa; Malczynski, Michael; Qi, Chao; Bolon, Maureen K.

2014-01-01

Optimal surveillance strategies for identifying patients colonized with and at risk for transmitting carbapenem-resistant Enterobacteriaceae (CRE) are urgently needed. We instituted an enhanced surveillance program for CRE that identified unrecognized CRE-colonized patients but failed to identify possible CRE transmissions. We also identified risk factors associated with transmitting CRE.

[Surveillance system for adverse events following immunization against yellow fever in Burkina Faso in 2008. Good practice recommendations].

Science.gov (United States)

Yaméogo, T M; Breugelmans, J G; Kambou, J L; Badolo, O; Tiendrebéogo, S; Traoré, E; Avokey, F; Yactayo, S

2009-08-01

Yellow fever (YF) remains a public health problem in Africa. In 2007 and 2008, Togo, Senegal, Mali and Burkina Faso became the first countries to implement mass YF immunization campaigns within the framework of the Yellow Fever Initiative. The goal of this initiative led by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) with the support of The Global Alliance for Vaccines and Immunization (GAVI) is to organize mass YF immunization campaigns in 12 African countries at high risk forYF transmission between 2006 and 2013. A total of 290 million USD have been allocated for vaccination of 180 million people with the highly effective attenuated 17DYF vaccine. Working in partnership with the WHO, the 12 member states are to identify and target high risk areas with the dual aim of preventing epidemics and increasing immunization coverage. Surveillance of adverse events following immunization (AEFI) is a mandatory component for organization of these campaigns. Purpose. The purpose of this article is to describe the AEFI surveillance system implemented in Burkina Faso in 2008. Methods. The strategy used in Burkina Faso was based on a combination of regular passive surveillance and active surveillance. General guidelines and related operational processes were established including reporting forms, investigation forms, and procedures for collection, storage and transport of biological specimens. Classification of cases was based on clearly defined criteria. Any patient meeting the defined criteria and requiring hospitalization was considered as a serious case. In addition to case definition criteria, serious cases were tracked according to presented signs and symptoms using a line-listing form at two university hospital centers in Ouagadougou and one regional hospital center. Emergency room admission records and patient charts were examined during the surveillance period (30 days after the end of the immunization campaign) and on

Polio Eradication Initiative contribution in strengthening immunization and integrated disease surveillance data management in WHO African region, 2014.

Science.gov (United States)

Poy, Alain; Minkoulou, Etienne; Shaba, Keith; Yahaya, Ali; Gaturuku, Peter; Dadja, Landoh; Okeibunor, Joseph; Mihigo, Richard; Mkanda, Pascal

2016-10-10

The PEI Programme in the WHO African region invested in recruitment of qualified staff in data management, developing data management system and standards operating systems since the revamp of the Polio Eradication Initiative in 1997 to cater for data management support needs in the Region. This support went beyond polio and was expanded to routine immunization and integrated surveillance of priority diseases. But the impact of the polio data management support to other programmes such as routine immunization and disease surveillance has not yet been fully documented. This is what this article seeks to demonstrate. We reviewed how Polio data management area of work evolved progressively along with the expansion of the data management team capacity and the evolution of the data management systems from initiation of the AFP case-based to routine immunization, other case based disease surveillance and Supplementary immunization activities. IDSR has improved the data availability with support from IST Polio funded data managers who were collecting them from countries. The data management system developed by the polio team was used by countries to record information related to not only polio SIAs but also for other interventions. From the time when routine immunization data started to be part of polio data management team responsibility, the number of reports received went from around 4000 the first year (2005) to >30,000 the second year and to >47,000 in 2014. Polio data management has helped to improve the overall VPD, IDSR and routine data management as well as emergency response in the Region. As we approach the polio end game, the African Region would benefit in using the already set infrastructure for other public health initiative in the Region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

National Research Council Canada - National Science Library

Bovbjerg, Dana

2003-01-01

The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against caner...

Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

National Research Council Canada - National Science Library

Bovbjerg, Dana

2001-01-01

The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

National Research Council Canada - National Science Library

Bovbjerg, Dana

2002-01-01

The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

National Research Council Canada - National Science Library

Bovbjerg, Dana

2000-01-01

The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

Inherited Susceptibility to Breast Cancer in Healthy Women: Mutation in Breast Cancer Genes, Immune Surveillance, and Psychological Distress

National Research Council Canada - National Science Library

Bovbjerg, Dana

1999-01-01

The purpose of the research supported by this IDEA grant award, is to provide the first critical test of the possibility that variability in the strength of immune surveillance mechanisms against cancer...

Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver Sinusoids

Directory of Open Access Journals (Sweden)

Geissmann Frederic

2005-01-01

Full Text Available We examined the in vivo behavior of liver natural killer T cells (NKT cells by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6+ cells in liver, were found to crawl within hepatic sinusoids at 10-20 µm/min and to stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered speed or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance.

Toward rubella elimination in Poland: need for supplemental immunization activities, enhanced surveillance, and further integration with measles elimination efforts.

Science.gov (United States)

Zimmerman, Laura; Rogalska, Justyna; Wannemuehler, Kathleen A; Haponiuk, Marzena; Kosek, Adam; Pauch, Ewa; Plonska, Elzbieta; Veltze, Daniel; Czarkowski, Miroslaw P; Buddh, Nilesh; Reef, Susan; Stefanoff, Pawel

2011-07-01

All Member States of the World Health Organization (WHO) European Region have endorsed rubella elimination and congenital rubella syndrome (CRS) prevention. However, Poland has continued high levels of reported rubella. We reviewed rubella incidence in Poland since 1966 and analyzed national aggregated surveillance data from the period 2003-2008 and case-based data from 4 provinces from the period 2006-2008. We described CRS cases since 1997 and assessed maternal receipt of vaccine. We reviewed national vaccination coverage from 1992 through 2008. Since 1966, rubella outbreaks have occurred every 4-6 years in Poland. Aggregate and case-based data from the period 2003-2008 indicate that rubella virus transmission has occurred across wide age ranges (from continues. To achieve rubella elimination, supplemental immunization activities among adolescent boys are needed, as is integration with measles elimination efforts. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.

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.

Immune status investigations for radiation workers

International Nuclear Information System (INIS)

Obreja, D.; Tulbure, R.; Marinescu, I.

2002-01-01

In Romania, the enhanced development of nuclear energy leads to an increase of number of occupational exposed persons to ionizing radiation. Hence, a good knowledge of effects of ionizing radiation exposure on human body is necessary. Beginning with this decade, the opinion regarding medical surveillance of occupational exposed persons to ionizing radiation has changed - the surveillance system has to insure firstly the prevention of professional diseases. It is important to select some biological tests as helpful indicators both in immediate assessment and in health status prognosis for occupational exposed people in the future. The fact that ionizing radiation leads to immune system modifications is well known. In the last 20 years, the effect of ionizing radiation upon immune system was extensively studied, as a result of an intense research activity and of an improvement of knowledge in the field of immunology. Researches have made important steps in understanding the mechanisms of action and control for immune responses

Enhanced surveillance program FY97 accomplishments. Progress report

Energy Technology Data Exchange (ETDEWEB)

Mauzy, A. [ed.; Laake, B. [comp.

1997-10-01

This annual report is one volume of the Enhanced Surveillance Program (ESP) FY97 Accomplishments. The complete accomplishments report consists of 11 volumes. Volume 1 includes an ESP overview and a summary of selected unclassified FY97 program highlights. Volume 1 specifically targets a general audience, reflecting about half of the tasks conducted in FY97 and emphasizing key program accomplishments and contributions. The remaining volumes of the accomplishments report are classified, organized by program focus area, and present in technical detail the progress achieved in each of the 104 FY97 program tasks. Focus areas are as follows: pits; high explosives; organics; dynamics; diagnostics; systems; secondaries; nonnuclear materials; nonnuclear components; and Surveillance Test Program upgrades.

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

Adoptive transfer of immune enhancement of experimental ulcerative colitis.

OpenAIRE

Onderdonk, A B; Steeves, R M; Cisneros, R L; Bronson, R T

1984-01-01

Previous experiments with the carrageenan model for ulcerative colitis have shown that the inflammatory response in guinea pigs can be enhanced by immunization with and subsequent feeding of Bacteroides vulgatus to experimental animals. The present studies showed that only certain strains of B. vulgatus are capable of provoking immune enhancement of ulcerative colitis. Animals were fed carrageenan and various strains of viable B. vulgatus after immunization with a strain of B. vulgatus isolat...

Switch from oral to inactivated poliovirus vaccine in Yogyakarta Province, Indonesia: summary of coverage, immunity, and environmental surveillance.

Science.gov (United States)

Wahjuhono, Gendro; Revolusiana; Widhiastuti, Dyah; Sundoro, Julitasari; Mardani, Tri; Ratih, Woro Umi; Sutomo, Retno; Safitri, Ida; Sampurno, Ondri Dwi; Rana, Bardan; Roivainen, Merja; Kahn, Anna-Lea; Mach, Ondrej; Pallansch, Mark A; Sutter, Roland W

2014-11-01

Inactivated poliovirus vaccine (IPV) is rarely used in tropical developing countries. To generate additional scientific information, especially on the possible emergence of vaccine-derived polioviruses (VDPVs) in an IPV-only environment, we initiated an IPV introduction project in Yogyakarta, an Indonesian province. In this report, we present the coverage, immunity, and VDPV surveillance results. In Yogyakarta, we established environmental surveillance starting in 2004; and conducted routine immunization coverage and seroprevalence surveys before and after a September 2007 switch from oral poliovirus vaccine (OPV) to IPV, using standard coverage and serosurvey methods. Rates and types of polioviruses found in sewage samples were analyzed, and all poliovirus isolates after the switch were sequenced. Vaccination coverage (>95%) and immunity (approximately 100%) did not change substantially before and after the IPV switch. No VDPVs were detected. Before the switch, 58% of environmental samples contained Sabin poliovirus; starting 6 weeks after the switch, Sabin polioviruses were rarely isolated, and if they were, genetic sequencing suggested recent introductions. This project demonstrated that under almost ideal conditions (good hygiene, maintenance of universally high IPV coverage, and corresponding high immunity against polioviruses), no emergence and circulation of VDPV could be detected in a tropical developing country setting. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Viral immune surveillance: Toward a TH17/TH9 gate to the central nervous system.

Science.gov (United States)

Barkhordarian, Andre; Thames, April D; Du, Angela M; Jan, Allison L; Nahcivan, Melissa; Nguyen, Mia T; Sama, Nateli; Chiappelli, Francesco

2015-01-01

Viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. It is questionable as to what extent the central nervous system (CNS) is an immune-privileged organ protected by the blood-brain barrier (BBB). Recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may alter the integrity of the blood-brain barrier, and lead to inflammation, swelling of the brain parenchyma and associated neurological syndromes. Here, we expand upon the recent "gateway theory", by which viral infection and other immune activation states may disrupt the specialized tight junctions of the BBB endothelium making it permeable to immune cells and factors. The model we outline here builds upon the proposition that this process may actually be initiated by cytokines of the IL-17 family, and recognizing the intimate balance between TH17 and TH9 cytokine profiles systemically. We argue that immune surveillance events, in response to viruses such as the Human Immunodeficiency Virus (HIV), cause a TH17/TH9 induced gateway through blood brain barrier, and thus lead to characteristic neuroimmune pathology. It is possible and even probable that the novel TH17/TH9 induced gateway, which we describe here, opens as a consequence of any state of immune activation and sustained chronic inflammation, whether associated with viral infection or any other cause of peripheral or central neuroinflammation. This view could lead to new, timely and critical patient-centered therapies for patients with neuroimmune pathologies across a variety of etiologies. BBB - blood brain barrier, BDV - Borna disease virus, CARD - caspase activation and recruitment domains, CD - clusters of differentiation, CNS - central nervous system, DAMP - damage-associated molecular patterns, DENV - Dengue

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

Science.gov (United States)

Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

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

Science.gov (United States)

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

2015-06-23

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

Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.

Science.gov (United States)

Date, Kashmira A; Bentsi-Enchill, Adwoa D; Fox, Kimberley K; Abeysinghe, Nihal; Mintz, Eric D; Khan, M Imran; Sahastrabuddhe, Sushant; Hyde, Terri B

2014-10-03

Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures.

Enhanced Surveillance for the Sports Festival in Tokyo 2013: Preparation for the Tokyo 2020 Olympic and Paralympic Games.

Science.gov (United States)

Shimatani, Naotaka; Sugishita, Yoshiyuki; Sugawara, Tamie; Nakamura, Yuuki; Ohkusa, Yasushi; Yamagishi, Takuya; Matsui, Tamano; Kawano, Masashi; Watase, Hirotoshi; Morikawa, Yukiko; Oishi, Kazunori

2015-01-01

Enhanced surveillance was conducted during the Sports Festival in Tokyo 2013 (September 28-October 14, 2013) for early detection of outbreaks of infectious diseases and other health emergencies. Through this enhanced surveillance, 15 cases were found that required additional gathering of information outside the routine process of creating/evaluating the Daily Report. However, none of these was assessed as critical. Through the enhanced surveillance, we structured a framework that allows for earlier response when detecting aberrations. It includes the role of the Tokyo Metropolitan Government in communications and contacts with relevant parties such as public health centers, as well as in monitoring of surveillance data. However, some issues need to be further considered toward the Tokyo 2020 Olympic and Paralympic Games, such as establishing the criteria for additional response steps, increasing the number of participating bodies in syndromic surveillance, and strengthening of cooperation with related departments, including those for crisis management assuming potential biological/chemical terrorism.

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

DEFF Research Database (Denmark)

Åkerström, Thorbjörn; Pedersen, Bente K

2007-01-01

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

The Acceptability and Feasibility of Implementing a Bio-Behavioral Enhanced Surveillance Tool for Sexually Transmitted Infections in England: Mixed-Methods Study.

Science.gov (United States)

Wayal, Sonali; Reid, David; Blomquist, Paula B; Weatherburn, Peter; Mercer, Catherine H; Hughes, Gwenda

2018-05-04

Sexually transmitted infection (STI) surveillance is vital for tracking the scale and pattern of epidemics; however, it often lacks data on the underlying drivers of STIs. This study aimed to assess the acceptability and feasibility of implementing a bio-behavioral enhanced surveillance tool, comprising a self-administered Web-based survey among sexual health clinic attendees, as well as linking this to their electronic health records (EHR) held in England's national STI surveillance system. Staff from 19 purposively selected sexual health clinics across England and men who have sex with men and black Caribbeans, because of high STI burden among these groups, were interviewed to assess the acceptability of the proposed bio-behavioral enhanced surveillance tool. Subsequently, sexual health clinic staff invited all attendees to complete a Web-based survey on drivers of STI risk using a study tablet or participants' own digital device. They recorded the number of attendees invited and participants' clinic numbers, which were used to link survey data to the EHR. Participants' online consent was obtained, separately for survey participation and linkage. In postimplementation phase, sexual health clinic staff were reinterviewed to assess the feasibility of implementing the bio-behavioral enhanced surveillance tool. Acceptability and feasibility of implementing the bio-behavioral enhanced surveillance tool were assessed by analyzing these qualitative and quantitative data. Prior to implementation of the bio-behavioral enhanced surveillance tool, sexual health clinic staff and attendees emphasized the importance of free internet/Wi-Fi access, confidentiality, and anonymity for increasing the acceptability of the bio-behavioral enhanced surveillance tool among attendees. Implementation of the bio-behavioral enhanced surveillance tool across sexual health clinics varied considerably and was influenced by sexual health clinics' culture of prioritization of research and

Systematic review of reporting rates of adverse events following immunization: an international comparison of post-marketing surveillance programs with reference to China.

Science.gov (United States)

Guo, Biao; Page, Andrew; Wang, Huaqing; Taylor, Richard; McIntyre, Peter

2013-01-11

China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse. To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally. Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages. Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3-37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3-181.1/100,000 doses for DTwP; range 3.5-92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world. Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Can probiotics enhance vaccine-specific immunity in children and adults?

Science.gov (United States)

Kwak, J Y; Lamousé-Smith, E S N

2017-10-13

The growing use of probiotics by the general public has heightened the interest in understanding the role of probiotics in promoting health and preventing disease. General practitioners and specialists often receive inquiries from their patients regarding probiotic products and their use to ward off systemic infection or intestinal maladies. Enhanced immune function is among the touted health benefits conferred by probiotics but has not yet been fully established. Results from recent clinical trials in adults suggest a potential role for probiotics in enhancing vaccine-specific immunity. Although almost all vaccinations are given during infancy and childhood, the numbers of and results from studies using probiotics in pediatric subjects are limited. This review evaluates recent clinical trials of probiotics used to enhance vaccine-specific immune responses in adults and infants. We highlight meaningful results and the implications of these findings for designing translational and clinical studies that will evaluate the potential clinical role for probiotics. We conclude that the touted health claims of probiotics for use in children to augment immunity warrant further investigation. In order to achieve this goal, a consensus should be reached on common study designs that apply similar treatment timelines, compare well-characterised probiotic strains and monitor effective responses against different classes of vaccines.

Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway.

Science.gov (United States)

McEwan, Deborah L; Feinbaum, Rhonda L; Stroustrup, Nicholas; Haas, Wilhelm; Conery, Annie L; Anselmo, Anthony; Sadreyev, Ruslan; Ausubel, Frederick M

2016-12-07

Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P. aeruginosa or ToxA. We find that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 MAPK signaling. Through mutagenesis screening, we identify mutants of the bZIP C/EBP transcription factor cebp-1 that suppress the hypersusceptibility defects of nipi-3 mutants. NIPI-3 is a negative regulator of CEBP-1, which in turn negatively regulates protective immune mechanisms. This pathway represents a previously unknown innate immune signaling pathway in intestinal epithelial cells that is involved in the surveillance of cellular homeostasis. Because NIPI-3 and CEBP-1 are also essential for C. elegans development, NIPI-3 is analogous to other key innate immune signaling molecules such as the Toll receptors in Drosophila that have an independent role during development.

Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating beta 7+T Cells in Crohn's Disease: Report of the TOSCA Study

NARCIS (Netherlands)

D'Haens, Geert; Vermeire, Séverine; Vogelsang, Harald; Allez, Matthieu; Desreumaux, Pierre; van Gossum, Andre; Sandborn, William J.; Baumgart, Daniel C.; Ransohoff, Richard M.; Comer, Gail M.; Ahmad, Alaa; Cataldi, Fabio; Cheng, John; Clare, Robert; Gorelick, Kenneth J.; Kaminski, Annamarie; Pradhan, Vivek; Rivers, Sunday; Sikpi, Matthew O.; Zhang, Yanhua; Hassan-Zahraee, Mina; Reinisch, Walter; Stuve, Olaf

2018-01-01

Background and Aims: Progressive multifocal leukoencephalopathy [PML], a brain infection associated with anti-integrin drugs that inhibit lymphocyte translocation from bloodstream to tissue, can be fatal. Decreased central nervous system [CNS] immune surveillance leading to this infection has been

Acute flaccid paralysis surveillance in bosnia and herzegovina: Recent isolation of two sabin like type 2 poliovirus.

Science.gov (United States)

Fontana, Stefano; Buttinelli, Gabriele; Fiore, Stefano; Mulaomerovic, Mirsada; Aćimović, Jela; Amato, Concetta; Delogu, Roberto; Rezza, Giovanni; Stefanelli, Paola

2017-09-01

The WHO Regional Commission for the Certification of Poliomyelitis Eradication has recently indicated Bosnia and Herzegovina (B&H) as a high risk country for transmission, following importation, of wild poliovirus (WPV) or circulating vaccine-derived poliovirus (cVDPV). We analyzed data on Acute Flaccid Paralysis (AFP) surveillance between 2007 to 2016, and the trend of polio immunization coverage in B&H. The majority of AFP cases was recorded in 2016 suggesting an enhancement of the AFP surveillance activities. However, the decline in the immunization coverage, around 74%, and the isolation of two Sabin-like poliovirus type 2 strains, one of them close to a VDPV, require a particular attention in the area. Although B&H has successfully maintained its polio-free status since 2002 several challenges need to be addressed. © 2017 Wiley Periodicals, Inc.

Active epidemiological surveillance in the program of poliomyelitis eradication in Serbia

Directory of Open Access Journals (Sweden)

Jevremović Ivana

2002-01-01

Full Text Available The main strategy of the worldwide Program of Poliomyelitis Eradication is based on immunization with oral poliovirus vaccine and active epidemiological surveillance aimed to demonstrate the absence of wild poliovirus circulation. The specification of the surveillance in the program, reporting and investigation of certain syndrome – the acute flaccid paralysis - as a specific feature of surveillance of poliomyelitis, is a new experience both for clinicians and epidemiologists. Along with the achieved results, problems in conducting the active epidemiological surveillance in Serbia, applied measures, and suggestions for improving its quality were presented. This experience might help in implementing the active surveillance for some other diseases that could be prevented by vaccine immunization.

The immune enhancement of propolis adjuvant on inactivated porcine parvovirus vaccine in guinea pig.

Science.gov (United States)

Ma, Xia; Guo, Zhenhuan; Shen, Zhiqiang; Wang, Jinliang; Hu, Yuanliang; Wang, Deyun

2011-01-01

Two experiments were carried out. In immune response test, the immune enhancement of propolis, oilemulsion and aluminium salt were compared in guinea pig vaccinated with inactivated porcine parvovirus (PPV) vaccine. The result showed that three adjuvants could enhance antibody titer, T lymphocyte proliferation, IL-2 and IL-4 secretion of splenic lymphocyte. The action of propolis was similar to that of oilemulsion and superior to that of aluminium salt, especially in early period of vaccination propolis could accelerate antibody production. In immune protection test, the effects of three adjuvants on PPV infection were compared in guinea pig vaccinated with PPV vaccine then challenged with PPV. The result showed that propolis and oilemulsion could enhance the antibody titer, IL-2 and IL-4 content in serum and decrease the PPV content in blood and viscera. In the effect of improving cellular immune response, the propolis was the best. These results indicated that propolis possessed better immune enhancement and would be exploited into a effective adjuvant of inactivated vaccine. Copyright © 2011 Elsevier Inc. All rights reserved.

Super-enhancers: Asset management in immune cell genomes.

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Witte, Steven; O'Shea, John J; Vahedi, Golnaz

2015-09-01

Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nongenetically modified Lactococcus lactis-adjuvanted vaccination enhanced innate immunity against Helicobacter pylori.

Science.gov (United States)

Liu, Wei; Tan, Zhoulin; Liu, Hai; Zeng, Zhiqin; Luo, Shuanghui; Yang, Huimin; Zheng, Lufeng; Xi, Tao; Xing, Yingying

2017-10-01

Gram-positive enhancer matrix particles (GEM) produced by Lactococcus lactis can enhance vaccine-induced immune response. However, the mechanism under which this adjuvant mounts the efficacy of orally administered vaccines remains unexplored. We used a prophylactic mice model to investigate the mechanism of GEM-adjuvanted vaccination. Helicobacter pylori urease-specific antibody response was monitored and detected in murine serum by ELISA. Urease-specific splenic cytokine profile was examined. Gastric inflammatory responses were measured on day 43 or 71 by quantitative real-time PCR, flow cytometry and histology. We found that GEM enhanced the efficiency of oral H. pylori vaccine by promoting innate immunity. The vaccine CUE-GEM composed of GEM particles and recombinant antigen CTB-UE provided protection of immunized mice against H. pylori insult. The protective response was associated with induction of postimmunization gastritis and local Th1/Th17 cell-medicated immune response. We showed that innate inflammatory responses including neutrophil chemokines CXCL1-2, neutrophils, and antimicrobial proteins S100A8 and MUC1 were significantly elevated. Within all infected mice, S100A8 and MUC1 levels were negatively correlated with H. pylori burden. Strikingly, mice receiving GEM also show reduction of colonization, possibly through natural host response pathways to recruit CD4 + T cells and promote S100A8 expression. These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection. © 2017 John Wiley & Sons Ltd.

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

Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.

Science.gov (United States)

Hopke, Alex; Brown, Alistair J P; Hall, Rebecca A; Wheeler, Robert T

2018-04-01

Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

γ-Oryzanol-Rich Black Rice Bran Extract Enhances the Innate Immune Response.

Science.gov (United States)

Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Lim, Yoongho; Kim, Jung-Bong; Lee, Young Han

2017-09-01

The innate immune response is an important host primary defense system against pathogens. γ-Oryzanol is one of the nutritionally important phytoceutical components in rice bran oil. The goal of this study was to investigate the effect of γ-oryzanol-rich extract from black rice bran (γORE) on the activation of the innate immune system. In this study, we show that γORE increased the expression of CD14 and Toll-like receptor 4 and enhanced the phagocytic activity of RAW264.7 macrophages. Furthermore, γORE and its active ingredient γ-oryzanol promoted the secretion of innate cytokines, interleukin-8, and CCL2, which facilitate phagocytosis by RAW264.7 cells. These findings suggest that γ-oryzanol in the γORE enhances innate immune responses.

Immunity and skin cancer

International Nuclear Information System (INIS)

Smith, E.B.; Brysk, M.M.

1981-01-01

Observations in humans and animal studies support the theory that immunologic surveillance plays an important role in limiting the development of skin malignancies. These immune responses undergo progressive diminution with age. In addition, other factors, such as bereavement, poor nutrition, and acute and chronic exposure to ultraviolet light, can further diminish immune mechanisms

Enhanced surveillance of Staphylococcus aureus bacteraemia to identify targets for infection prevention.

Science.gov (United States)

Morris, A K; Russell, C D

2016-06-01

Surveillance of Staphylococcus aureus bacteraemia (SAB) in Scotland is limited to the number of infections per 100,000 acute occupied bed-days and susceptibility to meticillin. To demonstrate the value of enhanced SAB surveillance to identify targets for infection prevention. Prospective cohort study of all patients identified with SAB over a five-year period in a single health board in Scotland. All patients were reviewed at the bedside by a clinical microbiologist. In all, 556 SAB episodes were identified: 261 (46.6%) were hospital-acquired; 209 (37.9%) were healthcare-associated; 80 (14.4%) were community-acquired; and in six (1.1%) the origin of infection was not hospital-acquired, but could not be separated into healthcare-associated or community-acquired. These were classified as non-hospital-acquired. Meticillin-resistant S. aureus (MRSA) bacteraemia was associated with hospital-acquired and healthcare-associated infections. In addition, there was a significantly higher 30-day mortality associated with hospital-acquired (31.4%) and healthcare-associated (16.3%) infections compared to community-acquired SAB (8.7%). Vascular access devices were associated with hospital-acquired SAB and peripheral venous cannulas were the source for most of these (43.9%). Community-acquired infections were associated with intravenous drug misuse, respiratory tract infections and skeletal and joint infections. Skin and soft tissue infections were more widely seen in healthcare-associated infections. The data indicate that enhanced surveillance of SAB by origin of infection and source of bacteraemia has implications for infection prevention, empirical antibiotic therapy, and health improvement interventions. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Enhanced Disease Surveillance during the 2012 Republican National Convention, Tampa, FL

Science.gov (United States)

Atrubin, David; Wiese, Michael; Snider, Rebecca; Workman, Kiley; McDougle, Warren

2013-01-01

deployed in Tampa during the RNC. Data was collected electronically and transmitted through ESSENCE as well. The HCHD also asked infection preventionists, health care providers, hotels, labs, and Mosquito Control to lower their reporting threshold to us during the RNC period. We provided updates to all our partners with respect to diseases and outbreaks of public health importance occurring in our county. Results No epidemiologic events linked to the RNC were detected through the HCHD’s enhanced surveillance that was conducted. Decreased patient volumes were seen during the RNC at our EDs closest to the convention site. No significant increases in ED visits from outside of our 5-county area were noted during the RNC. Urgent care centers reported seeing patients associated with the RNC for a variety of reasons including respiratory and gastrointestinal illness. DMAT surveillance showed mainly routine visits but four secret service agents did seek care for respiratory illness during the convention. Conclusions Substantial time and resources were devoted to disease surveillance in the 6 months leading up to the RNC and during the event. While no epidemiologic events were detected, the public health surveillance infrastructure has clearly been strengthened in our county. We are receiving our ED syndromic data, from many of our hospitals, every two hours as opposed to every day. We have established relationships with our urgent case centers and hope to begin receiving urgent care center data on a daily basis in the near future. Receiving DMAT data through ESSENCE could prove very useful in the future, especially in Florida where hurricanes are always a threat. Lastly the improved relationships with our health care providers should be beneficial as we move forward.

Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

Science.gov (United States)

Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

2010-01-01

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

Wide-band coherent receiver development for enhanced surveillance

International Nuclear Information System (INIS)

Simpson, M.L.; Richards, R.K.; Hutchinson, D.P.

1998-03-01

Oak Ridge National Laboratory (ORNL) has been developing advanced coherent IR heterodyne receivers for plasma diagnostics in fusion reactors for over 20 years. Recent progress in wide band IR detectors and high speed electronics has significantly enhanced the measurement capabilities of coherent receivers. In addition, developments in new HgCdTe and quantum well IR photodetector (QWIP) focal plane arrays are providing the possibility of both active and passive coherent imaging. In this paper the authors discuss the implications of these new enabling technologies to the IR remote sensing community for enhanced surveillance. Coherent receivers, as opposed to direct or thermal detection, provide multiple dimensions of information about a scene or target in a single detector system. Combinations of range, velocity, temperature, and chemical species information are all available from a coherent heterodyne receiver. They present laboratory data showing measured noise equivalent power (NEP) of new QWIP detectors with heterodyne bandwidths greater than 7 GHz. For absorption measurements, a wide band coherent receiver provides the capability of looking between CO 2 lines at off-resonance peaks and thus the measurement of lines normally inaccessible with conventional heterodyne or direct detection systems. Also described are differential absorption lidar (DIAL) and Doppler laboratory measurements using an 8 x 8 HgCdTe focal plane array demonstrating the snapshot capability of coherent receiver detector arrays for enhanced chemical plume and moving hardbody capture. Finally they discuss a variety of coherent receiver configurations that can suppress (or enhance) sensitivity of present active remote sensing systems to speckle, glint, and other measurement anomalies

Enhancement of Immune Memory Responses to Respiratory Infection

Science.gov (United States)

2017-08-01

Unlimited Distribution 13. SUPPLEMENTARY NOTES 14. ABSTRACT Maintenance of long - term immunological memory against pathogens is crucial for the rapid...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long - term memory B cells needed to protect against influenza...AWARD NUMBER: W81XWH-16-1-0361 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Farrah

Local and systemic tumor immune dynamics

Science.gov (United States)

Enderling, Heiko

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

Enhancing Security and Privacy in Video Surveillance through Role-Oriented Access Control Mechanism

DEFF Research Database (Denmark)

Mahmood Rajpoot, Qasim

sensitive regions, e.g. faces, from the videos. However, very few research efforts have focused on addressing the security aspects of video surveillance data and on authorizing access to this data. Interestingly, while PETs help protect the privacy of individuals, they may also hinder the usefulness....... Pervasive usage of such systems gives substantial powers to those monitoring the videos and poses a threat to the privacy of anyone observed by the system. Aside from protecting privacy from the outside attackers, it is equally important to protect the privacy of individuals from the inside personnel...... involved in monitoring surveillance data to minimize the chances of misuse of the system, e.g. voyeurism. In this context, several techniques to protect the privacy of individuals, called privacy enhancing techniques (PET) have therefore been proposed in the literature which detect and mask the privacy...

Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

Science.gov (United States)

Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

2013-01-01

, when a subclinical, mild thyroiditis was induced with soluble mTg and low doses of interleukin-1, to simulate pre-existing autoimmunity in patients subjected to cancer immunotherapy, mononuclear infiltration into the thyroid was enhanced. Conclusions: Our current findings indicate that genetic predisposition to autoimmune disease could enhance autoimmunity during induction of tumor immunity in thyroiditis-susceptible mice. Thus, HLA genotyping of cancer patients should be part of any risk assessment. PMID:23777580

Transgenerational effects enhance specific immune response in a wild passerine

Directory of Open Access Journals (Sweden)

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.

Oral antibiotics enhance antibody responses to keyhole limpet hemocyanin in orally but not muscularly immunized chickens.

Science.gov (United States)

Murai, Atsushi; Kitahara, Kazuki; Okumura, Shouta; Kobayashi, Misato; Horio, Fumihiko

2016-02-01

Recent studies have emphasized the crucial role of gut microbiota in triggering and modulating immune response. We aimed to determine whether the modification of gut microbiota by oral co-administration of two antibiotics, ampicillin and neomycin, would lead to changes in the antibody response to antigens in chickens. Neonatal chickens were given or not given ampicillin and neomycin (0.25 and 0.5 g/L, respectively) in drinking water. At 2 weeks of age, the chicks were muscularly or orally immunized with antigenic keyhole limpet hemocyanin (KLH), and then serum anti-KLH antibody levels were examined by ELISA. In orally immunized chicks, oral antibiotics treatment enhanced antibody responses (IgM, IgA, IgY) by 2-3-fold compared with the antibiotics-free control, while the antibiotics did not enhance antibody responses in the muscularly immunized chicks. Concomitant with their enhancement of antibody responses, the oral antibiotics also lowered the Lactobacillus species in feces. Low doses of antibiotics (10-fold and 100-fold lower than the initial trial), which failed to change the fecal Lactobacillus population, did not modify any antibody responses when chicks were orally immunized with KLH. In conclusion, oral antibiotics treatment enhanced the antibody response to orally exposed antigens in chickens. This enhancement of antibody response was associated with a modification of the fecal Lactobacillus content, suggesting a possible link between gut microbiota and antibody response in chickens. © 2015 Japanese Society of Animal Science.

SHORT-TERM STRESS ENHANCES CELLULAR IMMUNITY AND INCREASES EARLY RESISTANCE TO SQUAMOUS CELL CARCINOMA

OpenAIRE

Dhabhar, Firdaus S.; Saul, Alison N.; Daugherty, Christine; Holmes, Tyson H.; Bouley, Donna M.; Oberyszyn, Tatiana M.

2009-01-01

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposu...

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

WHO global rotavirus surveillance network: a strategic review of the first 5 years, 2008-2012.

Science.gov (United States)

Agócs, Mary M; Serhan, Fatima; Yen, Catherine; Mwenda, Jason M; de Oliveira, Lúcia H; Teleb, Nadia; Wasley, Annemarie; Wijesinghe, Pushpa R; Fox, Kimberley; Tate, Jacqueline E; Gentsch, Jon R; Parashar, Umesh D; Kang, Gagandeep

2014-07-25

Since 2008, the World Health Organization (WHO) has coordinated the Global Rotavirus Surveillance Network, a network of sentinel surveillance hospitals and laboratories that report to ministries of health (MoHs) and WHO clinical features and rotavirus testing data for children aged reporting and testing inclusion criteria for data analysis. Of the 37 countries with sites meeting inclusion criteria, 13 (35%) had introduced rotavirus vaccine nationwide. All 79 sites included in the analysis were meeting 2008 network objectives of documenting presence of disease and describing disease epidemiology, and all countries were using the rotavirus surveillance data for vaccine introduction decisions, disease burden estimates, and advocacy; countries were in the process of assessing the use of this surveillance platform for other vaccine-preventable diseases. However, the review also indicated that the network would benefit from enhanced management, standardized data formats, linkage of clinical data with laboratory data, and additional resources to support network functions. In November 2013, WHO's Strategic Advisory Group of Experts on Immunization (SAGE) endorsed the findings and recommendations made by the review team and noted potential opportunities for using the network as a platform for other vaccine-preventable disease surveillance. WHO will work to implement the recommendations to improve the network's functions and to provide higher quality surveillance data for use in decisions related to vaccine introduction and vaccination program sustainability.

Potential immediate hypersensitivity reactions following immunization in preschool aged children in Victoria, Australia.

Science.gov (United States)

Baxter, C-M; Clothier, H J; Perrett, K P

2018-04-06

Immediate hypersensitivity reactions (IHR) are rare but potentially serious adverse events following immunization (AEFI). Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC) is an enhanced passive surveillance system that collects, analyses and reports information about AEFI in Victoria, Australia. We describe the incidence, timing and type of potential IHR following vaccination in preschool children reported over an 8-year period. A total of 2110 AEFI were reported in 1620 children, of which 23.5% (496) were classified as potential IHR. Of these, 37.1% (184) were suspected to be IgE-mediated, (including anaphylaxis, angioedema and/or urticaria) and 83.5% (414) occurred within 15 minutes of vaccination. The incidence of potential IHR was 5.4 per 100,000 doses, with that of suspected IgE-mediated IHR being 2.0 per 100,000 doses. The incidence of anaphylaxis was extremely low (0.13 per 100,000 doses) and is consistent with other published studies. Potential IHR following immunization should be reported to appropriate local pharmacovigilance systems and patients reviewed by specialists able to evaluate, investigate and manage future vaccinations.

Use of m-Health in polio eradication and other immunization activities in developing countries.

Science.gov (United States)

Kim, Sara S; Patel, Manish; Hinman, Alan

2017-03-07

Reaching the children that are chronically missed by routine immunization services has been a key pillar of success in achieving progress toward polio eradication. The rapid advancement and accessibility of mobile technology ("mHealth") in low and lower middle income countries provides an important opportunity to apply novel, innovative approaches to provide vaccine services. We sought to document the use and effectiveness of mHealth in immunization programs in low and lower middle income countries. We particularly focused on mHealth approaches used in polio eradication efforts by the Global Polio Eradication Initiative (GPEI) to leverage the knowledge and lessons learned that may be relevant for enhancing ongoing immunization services. In June 2016, the electronic database PubMed was searched for peer reviewed studies that focused on efforts to improve immunization programs (both ongoing immunization services and supplemental immunization activities or campaigns) through mobile technology in low and lower middle income countries. The search yielded 317 papers of which 25 met the inclusion criteria. One additional article was included from the hand searching process. mHealth was used for reminder and recall, monitoring and surveillance, vaccine acceptance, and campaign strategic planning. Mobile phones were the most common mobile device used. Of the 26 studies, 21 of 26 studies (80.8%) reported that mHealth improved immunization efforts. mHealth interventions can effectively enhance immunization services in low and lower middle income countries. With the growing capacity and access to mobile technology, mHealth can be a powerful and sustainable tool for enhancing the reach and impact of vaccine programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Suppressive influences in the immune response to cancer.

Science.gov (United States)

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.

A GIS-driven integrated real-time surveillance pilot system for national West Nile virus dead bird surveillance in Canada

Directory of Open Access Journals (Sweden)

Aramini Jeff

2006-04-01

Full Text Available Abstract Background An extensive West Nile virus surveillance program of dead birds, mosquitoes, horses, and human infection has been launched as a result of West Nile virus first being reported in Canada in 2001. Some desktop and web GIS have been applied to West Nile virus dead bird surveillance. There have been urgent needs for a comprehensive GIS services and real-time surveillance. Results A pilot system was developed to integrate real-time surveillance, real-time GIS, and Open GIS technology in order to enhance West Nile virus dead bird surveillance in Canada. Driven and linked by the newly developed real-time web GIS technology, this integrated real-time surveillance system includes conventional real-time web-based surveillance components, integrated real-time GIS components, and integrated Open GIS components. The pilot system identified the major GIS functions and capacities that may be important to public health surveillance. The six web GIS clients provide a wide range of GIS tools for public health surveillance. The pilot system has been serving Canadian national West Nile virus dead bird surveillance since 2005 and is adaptable to serve other disease surveillance. Conclusion This pilot system has streamlined, enriched and enhanced national West Nile virus dead bird surveillance in Canada, improved productivity, and reduced operation cost. Its real-time GIS technology, static map technology, WMS integration, and its integration with non-GIS real-time surveillance system made this pilot system unique in surveillance and public health GIS.

Novel "Elements" of Immune Suppression within the Tumor Microenvironment.

Science.gov (United States)

Gurusamy, Devikala; Clever, David; Eil, Robert; Restifo, Nicholas P

2017-06-01

Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR . ©2017 American Association for Cancer Research.

Enhanced experimental tumor metastasis with age in senescence-accelerated mouse

International Nuclear Information System (INIS)

Shimizu, Kosuke; Kinouchi Shimizu, Naomi; Asai, Tomohiro; Oku, Naoto; Tsukada, Hideo

2008-01-01

Tumor metastasis is affected by the host immune surveillance system. Since aging may attenuate the host immune potential, the experimental tumor metastasis may be enhanced with age. In the present study, we investigated this alteration of experimental tumor metastasis with age. We used senescence-accelerated mice prone 10 (SAMP10) as a model of aged animals. Natural killer cell (NK) activity, as an indicator of immune surveillance potential, in 8-month-old (aged) SAMP10 mice was observed to be much lower than that in 2-month-old (young) mice. When we examined the in vivo trafficking of lung-metastatic K1735M2 melanoma cells in SAMP10 with positron emission tomography (PET), K1735M2 cells labeled with [2- 18 F]2-deoxy-2-fluoro-D-glucose ([ 18 F]FDG) were observed in both young and aged SAMP10 just after injection of the cells, whereas the clearance of 18 F from the lungs was retarded in aged animals. The accumulation of 5-[ 125 I]iodo-2'-deoxyuridine ([ 125 I]IUdR)-labeled K1735M2 cells in the lungs of SAMP10 at 24 h after injection was significantly higher in aged mice. Corresponding to these results, the number of metastatic colonies in the lung was larger in the aged SAMP10 of the experimental tumor metastasis model. The present study demonstrated that the aging process produced a susceptible environment allowing the tumor cells to metastasize due to decrease in the host immune surveillance potential with age. (author)

Improving microphage innate immunity by modulating protein ...

International Development Research Centre (IDRC) Digital Library (Canada)

Diseases that result from an infection are most often resolved by cells that use an immune response to clear foreign agents. ... The authors hypothesize that certain PTPs favour the generation of the pro-inflammatory M1 macrophages, thereby regulating the functions leading to promoting immune surveillance and killing of ...

Regional Disease Surveillance Meeting - Final Paper

Energy Technology Data Exchange (ETDEWEB)

Lesperance, Ann M.; Mahy, Heidi A.

2006-08-08

On June 1, 2006, public health officials working in surveillance, epidemiological modeling, and information technology communities from the Seattle/Tacoma area and State of Washington met with members of the Pacific Northwest National Laboratory (PNNL) to discuss the current state of disease surveillance and gaps and needs to improve the current systems. The meeting also included a discussion of PNNL initiatives that might be appropriate to enhance disease surveillance and the current tools being used for disease surveillance. Participants broke out into two groups to identify critical gaps and needs for improving a surveillance system, and discuss the requirements for developing improved surveillance. Each group developed a list of key priorities summarizing the requirements for improved surveillance. The objective of this meeting was to work towards the development of an improved disease surveillance system.

Measuring polio immunity to plan immunization activities.

Science.gov (United States)

Voorman, Arend; Lyons, Hil M

2016-11-21

The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Noise-Immune Cavity-Enhanced Optical Frequency Comb Spectroscopy

Science.gov (United States)

Rutkowski, Lucile; Khodabakhsh, Amir; Johanssson, Alexandra C.; Foltynowicz, Aleksandra

2015-06-01

We present noise-immune cavity-enhanced optical frequency comb spectroscopy (NICE-OFCS), a recently developed technique for sensitive, broadband, and high resolution spectroscopy. In NICE-OFCS an optical frequency comb (OFC) is locked to a high finesse cavity and phase-modulated at a frequency precisely equal to (a multiple of) the cavity free spectral range. Since each comb line and sideband is transmitted through a separate cavity mode in exactly the same way, any residual frequency noise on the OFC relative to the cavity affects each component in an identical manner. The transmitted intensity contains a beat signal at the modulation frequency that is immune to frequency-to-amplitude noise conversion by the cavity, in a way similar to continuous wave noise-immune cavity-enhanced optical heterodyne molecular spectroscopy (NICE-OHMS). The light transmitted through the cavity is detected with a fast-scanning Fourier-transform spectrometer (FTS) and the NICE-OFCS signal is obtained by fast Fourier transform of the synchronously demodulated interferogram. Our NICE-OFCS system is based on an Er:fiber femtosecond laser locked to a cavity with a finesse of ˜9000 and a fast-scanning FTS equipped with a high-bandwidth commercial detector. We measured NICE-OFCS signals from the 3νb{1}+νb{3} overtone band of CO_2 around 1.57 μm and achieved absorption sensitivity 6.4×10-11cm-1 Hz-1/2 per spectral element, corresponding to a minimum detectable CO_2 concentration of 25 ppb after 330 s integration time. We will describe the principles of the technique and its technical implementation, and discuss the spectral lineshapes of the NICE-OFCS signals. A. Khodabakhsh, C. Abd Alrahman, and A. Foltynowicz, Opt. Lett. 39, 5034-5037 (2014). J. Ye, L. S. Ma, and J. L. Hall, J. Opt. Soc. Am. B 15, 6-15 (1998). A. Khodabakhsh, A. C. Johansson, and A. Foltynowicz, Appl. Phys. B (2015) doi:10.1007/s00340-015-6010-7.

The role of recombinant IL-12 in enhancing immune responses induced by hepatitis B vaccine in mice

International Nuclear Information System (INIS)

Lu Qun; Zhou Lixia; Zhao Yanrong; Miao Xiaoguang; Jin Jie; Ke Jinshan; Qin Xuliang; He Zheng

2007-01-01

Objective: To study the role played by recombinant IL-12 in enhancing the intensity and quality of the immune response to hepatitis B vaccine in mice, and investigate the possibility of adding recombinant IL-12 as adjuvants to hepatitis B therapeutic vaccine. Methods: Recombinant IL-12 was injected together with hepatitis B vaccine into mice and special anti-HBsAb in the mice and the cellular immune responses were examined. Results: Recombinant IL-12 can obviously enhance T lymphocyte multiplication activity, accelerate excretion of cytokines IFN-γ and IL-2, and increase the IgG2a antibody in mice. Conclusion: Recombinant IL-12 can remarkably strengthen the cellular immune responses induced by the hepatitis B vaccine, and modulate the immune responses toward Thl. (authors)

Protocol for hospital based-surveillance of cerebral palsy (CP) in Hanoi using the Paediatric Active Enhanced Disease Surveillance mechanism (PAEDS-Vietnam): a study towards developing hospital-based disease surveillance in Vietnam.

Science.gov (United States)

Khandaker, Gulam; Van Bang, Nguyen; Dũng, Trịnh Quang; Giang, Nguyen Thi Huong; Chau, Cao Minh; Van Anh, Nguyen Thi; Van Thuong, Nguyen; Badawi, Nadia; Elliott, Elizabeth J

2017-11-09

The epidemiology, pathogenesis, management and outcomes of cerebral palsy (CP) in low-income and middle-income countries including Vietnam are unknown because of the lack of mechanisms for standardised collection of data. In this paper, we outline the protocol for developing a hospital-based surveillance system modelled on the Paediatric Active Enhanced Disease Surveillance (PAEDS) system in Australia. Using PAEDS-Vietnam we will define the aetiology, motor function and its severity, associated impairments, and nutritional and rehabilitation status of children with CP in Hanoi, Vietnam. These essential baseline data will inform future health service planning, health professional education and training, and family support. This is a hospital-based prospective surveillance of children with CP presenting to the rehabilitation, neurology and general paediatric services at the National Children's Hospital and St Paul Hospital in Hanoi. We will use active, prospective daily case-finding for all children with CP aged CP, known risk factors for CP, and nutrition, immunisation, education and rehabilitation status. This study was approved by the Hanoi Medical University Institutional Review Board (decision no 1722) and The University of Sydney Human Research Ethics Committee (approval no 2016/456). Establishment of PAEDS-Vietnam will enable hospital-based surveillance of CP for the first time in Vietnam. It will identify preventable causes of CP, patient needs and service gaps, and facilitate early diagnosis and intervention. Study findings will be disseminated through local and international conferences and peer-reviewed publications. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Science.gov (United States)

McGranahan, Nicholas; Furness, Andrew J. S.; Rosenthal, Rachel; Ramskov, Sofie; Lyngaa, Rikke; Saini, Sunil Kumar; Jamal-Hanjani, Mariam; Wilson, Gareth A.; Birkbak, Nicolai J.; Hiley, Crispin T.; Watkins, Thomas B. K.; Shafi, Seema; Murugaesu, Nirupa; Mitter, Richard; Akarca, Ayse U.; Linares, Joseph; Marafioti, Teresa; Henry, Jake Y.; Van Allen, Eliezer M.; Miao, Diana; Schilling, Bastian; Schadendorf, Dirk; Garraway, Levi A.; Makarov, Vladimir; Rizvi, Naiyer A.; Snyder, Alexandra; Hellmann, Matthew D.; Merghoub, Taha; Wolchok, Jedd D.; Shukla, Sachet A.; Wu, Catherine J.; Peggs, Karl S.; Chan, Timothy A.; Hadrup, Sine R.; Quezada, Sergio A.; Swanton, Charles

2016-01-01

As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8+ tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens. PMID:26940869

Multivalent Porous Silicon Nanoparticles Enhance the Immune Activation Potency of Agonistic CD40 Antibody

Science.gov (United States)

Gu, Luo; Ruff, Laura E.; Qin, Zhengtao; Corr, Maripat P.; Hedrick, Stephen M.; Sailor, Michael J.

2012-01-01

One of the fundamental paradigms in the use of nanoparticles to treat disease is to evade or suppress the immune system in order to minimize systemic side effects and deliver sufficient nanoparticle quantities to the intended tissues. However, the immune system is the body's most important and effective defense against diseases. It protects the host by identifying and eliminating foreign pathogens as well as selfmalignancies. Here we report a nanoparticle engineered to work with the immune system, enhancing the intended activation of antigen presenting cells (APCs). We show that luminescent porous silicon nanoparticles (LPSiNPs), each containing multiple copies of an agonistic antibody (FGK45) to the APC receptor CD40, greatly enhance activation of B cells. The cellular response to the nanoparticle-based stimulators is equivalent to a 30–40 fold larger concentration of free FGK45. The intrinsic near-infrared photoluminescence of LPSiNPs is used to monitor degradation and track the nanoparticles inside APCs. PMID:22689074

Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry

Science.gov (United States)

2007-05-30

Intercontinental circulation of human influenza A( H1N2 ) reassortant viruses during the 2001–2002 influenza season. J Infect Dis 186: 1490–1493. 6. Taubenberger...Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry Rangarajan Sampath1*, Kevin L. Russell2, Christian Massire1, Mark W...Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America Background. Effective influenza surveillance requires

Systèmes de surveillance de la fièvre jaune en Afrique : rôle des centres OMS et place de la surveillance entomologique

OpenAIRE

Thonnon, J.; Mathiot, C.; Fontenille, Didier

1998-01-01

WHO Collaborating Centers, or (by default) designated national laboratories, intervene at two levels in the surveillance of yellow fever : (1) upstream, through knowledge and analysis of risk factors linked to vectors and populations, including : collection of entomological data (surveillance of the sylvatic cycle, Kédougou, Senegal), measuring the risk of an outbreak in urban areas (quantity of larvae of #Aedes aegypti$), measuring the national immunity to yellow fever among human population...

Syndromic Surveillance: Enhancing Detection of Disease Outbreaks in Urban China

NARCIS (Netherlands)

Pilot, E.; Schwarz, C.; Wang, L.; Krafft, T.; Wang, W.; Krafft, T.; Rosenberg, M.; Pilot, E.

2014-01-01

Recently a number of innovative surveillance approaches have been piloted or implemented in several parts of the country. Though Chinese cities have usually a sufficient health infrastructure that is included in the national surveillance system, the differences in treatment seeking behavior of a

Kefir milk enhances intestinal immunity in young but not old rats.

Science.gov (United States)

Thoreux, K; Schmucker, D L

2001-03-01

The adjuvant effect of kefir fermented milk on the mucosal and systemic immune systems was examined in young (6 mo old) and old (26 mo old) rats. Kefir-fed rats consisted of young or old rats consuming kefir-fermented milk ad libitum on a daily basis in addition to the standard diet, for 28 d. Control rats consumed only the standard diet. The rats were immunized intraduodenally with cholera toxin (CT) on d 7 and 21 and killed on d 28. The nonspecific serum immunoglobulin (Ig)A titers in kefir-fed and control rats did not differ in either age group. The serum anti-CT IgA antibody concentrations were significantly higher in the kefir-fed young rats compared with their age-matched controls (+86%, P: 120%, P: kefir-fed rats compared with their respective controls. Nevertheless, these results demonstrate that a kefir-supplemented diet affects the intestinal mucosal and systemic immune responses to intraduodenal CT differently in young and old rats. Most importantly, our data suggest that orally administered kefir enhances the specific intestinal mucosal immune response against CT in young adult, but not in senescent rats.

Daidzein enhances immune function in late lactation cows under heat stress.

Science.gov (United States)

Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting

2014-01-01

Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.

C3d enhanced DNA vaccination induced humoral immune response to glycoprotein C of pseudorabies virus

International Nuclear Information System (INIS)

Tong Tiezhu; Fan Huiying; Tan Yadi; Xiao Shaobo; Ling Jieyu; Chen Huanchun; Guo Aizhen

2006-01-01

Murine C3d were utilized to enhance immunogenicity of pseudorabies virus (PrV) gC DNA vaccination. Three copies of C3d and four copies of CR2-binding domain M28 4 were fused, respectively, to truncated gC gene encoding soluble glycoprotein C (sgC) in pcDNA3.1. BALB/c mice were, respectively, immunized with recombinant plasmids, blank vector, and inactivated vaccine. The antibody ELISA titer for sgC-C3d 3 DNA was 49-fold more than that for sgC DNA, and the neutralizing antibody obtained 8-fold rise. Protection of mice from death after lethal PrV (316 LD 5 ) challenge was augmented from 25% to 100%. Furthermore, C3d fusion increased Th2-biased immune response by inducing IL-4 production. The IL-4 level for sgC-C3d 3 DNA immunization approached that for the inactivated vaccine. Compared to C3d, M28 enhanced sgC DNA immunogenicity to a lesser extent. In conclusion, we demonstrated that murine C3d fusion significantly enhanced gC DNA immunity by directing Th1-biased to a balanced and more effective Th1/Th2 response

Infectious disease surveillance for the London 2012 Olympic and Paralympic Games.

Science.gov (United States)

Severi, E; Heinsbroek, E; Watson, C; Catchpole, M

2012-08-02

The London 2012 Olympic and Paralympic Games will be one of the largest mass gathering events in British history. In order to minimise potential infectious disease threats related to the event, the Health Protection Agency (HPA) has set up a suite of robust and multisource surveillance systems. These include enhancements of already established systems (notification of infectious diseases, local and regional reporting,laboratory surveillance, mortality surveillance, international surveillance, and syndromic surveillance in primary care), as well as new systems created for the Games (syndromic surveillance in emergency departments and out-of-hours/unscheduled care,undiagnosed serious infectious illness surveillance).Enhanced existing and newly established surveillance systems will continue after the Games or will be ready for future reactivation should the need arise. In addition to the direct improvements to surveillance, the strengthening of relationships with national and international stakeholders will constitute a major post-Games legacy for the HPA.

Au@Pt nanoparticles as catalase mimics to attenuate tumor hypoxia and enhance immune cell-mediated cytotoxicity

Science.gov (United States)

Liang, Hong; Wu, Ying; Ou, Xiang-Yu; Li, Jing-Ying; Li, Juan

2017-11-01

Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor-1α expression. Furthermore, the integration of high catalytic efficiency of Au@Pt NPs with cytokine-induced killer (CIK) cell immunotherapy, could lead to significantly improve the effect of CIK cell-mediated cytotoxicity. These results suggest great potential of Au@Pt NPs for regulation of the hypoxic TME and enhance immune cell mediated anti-tumor immunity.

Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

Science.gov (United States)

Vinay, Dass S; Ryan, Elizabeth P; Pawelec, Graham; Talib, Wamidh H; Stagg, John; Elkord, Eyad; Lichtor, Terry; Decker, William K; Whelan, Richard L; Kumara, H M C Shantha; Signori, Emanuela; Honoki, Kanya; Georgakilas, Alexandros G; Amin, Amr; Helferich, William G; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Keith, W Nicol; Bilsland, Alan; Bhakta, Dipita; Halicka, Dorota; Fujii, Hiromasa; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan; Choi, Beom K; Kwon, Byoung S

2015-12-01

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion.

Science.gov (United States)

Prescher, Horst; Frank, Martin; Gütgemann, Stephan; Kuhfeldt, Elena; Schweizer, Astrid; Nitschke, Lars; Watzl, Carsten; Brossmer, Reinhard

2017-02-09

Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion. The compounds are Sialic acid derivatives and bind with low micromolar K d values to Siglec-7. They display up to a 5000-fold enhanced affinity over the unmodified sialic acid scaffold αMe Neu5Ac, the smallest known natural Siglec-7 ligand. Our results provide a novel immuno-oncology strategy employing natural immunity in the fight against cancers, in particular blocking Siglec-7 with low molecular weight compounds.

Vaccination Enhances Early Immune Responses in White Shrimp Litopenaeus vannamei after Secondary Exposure to Vibrio alginolyticus

Science.gov (United States)

Lin, Yong-Chin; Chen, Jiann-Chu; Morni, Wan Zabidii W.; Putra, Dedi Fazriansyah; Huang, Chien-Lun; Li, Chang-Che; Hsieh, Jen-Fang

2013-01-01

Background Recent work suggested that the presence of specific memory or some form of adaptive immunity occurs in insects and shrimp. Hypervariable pattern recognition molecules, known as Down syndrome cell adhesion molecules, are able to mount specific recognition, and immune priming in invertebrates. In the present study, we attempted to understand the immune response pattern of white shrimp Litopenaeus vannamei which received primary (PE) and secondary exposure (SE) to Vibrio alginolyticus. Methodology Immune parameters and proliferation of haematopoietic tissues (HPTs) of shrimp which had received PE and SE to V. alginolyticus were measured. In the PE trial, the immune parameters and proliferation of HPTs of shrimp that received heat-killed V. alginolyticus (HVa) and formalin-inactivated V. alginolyticus (FVa) were measured. Mortality, immune parameters and proliferation of HPTs of 7-day-HVa-PE shrimp (shrimp that received primary exposure to HVa after 7 days) and 7-day-FVa-PE shrimp (shrimp that received primary exposure to FVa after 7 days) following SE to live V. alginolyticus (LVa) were measured. Phagocytic activity and clearance efficiency were examined for the 7∼35-day-HVa-PE and FVa-PE shrimp. Results HVa-receiving shrimp showed an earlier increase in the immune response on day 1, whereas FVa-receiving shrimp showed a late increase in the immune response on day 5. The 7-day-FVa-PE shrimp showed enhancement of immunity when encountering SE to LVa, whereas 7-day-HVa-PE shrimp showed a minor enhancement in immunity. 7-day-FVa-PE shrimp showed higher proliferation and an HPT mitotic index. Both phagocytic activity and clearance maintained higher for both HVa-PE and FVa-PE shrimp after 28 days. Conclusions HVa- and FVa-receiving shrimp showed the bacteria agglutinated prior to being phagocytised. FVa functions as a vaccine, whereas HVa functions as an inducer and can be used as an immune adjuvant. A combined mixture of FVa and HVa can serve as a �

Cost analysis of an integrated vaccine-preventable disease surveillance system in Costa Rica.

Science.gov (United States)

Toscano, C M; Vijayaraghavan, M; Salazar-Bolaños, H M; Bolaños-Acuña, H M; Ruiz-González, A I; Barrantes-Solis, T; Fernández-Vargas, I; Panero, M S; de Oliveira, L H; Hyde, T B

2013-07-02

Following World Health Organization recommendations set forth in the Global Framework for Immunization Monitoring and Surveillance, Costa Rica in 2009 became the first country to implement integrated vaccine-preventable disease (iVPD) surveillance, with support from the U.S. Centers for Disease Control and Prevention (CDC) and the Pan American Health Organization (PAHO). As surveillance for diseases prevented by new vaccines is integrated into existing surveillance systems, these systems could cost more than routine surveillance for VPDs targeted by the Expanded Program on Immunization. We estimate the costs associated with establishing and subsequently operating the iVPD surveillance system at a pilot site in Costa Rica. We retrospectively collected data on costs incurred by the institutions supporting iVPD surveillance during the preparatory (January 2007 through August 2009) and implementation (September 2009 through August 2010) phases of the iVPD surveillance project in Costa Rica. These data were used to estimate costs for personnel, meetings, infrastructure, office equipment and supplies, transportation, and laboratory facilities. Costs incurred by each of the collaborating institutions were also estimated. During the preparatory phase, the estimated total cost was 128,000 U.S. dollars (US$), including 64% for personnel costs. The preparatory phase was supported by CDC and PAHO. The estimated cost for 1 year of implementation was US$ 420,000, including 58% for personnel costs, 28% for laboratory costs, and 14% for meeting, infrastructure, office, and transportation costs combined. The national reference laboratory and the PAHO Costa Rica office incurred 64% of total costs, and other local institutions supporting iVPD surveillance incurred the remaining 36%. Countries planning to implement iVPD surveillance will require adequate investments in human resources, laboratories, data management, reporting, and investigation. Our findings will be valuable for

Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K.; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-09-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

Discovery of stimulation-responsive immune enhancers with CRISPR activation

Science.gov (United States)

Simeonov, Dimitre R.; Gowen, Benjamin G.; Boontanrart, Mandy; Roth, Theodore L.; Gagnon, John D.; Mumbach, Maxwell R.; Satpathy, Ansuman T.; Lee, Youjin; Bray, Nicolas L.; Chan, Alice Y.; Lituiev, Dmytro S.; Nguyen, Michelle L.; Gate, Rachel E.; Subramaniam, Meena; Li, Zhongmei; Woo, Jonathan M.; Mitros, Therese; Ray, Graham J.; Curie, Gemma L.; Naddaf, Nicki; Chu, Julia S.; Ma, Hong; Boyer, Eric; Van Gool, Frederic; Huang, Hailiang; Liu, Ruize; Tobin, Victoria R.; Schumann, Kathrin; Daly, Mark J.; Farh, Kyle K; Ansel, K. Mark; Ye, Chun J.; Greenleaf, William J.; Anderson, Mark S.; Bluestone, Jeffrey A.; Chang, Howard Y.; Corn, Jacob E.; Marson, Alexander

2017-01-01

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues1–3. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption4–6, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa)7 to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs. PMID:28854172

Restoration of Immune Surveillance in Lung Cancer by Natural Killer Cells

Science.gov (United States)

2016-10-01

smoking affect /suppress the immune systems remains open to explore and is still critical for us to understand the mechanism of smoking to contribute to...the mechanisms that govern innate immune escape in lung cancer, including differences in immune function between smokers , e-cigarette users, and non ... smokers and as a function of smoking cessation. Role: Co-PI Kumar (PI) 07/01/2013 – 06/30/2016 Gateway for Cancer

Poliovirus Laboratory Based Surveillance: An Overview.

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Zaidi, Syed Sohail Zahoor; Asghar, Humayun; Sharif, Salmaan; Alam, Muhammad Masroor

2016-01-01

World Health Assembly (WHA) in 1988 encouraged the member states to launch Global Polio Eradication Initiative (GPEI) (resolution WHA41.28) against "the Crippler" called poliovirus, through strong routine immunization program and intensified surveillance systems. Since its launch, global incidence of poliomyelitis has been reduced by more than 99 % and the disease squeezed to only three endemic countries (Afghanistan, Pakistan, and Nigeria) out of 125. Today, poliomyelitis is on the verge of eradication, and their etiological agents, the three poliovirus serotypes, are on the brink of extinction from the natural environment. The last case of poliomyelitis due to wild type 2 strain occurred in 1999 in Uttar Pradesh, India whereas the last paralytic case due to wild poliovirus type 3 (WPV3) was seen in November, 2012 in Yobe, Nigeria. Despite this progress, undetected circulation cannot fully rule out the eradication as most of the poliovirus infections are entirely subclinical; hence sophisticated environmental surveillance is needed to ensure the complete eradication of virus. Moreover, the vaccine virus in under-immunized communities can sometimes revert and attain wild type characteristics posing a big challenge to the program.

Enhanced Anti-Mycobacterium tuberculosis Immunity over Time with Combined Drug and Immunotherapy Treatment

Directory of Open Access Journals (Sweden)

Sasha E. Larsen

2018-05-01

Full Text Available It is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb. This astounding statistic, in combination with costly and lengthy treatment regimens make the development of therapeutic vaccines paramount for controlling the global burden of tuberculosis. Unlike prophylactic vaccination, therapeutic immunization relies on the natural pulmonary infection with Mtb as the mucosal prime that directs boost responses back to the lung. The purpose of this work was to determine the protection and safety profile over time following therapeutic administration of our lead Mtb vaccine candidate, ID93 with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE, in combination with rifampicin, isoniazid, and pyrazinamide (RHZ drug treatment. We assessed the host inflammatory immune responses and lung pathology 7–22 weeks post infection, and determined the therapeutic efficacy of combined treatment by enumeration of the bacterial load and survival in the SWR/J mouse model. We show that drug treatment alone, or with immunotherapy, tempered the inflammatory responses measured in brochoalveolar lavage fluid and plasma compared to untreated cohorts. RHZ combined with therapeutic immunizations significantly enhanced TH1-type cytokine responses in the lung over time, corresponding to decreased pulmonary pathology evidenced by a significant decrease in the percentage of lung lesions and destructive lung inflammation. These data suggest that bacterial burden assessment alone may miss important correlates of lung architecture that directly contribute to therapeutic vaccine efficacy in the preclinical mouse model. We also confirmed our previous finding that in combination with antibiotics therapeutic immunizations provide an additive survival advantage. Moreover, therapeutic immunizations with ID93/GLA-SE induced differential T cell immune responses over the course of infection that correlated

Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.

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Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo

2017-11-01

Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.

Enhanced surveillance strategies for detecting and monitoring chronic wasting disease in free-ranging cervids

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Walsh, Daniel P.

2012-01-01

The purpose of this document is to provide wildlife management agencies with the foundation upon which they can build scientifically rigorous and cost-effective surveillance and monitoring programs for chronic wasting disease (CWD) or refine their existing programs. The first chapter provides an overview of potential demographic and spatial risk factors of susceptible wildlife populations that may be exploited for CWD surveillance and monitoring. The information contained in this chapter explores historic as well as recent developments in our understanding of CWD disease dynamics. It also contains many literature references for readers who may desire a more thorough review of the topics or CWD in general. The second chapter examines methods for enhancing efforts to detect CWD on the landscape where it is not presently known to exist and focuses on the efficiency and cost-effectiveness of the surveillance program. Specifically, it describes the means of exploiting current knowledge of demographic and spatial risk factors, as described in the first chapter, through a two-stage surveillance scheme that utilizes traditional design-based sampling approaches and novel statistical methods to incorporate information about the attributes of the landscape, environment, populations and individual animals into CWD surveillance activities. By accounting for these attributes, efficiencies can be gained and cost-savings can be realized. The final chapter is unique in relation to the first two chapters. Its focus is on designing programs to monitor CWD once it is discovered within a jurisdiction. Unlike the prior chapters that are more detailed or prescriptive, this chapter by design is considerably more general because providing comprehensive direction for creating monitoring programs for jurisdictions without consideration of their monitoring goals, sociopolitical constraints, or their biological systems, is not possible. Therefore, the authors draw upon their collective

HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.

Directory of Open Access Journals (Sweden)

Emiliano Mancini

Full Text Available Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity compared to continuous treatment. The cause of this failure is poorly understood and often attributed to drug resistance. Here we show that structured treatment interruptions would fail regardless of the emergence of drug resistance. Our computational model of the HIV infection dynamics in lymphoid tissue inside lymph nodes, demonstrates that HIV reservoirs and evasion from immune surveillance themselves are sufficient to cause the failure of structured interruptions. We validate our model with data from a clinical trial and show that it is possible to optimize the schedule of interruptions to perform as well as the continuous treatment in the absence of drug resistance. Our methodology enables studying the problem of treatment optimization without having impact on human beings. We anticipate that it is feasible to steer new clinical trials using computational models.

Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system.

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Newes-Adeyi, Gabriella; Greece, Jacey; Bozeman, Sam; Walker, Deborah Klein; Lewis, Faith; Gidudu, Jane

2012-02-01

We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings. We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website. 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms. It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

"Trans-generational immune priming": specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor.

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Moret, Yannick

2006-06-07

Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph.

Improving vaccine registries through mobile technologies: a vision for mobile enhanced Immunization information systems.

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Wilson, Kumanan; Atkinson, Katherine M; Deeks, Shelley L; Crowcroft, Natasha S

2016-01-01

Immunization registries or information systems are critical to improving the quality and evaluating the ongoing success of immunization programs. However, the completeness of these systems is challenged by a myriad of factors including the fragmentation of vaccine administration, increasing mobility of individuals, new vaccine development, use of multiple products, and increasingly frequent changes in recommendations. Mobile technologies could offer a solution, which mitigates some of these challenges. Engaging individuals to have more control of their own immunization information using their mobile devices could improve the timeliness and accuracy of data in central immunization information systems. Other opportunities presented by mobile technologies that could be exploited to improve immunization information systems include mobile reporting of adverse events following immunization, the capacity to scan 2D barcodes, and enabling bidirectional communication between individuals and public health officials. Challenges to utilizing mobile solutions include ensuring privacy of data, access, and equity concerns, obtaining consent and ensuring adoption of technology at sufficiently high rates. By empowering individuals with their own health information, mobile technologies can also serve as a mechanism to transfer immunization information as individuals cross local, regional, and national borders. Ultimately, mobile enhanced immunization information systems can help realize the goal of the individual, the healthcare provider, and public health officials always having access to the same immunization information. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Environmental Surveillance System To Track Wild Poliovirus Transmission

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Deshpande, Jagadish M.; Shetty, Sushmitha J.; Siddiqui, Zaeem A.

2003-01-01

Eradication of poliomyelitis from large metropolis cities in India has been difficult due to high population density and the presence of large urban slums. Three paralytic poliomyelitis cases were reported in Mumbai, India, in 1999 and 2000 in spite of high immunization coverage and good-quality supplementary immunization activities. We therefore established a systematic environmental surveillance study by weekly screening of sewage samples from three high-risk slum areas to detect the silent transmission of wild poliovirus. In 2001, from among the 137 sewage samples tested, wild poliovirus type 1 was isolated from 35 and wild poliovirus type 3 was isolated from 1. Acute flaccid paralysis (AFP) surveillance indicated one case of paralytic poliomyelitis from the city. Phylogenetic analysis with complete VP1 sequences revealed that the isolates from environmental samples belonged to four lineages of wild polioviruses recently isolated from poliomyelitis cases in Uttar Pradesh and not to those previously isolated from AFP cases in Mumbai. Wild poliovirus thus introduced caused one case of paralytic poliomyelitis. The virus was detected in environmental samples 3 months before. It was found that wild polioviruses introduced several times during the year circulated in Mumbai for a limited period before being eliminated. Environmental surveillance was found to be sensitive for the detection of wild poliovirus silent transmission. Nucleotide sequence analysis helped identify wild poliovirus reservoir areas. PMID:12732567

Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

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Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

2016-03-01

Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hericium caput-medusae (Bull.:Fr.) Pers. polysaccharide enhance innate immune response, immune-related genes expression and disease resistance against Aeromonas hydrophila in grass carp (Ctenopharyngodon idella).

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Gou, Changlong; Wang, Jiazhen; Wang, Yuqiong; Dong, Wenlong; Shan, Xiaofeng; Lou, Yujie; Gao, Yunhang

2018-01-01

The objective was to add 0, 400, 800 or 1200 mg/kg of Hericium caput-medusae polysaccharide (HCMP) to the basal diet of grass carp (Ctenopharyngodon idella) and determine effects on humoral innate immunity, expression of immune-related genes and disease resistance. Adding HCMP enhanced (P < 0.05) bactericidal activity at 1, 2 and 3 weeks and also lysozyme activity, complement C3, and SOD activity at 2 and 3 weeks. Supplementing 800 or 1200 mg/kg of HCMP for 2 or 3 weeks increased (P < 0.05) serum concentrations of total protein, albumin and globulin. Two immune-related genes (IL-1β and TNF-α) were up-regulated (P < 0.05) in HCMP supplemented groups given 800 or 1200 mg/kg HCMP after 2 and 3 weeks of feeding. Expression of anti-inflammatory cytokine IL-10 was down-regulated (P < 0.05) after receiving 800 or 1200 mg/kg HCMP for 2 or 3 weeks. Fish fed 800 mg/kg HCMP had maximal disease resistance against Aeromonas hydrophila (65.4%). In conclusion, HCMP enhanced immune response and expression of immune-related genes and increased disease resistance against Aeromonas hydrophila in grass carp, with greatest effects in fish given 800 mg/kg HCMP for 3 weeks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancing Syndromic Surveillance With Online Respondent-Driven Detection

NARCIS (Netherlands)

Stein, Mart L; van Steenbergen, Jim E; Buskens, Vincent; van der Heijden, Peter G M; Koppeschaar, Carl E; Bengtsson, Linus; Thorson, Anna; Kretzschmar, MEE

OBJECTIVES: We investigated the feasibility of combining an online chain recruitment method (respondent-driven detection) and participatory surveillance panels to collect previously undetected information on infectious diseases via social networks of participants. METHODS: In 2014, volunteers from 2

Enhancing syndromic surveillance with online respondent-driven detection

NARCIS (Netherlands)

Stein, Mart L.; Van Steenbergen, Jim E.; Buskens, Vincent; Van Der Heijden, Peter G M; Koppeschaar, Carl E.; Bengtsson, Linus; Thorson, Anna; Kretzschmar, Mirjam E E

2015-01-01

Objectives. We investigated the feasibility of combining an online chain recruitment method (respondent-driven detection) and participatory surveillance panels to collect previously undetected information on infectious diseases via social networks of participants. Methods. In 2014, volunteers from 2

Public involvement in environmental surveillance at Hanford

International Nuclear Information System (INIS)

Hanf, R.W. Jr.; Patton, G.W.; Woodruff, R.K.; Poston, T.M.

1994-08-01

Environmental surveillance at the Hanford Site began during the mid-1940s following the construction and start-up of the nation's first plutonium production reactor. Over the past approximately 45 years, surveillance operations on and off the Site have continued, with virtually all sampling being conducted by Hanford Site workers. Recently, the US Department of Energy Richland Operations Office directed that public involvement in Hanford environmental surveillance operations be initiated. Accordingly, three special radiological air monitoring stations were constructed offsite, near hanford's perimeter. Each station is managed and operated by two local school teaches. These three stations are the beginning of a community-operated environmental surveillance program that will ultimately involve the public in most surveillance operations around the Site. The program was designed to stimulate interest in Hanford environmental surveillance operations, and to help the public better understand surveillance results. The program has also been used to enhance educational opportunities at local schools

Impact of Pharmacist Immunization Authority on Seasonal Influenza Immunization Rates Across States.

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Drozd, Edward M; Miller, Laura; Johnsrud, Michael

2017-08-01

The goal of this study was to investigate the impact on immunization rates of policy changes that allowed pharmacists to administer influenza immunizations across the United States. Influenza immunization rates across states were compared before and after policy changes permitting pharmacists to administer influenza immunizations. The study used Behavioral Risk Factor Surveillance System (BRFSS) survey data on influenza immunization rates between 2003 and 2013. Logistic regression models were constructed and incorporated adjustments for the complex sample design of the BRFSS to predict the likelihood of a person receiving an influenza immunization based on various patient health, demographic, and access to care factors. Overall, as states moved to allow pharmacists to administer influenza immunizations, the odds that an adult resident received an influenza immunization rose, with the effect increasing over time. The average percentage of people receiving influenza immunizations in states was 35.1%, rising from 32.2% in 2003 to 40.3% in 2013. The policy changes were associated with a long-term increase of 2.2% to 7.6% in the number of adults aged 25 to 59 years receiving an influenza immunization (largest for those aged 35-39 years) and no significant change for those younger or older. These findings suggest that pharmacies and other nontraditional settings may offer accessible venues for patients when implementing other public health initiatives. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Global Cancer Surveillance Framework Within Noncommunicable Disease Surveillance: Making the Case for Population-Based Cancer Registries.

Science.gov (United States)

Piñeros, Marion; Znaor, Ariana; Mery, Les; Bray, Freddie

2017-01-01

The growing burden of cancer among several major noncommunicable diseases (NCDs) requires national implementation of tailored public health surveillance. For many emerging economies where emphasis has traditionally been placed on the surveillance of communicable diseases, it is critical to understand the specificities of NCD surveillance and, within it, of cancer surveillance. We propose a general framework for cancer surveillance that permits monitoring the core components of cancer control. We examine communalities in approaches to the surveillance of other major NCDs as well as communicable diseases, illustrating key differences in the function, coverage, and reporting in each system. Although risk factor surveys and vital statistics registration are the foundation of surveillance of NCDs, population-based cancer registries play a unique fundamental role specific to cancer surveillance, providing indicators of population-based incidence and survival. With an onus now placed on governments to collect these data as part of the monitoring of NCD targets, the integration of cancer registries into existing and future NCD surveillance strategies is a vital requirement in all countries worldwide. The Global Initiative for Cancer Registry Development, endorsed by the World Health Organization, provides a means to enhance cancer surveillance capacity in low- and middle-income countries. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection.

Directory of Open Access Journals (Sweden)

Daniel P Barry

Full Text Available Once acquired, Helicobacter pylori infection is lifelong due to an inadequate innate and adaptive immune response. Our previous studies indicate that interactions among the various pathways of arginine metabolism in the host are critical determinants of outcomes following infection. Cationic amino acid transporter 2 (CAT2 is essential for transport of L-arginine (L-Arg into monocytic immune cells during H. pylori infection. Once within the cell, this amino acid is utilized by opposing pathways that lead to elaboration of either bactericidal nitric oxide (NO produced from inducible NO synthase (iNOS, or hydrogen peroxide, which causes macrophage apoptosis, via arginase and the polyamine pathway. Because of its central role in controlling L-Arg availability in macrophages, we investigated the importance of CAT2 in vivo during H. pylori infection. CAT2(-/- mice infected for 4 months exhibited decreased gastritis and increased levels of colonization compared to wild type mice. We observed suppression of gastric macrophage levels, macrophage expression of iNOS, dendritic cell activation, and expression of granulocyte-colony stimulating factor in CAT2(-/- mice suggesting that CAT2 is involved in enhancing the innate immune response. In addition, cytokine expression in CAT2(-/- mice was altered from an antimicrobial Th1 response to a Th2 response, indicating that the transporter has downstream effects on adaptive immunity as well. These findings demonstrate that CAT2 is an important regulator of the immune response during H. pylori infection.

Enhanced immunity in intradermal vaccination by novel hollow microneedles.

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Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H

2018-04-29

The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?

Science.gov (United States)

Gessner, Bradford D; Halsey, Neal

2017-06-14

A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2-5years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2-5years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1-2 to years 3-5 of follow-up for all age groups and regions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

‘Trans-generational immune priming’: specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor

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Moret, Yannick

2006-01-01

Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph. PMID:16777729

Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

Science.gov (United States)

Mocellin, Simone; Nitti, Donato

2008-05-01

Despite the evidence 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 evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and 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 at reverting 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. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

Enhanced passive bat rabies surveillance in indigenous bat species from Germany--a retrospective study.

Directory of Open Access Journals (Sweden)

Juliane Schatz

2014-05-01

Full Text Available In Germany, rabies in bats is a notifiable zoonotic disease, which is caused by European bat lyssaviruses type 1 and 2 (EBLV-1 and 2, and the recently discovered new lyssavirus species Bokeloh bat lyssavirus (BBLV. As the understanding of bat rabies in insectivorous bat species is limited, in addition to routine bat rabies diagnosis, an enhanced passive surveillance study, i.e. the retrospective investigation of dead bats that had not been tested for rabies, was initiated in 1998 to study the distribution, abundance and epidemiology of lyssavirus infections in bats from Germany. A total number of 5478 individuals representing 21 bat species within two families were included in this study. The Noctule bat (Nyctalus noctula and the Common pipistrelle (Pipistrellus pipistrellus represented the most specimens submitted. Of all investigated bats, 1.17% tested positive for lyssaviruses using the fluorescent antibody test (FAT. The vast majority of positive cases was identified as EBLV-1, predominately associated with the Serotine bat (Eptesicus serotinus. However, rabies cases in other species, i.e. Nathusius' pipistrelle bat (Pipistrellus nathusii, P. pipistrellus and Brown long-eared bat (Plecotus auritus were also characterized as EBLV-1. In contrast, EBLV-2 was isolated from three Daubenton's bats (Myotis daubentonii. These three cases contribute significantly to the understanding of EBLV-2 infections in Germany as only one case had been reported prior to this study. This enhanced passive surveillance indicated that besides known reservoir species, further bat species are affected by lyssavirus infections. Given the increasing diversity of lyssaviruses and bats as reservoir host species worldwide, lyssavirus positive specimens, i.e. both bat and virus need to be confirmed by molecular techniques.

Enhanced Passive Bat Rabies Surveillance in Indigenous Bat Species from Germany - A Retrospective Study

Science.gov (United States)

Auer, Ernst; Goharriz, Hooman; Harbusch, Christine; Johnson, Nicholas; Kaipf, Ingrid; Mettenleiter, Thomas Christoph; Mühldorfer, Kristin; Mühle, Ralf-Udo; Ohlendorf, Bernd; Pott-Dörfer, Bärbel; Prüger, Julia; Ali, Hanan Sheikh; Stiefel, Dagmar; Teubner, Jens; Ulrich, Rainer Günter; Wibbelt, Gudrun; Müller, Thomas

2014-01-01

In Germany, rabies in bats is a notifiable zoonotic disease, which is caused by European bat lyssaviruses type 1 and 2 (EBLV-1 and 2), and the recently discovered new lyssavirus species Bokeloh bat lyssavirus (BBLV). As the understanding of bat rabies in insectivorous bat species is limited, in addition to routine bat rabies diagnosis, an enhanced passive surveillance study, i.e. the retrospective investigation of dead bats that had not been tested for rabies, was initiated in 1998 to study the distribution, abundance and epidemiology of lyssavirus infections in bats from Germany. A total number of 5478 individuals representing 21 bat species within two families were included in this study. The Noctule bat (Nyctalus noctula) and the Common pipistrelle (Pipistrellus pipistrellus) represented the most specimens submitted. Of all investigated bats, 1.17% tested positive for lyssaviruses using the fluorescent antibody test (FAT). The vast majority of positive cases was identified as EBLV-1, predominately associated with the Serotine bat (Eptesicus serotinus). However, rabies cases in other species, i.e. Nathusius' pipistrelle bat (Pipistrellus nathusii), P. pipistrellus and Brown long-eared bat (Plecotus auritus) were also characterized as EBLV-1. In contrast, EBLV-2 was isolated from three Daubenton's bats (Myotis daubentonii). These three cases contribute significantly to the understanding of EBLV-2 infections in Germany as only one case had been reported prior to this study. This enhanced passive surveillance indicated that besides known reservoir species, further bat species are affected by lyssavirus infections. Given the increasing diversity of lyssaviruses and bats as reservoir host species worldwide, lyssavirus positive specimens, i.e. both bat and virus need to be confirmed by molecular techniques. PMID:24784117

Stimulation of TLR7 with Gardiquimod Enhances Protection and Activation of Immune Cells from γ-Irradiation Exposure

International Nuclear Information System (INIS)

Yang, Young-Mi; Bang, Ji-Young; Lee, Suhl-Hyeong; Moon, Tae-Min; Jung, Yu-Jin

2007-01-01

Radiotherapy for cancer patients is based on the radiation-induced cell death, but high dose of radiation is able to cause break of immune system. Thus, protection of immune cells from radiation damage is required to enhance the efficiency and reduce the harmful side effects during cancer radiotherapy. Toll-like receptors (TLRs) are important not only in initiating innate immunity against microbial infection, but also inducing Th1-mediated immunity with producing cytokines and chemokines. Cell stimulation via TLRs leads to downstream activation of NF-kB and other transcription factors. Consequently, several genes encoding mediators and effector molecules of the innate as well as the adaptive immune response are transcribed. There are several previous findings that activated immune cells via TLR9 inducing pathways are resistant to chemical or radiation exposure. But it is not clear that the other TLRs also have the same abilities to protect immune cells against cellular damages including γ-irradiation. This research was performed to evaluate protective effect of immune cells from γ-irradiation through TLR-7 activation pathway

Immune mechanisms and immuno therapy of thyroid cancer

International Nuclear Information System (INIS)

Samuel, A.M.

1999-01-01

In recent years the role of immune mechanisms in the induction and progress of cancer has been established. The importance of oncogenes, growth suppressor genes, gene regulation immune surveillance and the interactions of the various components of the immune system in the pathogenesis and progress of cancers is being extensively studied. In fact, the newer concepts of using immune reactions as a modality of therapy is being explored in conjunction with the treatments for cancer. The increased hope and enthusiasm for tumor immunotherapy is in a large part due to animal studies and a better understanding about surface antigens on tumors, major histocompatibility complex molecules, adhesion molecules, cytokines and a variety of newly discovered molecules which play a role in immune interactions

The ubiquitin editing enzyme A20 maintains immune homeostasis and prevents autoimmunity

OpenAIRE

Tavares, Rita M.

2010-01-01

Dissertation presented to obtain the Doctorate degree (Ph.D.) in Biology at Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa The immune system is vital to ensure the surveillance of organisms against pathogens or malignant cells. However, the negative regulation of the immune system is equally essential, and defects in the termination of immune signals can result in autoimmunity and other pathologies. The functioning of the immune system results from the integrati...

Real-time monitoring of school absenteeism to enhance disease surveillance: a pilot study of a mobile electronic reporting system.

Science.gov (United States)

Lawpoolsri, Saranath; Khamsiriwatchara, Amnat; Liulark, Wongwat; Taweeseneepitch, Komchaluch; Sangvichean, Aumnuyphan; Thongprarong, Wiraporn; Kaewkungwal, Jaranit; Singhasivanon, Pratap

2014-05-12

School absenteeism is a common source of data used in syndromic surveillance, which can eventually be used for early outbreak detection. However, the absenteeism reporting system in most schools, especially in developing countries, relies on a paper-based method that limits its use for disease surveillance or outbreak detection. The objective of this study was to develop an electronic real-time reporting system on school absenteeism for syndromic surveillance. An electronic (Web-based) school absenteeism reporting system was developed to embed it within the normal routine process of absenteeism reporting. This electronic system allowed teachers to update students' attendance status via mobile tablets. The data from all classes and schools were then automatically sent to a centralized database for further analysis and presentation, and for monitoring temporal and spatial patterns of absent students. In addition, the system also had a disease investigation module, which provided a link between absenteeism data from schools and local health centers, to investigate causes of fever among sick students. The electronic school absenteeism reporting system was implemented in 7 primary schools in Bangkok, Thailand, with total participation of approximately 5000 students. During May-October 2012 (first semester), the percentage of absentees varied between 1% and 10%. The peak of school absenteeism (sick leave) was observed between July and September 2012, which coincided with the peak of dengue cases in children aged 6-12 years being reported to the disease surveillance system. The timeliness of a reporting system is a critical function in any surveillance system. Web-based application and mobile technology can potentially enhance the use of school absenteeism data for syndromic surveillance and outbreak detection. This study presents the factors that determine the implementation success of this reporting system.

Enhancing Arctic Surveillance With Space-Based Radars

Science.gov (United States)

2013-06-01

180 degrees (Sellers, 2005). xvii Right Ascension of the Ascending Node: from a geocentric origin perspective, describes how an orbital plane...fascination with remote sensing and intelligence, surveillance, and reconnaissance from space. • Dr. Ray Buettner, my co-advisor, whose positive approach ...48 N; 169 W (northwest maritime corner) • 74 43 N; 156 34 W (uppermost maritime point in the Beaufort Sea approaching the Arctic Ocean) • 72 53 N

Informatics enables public health surveillance

Directory of Open Access Journals (Sweden)

Scott J. N McNabb

2017-01-01

Full Text Available Over the past decade, the world has radically changed. New advances in information and communication technologies (ICT connect the world in ways never imagined. Public health informatics (PHI leveraged for public health surveillance (PHS, can enable, enhance, and empower essential PHS functions (i.e., detection, reporting, confirmation, analyses, feedback, response. However, the tail doesn't wag the dog; as such, ICT cannot (should not drive public health surveillance strengthening. Rather, ICT can serve PHS to more effectively empower core functions. In this review, we explore promising ICT trends for prevention, detection, and response, laboratory reporting, push notification, analytics, predictive surveillance, and using new data sources, while recognizing that it is the people, politics, and policies that most challenge progress for implementation of solutions.

Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation.

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Bald, Tobias; Landsberg, Jennifer; Lopez-Ramos, Dorys; Renn, Marcel; Glodde, Nicole; Jansen, Philipp; Gaffal, Evelyn; Steitz, Julia; Tolba, Rene; Kalinke, Ulrich; Limmer, Andreas; Jönsson, Göran; Hölzel, Michael; Tüting, Thomas

2014-06-01

Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell-poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies. Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell-poor tumors to cellular immune surveillance. ©2014 American Association for Cancer Research.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

Science.gov (United States)

Zhao, Ji-Hui; Zhang, Qi-Bo; Liu, Bao; Piao, Xiang-Hua; Yan, Yu-Lu; Hu, Xiao-Ge; Zhou, Kuan; Zhang, Yong-Tai; Feng, Nian-Ping

2017-01-01

To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture

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Federico Garrido

2017-02-01

Full Text Available Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL.

Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

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Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

2015-04-01

Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Semantic web technologies for video surveillance metadata

OpenAIRE

Poppe, Chris; Martens, Gaëtan; De Potter, Pieterjan; Van de Walle, Rik

2012-01-01

Video surveillance systems are growing in size and complexity. Such systems typically consist of integrated modules of different vendors to cope with the increasing demands on network and storage capacity, intelligent video analytics, picture quality, and enhanced visual interfaces. Within a surveillance system, relevant information (like technical details on the video sequences, or analysis results of the monitored environment) is described using metadata standards. However, different module...

Using Deep Learning Algorithm to Enhance Image-review Software for Surveillance Cameras

Energy Technology Data Exchange (ETDEWEB)

Cui, Yonggang

2018-05-07

We propose the development of proven deep learning algorithms to flag objects and events of interest in Next Generation Surveillance System (NGSS) surveillance to make IAEA image review more efficient. Video surveillance is one of the core monitoring technologies used by the IAEA Department of Safeguards when implementing safeguards at nuclear facilities worldwide. The current image review software GARS has limited automated functions, such as scene-change detection, black image detection and missing scene analysis, but struggles with highly cluttered backgrounds. A cutting-edge algorithm to be developed in this project will enable efficient and effective searches in images and video streams by identifying and tracking safeguards relevant objects and detect anomalies in their vicinity. In this project, we will develop the algorithm, test it with the IAEA surveillance cameras and data sets collected at simulated nuclear facilities at BNL and SNL, and implement it in a software program for potential integration into the IAEA’s IRAP (Integrated Review and Analysis Program).

Clinical application of immune-enhanced enteral nutrition in patients with advanced gastric cancer after total gastrectomy.

Science.gov (United States)

Liu, Hua; Ling, Wei; Shen, Zhi Yong; Jin, Xin; Cao, Hui

2012-08-01

To determine whether immune-enhanced enteral nutrition (EN) was effective on nutritional status, immune function, surgical outcomes and days of hospitalization after total gastrectomy for patients with advanced gastric cancer (AGC). From August 2005 to May 2011, 78 patients with AGC who underwent a total gastrectomy were enrolled and divided randomly into three groups: immune-enhanced EN (EN + glutamine [Gln]) group, standard EN group and control group. Serum parameters including total protein, albumin, proalbumin and transferrin were examined on preoperative day 1, postoperative day 2 and day 12. Levels of immunoglobulin M (IgM), immunoglobulin G (IgG), natural killer (NK) cells, CD4⁺ and CD8⁺ T cells were also compared. The formulas were tolerated well in all the patients except 5 with mild complications. The EN + Gln and EN groups showed a faster onset of flatus and shorter hospitalization duration than the control group. On postoperative day 12, serum total protein, albumin, proalbumin and transferrin levels of the EN + Gln and EN groups were significantly higher than those of the control group (P nutritional status and immune function for the patients with AGC after total gastrectomy. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Role of immunological surveillance in radiation carcinogenesis

International Nuclear Information System (INIS)

Sado, Toshihiko

2003-01-01

The immune system is known to be highly susceptible to various physical, chemical, and biological insults. The studies on the immediate and long-term effects of radiation on immune system of mice indicated very clearly that there was a dose-dependent reduction in the number of T and B cells, depression of antibody and cytotoxic T cell responses as well as proliferative responses of spleen cells to T and B cell mitogens shortly after irradiation, but they all recovered to the control level within a few months. Immunosuppression observed shortly after irradiation had little influence on the development of radiogenic tumors. The effects of radiation on the incidence of Friend leukemia virus (FLV)-induced leukemias are examined by using young adult B6C3F 1 male mice which are normally resistant to FLV-induced leukemogenesis. There was a clear threshold dose of 2 Gy below which the development of FLV induced leukemias was not observed but after exposure to >3 Gy high incidence of leukemias was observed. Fractionated, weekly exposure of young C57BL strain mice to 1.6 Gy of X-rays for four successive weeks causes most of the exposed mice to develop thymic lymphomas between 3 and 10 months. However, when the exposed mice are grafted with bone marrow cells from normal donors, the development of thymic lymphomas on the exposed mice is greatly inhibited. There was a clear dose response relationship between the number of bone marrow cells injected and the inhibition of the development of thymic lymphomas. It now appears clear that T cell-mediated immunological surveillance against newly arising neoplasms conceived by Thomas and Burnet does not hold true anymore in the original form, although virus-infected host cells and other host cells expressing altered-self' markers on their cell surfaces are constantly monitored by the immunological surveillance mechanism. A surveillance function against newly arising neoplasms may be a property of surrounding normal tissue cells rather

Activation of cellular immunity and marked inhibition of liver cancer in a mouse model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1.

Science.gov (United States)

Cheng, Mingrong; Zhi, Kangkang; Gao, Xiaoyan; He, Bing; Li, Yingchun; Han, Jiang; Zhang, Zhiping; Wu, Yan

2013-12-18

Cancer is both a systemic and a genetic disease. The pathogenesis of cancer might be related to dampened immunity. Host immunity recognizes nascent malignant cells - a process referred to as immune surveillance. Augmenting immune surveillance and suppressing immune escape are crucial in tumor immunotherapy. A recombinant plasmid capable of co-expressing granulocyte-macrophage colony- stimulating factor (GM-SCF), interleukin-21 (IL-21), and retinoic acid early transcription factor-1 (Rae-1) was constructed, and its effects determined in a mouse model of subcutaneous liver cancer. Serum specimens were assayed for IL-2 and INF-γ by ELISA. Liver cancer specimens were isolated for Rae-1 expression by RT-PCR and Western blot, and splenocytes were analyzed by flow cytometry. The recombinant plasmid inhibited the growth of liver cancer and prolonged survival of tumor-loaded mice. Activation of host immunity might have contributed to this effect by promoting increased numbers and cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) following expression of GM-SCF, IL-21, and Rae-1. By contrast, the frequency of regulatory T cells was decreased, Consequently, activated CTL and NK cells enhanced their secretion of INF-γ, which promoted cytotoxicity of NK cells and CTL. Moreover, active CTL showed dramatic secretion of IL-2, which stimulates CTL. The recombinant expression plasmid also augmented Rae-1 expression by liver cancer cells. Rae-1 receptor expressing CTL and NK cells removed liver cancer. The recombinant expression plasmid inhibited liver cancer by a mechanism that involved activation of cell-mediated immunity and Rae-1 in liver cancer.

Surveillance of wild birds for avian influenza virus.

Science.gov (United States)

Hoye, Bethany J; Munster, Vincent J; Nishiura, Hiroshi; Klaassen, Marcel; Fouchier, Ron A M

2010-12-01

Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics, has heralded a new era in wildlife disease surveillance. However, survey design, sampling, and interpretation in the context of host populations still present major challenges. We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds, including consideration of what, when, where, and how many to sample in the context of survey objectives. Recognizing that wildlife disease surveillance is logistically and financially constrained, we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host-pathogen system. We recommend hypothesis-driven surveillance through standardized, local surveys that are, in turn, strategically compiled over broad geographic areas. Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases.

Cancer exosomes and NKG2D receptor-ligand interactions: impairing NKG2D-mediated cytotoxicity and anti-tumour immune surveillance.

Science.gov (United States)

Mincheva-Nilsson, Lucia; Baranov, Vladimir

2014-10-01

Human cancers constitutively produce and release endosome-derived nanometer-sized vesicles called exosomes that carry biologically active proteins, messenger and micro RNAs and serve as vehicles of intercellular communication. The tumour exosomes are present in the blood, urine and various malignant effusions such as peritoneal and pleural fluid of cancer patients and can modulate immune cells and responses thus deranging the immune system of cancer patients and giving advantage to the cancer to establish and spread itself. Here, the role of exosomes in the NKG2D receptor-ligand system's interactions is discussed. The activating NK cell receptor NKG2D and its multiple ligands, the MHC class I-related chain (MIC) A/B and the retinoic acid transcript-1/UL-16 binding proteins (RAET1/ULBP) 1-6 comprise a powerful stress-inducible danger detector system that targets infected, inflamed and malignantly transformed cells and plays a decisive role in anti-tumour immune surveillance. Mounting evidence reveals that the MIC- and RAET1/ULBP ligand family members are enriched in the endosomal compartment of various tumour cells and expressed and released into the intercellular space and bodily fluids on exosomes thus preserving their entire molecule, three-dimensional protein structure and biologic activity. The NKG2D ligand-expressing exosomes serve as decoys with a powerful ability to down regulate the cognate receptor and impair the cytotoxic function of NK-, NKT-, gamma/delta- and cytotoxic T cells. This review summarizes recent findings concerning the role of NKG2D receptor-ligand system in cancer with emphasis on regulation of NKG2D ligand expression and the immunosuppressive role of exosomally expressed NKG2D ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

The immune-enhancing activity of Cervus nippon mantchuricus extract (NGE) in RAW264.7 macrophage cells and immunosuppressed mice.

Science.gov (United States)

Hong, Se Hyang; Ku, Jin Mo; In Kim, Hyo; Ahn, Chang-Won; Park, Soo-Hyun; Seo, Hye Sook; Shin, Yong Cheol; Ko, Seong-Gyu

2017-09-01

Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aneuploidy theory explains tumor formation, the absence of immune surveillance, and the failure of chemotherapy.

Science.gov (United States)

Rasnick, David

2002-07-01

The autocatalyzed progression of aneuploidy accounts for all cancer-specific phenotypes, the Hayflick limit of cultured cells, carcinogen-induced tumors in mice, the age distribution of human cancer, and multidrug-resistance. Here aneuploidy theory addresses tumor formation. The logistic equation, phi(n)(+1) = rphi(n) (1 - phi(n)), models the autocatalyzed progression of aneuploidy in vivo and in vitro. The variable phi(n)(+1) is the average aneuploid fraction of a population of cells at the n+1 cell division and is determined by the value at the nth cell division. The value r is the growth control parameter. The logistic equation was used to compute the probability distribution for values of phi after numerous divisions of aneuploid cells. The autocatalyzed progression of aneuploidy follows the laws of deterministic chaos, which means that certain values of phi are more probable than others. The probability map of the logistic equation shows that: 1) an aneuploid fraction of at least 0.30 is necessary to sustain a population of cancer cells; and 2) the most likely aneuploid fraction after many population doublings is 0.70, which is equivalent to a DNA(index)=1.7, the point of maximum disorder of the genome that still sustains life. Aneuploidy theory also explains the lack of immune surveillance and the failure of chemotherapy.

Towards One Health disease surveillance: The Southern African Centre for Infectious Disease Surveillance approach

Directory of Open Access Journals (Sweden)

Esron D. Karimuribo

2012-06-01

Full Text Available Africa has the highest burden of infectious diseases in the world and yet the least capacity for its risk management. It has therefore become increasingly important to search for ‘fit-for- purpose’ approaches to infectious disease surveillance and thereby targeted disease control. The fact that the majority of human infectious diseases are originally of animal origin means we have to consider One Health (OH approaches which require inter-sectoral collaboration for custom-made infectious disease surveillance in the endemic settings of Africa. A baseline survey was conducted to assess the current status and performance of human and animal health surveillance systems and subsequently a strategy towards OH surveillance system was developed. The strategy focused on assessing the combination of participatory epidemiological approaches and the deployment of mobile technologies to enhance the effectiveness of disease alerts and surveillance at the point of occurrence, which often lies in remote areas. We selected three study sites, namely the Ngorongoro, Kagera River basin and Zambezi River basin ecosystems. We have piloted and introduced the next-generation Android mobile phones running the EpiCollect application developed by Imperial College to aid geo-spatial and clinical data capture and transmission of this data from the field to the remote Information Technology (IT servers at the research hubs for storage, analysis, feedback and reporting. We expect that the combination of participatory epidemiology and technology will significantly improve OH disease surveillance in southern Africa.

Towards one health disease surveillance: the Southern African Centre for Infectious Disease Surveillance approach.

Science.gov (United States)

Karimuribo, Esron D; Sayalel, Kuya; Beda, Eric; Short, Nick; Wambura, Philemon; Mboera, Leonard G; Kusiluka, Lughano J M; Rweyemamu, Mark M

2012-06-20

Africa has the highest burden of infectious diseases in the world and yet the least capacity for its risk management. It has therefore become increasingly important to search for 'fit-for- purpose' approaches to infectious disease surveillance and thereby targeted disease control. The fact that the majority of human infectious diseases are originally of animal origin means we have to consider One Health (OH) approaches which require inter-sectoral collaboration for custom-made infectious disease surveillance in the endemic settings of Africa. A baseline survey was conducted to assess the current status and performance of human and animal health surveillance systems and subsequently a strategy towards OH surveillance system was developed. The strategy focused on assessing the combination of participatory epidemiological approaches and the deployment of mobile technologies to enhance the effectiveness of disease alerts and surveillance at the point of occurrence, which often lies in remote areas. We selected three study sites, namely the Ngorongoro, Kagera River basin and Zambezi River basin ecosystems. We have piloted and introduced the next-generation Android mobile phones running the EpiCollect application developed by Imperial College to aid geo-spatial and clinical data capture and transmission of this data from the field to the remote Information Technology (IT) servers at the research hubs for storage, analysis, feedback and reporting. We expect that the combination of participatory epidemiology and technology will significantly improve OH disease surveillance in southern Africa.

Pilot Study on the Use of DNA Priming Immunization to Enhance Y. pestis LcrV-Specific B Cell Responses Elicited by a Recombinant LcrV Protein Vaccine

Directory of Open Access Journals (Sweden)

Wei Li

2013-12-01

Full Text Available Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis. Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems.

Anticipating the Species Jump: Surveillance for Emerging Viral Threats

Science.gov (United States)

2010-12-01

entails monitoring of pathogens within wildlife populations (e.g. H5N1 influenza in migratory birds ), while animal health surveillance generally...refers to monitoring of livestock, pet or captive animal populations. The prospects for predicting infectious disease outbreaks have been reviewed and...gender, nutritional status, health status (co-infections or chronic illness), immune status, income, occupation (rural or urban), etc. Environmental

Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults with Autoimmune Inflammatory Diseases.

Science.gov (United States)

Kirchner, Elizabeth; Ruffing, Victoria

2017-02-01

For as long as there have been immunizations, there have been barriers to them. Immunization rates in the United States are below target. Rheumatologists and rheumatology practitioners need to understand the issues of immunizations in patients with autoimmune inflammatory disease to identify and overcome barriers to immunization. Several strategies for overcoming these barriers are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

78 FR 46588 - Solicitation of Written Comments on the Global Immunizations Working Group's Draft Report and...

Science.gov (United States)

2013-08-01

... NVAC was also asked to make recommendations on how to best communicate this information to decision... a series of teleconferences and electronic communications, the NVAC Global Immunizations working... Vaccine Safety Monitoring and Post-Marketing Surveillance 4. Building Global Immunization Research and...

Advanced Integrated Multi-Sensor Surveillance (AIMS. Operator Machine Interface (OMI) Definition Study

National Research Council Canada - National Science Library

Baker, Kevin; Youngson, Gord

2007-01-01

To enhance the capability of airborne search and rescue (SAR) and surveillance, particularly at night and in poor weather, a multi sensor electro optical imaging system, the Advanced Integrated Multi sensor Surveillance (AIMS...

Public Health Surveillance Strategies for Mass Gatherings: Super Bowl XLIX and Related Events, Maricopa County, Arizona, 2015.

Science.gov (United States)

Ayala, Aurimar; Berisha, Vjollca; Goodin, Kate; Pogreba-Brown, Kristen; Levy, Craig; McKinney, Benita; Koski, Lia; Imholte, Sara

2016-01-01

Super Bowl XLIX took place on February 1, 2015, in Glendale, Arizona. In preparation for this event and associated activities, the Maricopa County Department of Public Health (MCDPH) developed methods for enhanced surveillance, situational awareness, and early detection of public health emergencies. Surveillance strategies implemented from January 22 to February 6, 2015, included enhanced surveillance alerts; animal disease surveillance; review of NFL clinic visits; syndromic surveillance for emergency room visits, urgent care facilities, and hotels; real-time onsite syndromic surveillance; all-hazards mortality surveillance; emergency medical services surveillance, review of poison control center reports; media surveillance; and aberration detection algorithms for notifiable diseases. Surveillance results included increased influenzalike illness activity reported from urgent care centers and a few influenza cases reported in the NFL clinic. A cyanide single event exposure was investigated and determined not to be a public health threat. Real-time field syndromic surveillance documented minor injuries at all events and sporadic cases of gastrointestinal and neurological (mostly headaches) disease. Animal surveillance reports included a cat suspected of carrying plague and tularemia and an investigation of highly pathogenic avian influenza in a backyard chicken flock. Laboratory results in both instances were negative. Aberration detection and syndromic surveillance detected an increase in measles reports associated with a Disneyland exposure, and syndromic surveillance was used successfully during this investigation. Coordinated enhanced epidemiologic surveillance during Super Bowl XLIX increased the response capacity and preparedness of MCDPH to make informed decisions and take public health actions in a timely manner during these mass gathering events.

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

Science.gov (United States)

Sorsby, Eleanor; Mahtey, Nabeel; Brown, Ian

2017-01-01

Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection. PMID:28542528

Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.

Directory of Open Access Journals (Sweden)

Sarah L Sherrington

2017-05-01

Full Text Available Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

Science.gov (United States)

de Vos, Paul; Mujagic, Zlatan; de Haan, Bart J.; Siezen, Roland J.; Bron, Peter A.; Meijerink, Marjolein; Wells, Jerry M.; Masclee, Ad A. M.; Boekschoten, Mark V.; Faas, Marijke M.; Troost, Freddy J.

2017-01-01

Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on

Lactobacillus plantarum Strains Can Enhance Human Mucosal and Systemic Immunity and Prevent Non-steroidal Anti-inflammatory Drug Induced Reduction in T Regulatory Cells

Directory of Open Access Journals (Sweden)

Paul de Vos

2017-08-01

Full Text Available Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1 or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience.

Science.gov (United States)

Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

2014-05-01

To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010). Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Gold nanoparticles conjugating recombinant influenza hemagglutinin trimers and flagellin enhanced mucosal cellular immunity.

Science.gov (United States)

Wang, Chao; Zhu, Wandi; Luo, Yuan; Wang, Bao-Zhong

2018-04-09

The immunogenicity of subunit vaccines can be augmented by formulating them into nanoparticles. We conjugated recombinant trimetric influenza A/Aichi/2/68(H3N2) hemagglutinin (HA) onto functionalized gold nanoparticles (AuNPs) surfaces in a repetitive, oriented configuration. To further improve the immunogenicity, we generated Toll-like receptor 5 (TLR5) agonist flagellin (FliC)-coupled AuNPs as particulate adjuvants. Intranasal immunizations with an AuNP-HA and AuNP-FliC particle mixture elicited strong mucosal and systemic immune responses that protected hosts against lethal influenza challenges. Compared with the AuNP-HA alone group, the addition of AuNP-FliC improved mucosal B cell responses as characterized by elevated influenza specific IgA and IgG levels in nasal, tracheal, and lung washes. AuNP-HA/AuNP-FliC also stimulated antigen-specific interferon-γ (IFN-γ)-secreting CD4 + cell proliferation and induced strong effector CD8 + T cell activation. Our results indicate that intranasal co-delivery of antigen and adjuvant-displaying AuNPs enhanced vaccine efficacy by inducing potent cellular immune responses. Copyright © 2018. Published by Elsevier Inc.

Real-Time Observation of Target Search by the CRISPR Surveillance Complex Cascade

Directory of Open Access Journals (Sweden)

Chaoyou Xue

2017-12-01

Full Text Available CRISPR-Cas systems defend bacteria and archaea against infection by bacteriophage and other threats. The central component of these systems are surveillance complexes that use guide RNAs to bind specific regions of foreign nucleic acids, marking them for destruction. Surveillance complexes must locate targets rapidly to ensure timely immune response, but the mechanism of this search process remains unclear. Here, we used single-molecule FRET to visualize how the type I-E surveillance complex Cascade searches DNA in real time. Cascade rapidly and randomly samples DNA through nonspecific electrostatic contacts, pausing at short PAM recognition sites that may be adjacent to the target. We identify Cascade motifs that are essential for either nonspecific sampling or positioning and readout of the PAM. Our findings provide a comprehensive structural and kinetic model for the Cascade target-search mechanism, revealing how CRISPR surveillance complexes can rapidly search large amounts of genetic material en route to target recognition.

Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers

International Nuclear Information System (INIS)

Reizenstein, P.; Ogier, C.; Blomgren, H.; Petrini, B.; Wasserman, J.

1985-01-01

Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). 154 references

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

Science.gov (United States)

Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

2014-08-21

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

Science.gov (United States)

Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

2014-01-01

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

Vitamin E analogues and immune response in cancer treatment

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Neužil, Jiří

2007-01-01

Roč. 76, - (2007), s. 463-491 ISSN 0083-6729 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogues * inducers of apoptosis * immune surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.889, year: 2007

Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

Science.gov (United States)

Yamanaka, Atsushi; Konishi, Eiji

2017-09-25

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.

Adaptive immunity to leukemia is inhibited by cross-reactive induced regulatory T cells

OpenAIRE

Manlove, Luke S.; Berquam-Vrieze, Katherine E.; Pauken, Kristen E.; Williams, Richard T.; Jenkins, Marc K.; Farrar, Michael A.

2015-01-01

BCR-ABL+ acute lymphoblastic leukemia patients have transient responses to current therapies. However, the fusion of BCR to ABL generates a potential leukemia-specific antigen that could be a target for immunotherapy. We demonstrate that the immune system can limit BCR-ABL+ leukemia progression although ultimately this immune response fails. To address how BCR-ABL+ leukemia escapes immune surveillance, we developed a peptide: MHC-II tetramer that labels endogenous BCR-ABL-specific CD4+ T cell...

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.

Ebola Surveillance - Guinea, Liberia, and Sierra Leone.

Science.gov (United States)

McNamara, Lucy A; Schafer, Ilana J; Nolen, Leisha D; Gorina, Yelena; Redd, John T; Lo, Terrence; Ervin, Elizabeth; Henao, Olga; Dahl, Benjamin A; Morgan, Oliver; Hersey, Sara; Knust, Barbara

2016-07-08

Developing a surveillance system during a public health emergency is always challenging but is especially so in countries with limited public health infrastructure. Surveillance for Ebola virus disease (Ebola) in the West African countries heavily affected by Ebola (Guinea, Liberia, and Sierra Leone) faced numerous impediments, including insufficient numbers of trained staff, community reticence to report cases and contacts, limited information technology resources, limited telephone and Internet service, and overwhelming numbers of infected persons. Through the work of CDC and numerous partners, including the countries' ministries of health, the World Health Organization, and other government and nongovernment organizations, functional Ebola surveillance was established and maintained in these countries. CDC staff were heavily involved in implementing case-based surveillance systems, sustaining case surveillance and contact tracing, and interpreting surveillance data. In addition to helping the ministries of health and other partners understand and manage the epidemic, CDC's activities strengthened epidemiologic and data management capacity to improve routine surveillance in the countries affected, even after the Ebola epidemic ended, and enhanced local capacity to respond quickly to future public health emergencies. However, the many obstacles overcome during development of these Ebola surveillance systems highlight the need to have strong public health, surveillance, and information technology infrastructure in place before a public health emergency occurs. Intense, long-term focus on strengthening public health surveillance systems in developing countries, as described in the Global Health Security Agenda, is needed.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Foot-and-mouth disease control and eradication in the Bicol Surveillance Buffer Zone of the Philippines.

Science.gov (United States)

Windsor, P A; Freeman, P G; Abila, R; Benigno, C; Verin, B; Nim, V; Cameron, A

2011-10-01

Following the onset of an epidemic of foot and mouth disease (FMD) commencing in 1994 and affecting mainly pigs in the Philippines, a National Plan for the Control and Eradication of the disease was initiated. A disease surveillance buffer zone in the southern Luzon region of Bicol was established to protect the Visayas and Mindanao from infection and enable eventual elimination of the disease in Luzon. With achievement of Office International Epizooties (OIE)-certified FMD freedom with vaccination in the Philippines now imminent, the four components of the disease control strategy are reviewed, including quarantine and animal movement controls, strategic vaccination, surveillance and disease investigation, and enhanced public awareness with school on the air radio programmes. Although numbers of outbreaks declined following widespread vaccination, evaluation of serological responses in vaccinates suggested low levels of immune protection. The cessation of outbreaks was considered more likely a result of animal movement controls, improved surveillance and emergency response capability, and reduction in FMD-risk behaviours by livestock owners, particularly through efforts to enhance public awareness of biosecurity measures by the training of traders, livestock industry personnel and both commercial and smallholder farmers. A two-stage random sampling serosurveillance strategy enabled identification of residual infection that was not detected through opportunistic sampling and negative incident reporting. Intensive investigations of FMD outbreaks, particularly in Albay province in 1999, enabled improved understanding of the risk factors involved in disease transmission and implementation of appropriate interventions. The findings from this review are offered to assist development of FMD control and eradication programmes in other countries in south-east Asia that are now being encouraged to support the OIE goal of FMD freedom with vaccination by 2020. © 2011

Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

Directory of Open Access Journals (Sweden)

Shulei Qiu

Full Text Available The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(3(4 to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h.

Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen via Microneedles.

Science.gov (United States)

Pamornpathomkul, Boonnada; Rojanarata, Theerasak; Opanasopit, Praneet; Ngawhirunpat, Tanasait

2017-10-01

The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8 h after administering with various conditions could be ranked as follows: hollow MN; high dose > medium dose > low dose > MN patch; high dose > medium dose > low dose > untreated skin; high dose > medium dose > low dose > without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500 μg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.

Enhancement of anamnestic immunospecific antibody response in orally immunized chickens

DEFF Research Database (Denmark)

Mayo, Susan; Carlsson, Hans-Erik; Zagon, Andrea

2008-01-01

Production of immunospecific egg yolk antibodies (IgY antibodies) in egg laying hens through oral immunization is an attractive alternative to conventional antibody production in mammals for economic reasons as well as for animal welfare reasons. Oral immunization results in a systemic humoral...... of the immunization in week 18, demonstrating the presence of memory cells following the two initial oral immunizations. Considering that oral immunization results in approximately ten times lower concentrations of immunospecific antibodies in the egg yolk, compared to traditional subcutaneous immunization schemes...

Cefditoren and ceftriaxone enhance complement-mediated immunity in the presence of specific antibodies against antibiotic-resistant pneumococcal strains.

Directory of Open Access Journals (Sweden)

Elisa Ramos-Sevillano

Full Text Available BACKGROUND: Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae. CONCLUSIONS/SIGNIFICANCE: Using cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

Twitter Influenza Surveillance: Quantifying Seasonal Misdiagnosis Patterns and their Impact on Surveillance Estimates.

Science.gov (United States)

Mowery, Jared

2016-01-01

Influenza (flu) surveillance using Twitter data can potentially save lives and increase efficiency by providing governments and healthcare organizations with greater situational awareness. However, research is needed to determine the impact of Twitter users' misdiagnoses on surveillance estimates. This study establishes the importance of Twitter users' misdiagnoses by showing that Twitter flu surveillance in the United States failed during the 2011-2012 flu season, estimates the extent of misdiagnoses, and tests several methods for reducing the adverse effects of misdiagnoses. Metrics representing flu prevalence, seasonal misdiagnosis patterns, diagnosis uncertainty, flu symptoms, and noise were produced using Twitter data in conjunction with OpenSextant for geo-inferencing, and a maximum entropy classifier for identifying tweets related to illness. These metrics were tested for correlations with World Health Organization (WHO) positive specimen counts of flu from 2011 to 2014. Twitter flu surveillance erroneously indicated a typical flu season during 2011-2012, even though the flu season peaked three months late, and erroneously indicated plateaus of flu tweets before the 2012-2013 and 2013-2014 flu seasons. Enhancements based on estimates of misdiagnoses removed the erroneous plateaus and increased the Pearson correlation coefficients by .04 and .23, but failed to correct the 2011-2012 flu season estimate. A rough estimate indicates that approximately 40% of flu tweets reflected misdiagnoses. Further research into factors affecting Twitter users' misdiagnoses, in conjunction with data from additional atypical flu seasons, is needed to enable Twitter flu surveillance systems to produce reliable estimates during atypical flu seasons.

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

Science.gov (United States)

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

2016-04-01

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

Privacy information management for video surveillance

Science.gov (United States)

Luo, Ying; Cheung, Sen-ching S.

2013-05-01

The widespread deployment of surveillance cameras has raised serious privacy concerns. Many privacy-enhancing schemes have been proposed to automatically redact images of trusted individuals in the surveillance video. To identify these individuals for protection, the most reliable approach is to use biometric signals such as iris patterns as they are immutable and highly discriminative. In this paper, we propose a privacy data management system to be used in a privacy-aware video surveillance system. The privacy status of a subject is anonymously determined based on her iris pattern. For a trusted subject, the surveillance video is redacted and the original imagery is considered to be the privacy information. Our proposed system allows a subject to access her privacy information via the same biometric signal for privacy status determination. Two secure protocols, one for privacy information encryption and the other for privacy information retrieval are proposed. Error control coding is used to cope with the variability in iris patterns and efficient implementation is achieved using surrogate data records. Experimental results on a public iris biometric database demonstrate the validity of our framework.

What Could Be Future Scenarios?-Lessons from the History of Public Health Surveillance for the Future: --A keynote address presented at the 8th World Alliance for Risk Factor Surveillance (WARFS) Global Conference on October 30, 2013, Beijing, China.

Science.gov (United States)

Choi, Bernard C K

2015-01-01

This article provides insights into the future based on a review of the past and present of public health surveillance-the ongoing systematic collection, analysis, interpretation, and dissemination of health data for the planning, implementation, and evaluation of public health action. Public health surveillance dates back to the first recorded epidemic in 3180 BC in Egypt. A number of lessons and items of interest are summarised from a review of historical perspectives in the past 5,000 years and the current practice of surveillance. Some future scenarios are presented: exploring new frontiers; enhancing computer technology; improving epidemic investigations; improving data collection, analysis, dissemination and use; building on lessons from the past; building capacity; and enhancing global surveillance. It is concluded that learning from the past, reflecting on the present, and planning for the future can further enhance public health surveillance.

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.

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination.

Science.gov (United States)

Holechek, Susan A; McAfee, Megan S; Nieves, Lizbeth M; Guzman, Vanessa P; Manhas, Kavita; Fouts, Timothy; Bagley, Kenneth; Blattman, Joseph N

2016-11-04

In order for vaccines to induce efficacious immune responses against mucosally transmitted pathogens, such as HIV-1, activated lymphocytes must efficiently migrate to and enter targeted mucosal sites. We have previously shown that all-trans retinoic acid (ATRA) can be used as a vaccine adjuvant to enhance mucosal CD8 + T cell responses during vaccination and improve protection against mucosal viral challenge. However, the ATRA formulation is incompatible with most recombinant vaccines, and the teratogenic potential of ATRA at high doses limits its usage in many clinical settings. We hypothesized that increasing in vivo production of retinoic acid (RA) during vaccination with a DNA vector expressing retinaldehyde dehydrogenase 2 (RALDH2), the rate-limiting enzyme in RA biosynthesis, could similarly provide enhanced programming of mucosal homing to T cell responses while avoiding teratogenic effects. Administration of a RALDH2- expressing plasmid during immunization with a HIVgag DNA vaccine resulted in increased systemic and mucosal CD8 + T cell numbers with an increase in both effector and central memory T cells. Moreover, mice that received RALDH2 plasmid during DNA vaccination were more resistant to intravaginal challenge with a recombinant vaccinia virus expressing the same HIVgag antigen (VACVgag). Thus, RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection from viral infection at mucosal sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

Science.gov (United States)

Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

2017-12-01

construct self-adjuvanting polymer-based intranasal mRNA vaccines to enhance lymph node trafficking and further improve immune responses. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Lenalidomide-based maintenance therapy reduces TNF receptor 2 on CD4 T cells and enhances immune effector function in acute myeloid leukemia patients.

Science.gov (United States)

Govindaraj, Chindu; Madondo, Mutsa; Kong, Ying Ying; Tan, Peter; Wei, Andrew; Plebanski, Magdalena

2014-08-01

A major limitation to improved outcomes in acute myelogenous leukemia (AML) is relapse resulting from leukemic cells that persist at clinical remission. Regulatory T cells (Tregs), which are increased in AML patients, can contribute to immune evasion by residual leukemic cells. Tumor necrosis factor (TNF), a pro-inflammatory cytokine present at high levels within patients, can induce TNF receptor-2 (TNFR2) expression on Tregs. We hypothesized that since TNFR2 is required for Treg stabilization and TNFR2+ Tregs are potent suppressors, targeting TNFR2+ Tregs may restore the effectiveness of immune-surveillance mechanisms. In this pilot study, we report AML patients in clinical remission have substantially increased levels of TNFR2+ T cells, including TNFR2+ Tregs and impaired effector CD4 T cell function with reduced IL-2 and IFNγ production. The immunomodulatory drug, lenalidomide, and the demethylating agent, azacitidine have been moderately successful in treating AML patients, but their combined effects on TNFR2+ T cells, including Tregs are currently unknown. Our data indicates that although treatment with lenalidomide and azacitidine increased cytokine production by effector T cells in all patients, durable clinical remissions may be observed in patients with a concomitant reduction in TNFR2+ T cells and TNFR2+ Tregs. In vitro studies further demonstrated that lenalidomide can reduce TNFR2 expression and can augment effector cytokine production by T cells, which can be further enhanced by azacitidine. These results indicate that reduction of TNFR2+ T cells in AML postremission phase may result from combined azacitidine/lenalidomide therapy and may contribute to an improved clinical outcome. © 2014 Wiley Periodicals, Inc.

Silhouettes of War: Technologies of U.S. Soldiering and Surveillance

Directory of Open Access Journals (Sweden)

Jessica J. Behm

2010-03-01

Full Text Available This paper forwards a theory of silhouetting in relation to technological augmenta-tion in U.S. Military uniforms and suggests that the increasing utilization of metamaterials, nanotechnology, and surveillance technologies operates under a rhetoric of invisibility that complicates the technologies' visible destruction. Methodologically, the paper attends to three general technological developments in the evolution of the U.S. Army uniform: the design of the new Army Combat Uniform (ACU; the technological advances in the uniform, including embedded wearables, biometric identification devices, and 3D combat enhancement systems; and the bio-networking, GPS, and digital communication arrays that physically link digital uniforms to a larger geopolitical network of U.S. military strategy and surveillance. Throughout, the work traces the aforementioned theory of silhouet-ting in relation to select sociopolitical consequences of linking digitally enhanced soldiers into a transnational grid of surveillance.

Experimental increase in baseline corticosterone level reduces oxidative damage and enhances innate immune response.

Directory of Open Access Journals (Sweden)

Csongor I Vágási

Full Text Available Glucocorticoid (GC hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long as well as on their circulating levels (baseline vs. stress-induced. Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation and physiological state (humoral innate immune system activity and oxidative balance. We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days elevation of baseline CORT might have a positive and stimulatory effect on animal physiology.

Identification and characterization of the related immune-enhancing proteins in crab Scylla paramamosain stimulated with rhubarb polysaccharides.

Science.gov (United States)

Cao, Jingsong; Wang, Zehuan; Zhang, Yueling; Qu, Fengliang; Guo, Lingling; Zhong, Mingqi; Li, Shengkang; Zou, Haiying; Chen, Jiehui; Wang, Xiuying

2014-02-01

Recently, considerable interest has been focused on immunostimulants to reduce diseases in crab aquaculture. However, information regarding to the related immune-enhancing proteins in crabs is not available yet. In this study, rhubarb polysaccharides were tested for enhancement of the immune activity in crab Scylla paramamosain. Compared with those in the control group, values of, phenoloxidase (PO), alkaline phosphatase (AKP) and alkaline phosphatasein (ACP) activity in the, experimental group were improved significantly 4 d after the treatment. Furthermore, 15 and 17 altered proteins from haemocytes and hepatopancreas, respectively, were found in rhubarb polysaccharide-treated crabs using 2-DE approach. Of these, hemocyanin, chymotrypsin, cryptocyanin, C-type lectin receptor, and ferritin protein were identified by mass spectrometry. In addition, RT-PCR, analysis showed that the mRNA levels of hemocyanin and chymotrypsin increased about 2.4- and 1.4-fold in the experiment group. Moreover, the hemocyanin gene in S. paramamosain (SpHMC) was, cloned and characterized. SpHMC contains one open reading frame of 2022 bp and encodes a polypeptide of 673 amino acids. It is clustered into one branch along with crab hemocyanin in a phylogenetic tree. The mRNA transcripts of SpHMC were detected mainly in the tissues of, hepatopancreas, hemocyte and intestines, and its levels were up-regulated significantly in hemocytes, of S. paramamosain treated with Vibrio parahemolyticus, Beta streptococcus or poly I:C for 6-48 h. Taken together, these studies found 5 related immune-enhancing proteins and a novel heomcyanin homologue with potential pathogen-resistant activities in crab. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States.

Science.gov (United States)

Ghosh, Smita; Moonan, Patrick K; Cowan, Lauren; Grant, Juliana; Kammerer, Steve; Navin, Thomas R

2012-06-01

Molecular characterization of Mycobacterium tuberculosis complex isolates (genotyping) can be used by public health programs to more readily identify tuberculosis (TB) transmission. The Centers for Disease Control and Prevention's National Tuberculosis Genotyping Service has offered M. tuberculosis genotyping for every culture-confirmed case in the United States since 2004. The TB Genotyping Information Management System (TB GIMS), launched in March 2010, is a secure online database containing genotype results linked with case characteristics from the national TB registry for state and local TB programs to access, manage and analyze these data. As of September 2011, TB GIMS contains genotype results for 89% of all culture-positive TB cases for 2010. Over 400 users can generate local and national reports and maps using TB GIMS. Automated alerts on geospatially concentrated cases with matching genotypes that may represent outbreaks are also generated by TB GIMS. TB genotyping results are available to enhance national TB surveillance and apply genotyping results to conduct TB control activities in the United States. Published by Elsevier B.V.

Organization of surveillance in GI practice.

Science.gov (United States)

Senore, Carlo; Bellisario, Cristina; Hassan, Cesare

2016-12-01

Several reports documented an inefficient utilisation of available resources, as well as a suboptimal compliance with surveillance recommendations. Although, evidence suggests that organisational issues can influence the quality of care delivered, surveillance protocols are usually based on non-organized approaches. We conducted a literature search (publication date: 01/2000-06/2016) on PubMed and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials for guidelines, or consensus statements, for surveys of practice, reporting information about patients, or providers attitudes and behaviours, for intervention studies to enhance compliance with guidelines. Related articles were also scrutinised. Based on the clinical relevance and burden on endoscopy services this review was focused on surveillance for Barrett's oesophagus, IBD and post-polypectomy surveillance of colonic adenomas. Existing guidelines are generally recognising structure and process requirements influencing delivery of surveillance interventions, while less attention had been devoted to transitions and interfaces in the care process. Available evidence from practice surveys is suggesting the need to design organizational strategies aimed to enable patients to attend and providers to deliver timely and appropriate care. Well designed studies assessing the effectiveness of specific interventions in this setting are however lacking. Indirect evidence from screening settings would suggest that the implementation of automated standardized recall systems, utilisation of clinical registries, removing financial barriers, could improve appropriateness of use and compliance with recommendations. Lack of sound evidence regarding utility and methodology of surveillance can contribute to explain the observed variability in providers and patients attitudes and in compliance with the recommended surveillance. Copyright © 2016 Elsevier

Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.

Science.gov (United States)

Heler, Robert; Wright, Addison V; Vucelja, Marija; Bikard, David; Doudna, Jennifer A; Marraffini, Luciano A

2017-01-05

CRISPR loci and their associated (Cas) proteins encode a prokaryotic immune system that protects against viruses and plasmids. Upon infection, a low fraction of cells acquire short DNA sequences from the invader. These sequences (spacers) are integrated in between the repeats of the CRISPR locus and immunize the host against the matching invader. Spacers specify the targets of the CRISPR immune response through transcription into short RNA guides that direct Cas nucleases to the invading DNA molecules. Here we performed random mutagenesis of the RNA-guided Cas9 nuclease to look for variants that provide enhanced immunity against viral infection. We identified a mutation, I473F, that increases the rate of spacer acquisition by more than two orders of magnitude. Our results highlight the role of Cas9 during CRISPR immunization and provide a useful tool to study this rare process and develop it as a biotechnological application. Copyright © 2017 Elsevier Inc. All rights reserved.

Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

NARCIS (Netherlands)

de Witte, Lot; Zoughlami, Younes; Aengeneyndt, Birgit; David, Guido; van Kooyk, Yvette; Gissmann, Lutz; Geijtenbeek, Teunis B. H.

2007-01-01

Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to

Impact of clinical surveillance during a foot-and-mouth disease epidemic

DEFF Research Database (Denmark)

Hisham Beshara Halasa, Tariq; Boklund, Anette

duration, number of infected herds and the economic losses from an epidemic. The stochastic spatial simulation model DTU-DADS was enhanced to include simulation of surveillance of herds within the protection and surveillance zones and the model was used to model spread of FMD between herds. A queuing......The objectives of this study were to assess, whether the current surveillance capacity is sufficient to fulfill EU and Danish regulations to control a hypothetical foot-and-mouth disease (FMD) epidemic in Denmark, and whether enlarging the protection and/or surveillance zones could reduce epidemic...... showed that the default surveillance capacity is sufficient to survey herds within one week of the zones establishment, as the regulations demand. Extra resources for surveillance did not reduce the costs of the epidemics, but fewer resources could result in larger epidemics and costs. Furthermore...

Polio eradication in India: progress, but environmental surveillance and vigilance still needed.

Science.gov (United States)

Chatterjee, Animesh; Vidyant, Sanjukta; Dhole, Tapan N

2013-02-18

Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and has been reduced to near elimination, all within the span of documented medical history. Nevertheless, effective vaccinations, global surveillance network, development of accurate viral diagnosis prompted the historical challenge, global polio eradication initiative (GPEI). Environmental surveillance of poliovirus means monitoring of wild polio virus (WPV) and vaccine derived polio virus (cVDPV) circulation in human populations by examining environmental specimens supposedly contaminated by human feces. The rationale for surveillance is based on the fact that PV-infected individuals, whether presenting with disease symptoms or not, shed large amounts of PV in the feces for several weeks. As the morbidity: infection ratio of PV infection is very low, and therefore this fact contributes to the sensitivity of poliovirus surveillance, which under optimal conditions can be better than that of the standard acute flaccid paralysis (AFP) surveillance. The World Health Organization (WHO) has included environmental surveillance of poliovirus in the new Strategic Plan of the Global Polio Eradication Initiative for years 2010-2012 to be increasingly used in PV surveillance, supplementing AFP surveillance and the strategic advisory group of experts on immunization (SAGE) recommended a switch from tOPV-bOPV to remove the threat of cVDPV2 and to accelerate the elimination of WPV type 1 and 3 as bOPV is a more immunogenic vaccine and to introduce one dose of IPV in their vaccination schedule prior to OPV cessation. Copyright © 2012 Elsevier Ltd. All rights reserved.

On-line surveillance system for Borssele nuclear power plant monitoring and diagnostics

International Nuclear Information System (INIS)

Tuerkcan, E.; Ciftcioglu, Oe.

1993-08-01

An operating on-line surveillance and diagnostic system is described where information processing for monitoring and fault diagnosis and plant maintenance are addressed. The surveillance system by means of its realtime multiprocessing, multitasking execution capabilities can perform plant-wide and wide-range monitoring for enhanced plant safety and operational reliability as well as enhanced maintenance. At the same time the system provides the possibilities for goal-oriented research and development such as estimation, filtering, verification and validation and neural networks. (orig./HP)

Experiences and Lessons From Polio Eradication Applied to Immunization in 10 Focus Countries of the Polio Endgame Strategic Plan

Science.gov (United States)

Mallya, Apoorva; Sandhu, Hardeep; Anya, Blanche-Philomene; Yusuf, Nasir; Ntakibirora, Marcelline; Hasman, Andreas; Fahmy, Kamal; Agbor, John; Corkum, Melissa; Sumaili, Kyandindi; Siddique, Anisur Rahman; Bammeke, Jane; Braka, Fiona; Andriamihantanirina, Rija; Ziao, Antoine-Marie C.; Djumo, Clement; Yapi, Moise Desire; Sosler, Stephen; Eggers, Rudolf

2017-01-01

Abstract Nine polio areas of expertise were applied to broader immunization and mother, newborn and child health goals in ten focus countries of the Polio Eradication Endgame Strategic Plan: policy & strategy development, planning, management and oversight (accountability framework), implementation & service delivery, monitoring, communications & community engagement, disease surveillance & data analysis, technical quality & capacity building, and partnerships. Although coverage improvements depend on multiple factors and increased coverage cannot be attributed to the use of polio assets alone, 6 out of the 10 focus countries improved coverage in three doses of diphtheria tetanus pertussis containing vaccine between 2013 and 2015. Government leadership, evidence-based programming, country-driven comprehensive operational annual plans, community partnership and strong accountability systems are critical for all programs and polio eradication has illustrated these can be leveraged to increase immunization coverage and equity and enhance global health security in the focus countries. PMID:28838187

LOCAL IMMUNITY BY TISSUE-RESIDENT CD8+ MEMORY T CELLS

Directory of Open Access Journals (Sweden)

Thomas eGebhardt

2012-11-01

Full Text Available Microbial infection primes a CD8+ cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8+ T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103+ memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Here, we review evolving concepts regarding the generation and long-term persistence of these tissue-resident memory T cells (TRM in epithelial and neuronal tissues. We further discuss the role of TRM cells in local infection control and their contribution to localized immune phenomena, in both mice and humans.

Proteomic identification of the related immune-enhancing proteins in shrimp Litopenaeus vannamei stimulated with vitamin C and Chinese herbs.

Science.gov (United States)

Qiao, Jie; Du, Zhiheng; Zhang, Yueling; Du, Hong; Guo, Lingling; Zhong, Mingqi; Cao, Jingsong; Wang, Xiuying

2011-12-01

Recently, strong interest has been focused on immunostimulants to reducing the diseases in shrimp aquaculture. However, information regarding to the related immune-enhancing proteins in shrimps is not available yet. In this study, vitamin C (Vc), Chinese herbs (CH), and the mixture of vitamin C and Chinese herbs (Mix) were tested for their enhancement on shrimp's immune activity. Compared with those in the control group, values of phenoloxidase (PO), superoxide dismutase (SOD) and antibacterial (Ua) activity in the Mix-treated group were improved significantly 12 or 24 days after the treatment. The cumulative mortality was also lower in the Mix-treated group after infection with Vibrio parahemolyticus. Furthermore, comparative proteomic approach was used to assess the protein expression profile in shrimps. Approximately 220-290 and 300-400 protein spots were observed in the 2-DE gels. Among them, 29 and 28 altered proteins from hemocytes and hepatopancreas, respectively, were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The results revealed that the main altered proteins showed high homologies with Litopenaeus vannamei hemocyanin, hemolymph clottable protein, hemoglobin beta, cytosolic MnSOD, trypsin, cathepsin I(L) and zinc proteinase Mpc1. Together, these studies found Vc and CH were suitable immunostimulants to shrimp L. vannamei, and 7 altered proteins could be involved in the enhanced immune activities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exosomes and their roles in immune regulation and cancer.

Science.gov (United States)

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

2015-04-01

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

AUTOMATED DEAD-END ULTRAFILTRATION FOR ENHANCED SURVEILLANCE OF LEGIONELLA 2 PNEUMOPHILA AND LEGIONELLA SPP. IN COOLING TOWER WATERS

Energy Technology Data Exchange (ETDEWEB)

Brigmon, R.; Leskinen, S.; Kearns, E.; Jones, W.; Miller, R.; Betivas, C.; Kingsley, M.; Lim, D.

2011-10-10

Detection of Legionella pneumophila in cooling towers and domestic hot water systems involves concentration by centrifugation or membrane filtration prior to inoculation onto growth media or analysis using techniques such as PCR or immunoassays. The Portable Multi-use Automated Concentration System (PMACS) was designed for concentrating microorganisms from large volumes of water in the field and was assessed for enhancing surveillance of L. pneumophila at the Savannah River Site, SC. PMACS samples (100 L; n = 28) were collected from six towers between August 2010 and April 2011 with grab samples (500 ml; n = 56) being collected before and after each PMACS sample. All samples were analyzed for the presence of L. pneumophila by direct fluorescence immunoassay (DFA) using FITC-labeled monoclonal antibodies targeting serogroups 1, 2, 4 and 6. QPCR was utilized for detection of Legionella spp. in the same samples. Counts of L. pneumophila from DFA and of Legionella spp. from qPCR were normalized to cells/L tower water. Concentrations were similar between grab and PMACS samples collected throughout the study by DFA analysis (P = 0.4461; repeated measures ANOVA). The same trend was observed with qPCR. However, PMACS concentration proved advantageous over membrane filtration by providing larger volume, more representative samples of the cooling tower environment, which led to reduced variability among sampling events and increasing the probability of detection of low level targets. These data highlight the utility of the PMACS for enhanced surveillance of L. pneumophila by providing improved sampling of the cooling tower environment.

Extended surveillance as a support to PLIM

International Nuclear Information System (INIS)

Walle, Eric van

2002-01-01

space) calculus tools trying to predict macroscopic radiation damage behaviour of materials are under accelerated development. For latter research area, realistic application to reactor pressure vessel materials will need its time, but these efforts should be encouraged and supported by dedicated experiments; 5. New methodologies, like the master curve approach to directly assess the initiation fracture toughness of the material, have been very successful; they mostly support the actual regulatory surveillance methodologies, shed light on some of the deficiencies of the actual regulation and allow to make an independent 'absolute' assessment of fracture toughness; 6. Reconstitution technology is an indispensable tool to prepare additional specimens. The technique is mature for use on irradiated samples and is an integral part of enhanced surveillance. These tools that involve the interpretation of instrumented impact testing, reconstitution of test specimens and three-point bend quasi-static fracture toughness testing on small geometry specimens have triggered a different approach towards so-called enhanced surveillance strategies for reactor pressure vessel life time management. Moreover, consistent analysis and understanding of information is a powerful asset to detect irregularities in the surveillance approach or in the vessel surveillance material. (author)

Enhancing immune responses to inactivated porcine parvovirus oil emulsion vaccine by co-inoculating porcine transfer factor in mice.

Science.gov (United States)

Wang, Rui-ning; Wang, Ya-bin; Geng, Jing-wei; Guo, Dong-hui; Liu, Fang; Chen, Hong-ying; Zhang, Hong-ying; Cui, Bao-an; Wei, Zhan-yong

2012-07-27

Inactivated porcine parvovirus (PPV) vaccines are available commercially and widely used in the breeding herds. However, inactivated PPV vaccines have deficiencies in induction of specific cellular immune response. Transfer factor (TF) is a material that obtained from the leukocytes, and is a novel immune-stimulatory reagent that as a modulator of the immune system. In this study, the immunogenicity of PPV oil emulsion vaccine and the immuno-regulatory activities of TF were investigated. The inactivated PPV oil emulsion vaccines with or without TF were inoculated into BALB/c mice by subcutaneous injection. Then humoral and cellular immune responses were evaluated by indirect enzyme-linked immunosorbent assays (ELISA), fluorescence-activated cell sorter analyses (FACS). The results showed that the PPV specific immune responses could be evoked in mice by inoculating with PPV oil emulsion vaccine alone or by co-inoculation with TF. The cellular immune response levels in the co-inoculation groups were higher than those groups receiving the PPV oil emulsion vaccine alone, with the phenomena of higher level of IFN-γ, a little IL-6 and a trace of IL-4 in serum, and a vigorous T-cell response. However, there was no significant difference in antibody titers between TF synergy inactivated vaccine and the inactivated vaccine group (P>0.05). In conclusion, these results suggest that TF possess better cellular immune-enhancing capability and would be exploited into an effective immune-adjuvant for inactivated vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Burden of vaccine-preventable pneumococcal disease in hospitalized adults: A Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) network study.

Science.gov (United States)

LeBlanc, Jason J; ElSherif, May; Ye, Lingyun; MacKinnon-Cameron, Donna; Li, Li; Ambrose, Ardith; Hatchette, Todd F; Lang, Amanda L; Gillis, Hayley; Martin, Irene; Andrew, Melissa K; Boivin, Guy; Bowie, William; Green, Karen; Johnstone, Jennie; Loeb, Mark; McCarthy, Anne; McGeer, Allison; Moraca, Sanela; Semret, Makeda; Stiver, Grant; Trottier, Sylvie; Valiquette, Louis; Webster, Duncan; McNeil, Shelly A

2017-06-22

Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes. Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay. In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized

Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011-2015.

Science.gov (United States)

Semá Baltazar, Cynthia; Langa, José Paulo; Dengo Baloi, Liliana; Wood, Richard; Ouedraogo, Issaka; Njanpop-Lafourcade, Berthe-Marie; Inguane, Dorteia; Elias Chitio, Jucunu; Mhlanga, Themba; Gujral, Lorna; D Gessner, Bradford; Munier, Aline; A Mengel, Martin

2017-10-01

Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and control efforts during major cholera outbreaks in recent years.

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

Science.gov (United States)

Cohen, Luchino

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

Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways

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Qishi Zheng

2015-09-01

Full Text Available Background/Aims: Regular physical exercise can enhance resistance to many microbial infections. However, little is known about the mechanism underlying the changes in the immune system induced by regular exercise. Methods: We recruited members of a university badminton club as the regular exercise (RE group and healthy sedentary students as the sedentary control (SC group. We investigated the distribution of peripheral blood mononuclear cell (PBMC subsets and functions in the two groups. Results: There were no significant differences in plasma cytokine levels between the RE and SC groups in the true resting state. However, enhanced levels of IFN-γ, TNF-α, IL-6, IFN-α and IL-12 were secreted by PBMCs in the RE group following microbial antigen stimulation, when compared to the SC group. In contrast, the levels of TNF-α and IL-6 secreted by PBMC in the RE group were suppressed compared with those in SC group following non-microbial antigen stimulation (concanavalin A or α-galactosylceramide. Furthermore, PBMC expression of TLR2, TLR7 and MyD88 was significantly increased in the RE group in response to microbial antigen stimulation. Conclusion: Regular exercise enhances immune cell activation in response to pathogenic stimulation leading to enhanced cytokine production mediated via the TLR signaling pathways.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

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Zhao JH

2017-07-01

Full Text Available Ji-Hui Zhao,1,* Qi-Bo Zhang,1,* Bao Liu,2 Xiang-Hua Piao,1 Yu-Lu Yan,1 Xiao-Ge Hu,1 Kuan Zhou,1 Yong-Tai Zhang,1 Nian-Ping Feng1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Anethesiology Department, Augusta University, Augusta, GA, USA *These authors contributed equally to this work Purpose: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA was combined with platycodin (PD, a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array.Methods: OVA- and PD-loaded liposomes (OVA-PD-Lipos were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs, and hemolytic activity to rabbit red blood cells (RBCs were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.Results: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin.Conclusion: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant. Keywords: subunit vaccine, saponin adjuvant, liposomes, dissolving microneedle array, intradermal vaccination

Immune Effector Recovery in Chronic Myeloid Leukemia and Treatment-Free Remission

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Agnes S. M. Yong

2017-04-01

Full Text Available Chronic myeloid leukemia (CML is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01% in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR, which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56dim NK cells may be important

Immune Effector Recovery in Chronic Myeloid Leukemia and Treatment-Free Remission

Science.gov (United States)

Hughes, Amy; Yong, Agnes S. M.

2017-01-01

Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR), which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK) cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56dim NK cells may be important in mediating

Surveillance

DEFF Research Database (Denmark)

Albrechtslund, Anders; Coeckelbergh, Mark; Matzner, Tobias

Studying surveillance involves raising questions about the very nature of concepts such as information, technology, identity, space and power. Besides the maybe all too obvious ethical issues often discussed with regard to surveillance, there are several other angles and approaches that we should...... like to encourage. Therefore, our panel will focus on the philosophical, yet non-ethical issues of surveillance in order to stimulate an intense debate with the audience on the ethical implications of our enquiries. We also hope to provide a broader and deeper understanding of surveillance....

Framework for evaluating public health surveillance systems for early detection of outbreaks: recommendations from the CDC Working Group.

Science.gov (United States)

Buehler, James W; Hopkins, Richard S; Overhage, J Marc; Sosin, Daniel M; Tong, Van

2004-05-07

The threat of terrorism and high-profile disease outbreaks has drawn attention to public health surveillance systems for early detection of outbreaks. State and local health departments are enhancing existing surveillance systems and developing new systems to better detect outbreaks through public health surveillance. However, information is limited about the usefulness of surveillance systems for outbreak detection or the best ways to support this function. This report supplements previous guidelines for evaluating public health surveillance systems. Use of this framework is intended to improve decision-making regarding the implementation of surveillance for outbreak detection. Use of a standardized evaluation methodology, including description of system design and operation, also will enhance the exchange of information regarding methods to improve early detection of outbreaks. The framework directs particular attention to the measurement of timeliness and validity for outbreak detection. The evaluation framework is designed to support assessment and description of all surveillance approaches to early detection, whether through traditional disease reporting, specialized analytic routines for aberration detection, or surveillance using early indicators of disease outbreaks, such as syndromic surveillance.

Global invasive bacterial vaccine-preventable diseases surveillance--2008-2014.

Science.gov (United States)

Murray, Jillian; Agócs, Mary; Serhan, Fatima; Singh, Simarjit; Deloria-Knoll, Maria; O'Brien, Katherine; Mwenda, Jason M; Mihigo, Richard; Oliveira, Lucia; Teleb, Nadia; Ahmed, Hinda; Wasley, Annemarie; Videbaek, Dovile; Wijesinghe, Pushpa; Thapa, Arun Bhadra; Fox, Kimberly; Paladin, Fem Julia; Hajjeh, Rana; Schwartz, Stephanie; Van Beneden, Chris; Hyde, Terri; Broome, Claire; Cherian, Thomas

2014-12-12

Meningitis and pneumonia are leading causes of morbidity and mortality in children globally infected with Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis, and Haemophilus influenzae causing a large proportion of disease. Vaccines are available to prevent many of the common types of these infections. S. pneumoniae was estimated to have caused 11% of deaths in children aged Organization (WHO) has recommended inclusion of PCV in childhood immunization programs worldwide, especially in countries with high child mortality. As of November 26, 2014, a total of 112 (58%) of all 194 WHO member states and 44 (58%) of the 76 member states ever eligible for support from Gavi, the Vaccine Alliance (Gavi), have introduced PCV. Invasive pneumococcal disease (IPD) surveillance that includes data on serotypes, along with meningitis and pneumonia syndromic surveillance, provides important data to guide decisions to introduce PCV and monitor its impact.

Improvements to Technical Specifications surveillance requirements

International Nuclear Information System (INIS)

Lobel, R.; Tjader, T.R.

1992-12-01

In August 1983 an NRC task group was formed to investigate problems with surveillance testing required by Technical Specifications, and to recommend approaches to effect improvements. NUREG-1024 (''Technical Specifications-Enhancing Safety Impact'') resulted, and it contained recommendations to review the basis for test frequencies; to ensure that the tests promote safety and do not degrade equipment; and to review surveillance tests so that they do not unnecessarily burden personnel. The Technical Specifications Improvement Program (TSIP) was established in December 1984 to provide the framework for rewriting and improving the Technical Specifications. As an element of the TSIP, all Technical Specifications surveillance requirements were comprehensively examined as recommended in NUREG-1024. The results of that effort are presented in this report. The study found that while some testing at power is essential to verify equipment and system operability, safety can be improved, equipment degradation decreased, and unnecessary personnel burden relaxed by reducing the amount of testing at power

A tritherapy combination of inactivated allogeneic leukocytes infusion and cell vaccine with cyclophosphamide in a sequential regimen enhances antitumor immunity

OpenAIRE

Yishu Tang; Wenbo Ma; Chunxia Zhou; Dongmei Wang; Shuren Zhang

2018-01-01

Background: Tumor-induced immunosuppression can impede tumor-specific immune responses and limit the effects of cancer immunotherapy. The aim of this study was to investigate the possible effects of sequential chemoimmunotherapeutic strategies to enhance antitumor immune responses. Methods: Using the E7-expressing tumor TC-1 as the tumor model, the treatment groups were divided into the following groups: (1) inactivated allogeneic leukocyte infusion (ALI), (2) ALI + MMC-inactivated TC-1 cell ...

Keeping the immune system in check: a role for mitophagy.

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Lazarou, Michael

2015-01-01

Mitochondria play a central role in many facets of cellular function including energy production, control of cell death and immune signaling. Breakdown of any of these pathways because of mitochondrial deficits or excessive reactive oxygen species production has detrimental consequences for immune system function and cell viability. Maintaining the functional integrity of mitochondria is therefore a critical challenge for the cell. Surveillance systems that monitor mitochondrial status enable the cell to identify and either repair or eliminate dysfunctional mitochondria. Mitophagy is a selective form of autophagy that eliminates dysfunctional mitochondria from the population to maintain overall mitochondrial health. This review covers the major players involved in mitophagy and explores the role mitophagy plays to support the immune system.

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

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Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

2011-02-01

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

Complex pattern of immune evasion in MSI colorectal cancer.

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Ozcan, Mine; Janikovits, Jonas; von Knebel Doeberitz, Magnus; Kloor, Matthias

2018-01-01

Mismatch repair (MMR)-deficient cancers accumulate multiple insertion/deletion mutations at coding microsatellites (cMS), which give rise to frameshift peptide neoantigens. The high mutational neoantigen load of MMR-deficient cancers is reflected by pronounced anti-tumoral immune responses of the host and high responsiveness towards immune checkpoint blockade. However, immune evasion mechanisms can interfere with the immune response against MMR-deficient tumors. We here performed a comprehensive analysis of immune evasion in MMR-deficient colorectal cancers, focusing on HLA class I-mediated antigen presentation. 72% of MMR-deficient colorectal cancers of the DFCI database harbored alterations affecting genes involved in HLA class I-mediated antigen presentation, and 54% of these mutations were predicted to abrogate function. Mutations affecting the HLA class I transactivator NLRC5 were observed as a potential new immune evasion mechanism in 26% (6% abrogating) of the analyzed tumors. NLRC5 mutations in MMR-deficient cancers were associated with decreased levels of HLA class I antigen expression. In summary, the majority of MMR-deficient cancers display mutations interfering with HLA class I antigen presentation that reflect active immune surveillance and immunoselection during tumor development. Clinical studies focusing on immune checkpoint blockade in MSI cancer should account for the broad variety of immune evasion mechanisms as potential biomarkers of therapy success.

Evaluating surveillance indicators supporting the Global Polio Eradication Initiative, 2011-2012.

Science.gov (United States)

2013-04-12

The Global Polio Eradication Initiative (GPEI) was established in 1988 by the World Health Assembly to interrupt transmission of wild poliovirus (WPV); completion of this initiative was declared a programmatic emergency of public health in January 2012. Polio cases are detected through surveillance for acute flaccid paralysis (AFP) with linked stool specimens tested for polioviruses (PVs) at accredited laboratories within the Global Polio Laboratory Network (GPLN). AFP surveillance findings are supplemented by testing sewage samples (environmental surveillance) collected at selected sites. Virologic data guide where targeted immunization activities should be conducted or improved. Key performance indicators are used to 1) monitor AFP surveillance quality at national and subnational levels to identify gaps where PV transmission could occur undetected; 2) provide evidence of where PV circulation has been interrupted; and 3) allow timely detection of an outbreak. Standardized surveillance indicators allow progress to be monitored over time and compared among countries. This report presents AFP surveillance performance indicators at national and subnational levels for countries affected by polio during 2011-2012, and trends in environmental surveillance, updating previous reports. In the 19 countries with transmission of PV (WPV and/or circulating vaccine-derived poliovirus [cVDPV]) during 2011-2012, national performance indicator targets were met in 12 (63%) countries in 2011 and 13 (68%) countries in 2012. Seven countries (37%) in 2011 had ≥80% of the population living in areas meeting performance indicators, increasing to nine countries (47%) in 2012. Performance indicators for timely reporting of PV isolation and characterization were met in four of six World Health Organization (WHO) regions in 2011 and five regions in 2012. To achieve global polio eradication, efforts are needed to improve and maintain AFP surveillance and laboratory performance.

Immune reaction and colorectal cancer: friends or foes?

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Formica, Vincenzo; Cereda, Vittore; Nardecchia, Antonella; Tesauro, Manfredi; Roselli, Mario

2014-09-21

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.

Overexpression of angiotensin-converting enzyme in myelomonocytic cells enhances the immune response [version 1; referees: 3 approved

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Kenneth E. Bernstein

2016-03-01

Full Text Available Angiotensin-converting enzyme (ACE converts angiotensin I to the vasoconstrictor angiotensin II and thereby plays an important role in blood pressure control. However, ACE is relatively non-specific in its substrate specificity and cleaves many other peptides. Recent analysis of mice overexpressing ACE in monocytes, macrophages, and other myelomonocytic cells shows that these animals have a marked increase in resistance to experimental melanoma and to infection by Listeria monocytogenes or methicillin-resistant Staphylococcus aureus (MRSA. Several other measures of immune responsiveness, including antibody production, are enhanced in these animals. These studies complement a variety of studies indicating an important role of ACE in the immune response.

Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance.

Science.gov (United States)

Gebhardt, Thomas; Palendira, Umaimainthan; Tscharke, David C; Bedoui, Sammy

2018-05-01

A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (T RM ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of T RM cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function. Nevertheless, certain transcriptional programs are shared and appear as important unifying features for the overall population of T RM cells and tissue-resident lymphocytes. It is now widely appreciated that T RM cells are a critical component of our immune defense by acting as peripheral sentinels capable of rapidly mobilizing protective tissue immunity upon pathogen recognition. This function is of particular importance in anatomical sites that are not effectively surveilled by blood-borne memory T cells in absence of inflammation, such as neuronal tissues or epithelial compartments in skin and mucosae. Focusing on the well-characterized subtype of CD8 +  CD69 +  CD103 + T RM cells, we will review current concepts on the generation, persistence and function of T RM cells and will summarize commonly used tools to study these cells. Furthermore, we will discuss accumulating data that emphasize localized T RM responses as an important determinant of tissue homeostasis and immune defense in the context of microbiota-immune interactions, persistent infections and cancer surveillance. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kestrel: force protection and Intelligence, Surveillance, and Reconnaissance (ISR) persistent surveillance on aerostats

Science.gov (United States)

Luber, David R.; Marion, John E.; Fields, David

2012-05-01

Logos Technologies has developed and fielded the Kestrel system, an aerostat-based, wide area persistent surveillance system dedicated to force protection and ISR mission execution operating over forward operating bases. Its development included novel imaging and stabilization capability for day/night operations on military aerostat systems. The Kestrel system's contribution is a substantial enhancement to aerostat-based, force protection systems which to date have relied on narrow field of view ball gimbal sensors to identify targets of interest. This inefficient mechanism to conduct wide area field of view surveillance is greatly enhanced by Kestrel's ability to maintain a constant motion imagery stare of the entire forward operating base (FOB) area. The Kestrel airborne sensor enables 360° coverage out to extended ranges which covers a city sized area at moderate resolution, while cueing a narrow field of view sensor to provide high resolution imagery of targets of interest. The ground station exploitation system enables operators to autonomously monitor multiple regions of interest in real time, and allows for backtracking through the recorded imagery, while continuing to monitor ongoing activity. Backtracking capability allows operators to detect threat networks, their CONOPS, and locations of interest. Kestrel's unique advancement has already been utilized successfully in OEF operations.

Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

Science.gov (United States)

Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

2008-06-01

Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

Role of NKG2D-Expressing NK Cells and sMICA in Immune Surveillance of Advanced Lung Cancer

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Jing LIANG

2009-01-01

Full Text Available Background and objective NKG2D-expressing NK cells and soluble major histocompatibility complex class Ⅰ-related chain A (sMICA is one of aroused general interests in tumor research area recently. The aimof the study is to investigate the levels of NKG2D-expressing NK cells and sMICA in peripheral blood of advanced lung cancer which are remarkably related to clinical significance and analyse the role of NKG2D-expressing NK cells and sMICA in immune surveillance. Methods Flow cytometry was used to determine the percentage of NKG2D-expressing NK cells, T cell subsets, NK cells, and ELISA was used to mesure the levels of sMICA in peripheral blood of 115 advanced lung cancer patients and 50 healthy controls. Results Compared with control group, the levels of sMICA、CD8+T cells, NK cells increased, while the levels of NKG2D-expressing NK cells, CD3+ T cells, CD4+ T cells, CD4+ T/CD8+ T in experimental group decreased. NKG2D-expressing NK cells had a perfect negative correlation with sMICA (r =-0.319, P <0.05. NKG2D-expressing NK cells had positive correlation with CD4+ T cells, CD4+ T/CD8+ T and negative correlationwith CD8+ T cells (P <0.05, sMICA had negative correlation with CD4+ T cells, CD4+ T/CD8+ T and positive correlation with CD8+ T cells (P <0.05, they had no significant correlation with CD3+ T cells, NK cells respectively (P <0.05. Conclusion Accumulation of sMICA in serum may lead to the down-modulation of NKG2D-expressing NK which has been proposed to be a novel mechanism used by cancer cells to evade the tumor immunosurveillance. They may be potential indicators investigating immune functions and helpful in the evaluation of their happening and proceeding.

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

Science.gov (United States)

Sattler, Susanne

2017-01-01

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

Regulation of IgE antibody production by serum molecules. I. Serum from complete Freund's adjuvant-immune donors suppresses irradiation-enhanced IgE production in low responder mouse strains

International Nuclear Information System (INIS)

Tung, A.S.; Chiorazzi, N.; Katz, D.H.

1978-01-01

Exposure of mice to low doses of x irradiation at or near the time of primary immunization with 2,4-dinitrophenyl (DNP)-Ascaris suum extract (ASC) results in substantial enhancement of IgE anti-DNP antibody responses; the IgG antibody responses of such mice do not increase after such manipulations. This selective enhancement of IgE antibody production occurs in mice of both high and low IgE responder phenotype, although the extent of enhancement compared to unmanipulated control animals is more striking in low IgE responder mice. The studies presented here demonstrate that the irradiation-enhanced IgE antibody responses of low responder SJL and C57BL/6 mice as well as of intermediate responder AKR mice can be effectively suppressed by passive transfer of CFA-immune serum obtained from isologous donor mice. Moreover, adoptive secondary IgE antibody responses in SJL recipients of primed syngeneic spleen cells can be totally abolished by passive transfer of CFA-immune serum or ascitic fluid from CFA-immune mice. The suppressive activity of CFA-immune serum can be diminished or eliminated by exposure of CFA-primed donor mice to low dose x irradiation at an appropriate point during the priming regimen, after a single inoculation of CFA, and before collection of serum. Low dose x irradiation was not effective in eliminating suppressive activity of CFA-induced ascites fluid obtained from donor mice inoculated repeatedly with CFA. In contrast to the capacity of CFA-immune serum from isologous donors to suppress irradiation-enhanced IgE responses of low responder mice, similar sera or ascites fluids were ineffective in suppressing irradiation-enhanced responses of high responder BALB/c or (SJL x BALB/c)F 1 hybrid mice

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

OpenAIRE

Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

2014-01-01

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delive...

Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011–2015

Science.gov (United States)

Langa, José Paulo; Dengo Baloi, Liliana; Wood, Richard; Ouedraogo, Issaka; Njanpop-Lafourcade, Berthe-Marie; Inguane, Dorteia; Elias Chitio, Jucunu; Mhlanga, Themba; Gujral, Lorna; D. Gessner, Bradford; Munier, Aline; A. Mengel, Martin

2017-01-01

Background Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country. Methodology/Principal findings Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models. A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking. Conclusions/Significance Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and

Efficacy of duplex ultrasound surveillance after infrainguinal vein bypass may be enhanced by identification of characteristics predictive of graft stenosis development.

Science.gov (United States)

Tinder, Chelsey N; Chavanpun, Joe P; Bandyk, Dennis F; Armstrong, Paul A; Back, Martin R; Johnson, Brad L; Shames, Murray L

2008-09-01

(15%) limbs, the bypass graft failed and 20 (6%) limbs required amputation. The efficacy of duplex surveillance after infrainguinal vein bypass may be enhanced by modifying testing protocols, eg, rigorous surveillance for "higher risk" bypasses, based on the initial duplex scan results and other characteristics (warfarin therapy, non- single segment saphenous vein conduit, redo bypass) predictive for stenosis development.

Effect of oral administration of Lactobacillus paracasei L9 on mouse systemic immunity and the immune response in the intestine

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Zhu Yuanbo

2016-01-01

Full Text Available A probiotic strain Lactobacillus paracasei L9,which was isolated from human intestine, was investigated for its immunomodulatory activity in vivo. Results showed that L9 improved systemic immunity by enhancing the phagocytic activity of peritoneal macrophages, the proliferation ratio of splenocytes, the IgG level in the serum and the level of IgA in the mucosa. Further, L9induced theTh1-polarized immune response by elevating the IFN-γ/IL-4 ratio in the mucosa. This effect was confirmed by the enhanced IL-12-inducing activity of macrophages after in vitro stimulation of L9. Also detected was increased expression of TLR-2mRNA in the mucosa. We predict that L9 could enhance innate immunity by activating TLR-2 in the mucosa, and enhance acquired immunity by promoting Th1 polarization through induced production of IL-12 by macrophages.

Experiences and Lessons From Polio Eradication Applied to Immunization in 10 Focus Countries of the Polio Endgame Strategic Plan.

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van den Ent, Maya M V X; Mallya, Apoorva; Sandhu, Hardeep; Anya, Blanche-Philomene; Yusuf, Nasir; Ntakibirora, Marcelline; Hasman, Andreas; Fahmy, Kamal; Agbor, John; Corkum, Melissa; Sumaili, Kyandindi; Siddique, Anisur Rahman; Bammeke, Jane; Braka, Fiona; Andriamihantanirina, Rija; Ziao, Antoine-Marie C; Djumo, Clement; Yapi, Moise Desire; Sosler, Stephen; Eggers, Rudolf

2017-07-01

Nine polio areas of expertise were applied to broader immunization and mother, newborn and child health goals in ten focus countries of the Polio Eradication Endgame Strategic Plan: policy & strategy development, planning, management and oversight (accountability framework), implementation & service delivery, monitoring, communications & community engagement, disease surveillance & data analysis, technical quality & capacity building, and partnerships. Although coverage improvements depend on multiple factors and increased coverage cannot be attributed to the use of polio assets alone, 6 out of the 10 focus countries improved coverage in three doses of diphtheria tetanus pertussis containing vaccine between 2013 and 2015. Government leadership, evidence-based programming, country-driven comprehensive operational annual plans, community partnership and strong accountability systems are critical for all programs and polio eradication has illustrated these can be leveraged to increase immunization coverage and equity and enhance global health security in the focus countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Conditional predictive inference for online surveillance of spatial disease incidence

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Corberán-Vallet, Ana; Lawson, Andrew B.

2012-01-01

This paper deals with the development of statistical methodology for timely detection of incident disease clusters in space and time. The increasing availability of data on both the time and the location of events enables the construction of multivariate surveillance techniques, which may enhance the ability to detect localized clusters of disease relative to the surveillance of the overall count of disease cases across the entire study region. We introduce the surveillance conditional predictive ordinate as a general Bayesian model-based surveillance technique that allows us to detect small areas of increased disease incidence when spatial data are available. To address the problem of multiple comparisons, we incorporate a common probability that each small area signals an alarm when no change in the risk pattern of disease takes place into the analysis. We investigate the performance of the proposed surveillance technique within the framework of Bayesian hierarchical Poisson models using a simulation study. Finally, we present a case study of salmonellosis in South Carolina. PMID:21898522

Introduction to surveillance studies

CERN Document Server

Petersen, JK

2012-01-01

Introduction & OverviewIntroduction Brief History of Surveillance Technologies & TechniquesOptical SurveillanceAerial Surveillance Audio Surveillance Radio-Wave SurveillanceGlobal Positioning Systems Sensors Computers & the Internet Data Cards Biochemical Surveillance Animal Surveillance Biometrics Genetics Practical ConsiderationsPrevalence of Surveillance Effectiveness of Surveillance Freedom & Privacy IssuesConstitutional Freedoms Privacy Safeguards & Intrusions ResourcesReferences Glossary Index

Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity

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Mari Hirvinen

2016-01-01

Full Text Available In oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. Vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. However, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. To overcome this problem, we developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI to boost the innate immune system and to activate adaptive immune cells in the tumor. We showed that infection with DAI-expressing VV increases expression of several genes related to important immunological pathways. Treatment with DAI-armed VV resulted in significant reduction in the size of syngeneic melanoma tumors in mice. When the mice were rechallenged with the same tumor, DAI-VV-treated mice completely rejected growth of the new tumor, which indicates immunity established against the tumor. We also showed enhanced control of growth of human melanoma tumors and elevated levels of human T-cells in DAI-VV-treated mice humanized with human peripheral blood mononuclear cells. We conclude that expression of DAI by an oncolytic VV is a promising way to amplify the vaccine potency of an oncolytic vaccinia virus to trigger the innate—and eventually the long-lasting adaptive immunity against cancer.

Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy.

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Jiang, Hong; Hegde, Samarth; DeNardo, David G

2017-08-01

Tumor-associated fibrosis is characterized by unchecked pro-fibrotic and pro-inflammatory signaling. The components of fibrosis including significant numbers of cancer-associated fibroblasts, dense collagen deposition, and extracellular matrix stiffness, are well appreciated regulators of tumor progression but may also be critical regulators of immune surveillance. While this suggests that the efficacy of immunotherapy may be limited in highly fibrotic cancers like pancreas, it also suggests a therapeutic opportunity to target fibrosis in these tumor types to reawaken anti-tumor immunity. This review discusses the mechanisms by which fibrosis might subvert tumor immunity and how to overcome these mechanisms.

Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

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Osada, Takuya; Berglund, Peter; Morse, Michael A.; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

2013-01-01

We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)) and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12 and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing anti-tumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted. PMID:22488274

Pathogen-induced maternal effects result in enhanced immune responsiveness across generations.

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Rosengaus, Rebeca B; Hays, Nicole; Biro, Colette; Kemos, James; Zaman, Muizz; Murray, Joseph; Gezahegn, Bruck; Smith, Wendy

2017-05-01

Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context-dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers. By using an in vivo "clearance of infection" assay, we also show that challenged larvae born to heat-killed- or live- Serratia -injected mothers, supported lower microbial loads and cleared the infection faster than progeny of control mothers. Our data support the notion that mothers can anticipate the future pathogenic risks and immunological needs of their unborn offspring, providing progeny with enhanced immune protection likely through transgenerational immune priming. Although the inclusion of live Serratia into oocytes does not appear to be the mechanism by which mothers confer protection to their young, other mechanisms, including epigenetic modifications in the progeny due to maternal pathogenic stress, may be at play. The adaptive nature of maternal effects in the face of pathogenic stress provides insights into parental investment, resource allocation, and life-history theories and highlights the significant role that pathogen-induced maternal effects play as generators and modulators of evolutionary change.

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

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Nava Gerardo M

2009-03-01

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

Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles.

Science.gov (United States)

Mui, B; Raney, S G; Semple, S C; Hope, M J

2001-09-01

The therapeutic benefit from phosphorothioate oligodeoxynucleotides (PS ODN) containing immune stimulatory sequences (ISS) has been demonstrated in animal models of cancer and infection. In particular, when CpG-containing PS ODN are administered to mice, activation of macrophages and dendritic, NK, T, and B cells occurs, resulting in the release of an array of cytokines, including interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We have previously described stabilized antisense-lipid particles (SALP) for the i.v. administration of antisense ODN [Biochim Biophys Acta (2001) 1510:152--166]. Given the propensity for SALP to target macrophages in vivo it was of interest to determine whether they could enhance the potency of CpG ODN to induce an immune response. In this report we show that when CpG-containing SALP are administered intravenously to ICR mice the plasma concentrations of IL-12, IFN-gamma, IL-6, monocyte chemoattractant protein-1, and TNF-alpha are greatly increased compared with the same dose of free ODN. The pattern of cytokine induction indicates that the immune response is T helper cell type 1-biased, similar to that observed for PS CpG ODN ISS in general. Furthermore, when phosphodiester (PO) ODN is substituted for PS ODN in the SALP formulation cytokine induction is even greater at the early time points, in marked contrast to free PO ODN, which is inactive. These results demonstrate that the immunogenicity of ISS is not only enhanced by encapsulation in lipid particles, which more closely mimic the way ISS DNA would normally be presented to antigen presenting cells by pathogens in vivo, but also SALP enable unmodified PO CpG ODN to be used as immune stimulants.

Development and refinement of new statistical methods for enhanced syndromic surveillance during the 2012 Olympic and Paralympic Games.

Science.gov (United States)

Morbey, Roger A; Elliot, Alex J; Charlett, Andre; Andrews, Nick; Verlander, Neville Q; Ibbotson, Sue; Smith, Gillian E

2015-06-01

Prior to the 2012 London Olympic and Paralympic Games, new statistical methods had to be developed for the enhanced syndromic surveillance during the Games. Different methods were developed depending on whether or not historical data were available. Practical solutions were needed to cope with the required daily reporting and data quality issues. During the Games, nearly 4800 signals were tested on average each day, generating statistical alarms that were assessed to provide information on areas of potential public health concern and reassurance that no major adverse incident had occurred. spjhi;21/2/159/FIG41460458213517577 F1 fig4-1460458213517577. © The Author(s) 2013.

Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013.

Science.gov (United States)

van Dorp, Sofie M; Kinross, Pete; Gastmeier, Petra; Behnke, Michael; Kola, Axel; Delmée, Michel; Pavelkovich, Anastasia; Mentula, Silja; Barbut, Frédéric; Hajdu, Agnes; Ingebretsen, André; Pituch, Hanna; Macovei, Ioana S; Jovanović, Milica; Wiuff, Camilla; Schmid, Daniela; Olsen, Katharina Ep; Wilcox, Mark H; Suetens, Carl; Kuijper, Ed J

2016-07-21

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe. This article is copyright of The Authors, 2016.

Management of environmental health issues for the 2004 Athens Olympic Games: is enhanced integrated environmental health surveillance needed in every day routine operation?

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Chervoni Julia

2006-12-01

Full Text Available Abstract Background Management of environmental health issues is an integral part of public health systems. An active integrated environmental health surveillance and response system was developed for the Athens Olympics to monitor and prevent exposure to environmental hazards. The potential for permanent implementation of the program was examined. Methods The environmental health surveillance and response system included standardization, computerization and electronic transmission of data concerning environmental inspections of 17 site categories (restaurants, swimming pools etc of public health interest, drinking and recreational water examinations and suggested corrective actions. The Olympic Planning Unit integrated and centrally managed data from 13 public health agencies, recommended, supervised and coordinated prompt corrective actions. Methods used to test the effectiveness of the program were the assessment of water quality test and inspection results trends over time using linear regression and epidemiological surveillance findings. Results Between January 2003 and September the 30th, 2004, 196 inspectors conducted 8562 inspections, collected 5024 water samples and recommended 17 027 corrective actions. In 10 cruise ships used as floating hotels inspectors conducted 10 full inspections, 2 re-inspections, and 27 follow-up inspections. Unsatisfactory inspection results (r = 0.44, p Conclusion Lessons learned for future events include timely implementation and installation of communication processes, and rapid and coordinated response to unsatisfactory inspection results. Routine national programs need to adopt enhanced environmental health surveillance aimed at public health decision-making, but with a different perspective.

Management of environmental health issues for the 2004 Athens Olympic Games: is enhanced integrated environmental health surveillance needed in every day routine operation?

Science.gov (United States)

Hadjichristodoulou, Christos; Mouchtouri, Varvara; Vaitsi, Vasiliki; Kapoula, Christina; Vousoureli, Anastasia; Kalivitis, Isidiros; Chervoni, Julia; Papastergiou, Panagiotis; Vasilogiannakopoulos, Antonios; Daniilidis, Vasilis D; Kremastinou, Jenny

2006-12-18

Management of environmental health issues is an integral part of public health systems. An active integrated environmental health surveillance and response system was developed for the Athens Olympics to monitor and prevent exposure to environmental hazards. The potential for permanent implementation of the program was examined. The environmental health surveillance and response system included standardization, computerization and electronic transmission of data concerning environmental inspections of 17 site categories (restaurants, swimming pools etc) of public health interest, drinking and recreational water examinations and suggested corrective actions. The Olympic Planning Unit integrated and centrally managed data from 13 public health agencies, recommended, supervised and coordinated prompt corrective actions. Methods used to test the effectiveness of the program were the assessment of water quality test and inspection results trends over time using linear regression and epidemiological surveillance findings. Between January 2003 and September the 30th, 2004, 196 inspectors conducted 8562 inspections, collected 5024 water samples and recommended 17 027 corrective actions. In 10 cruise ships used as floating hotels inspectors conducted 10 full inspections, 2 re-inspections, and 27 follow-up inspections. Unsatisfactory inspection results (r = 0.44, p quality tests (r = 0.39, p restaurant which accommodated athletes during a test event. Lessons learned for future events include timely implementation and installation of communication processes, and rapid and coordinated response to unsatisfactory inspection results. Routine national programs need to adopt enhanced environmental health surveillance aimed at public health decision-making, but with a different perspective.

Trial of Immune Globulin in Infant Botulism

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J Gordon Millichap

2006-02-01

Full Text Available A 5-year, randomized, double-blind, placebo-controlled trial of the orphan drug Human Botulism Immune Globulin Intravenous (BIG-IV in 122 infants in California with confirmed infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin was conducted at the California Department of Health Services, Richmond, CA; National Botulism Surveillance and Reference Laboratory, CDC and P, Atlanta; and Division of Biostatistics, University of California, Berkeley.

Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

Science.gov (United States)

Thomas, Stephen J.; Aldstadt, Jared; Jarman, Richard G.; Buddhari, Darunee; Yoon, In-Kyu; Richardson, Jason H.; Ponlawat, Alongkot; Iamsirithaworn, Sopon; Scott, Thomas W.; Rothman, Alan L.; Gibbons, Robert V.; Lambrechts, Louis; Endy, Timothy P.

2015-01-01

Dengue is of public health importance in tropical and sub-tropical regions. Dengue virus (DENV) transmission dynamics was studied in Kamphaeng Phet Province, Thailand, using an enhanced spatiotemporal surveillance of 93 hospitalized subjects with confirmed dengue (initiates) and associated cluster individuals (associates) with entomologic sampling. A total of 438 associates were enrolled from 208 houses with household members with a history of fever, located within a 200-m radius of an initiate case. Of 409 associates, 86 (21%) had laboratory-confirmed DENV infection. A total of 63 (1.8%) of the 3,565 mosquitoes collected were dengue polymerase chain reaction positive (PCR+). There was a significant relationship between spatial proximity to the initiate case and likelihood of detecting DENV from associate cases and Aedes mosquitoes. The viral detection rate from human hosts and mosquito vectors in this study was higher than previously observed by the study team in the same geographic area using different methodologies. We propose that the sampling strategy used in this study could support surveillance of DENV transmission and vector interactions. PMID:25986580

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.

Poliomyelitis surveillance: the model used in India for polio eradication.

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Banerjee, K.; Hlady, W. G.; Andrus, J. K.; Sarkar, S.; Fitzsimmons, J.; Abeykoon, P.

2000-01-01

Poliomyelitis surveillance in India previously involved the passive reporting of clinically suspected cases. The capacity for detecting the disease was limited because there was no surveillance of acute flaccid paralysis (AFP). In October 1997, 59 specially trained Surveillance Medical Officers were deployed throughout the country to establish active AFP surveillance; 11,533 units were created to report weekly on the occurrence of AFP cases at the district, state and national levels; timely case investigation and the collection of stool specimens from AFP cases was undertaken; linkages were made to support the polio laboratory network; and extensive training of government counterparts of the Surveillance Medical Officers was conducted. Data reported at the national level are analysed and distributed weekly. Annualized rates of non-polio AFP increased from 0.22 per 100,000 children aged under 15 years in 1997 to 1.39 per 100,000 in 1999. The proportion of cases with two adequate stools collected within two weeks of the onset of paralysis increased from 34% in 1997 to 68% in 1999. The number of polio cases associated with the isolation of wild poliovirus decreased from 211 in the first quarter of 1998 to 77 in the first quarter of 1999. Widespread transmission of wild poliovirus types 1 and 3 persists throughout the country; type 2 occurs only in Bihar and Uttar Pradesh. In order to achieve polio eradication in India during 2000, extra national immunization days and house-to-house mopping-up rounds should be organized. PMID:10812728

Enhancing capacity for risk factor surveillance at the regional/local level: a follow-up review of the findings of the Canadian Think Tank Forum after 4 years.

Science.gov (United States)

Choi, Bernard Ck; Decou, Mary Lou; Rasali, Drona; Martens, Patricia J; Mancuso, Michelina; Plotnikoff, Ronald C; Neudorf, Cory; Thanos, Joanne; Svenson, Lawrence W; Denny, Keith; Orpana, Heather; Stewart, Paula; King, Michael; Griffith, Jane; Erickson, Tannis; van Dorp, Renate; White, Deanna; Ali, Amira

2014-01-22

National health surveys are sometimes used to provide estimates on risk factors for policy and program development at the regional/local level. However, as regional/local needs may differ from national ones, an important question is how to also enhance capacity for risk factor surveillance regionally/locally. A Think Tank Forum was convened in Canada to discuss the needs, characteristics, coordination, tools and next steps to build capacity for regional/local risk factor surveillance. A series of follow up activities to review the relevant issues pertaining to needs, characteristics and capacity of risk factor surveillance were conducted. Results confirmed the need for a regional/local risk factor surveillance system that is flexible, timely, of good quality, having a communication plan, and responsive to local needs. It is important to conduct an environmental scan and a gap analysis, to develop a common vision, to build central and local coordination and leadership, to build on existing tools and resources, and to use innovation. Findings of the Think Tank Forum are important for building surveillance capacity at the local/county level, both in Canada and globally. This paper provides a follow-up review of the findings based on progress over the last 4 years.

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

Science.gov (United States)

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

2013-01-01

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

An effective surveillance strategy for reactor pressure vessel assessment in the long term operation perspective

International Nuclear Information System (INIS)

Chaouadi, R.; Gerard, R.

2015-01-01

The reactor pressure vessel (RPV) irradiation embrittlement is monitored by means of surveillance capsules containing the RPV belt-line materials, inserted inside the reactor pressure vessel (RPV) before the start of operation. These capsules are placed at location where they receive a higher neutron flux than the vessel wall, by a factor of the order of 2 to 3. They are regularly retrieved and tested to evaluate the RPV irradiation embrittlement according to specific regulatory procedures and standards, in order to guarantee the safe operation of the RPV throughout its lifetime. These procedures are often relying on empirical but conservative concepts. In parallel, material research reactor (MTR) irradiations are often used to support the surveillance data and to develop a better understanding of irradiation effects, not only qualitatively but also quantitatively. Taking advantage of the increased understanding of irradiation effects, analytical tools were developed to improve the evaluation embrittlement and quality assurance of the RPV embrittlement assessment. In this framework, an alternative but complementary surveillance program assessment was developed in Belgium, the so-called enhanced surveillance, in order to benefit from the latest developments in the area of materials science and irradiation effects. The neutron flux and fracture properties of the surveillance materials can be reliably characterized and correlated to each other using physically-based rather than empirical concepts. The enhanced surveillance approach is complementary to the mandatory regulatory procedure and allows quantifying the conservatism of the regulatory approach. The enhanced surveillance approach that uses the reconstitution technology to fabricate additional small size specimens, appropriate modeling tools and microstructural examination when required, makes it possible to rationalize all available information in a physically-based way

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

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Gary Burness

2018-04-01

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

N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride: An immune-enhancing adjuvant for hepatitis E virus recombinant polypeptide vaccine in mice.

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Tao, Wei; Zheng, Hai-Qun; Fu, Ting; He, Zhuo-Jing; Hong, Yan

2017-08-03

Adjuvants are essential for enhancing vaccine potency by improving the humoral and/or cell-mediated immune response to vaccine antigens. This study was performed to evaluate the immuno-enhancing characteristic of N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride (HTCC), the cationically modified chitosan, as an adjuvant for hepatitis E virus (HEV) recombinant polypeptide vaccine. Animal experiments showed that HTCC provides adjuvant activity when co-administered with HEV recombinant polypeptide vaccine by intramuscularly route. Vaccination using HTCC as an adjuvant was associated with increases of the serum HEV-specific IgG antibodies, splenocytes proliferation and the growths of CD4 + CD8 - T lymphocytes and IFN-γ-secreting T lymphocytes in peripheral blood. These findings suggested that HTCC had strong immuno-enhancing effect. Our findings are the first to demonstrate that HTCC is safe and effective in inducing a good antibody response and stimulating Th1-biased immune responses for HEV recombinant polypeptide vaccine.

Opportunities for Enhanced Strategic Use of Surveys, Medical Records, and Program Data for HIV Surveillance of Key Populations: Scoping Review

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Baral, Stefan D; Edwards, Jessie K; Zadrozny, Sabrina; Hargreaves, James; Zhao, Jinkou; Sabin, Keith

2018-01-01

Background Normative guidelines from the World Health Organization recommend tracking strategic information indicators among key populations. Monitoring progress in the global response to the HIV epidemic uses indicators put forward by the Joint United Nations Programme on HIV/AIDS. These include the 90-90-90 targets that require a realignment of surveillance data, routinely collected program data, and medical record data, which historically have developed separately. Objective The aim of this study was to describe current challenges for monitoring HIV-related strategic information indicators among key populations ((men who have sex with men [MSM], people in prisons and other closed settings, people who inject drugs, sex workers, and transgender people) and identify future opportunities to enhance the use of surveillance data, programmatic data, and medical record data to describe the HIV epidemic among key populations and measure the coverage of HIV prevention, care, and treatment programs. Methods To provide a historical perspective, we completed a scoping review of the expansion of HIV surveillance among key populations over the past three decades. To describe current efforts, we conducted a review of the literature to identify published examples of SI indicator estimates among key populations. To describe anticipated challenges and future opportunities to improve measurement of strategic information indicators, particularly from routine program and health data, we consulted participants of the Third Global HIV Surveillance Meeting in Bangkok, where the 2015 World Health Organization strategic information guidelines were launched. Results There remains suboptimal alignment of surveillance and programmatic data, as well as routinely collected medical records to facilitate the reporting of the 90-90-90 indicators for HIV among key populations. Studies (n=3) with estimates of all three 90-90-90 indicators rely on cross-sectional survey data. Programmatic data and

Approaches Mediating Oxytocin Regulation of the Immune System.

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

2016-01-01

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

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

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Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects.

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Moro-García, Marco Antonio; Alonso-Arias, Rebeca; Baltadjieva, Maria; Fernández Benítez, Carlos; Fernández Barrial, Manuel Amadeo; Díaz Ruisánchez, Enrique; Alonso Santos, Ricardo; Alvarez Sánchez, Magdalena; Saavedra Miján, Juan; López-Larrea, Carlos

2013-08-01

Throughout life, there is an aging of the immune system that causes impairment of its defense capability. Prevention or delay of this deterioration is considered crucial to maintain general health and increase longevity. We evaluated whether dietary supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 could enhance the immune response in the elderly. This multi-center, double-blind, and placebo controlled study enrolled 61 elderly volunteers who were randomly assigned to receive either placebo or probiotics. Each capsule of probiotics contained at least 3 × 10(7)  L. delbrueckii subsp. bulgaricus 8481. Individuals in the study were administered three capsules per day for 6 months. Blood samples were obtained at baseline (time 0), end of month 3, and month 6. We characterized cell subpopulations, measured cytokines by flow cytometry, quantified T cell receptor excision circle (TREC) by real-time PCR (RT-PCR), and determined human β-defensin-2 (hBD-2) concentrations and human cytomegalovirus (CMV) titers by enzyme-linked immunosorbent assay (ELISA). Elderly responded to the intake of probiotic with an increase in the percentage of NK cells, an improvement in the parameters defining the immune risk profile (IRP), and an increase in the T cell subsets that are less differentiated. The probiotic group also showed decreased concentrations of the pro-inflammatory cytokine IL-8 but increased antimicrobial peptide hBD-2. These effects disappeared within 6 months of stopping the probiotic intake. Immunomodulation induced by L. delbrueckii subsp. bulgaricus 8481 could favor the maintenance of an adequate immune response, mainly by slowing the aging of the T cell subpopulations and increasing the number of immature T cells which are potential responders to new antigens.

Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications.

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Greenstein, Robert J; Su, Liya; Shahidi, Azra; Brown, William D; Clifford, Anya; Brown, Sheldon T

2014-09-01

The development of novel antibiotics to treat multidrug-resistant (MDR) tuberculosis is time-consuming and expensive. Multiple immune modulators, immune suppressants, anti-inflammatories, and growth enhancers, and vitamins A and D, inhibit Mycobacterium avium subspecies paratuberculosis (MAP) in culture. We studied the culture inhibition of Mycobacterium tuberculosis complex by these agents. Biosafety level two M. tuberculosis complex (ATCC 19015 and ATCC 25177) was studied in radiometric Bactec or MGIT culture. Agents evaluated included clofazimine, methotrexate, 6-mercaptopurine, cyclosporine A, rapamycin, tacrolimus, monensin, and vitamins A and D. All the agents mentioned above caused dose-dependent inhibition of the M. tuberculosis complex. There was no inhibition by the anti-inflammatory 5-aminosalicylic acid, which causes bacteriostatic inhibition of MAP. We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and disease resistance of Indian major carp, Catla catla (Ham.).

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Kaleeswaran, B; Ilavenil, S; Ravikumar, S

2011-12-01

Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the experimental diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the experimental diet groups than the control. All these experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish. Copyright © 2011 Elsevier Ltd. All rights reserved.

Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

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Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

2011-08-05

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

International Nuclear Information System (INIS)

Weir, Genevieve M.; Liwski, Robert S.; Mansour, Marc

2011-01-01

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments

Attaching Hollywood to a Surveillant Assemblage: Normalizing Discourses of Video Surveillance

Directory of Open Access Journals (Sweden)

Randy K Lippert

2015-10-01

Full Text Available This article examines video surveillance images in Hollywood film. It moves beyond previous accounts of video surveillance in relation to film by theoretically situating the use of these surveillance images in a broader “surveillant assemblage”. To this end, scenes from a sample of thirty-five (35 films of several genres are examined to discern dominant discourses and how they lend themselves to normalization of video surveillance. Four discourses are discovered and elaborated by providing examples from Hollywood films. While the films provide video surveillance with a positive associative association it is not without nuance and limitations. Thus, it is found that some forms of resistance to video surveillance are shown while its deterrent effect is not. It is ultimately argued that Hollywood film is becoming attached to a video surveillant assemblage discursively through these normalizing discourses as well as structurally to the extent actual video surveillance technology to produce the images is used.

Prebiotics modulate immune responses in the gut-associated lymphoid tissue of chickens.

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Janardhana, Vijaya; Broadway, Mary M; Bruce, Matthew P; Lowenthal, John W; Geier, Mark S; Hughes, Robert J; Bean, Andrew G D

2009-07-01

The recent European Union ban on the prophylactic use of in-feed antibiotics has escalated the search for alternatives for use within the poultry industry. When evaluating the efficacy of potential antibiotic alternatives on bird health and productivity, it is important to analyze the competence of the immune cells in the gut-associated lymphoid tissue (GALT), because it is routinely involved in the surveillance of colonizing microbes as well as in interacting with the ingested feed antigens. Therefore, we studied the effect of the prebiotics mannan-oligosaccharide (MOS) and fructo-oligosaccharide (FOS) on the phenotypic and functional competence of immune cells in cecal tonsil (CT), which is a major GALT. Day-old Cobb 500 male broilers were randomized to 4 groups. Control chickens were fed the basal diet only. Chickens in experimental groups received 0.05 g/kg zinc bacitracin or 5 g/kg of either FOS or MOS in addition to basal diet. At the end of 25 d, our comparison of the experimental groups with controls revealed that the addition of prebiotics to diet resulted in a significant reduction in the proportion of B cells and in mitogen responsiveness of lymphocytes in CT. Furthermore, FOS treatment significantly enhanced the IgM and IgG antibody titers in plasma. These findings emphasize the need for the analyses of the gut immune function following treatment with novel feed additives. The knowledge obtained from such analyses may aid in understanding the mechanisms underlying the immune competence of the birds, which needs consideration when selecting and optimizing new feed additives instead of antibiotics for poultry production.

The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome.

Science.gov (United States)

Emami, Tara; Rezayat, Seyed Mahdi; Khamesipour, Ali; Madani, Rasool; Habibi, Gholamreza; Hojatizade, Mansure; Jaafari, Mahmoud Reza

2018-04-01

Adjuvants play an essential role in the induction of immunity against leishmaniasis. In this study, monophosphoryl lipid A (MPL) and imiquimod (IMQ) were used as TLR ligands adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Nanoliposomes containing soluble Leishmania antigens (SLA) and adjuvants were consisted of DSPC, DSPG and Chol prepared by using lipid film method followed by bath sonication. The size of nanoliposomes was around 95 nm and their zeta potential was negative. BALB/c mice were immunized by liposomal formulations of lip/SLA, lip/MPL/SLA, lip/IMQ/SLA, lip/MPL/IMQ/SLA, lip/SLA + lip/IMQ, lip/SLA + lip/MPL, lip/SLA + lip/MPL/IMQ and five controls of SLA, lip/MPL, lip/IMQ, lip/MPL/IMQ and buffer by subcutaneously (SC) injections, three times in 2 weeks intervals. The synergic effect of two adjuvants when they are used in one formulation showed significantly (p MPL and IMQ adjuvants and antigen in nanoliposome carrier could be an appropriate delivery system to induce cellular immunity pathway against leishmaniasis.

Surveillance system for nuclear power plants

International Nuclear Information System (INIS)

Mizeracki, M.T.

1981-01-01

This paper describes an integrated surveillance system for nuclear power plant application. The author explores an expanded role for closed circuit television, with remotely located cameras and infrared scanners as the basic elements. The video system, integrated with voice communication, can enhance the safe and efficient operation of the plant, by improving the operator's knowledge of plant conditions. 7 refs

Células natural killer e vigilância imunológica Natural killer cells and immune surveillance

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Mariana Jobim

2008-08-01

Full Text Available OBJETIVOS: Analisar a importância das células natural killer, de seus receptores killer immunoglobulin-like receptors e correspondentes genes (KIR na vigilância imunológica do organismo contra agentes infecciosos, transplantes de células-tronco hematopoiéticas, assim como sua participação na auto-imunidade. As características e o polimorfismo dos genes e receptores KIR na população brasileira serão descritos. FONTES DOS DADOS: Livros, artigos de revisão e artigos científicos recentes são citados e listados na bibliografia. A experiência pessoal é também apresentada. SÍNTESE DOS DADOS: Identificamos o perfil de genes e haplótipos KIR na população caucasóide brasileira, sendo de importância esse conhecimento para a análise da relação desse sistema com doenças. Examinamos 116 indivíduos doadores voluntários de medula óssea, identificando-se 32 genótipos e a presença de 51 e 49% de haplótipos A e B, respectivamente. Foi realizado estudo comparativo entre os nossos genótipos e os de outras populações. CONCLUSÕES: A imunidade inata é uma barreira antiinfecciosa de importância em pediatria. Ela atua de maneira independente da imunidade celular e humoral, sendo mais rápida que as demais fontes de proteção do organismo. Ao mesmo tempo, ela estimula os linfócitos T CD8 a agirem e amplificarem a rede de proteção imunológica. Entretanto, como na maioria das vezes em que a imunidade atua, ela também pode ser prejudicial, agredindo o organismo por mecanismos auto-imunes ou mesmo, na sua ausência, oferecer espaço aos agentes infecciosos para agirem de forma impune.OBJECTIVES: To analyze the importance of natural killer cells, their killer immunoglobulin-like receptors (KIR and genes in autoimmunity and in the immune surveillance against infectious agents and stem cells transplantation. The characteristics and polymorphisms of the KIR genes and receptors in the Brazilian population is described. SOURCES

Recombinant Secreted Antigens from Mycoplasma hyopneumoniae Delivered as a Cocktail Vaccine Enhance the Immune Response of Mice

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Galli, Vanessa; Simionatto, Simone; Marchioro, Silvana Beutinger; Klabunde, Gustavo Henrique Ferrero; Conceição, Fabricio Rochedo

2013-01-01

Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (EP), which is a respiratory disease responsible for huge economic losses in the pig industry worldwide. The commercially available vaccines provide only partial protection and are expensive. Thus, the development of alternatives for the prophylaxis of EP is critical for improving pig health. The use of multiple antigens in the same immunization may represent a promising alternative. In the present study, seven secreted proteins of M. hyopneumoniae were cloned, expressed in Escherichia coli, and evaluated for antigenicity using serum from naturally and experimentally infected pigs. In addition, the immunogenicity of the seven recombinant proteins delivered individually or in protein cocktail vaccines was evaluated in mice. In Western blot assays and enzyme-linked immunosorbent assays, most of the recombinant proteins evaluated were recognized by convalescent-phase serum from the animals, indicating that they are expressed during the infectious process. The recombinant proteins were also immunogenic, and most induced a mixed IgG1/IgG2a humoral immune response. The use of these proteins in a cocktail vaccine formulation enhanced the immune response compared to their use as antigens delivered individually, providing evidence of the efficacy of the multiple-antigen administration strategy for the induction of an immune response against M. hyopneumoniae. PMID:23803903

Squamous cell carcinomas escape immune surveillance via inducing chronic activation and exhaustion of CD8+ T Cells co-expressing PD-1 and LAG-3 inhibitory receptors.

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Mishra, Ameet K; Kadoishi, Tanya; Wang, Xiaoguang; Driver, Emily; Chen, Zhangguo; Wang, Xiao-Jing; Wang, Jing H

2016-12-06

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer. Moreover, about 90% of head and neck cancers are SCCs. SCCs develop at a significantly higher rate under chronic immunosuppressive conditions, implicating a role of immune surveillance in controlling SCCs. It remains largely unknown how SCCs evade immune recognition. Here, we established a mouse model by injecting tumor cells derived from primary SCCs harboring KrasG12D mutation and Smad4 deletion into wild-type (wt) or CD8-/- recipients. We found comparable tumor growth between wt and CD8-/- recipients, indicating a complete escape of CD8+ T cell-mediated anti-tumor responses by these SCCs. Mechanistically, CD8+ T cells apparently were not defective in infiltrating tumors given their relatively increased percentage among tumor infiltrating lymphocytes (TILs). CD8+ TILs exhibited phenotypes of chronic activation and exhaustion, including overexpression of activation markers, co-expression of programmed cell death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), as well as TCRβ downregulation. Among CD4+ TILs, T regulatory cells (Tregs) were preferentially expanded. Contradictory to prior findings in melanoma, Treg expansion was independent of CD8+ T cells in our SCC model. Unexpectedly, CD8+ T cells were required for promoting NK cell infiltration within SCCs. Furthermore, we uncovered AKT-dependent lymphocyte-induced PD-L1 upregulation on SCCs, which was contributed greatly by combinatorial effects of CD8+ T and NK cells. Lastly, dual blockade of PD-1 and LAG-3 inhibited the tumor growth of SCCs. Thus, our findings identify novel immune evasion mechanisms of SCCs and suggest that immunosuppressive mechanisms operate in a cancer-type specific and context-dependent manner.

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

Directory of Open Access Journals (Sweden)

L Xu

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

Enhancing crop innate immunity: new promising trends

Directory of Open Access Journals (Sweden)

Pin-Yao eHuang

2014-11-01

Full Text Available Plants are constantly exposed to potentially pathogenic microbes present in their surrounding environment. Due to the activation of the pattern-triggered immunity (PTI response that largely relies on accurate detection of pathogen- or microbe-associated molecular patterns by pattern-recognition receptors (PRRs, plants are resistant to the majority of potential pathogens. However, adapted pathogens may avoid recognition or repress plant PTI and resulting diseases significantly affect crop yield worldwide. PTI provides protection against a wide range of pathogens. Reinforcement of PTI through genetic engineering may thus generate crops with broad-spectrum field resistance. In this review, new approaches based on fundamental discoveries in PTI to improve crop immunity are discussed. Notably, we highlight recent studies describing the interfamily transfer of PRRs or key regulators of PTI signalling.

Developing a new national approach to surveillance for ventilator-associated events: executive summary.

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Magill, Shelley S; Klompas, Michael; Balk, Robert; Burns, Suzanne M; Deutschman, Clifford S; Diekema, Daniel; Fridkin, Scott; Greene, Linda; Guh, Alice; Gutterman, David; Hammer, Beth; Henderson, David; Hess, Dean R; Hill, Nicholas S; Horan, Teresa; Kollef, Marin; Levy, Mitchell; Septimus, Edward; VanAntwerpen, Carole; Wright, Don; Lipsett, Pamela

2013-11-01

In September 2011, the Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group to organize a formal process for leaders and experts of key stakeholder organizations to discuss the challenges of VAP surveillance definitions and to propose new approaches to VAP surveillance in adult patients (Table 1). The charges to the Working Group were to (1) critically review a draft, streamlined VAP surveillance definition developed for use in adult patients; (2) suggest modifications to enhance the reliability and credibility of the surveillance definition within the critical care and infection prevention communities; and (3) propose a final adult surveillance definition algorithm to be implemented in the CDC's National Healthcare Safety Network (NHSN), taking into consideration the potential future use of the definition algorithm in public reporting, interfacility comparisons, and pay-for-reporting and pay-for-performance programs. Published by Mosby, Inc.

Hepatocellular Carcinoma Surveillance Among Cirrhotic Patients With Commercial Health Insurance.

Science.gov (United States)

Goldberg, David S; Valderrama, Adriana; Kamalakar, Rajesh; Sansgiry, Sujit S; Babajanyan, Svetlana; Lewis, James D

2016-03-01

To evaluate hepatocellular carcinoma (HCC) surveillance rates among commercially insured patients, and evaluate factors associated with compliance with surveillance recommendations. Most HCC occurs in patients with cirrhosis. American Association for the Study of Liver Diseases and European Association for the Study of the Liver guidelines each recommend biannual HCC surveillance for cirrhotic patients to diagnose HCC at an early, curable stage. However, compliance with these guidelines in commercially insured patients is unknown. We used the Truven Health Analytics databases from 2006 to 2010, using January 1, 2006 as the anchor date for evaluating outcomes. The primary outcome was continuous surveillance measure, defined as the proportion of time "up-to-date" with surveillance (PTUDS), with the 6-month interval immediately following each ultrasound categorized as "up-to-date." During a median follow-up of 22.9 (interquartile range, 16.3 to 33.9) months among 8916 cirrhotic patients, the mean PTUDS was 0.34 (SD, 0.29), and the median was 0.31 (interquartile range, 0.03 to 0.52). These values increased only modestly with inclusion of serum alpha-fetoprotein testing, contrast-enhanced abdominal computed tomographic scans or magnetic resonance imagings, and/or extension of up-to-date time to 12 months. Being diagnosed by a nongastroenterology provider and increasing age were significantly associated with decreased HCC surveillance (Psurveillance (Psurveillance rates remained low. HCC surveillance rates in commercially insured at-risk patients remain poor despite formalized guidelines, highlighting the need to develop interventions to improve surveillance rates.

Falling-incident detection and throughput enhancement in a multi-camera video-surveillance system.

Science.gov (United States)

Shieh, Wann-Yun; Huang, Ju-Chin

2012-09-01

For most elderly, unpredictable falling incidents may occur at the corner of stairs or a long corridor due to body frailty. If we delay to rescue a falling elder who is likely fainting, more serious consequent injury may occur. Traditional secure or video surveillance systems need caregivers to monitor a centralized screen continuously, or need an elder to wear sensors to detect falling incidents, which explicitly waste much human power or cause inconvenience for elders. In this paper, we propose an automatic falling-detection algorithm and implement this algorithm in a multi-camera video surveillance system. The algorithm uses each camera to fetch the images from the regions required to be monitored. It then uses a falling-pattern recognition algorithm to determine if a falling incident has occurred. If yes, system will send short messages to someone needs to be noticed. The algorithm has been implemented in a DSP-based hardware acceleration board for functionality proof. Simulation results show that the accuracy of falling detection can achieve at least 90% and the throughput of a four-camera surveillance system can be improved by about 2.1 times. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Developing a database management system to support birth defects surveillance in Florida.

Science.gov (United States)

Salemi, Jason L; Hauser, Kimberlea W; Tanner, Jean Paul; Sampat, Diana; Correia, Jane A; Watkins, Sharon M; Kirby, Russell S

2010-01-01

The value of any public health surveillance program is derived from the ways in which data are managed and used to improve the public's health. Although birth defects surveillance programs vary in their case volume, budgets, staff, and objectives, the capacity to operate efficiently and maximize resources remains critical to long-term survival. The development of a fully-integrated relational database management system (DBMS) can enrich a surveillance program's data and improve efficiency. To build upon the Florida Birth Defects Registry--a statewide registry relying solely on linkage of administrative datasets and unconfirmed diagnosis codes-the Florida Department of Health provided funding to the University of South Florida to develop and pilot an enhanced surveillance system in targeted areas with a more comprehensive approach to case identification and diagnosis confirmation. To manage operational and administrative complexities, a DBMS was developed, capable of managing transmission of project data from multiple sources, tracking abstractor time during record reviews, offering tools for defect coding and case classification, and providing reports to DBMS users. Since its inception, the DBMS has been used as part of our surveillance projects to guide the receipt of over 200 case lists and review of 12,924 fetuses and infants (with associated maternal records) suspected of having selected birth defects in over 90 birthing and transfer facilities in Florida. The DBMS has provided both anticipated and unexpected benefits. Automation of the processes for managing incoming case lists has reduced clerical workload considerably, while improving accuracy of working lists for field abstraction. Data quality has improved through more effective use of internal edits and comparisons with values for other data elements, while simultaneously increasing abstractor efficiency in completion of case abstraction. We anticipate continual enhancement to the DBMS in the future

ROUTINE IMMUNIZATION IN INDIA: A PERSPECTIVE

Directory of Open Access Journals (Sweden)

G Taneja

2013-08-01

Full Text Available The Universal Immunization Programme is possibly the longest and one of the biggest public health intervention measures undertaken in India. To improve immunization coverage in the country various initiatives have been undertaken since the inception of the programme in 1985; key inputs being strengthening and expanding the cold chain system, establishing a network of outreach immunization sites, alternate vaccine delivery model, capacity building of health functionaries and medical officers and intensified polio control measures. Introduction of new and underutilized vaccines, drafting of the national vaccine policy, tracking of beneficiaries through the Maternal and Child Tracking system are some of the recent developments. However in spite of more than 25 years since inception the programme is still adversely impacted by challenges across key thematic areas of programme management, cold chain and vaccine management, recording and reporting and injection safety. To further strengthen and improve service delivery 2012-13 has been declared as the “Year of Intensification of Routine Immunization” with the objective of improving immunization coverage rates across poor performing districts and states so as to attain Global Immunization Vision and Strategy goals of 90% coverage at national and more than 80% coverage at district level. Key activities planned during the year include sustained advocacy at all levels, improved communication and social mobilization, robust and regular program reviews, comprehensive microplanning, strengthening cold chain and vaccine logistics system, special catch up rounds through immunization weeks, piloting the teeka express, improved surveillance systems, strengthened partnerships and operational research activities. The current review pertains to the existing scenario of Universal Immunization Program in the country with impetus on the existing challenges, progress achieved till date as a result of various

What is a missing link among wireless persistent surveillance?

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Hsu, Charles; Szu, Harold

2011-06-01

The next generation surveillance system will equip with versatile sensor devices and information focus capable of conducting regular and irregular surveillance and security environments worldwide. The community of the persistent surveillance must invest the limited energy and money effectively into researching enabling technologies such as nanotechnology, wireless networks, and micro-electromechanical systems (MEMS) to develop persistent surveillance applications for the future. Wireless sensor networks can be used by the military for a number of purposes such as monitoring militant activity in remote areas and force protection. Being equipped with appropriate sensors these networks can enable detection of enemy movement, identification of enemy force and analysis of their movement and progress. Among these sensor network technologies, covert communication is one of the challenging tasks in the persistent surveillance because it is highly demanded to provide secured sensor nodes and linkage for fear of deliberate sabotage. Due to the matured VLSI/DSP technologies, affordable COTS of UWB technology with noise-like direct sequence (DS) time-domain pulses is a potential solution to support low probability of intercept and low probability of detection (LPI/LPD) data communication and transmission. This paper will describe a number of technical challenges in wireless persistent surveillance development include covert communication, network control and routing, collaborating signal and information processing, and etc. The paper concludes by presenting Hermitian Wavelets to enhance SNR in support of secured communication.

The role of TLR2 and bacterial lipoprotein in enhancing airway inflammation and immunity

Directory of Open Access Journals (Sweden)

Amit A Lugade

2011-04-01

Full Text Available Non-typeable Haemophilus influenzae (NTHI colonizes the lower respiratory tract of patients with chronic obstructive pulmonary disease (COPD and also causes exacerbations of the disease. The 16-kDa lipoprotein P6 has been widely studied as a potential vaccine antigen due to its highly conserved expression amongst NTHI strains. Although P6 is known to induce potent inflammatory responses, its role in the pathogenesis of NTHI infection in vivo has not been examined. Additionally, the presence of an amino-terminal lipid motif on P6 serves to activate host TLR2 signaling. The role of host Toll-like receptor 2 (TLR2 and NTHI expression of the lipoprotein P6 on the induction of airway inflammation and generation of adaptive immune responses following chronic NTHI stimulation was evaluated with TLR2-deficient mice and a P6-deficient NTHI strain. Absence of either host TLR2 or bacterial P6 resulted in diminished levels of immune cell infiltration within lungs of mice exposed to NTHI. Pro-inflammatory cytokine secretion was also reduced in lungs that did not express TLR2 or were exposed to NTHI devoid of P6. Induction of specific antibodies to P6 was severely limited in TLR2-deficient mice. Although mice exposed to the P6-deficient NTHI strain were capable of generating antibodies to other surface antigens of NTHI, these levels were lower compared to those observed in mice exposed to P6-expressing NTHI. Therefore, cognate interaction between host TLR2 and bacterial P6 serves to enhance lung inflammation and elicit robust adaptive immune responses during NTHI exposure. Strategies to limit NTHI inflammation while simultaneously promoting robust immune responses may benefit from targeting the TLR2:P6 signaling axis.

Assessing the impact of the Lebanese National Polio Immunization Campaign using a population-based computational model.

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Alawieh, Ali; Sabra, Zahraa; Langley, E Farris; Bizri, Abdul Rahman; Hamadeh, Randa; Zaraket, Fadi A

2017-11-25

After the re-introduction of poliovirus to Syria in 2013, Lebanon was considered at high transmission risk due to its proximity to Syria and the high number of Syrian refugees. However, after a large-scale national immunization initiative, Lebanon was able to prevent a potential outbreak of polio among nationals and refugees. In this work, we used a computational individual-simulation model to assess the risk of poliovirus threat to Lebanon prior and after the immunization campaign and to quantitatively assess the healthcare impact of the campaign and the required standards that need to be maintained nationally to prevent a future outbreak. Acute poliomyelitis surveillance in Lebanon was along with the design and coverage rate of the recent national polio immunization campaign were reviewed from the records of the Lebanese Ministry of Public Health. Lebanese population demographics including Syrian and Palestinian refugees were reviewed to design individual-based models that predicts the consequences of polio spread to Lebanon and evaluate the outcome of immunization campaigns. The model takes into account geographic, demographic and health-related features. Our simulations confirmed the high risk of polio outbreaks in Lebanon within 10 days of case introduction prior to the immunization campaign, and showed that the current immunization campaign significantly reduced the speed of the infection in the event poliomyelitis cases enter the country. A minimum of 90% national immunization coverage was found to be required to prevent exponential propagation of potential transmission. Both surveillance and immunization efforts should be maintained at high standards in Lebanon and other countries in the area to detect and limit any potential outbreak. The use of computational population simulation models can provide a quantitative approach to assess the impact of immunization campaigns and the burden of infectious diseases even in the context of population migration.

Assessing the impact of the Lebanese National Polio Immunization Campaign using a population-based computational model

Directory of Open Access Journals (Sweden)

Ali Alawieh

2017-11-01

Full Text Available Abstract Background After the re-introduction of poliovirus to Syria in 2013, Lebanon was considered at high transmission risk due to its proximity to Syria and the high number of Syrian refugees. However, after a large-scale national immunization initiative, Lebanon was able to prevent a potential outbreak of polio among nationals and refugees. In this work, we used a computational individual-simulation model to assess the risk of poliovirus threat to Lebanon prior and after the immunization campaign and to quantitatively assess the healthcare impact of the campaign and the required standards that need to be maintained nationally to prevent a future outbreak. Methods Acute poliomyelitis surveillance in Lebanon was along with the design and coverage rate of the recent national polio immunization campaign were reviewed from the records of the Lebanese Ministry of Public Health. Lebanese population demographics including Syrian and Palestinian refugees were reviewed to design individual-based models that predicts the consequences of polio spread to Lebanon and evaluate the outcome of immunization campaigns. The model takes into account geographic, demographic and health-related features. Results Our simulations confirmed the high risk of polio outbreaks in Lebanon within 10 days of case introduction prior to the immunization campaign, and showed that the current immunization campaign significantly reduced the speed of the infection in the event poliomyelitis cases enter the country. A minimum of 90% national immunization coverage was found to be required to prevent exponential propagation of potential transmission. Conclusions Both surveillance and immunization efforts should be maintained at high standards in Lebanon and other countries in the area to detect and limit any potential outbreak. The use of computational population simulation models can provide a quantitative approach to assess the impact of immunization campaigns and the burden of

Mobile Surveillance and Monitoring Robots

International Nuclear Information System (INIS)

Kimberly, Howard R.; Shipers, Larry R.

1999-01-01

Long-term nuclear material storage will require in-vault data verification, sensor testing, error and alarm response, inventory, and maintenance operations. System concept development efforts for a comprehensive nuclear material management system have identified the use of a small flexible mobile automation platform to perform these surveillance and maintenance operations. In order to have near-term wide-range application in the Complex, a mobile surveillance system must be small, flexible, and adaptable enough to allow retrofit into existing special nuclear material facilities. The objective of the Mobile Surveillance and Monitoring Robot project is to satisfy these needs by development of a human scale mobile robot to monitor the state of health, physical security and safety of items in storage and process; recognize and respond to alarms, threats, and off-normal operating conditions; and perform material handling and maintenance operations. The system will integrate a tool kit of onboard sensors and monitors, maintenance equipment and capability, and SNL developed non-lethal threat response technology with the intelligence to identify threats and develop and implement first response strategies for abnormal signals and alarm conditions. System versatility will be enhanced by incorporating a robot arm, vision and force sensing, robust obstacle avoidance, and appropriate monitoring and sensing equipment

Linking tumor glycolysis and immune evasion in cancer: Emerging concepts and therapeutic opportunities.

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Ganapathy-Kanniappan, Shanmugasundaram

2017-08-01

Metabolic reprogramming and immune evasion are two hallmarks of cancer. Metabolic reprogramming is exemplified by cancer's propensity to utilize glucose at an exponential rate which in turn is linked with "aerobic glycolysis", popularly known as the "Warburg effect". Tumor glycolysis is pivotal for the efficient management of cellular bioenergetics and uninterrupted cancer growth. Mounting evidence suggests that tumor glycolysis also plays a key role in instigating immunosuppressive networks that are critical for cancer cells to escape immune surveillance ("immune evasion"). Recent data show that induction of cellular stress or metabolic dysregulation sensitize cancer cells to antitumor immune cells implying that metabolic reprogramming and immune evasion harmonize during cancer progression. However, the molecular link between these two hallmarks of cancer remains obscure. In this review the molecular intricacies of tumor glycolysis that facilitate immune evasion has been discussed in the light of recent research to explore immunotherapeutic potential of targeting cancer metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced acquired antibodies to a chimeric Plasmodium falciparum antigen; UB05-09 is associated with protective immunity against malaria.

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Dinga, J N; Gamua, S D; Titanji, V P K

2017-08-01

It has been shown that covalently linking two antigens could enhance the immunogenicity of the chimeric construct. To prioritize such a chimera for malaria vaccine development, it is necessary to demonstrate that naturally acquired antibodies against the chimera are associated with protection from malaria. Here, we probe the ability of a chimeric construct of UB05 and UB09 antigens (UB05-09) to better differentiate between acquired immune protection and susceptibility to malaria. In a cross-sectional study, recombinant UB05-09 chimera and the constituent antigens were used to probe for specific antibodies in the plasma from children and adults resident in a malaria-endemic zone, using the enzyme-linked immunosorbent assay (ELISA). Anti-UB05-09 antibody levels doubled that of its constituent antigens, UB09 and UB05, and this correlated with protection against malaria. The presence of enhanced UB05-09-specific antibody correlated with the absence of fever and parasitaemia, which are the main symptoms of malaria infection. The chimera is more effective in detecting and distinguishing acquired protective immunity against malaria than any of its constituents taken alone. Online B-cell epitope prediction tools confirmed the presence of B-cell epitopes in the study antigens. UB05-09 chimera is a marker of protective immunity against malaria that needs to be studied further. © 2017 John Wiley & Sons Ltd.

Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths

Science.gov (United States)

Gause, William C.; Wynn, Thomas A.; Allen, Judith E.

2013-01-01

Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance. PMID:23827958

GanedenBC30 cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro.

Science.gov (United States)

Jensen, Gitte S; Benson, Kathleen F; Carter, Steve G; Endres, John R

2010-03-24

This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM). In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cultures were grown. The culture supernatant was harvested as a source of metabolites (MTB), and the bacteria were used to isolate cell wall fragments (CW). Both of these fractions were compared in a series of in vitro assays. Both MTB and CW inhibited spontaneous and oxidative stress-induced ROS formation in human PMN cells and increased the phagocytic activity of PMN cells in response to bacteria-like carboxylated fluorospheres. Both fractions supported random PMN and f-MLP-directed PMN cell migration, indicating a support of immune surveillance and antibacterial defense mechanisms. In contrast, low doses of both fractions inhibited PMN cell migration towards the inflammatory mediators IL-8 and LTB4. The anti-inflammatory activity was strongest for CW, where the PMN migration towards IL-8 was inhibited down to dilutions of 1010.Both MTB and CW induced the expression of the CD69 activation marker on human CD3- CD56+ NK cells, and enhanced the expression of CD107a when exposed to K562 tumor cells in vitro.The fractions directly modulated cytokine production, inducing production of the Th2 cytokines IL-4, IL-6, and IL-10, and inhibiting production of IL-2.Both fractions further modulated mitogen-induced cytokine production in the following manner: Both fractions enhanced the PHA-induced production of IL-6 and reduced the PHA-induced production of TNF-alpha. Both fractions enhanced the PWM-induced production of TNF-alpha and IFN-gamma. In addition, MTB also enhanced both the PHA- and the PWM

Reassembling Surveillance Creep

DEFF Research Database (Denmark)

Bøge, Ask Risom; Lauritsen, Peter

2017-01-01

We live in societies in which surveillance technologies are constantly introduced, are transformed, and spread to new practices for new purposes. How and why does this happen? In other words, why does surveillance “creep”? This question has received little attention either in theoretical developm......We live in societies in which surveillance technologies are constantly introduced, are transformed, and spread to new practices for new purposes. How and why does this happen? In other words, why does surveillance “creep”? This question has received little attention either in theoretical...... development or in empirical analyses. Accordingly, this article contributes to this special issue on the usefulness of Actor-Network Theory (ANT) by suggesting that ANT can advance our understanding of ‘surveillance creep’. Based on ANT’s model of translation and a historical study of the Danish DNA database......, we argue that surveillance creep involves reassembling the relations in surveillance networks between heterogeneous actors such as the watchers, the watched, laws, and technologies. Second, surveillance creeps only when these heterogeneous actors are adequately interested and aligned. However...

Enhancement of innate immune system in monocot rice by transferring the dicotyledonous elongation factor Tu receptor EFR

Institute of Scientific and Technical Information of China (English)

Fen Lu; Huiqin Wang; Shanzhi Wang; Wendi Jiang; Changlin Shan; Bin Li; Jun Yang; Shiyong Zhang; Wenxian Sun

2015-01-01

The elongation factor Tu (EF-Tu) receptor (EFR) in cruciferous plants specifical y recognizes the N-terminal acetylated elf18 region of bacterial EF-Tu and thereby activates plant immunity. It has been demonstrated that Arabidopsis EFR confers broad-spectrum bacterial resistance in the EFR transgenic solanaceous plants. Here, the transgenic rice plants (Oryza sativa L. ssp. japonica cv. Zhonghua 17) and cel cultures with constitutive expression of AtEFR were developed to investigate whether AtEFR senses EF-Tu and thus enhances bacterial resistance in the monocot plants. We demonstrated that the Xanthomonas oryzae-derived elf18 peptide induced oxidative burst and mitogen-activated protein kinase activa-tion in the AtEFR transgenic rice cel s and plants, respectively. Pathogenesis-related genes, such as OsPBZ1, were upregulated dramatical y in transgenic rice plant and cel lines in response to elf18 stimulation. Importantly, pretreatment with elf18 trig-gered strong resistance to X. oryzae pv. oryzae in the transgenic plants, which was largely dependent on the AtEFR expression level. These plants also exhibited enhanced resistance to rice bacterial brown stripe, but not to rice fungal blast. Col ectively, the results indicate that the rice plants with heterologous expression of AtEFR recognize bacterial EF-Tu and exhibit enhanced broad-spectrum bacterial disease resistance and that pattern recognition receptor-mediated immunity may be manipulated across the two plant classes, dicots and monocots.

Positive predictive value and effectiveness of measles case-based surveillance in Uganda, 2012-2015.

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Fred Nsubuga

Full Text Available Disease surveillance is a critical component in the control and elimination of vaccine preventable diseases. The Uganda National Expanded Program on Immunization strives to have a sensitive surveillance system within the Integrated Disease Surveillance and Response (IDSR framework. We analyzed measles surveillance data to determine the effectiveness of the measles case-based surveillance system and estimate its positive predictive value in order to inform policy and practice.An IDSR alert was defined as ≥1 suspected measles case reported by a district in a week, through the electronic Health Management Information System. We defined an alert in the measles case-based surveillance system (CBS as ≥1 suspected measles case with a blood sample collected for confirmation during the corresponding week in a particular district. Effectiveness of CBS was defined as having ≥80% of IDSR alerts with a blood sample collected for laboratory confirmation. Positive predictive value was defined as the proportion of measles case-patients who also had a positive measles serological result (IgM +. We reviewed case-based surveillance data with laboratory confirmation and measles surveillance data from the electronic Health Management Information System from 2012-2015.A total of 6,974 suspected measles case-persons were investigated by the measles case-based surveillance between 2012 and 2015. Of these, 943 (14% were measles specific IgM positive. The median age of measles case-persons between 2013 and 2015 was 4.0 years. Between 2013 and 2015, 72% of the IDSR alerts reported in the electronic Health Management Information System, had blood samples collected for laboratory confirmation. This was however less than the WHO recommended standard of ≥80%. The PPV of CBS between 2013 and 2015 was 8.6%.In conclusion, the effectiveness of measles case-based surveillance was sub-optimal, while the PPV showed that true measles cases have significantly reduced in Uganda

Evaluation of Syndromic Surveillance Systems in 6 US State and Local Health Departments.

Science.gov (United States)

Thomas, Mathew J; Yoon, Paula W; Collins, James M; Davidson, Arthur J; Mac Kenzie, William R

Evaluating public health surveillance systems is critical to ensuring that conditions of public health importance are appropriately monitored. Our objectives were to qualitatively evaluate 6 state and local health departments that were early adopters of syndromic surveillance in order to (1) understand the characteristics and current uses, (2) identify the most and least useful syndromes to monitor, (3) gauge the utility for early warning and outbreak detection, and (4) assess how syndromic surveillance impacted their daily decision making. We adapted evaluation guidelines from the Centers for Disease Control and Prevention and gathered input from the Centers for Disease Control and Prevention subject matter experts in public health surveillance to develop a questionnaire. We interviewed staff members from a convenience sample of 6 local and state health departments with syndromic surveillance programs that had been in operation for more than 10 years. Three of the 6 interviewees provided an example of using syndromic surveillance to identify an outbreak (ie, cluster of foodborne illness in 1 jurisdiction) or detect a surge in cases for seasonal conditions (eg, influenza in 2 jurisdictions) prior to traditional, disease-specific systems. Although all interviewees noted that syndromic surveillance has not been routinely useful or efficient for early outbreak detection or case finding in their jurisdictions, all agreed that the information can be used to improve their understanding of dynamic disease control environments and conditions (eg, situational awareness) in their communities. In the jurisdictions studied, syndromic surveillance may be useful for monitoring the spread and intensity of large outbreaks of disease, especially influenza; enhancing public health awareness of mass gatherings and natural disasters; and assessing new, otherwise unmonitored conditions when real-time alternatives are unavailable. Future studies should explore opportunities to

Using Acute Flaccid Paralysis Surveillance as a Platform for Vaccine-Preventable Disease Surveillance.

Science.gov (United States)

Wassilak, Steven G F; Williams, Cheryl L; Murrill, Christopher S; Dahl, Benjamin A; Ohuabunwo, Chima; Tangermann, Rudolf H

2017-07-01

Surveillance for acute flaccid paralysis (AFP) is a fundamental cornerstone of the global polio eradication initiative (GPEI). Active surveillance (with visits to health facilities) is a critical strategy of AFP surveillance systems for highly sensitive and timely detection of cases. Because of the extensive resources devoted to AFP surveillance, multiple opportunities exist for additional diseases to be added using GPEI assets, particularly because there is generally 1 district officer responsible for all disease surveillance. For this reason, integrated surveillance has become a standard practice in many countries, ranging from adding surveillance for measles and rubella to integrated disease surveillance for outbreak-prone diseases (integrated disease surveillance and response). This report outlines the current level of disease surveillance integration in 3 countries (Nepal, India, and Nigeria) and proposes that resources continue for long-term maintenance in resource-poor countries of AFP surveillance as a platform for surveillance of vaccine-preventable diseases and other outbreak-prone diseases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Information Systems to Support Surveillance for Malaria Elimination

Science.gov (United States)

Ohrt, Colin; Roberts, Kathryn W.; Sturrock, Hugh J. W.; Wegbreit, Jennifer; Lee, Bruce Y.; Gosling, Roly D.

2015-01-01

Robust and responsive surveillance systems are critical for malaria elimination. The ideal information system that supports malaria elimination includes: rapid and complete case reporting, incorporation of related data, such as census or health survey information, central data storage and management, automated and expert data analysis, and customized outputs and feedback that lead to timely and targeted responses. Spatial information enhances such a system, ensuring cases are tracked and mapped over time. Data sharing and coordination across borders are vital and new technologies can improve data speed, accuracy, and quality. Parts of this ideal information system exist and are in use, but have yet to be linked together coherently. Malaria elimination programs should support the implementation and refinement of information systems to support surveillance and response and ensure political and financial commitment to maintain the systems and the human resources needed to run them. National malaria programs should strive to improve the access and utility of these information systems and establish cross-border data sharing mechanisms through the use of standard indicators for malaria surveillance. Ultimately, investment in the information technologies that support a timely and targeted surveillance and response system is essential for malaria elimination. PMID:26013378

Editorial brain malformation surveillance in the Zika era

Science.gov (United States)

Trevathan, Edwin

2016-01-01

The current surveillance systems for congenital microcephaly are necessary to monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as the ZIKV prevention efforts. However, these congenital microcephaly surveillance systems are insufficient. Abnormalities of neuronal differentiation, development and migration may occur among infants with normal head circumference who have intrauterine exposure to ZIKV. Therefore, surveillance for congenital microcephaly does not ascertain many of the infants seriously impacted by congenital ZIKV infection. Furthermore, many infants with normal head circumference and with malformations of the brain cortex do not have clinical manifestations of their congenital malformations until several months to many years after birth, when they present with clinical manifestations such as seizures/epilepsy, developmental delays with or without developmental regression, and/or motor impairment. In response to the ZIKV threat, public health surveillance systems must be enhanced to ascertain a wide variety of congenital brain malformations, as well as their clinical manifestations that lead to diagnostic brain imaging. Birth Defects Research (Part A) 106:869–874, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27891785

Redefining syndromic surveillance

Directory of Open Access Journals (Sweden)

Rebecca Katz

2011-12-01

Full Text Available With growing concerns about international spread of disease and expanding use of early disease detection surveillance methods, the field of syndromic surveillance has received increased attention over the last decade. The purpose of this article is to clarify the various meanings that have been assigned to the term syndromic surveillance and to propose a refined categorization of the characteristics of these systems. Existing literature and conference proceedings were examined on syndromic surveillance from 1998 to 2010, focusing on low- and middle-income settings. Based on the 36 unique definitions of syndromic surveillance found in the literature, five commonly accepted principles of syndromic surveillance systems were identified, as well as two fundamental categories: specific and non-specific disease detection. Ultimately, the proposed categorization of syndromic surveillance distinguishes between systems that focus on detecting defined syndromes or outcomes of interest and those that aim to uncover non-specific trends that suggest an outbreak may be occurring. By providing an accurate and comprehensive picture of this field’s capabilities, and differentiating among system types, a unified understanding of the syndromic surveillance field can be developed, encouraging the adoption, investment in, and implementation of these systems in settings that need bolstered surveillance capacity, particularly low- and middle-income countries.

Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

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Rafael Fenutría

Full Text Available CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg, expressing a circulating soluble form of human CD5 (shCD5 as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE, as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma. This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+, and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.

Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

Energy Technology Data Exchange (ETDEWEB)

Pimenta, Erica M. [Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States); Barnes, Betsy J., E-mail: barnesbe@njms.rutgers.edu [Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States)

2014-04-23

Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin{sup ®}) and rituximab (Rituxan{sup ®})) and the first approved cancer vaccine, Provenge{sup ®} (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response.

Role of Tertiary Lymphoid Structures (TLS in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

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Erica M. Pimenta

2014-04-01

Full Text Available Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin® and rituximab (Rituxan® and the first approved cancer vaccine, Provenge® (sipuleucel-T, investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS within the tumor microenvironment may be used to enhance immunotherapy response.

Diablo Canyon ECCS enhancements

International Nuclear Information System (INIS)

Lin, A.; Lee, T.P.; Walter, L.E.

2004-01-01

Diablo Canyon Power Plant (DCPP) operated by Pacific Gas and Electric Co. (PG and E) is a Westinghouse designed four loop plant. In recent years, several issues were identified regarding the compliance of the Emergency Core Cooling System (ECCS) surveillance tests to the ECCS analyses assumptions. These concerns are related mostly to the High Head Safety Injection (HHSI) and the Intermediate Head Safety Injection (IHSI) systems where the injection line throttle valves are adjusted during outage surveillance testing to ensure compliance with the Technical Specifications (TS). To resolve all of the identified issues PG and E performed an ECCS reanalysis and upgraded the ECCS surveillance test program and also had Westinghouse perform a containment reanalysis using their latest model. As a result of these plant specific enhancement efforts, DCPP widened the operating window for TS surveillance testing, lowered the ECCS pumps' acceptance performance curves, and re-gained Peak Clad Temperature (PCT) and containment peak pressure margins. These enhancements are generically applicable to other plants and are addressed in this paper. (author)

The critical role of acute flaccid paralysis surveillance in the Global Polio Eradication Initiative.

Science.gov (United States)

Tangermann, Rudolf H; Lamoureux, Christine; Tallis, Graham; Goel, Ajay

2017-05-01

Acute flaccid paralysis (AFP) surveillance is a key strategy used by the Global Polio Eradication Initiative (GPEI) to measure progress towards reaching the global eradication goal. Supported by a global polio laboratory network, AFP surveillance is conducted in 179 of 194 WHO member states. Active surveillance visits to priority health facilities are used to assure all children polio laboratories. The quality of AFP surveillance is regularly monitored with standardized surveillance quality indicators. In highest risk countries and areas, the sensitivity of AFP surveillance is enhanced by environmental surveillance (testing of sewage samples). Genetic sequencing of detected poliovirus isolates yields programmatically important information on polio transmission pathways. AFP surveillance is one of the most valuable assets of the GPEI, with the potential to serve as a platform to build integrated disease surveillance systems. Continued support to maintain AFP surveillance systems will be essential, to reliably monitor the completion of global polio eradication, and to assure that a key resource for building surveillance capacity is transitioned post-eradication to support other health priorities. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Use of a Digital Health Application for Influenza Surveillance in China.

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Hswen, Yulin; Brownstein, John S; Liu, Jeremiah; Hawkins, Jared B

2017-07-01

To examine whether a commercial digital health application could support influenza surveillance in China. We retrieved data from the Thermia online and mobile educational tool, which allows parents to monitor their children's fever and infectious febrile illnesses including influenza. We modeled monthly aggregated influenza-like illness case counts from Thermia users over time and compared them against influenza monthly case counts obtained from the National Health and Family Planning Commission of the People's Republic of China by using time series regression analysis. We retrieved 44 999 observations from January 2014 through July 2016 from Thermia China. Thermia appeared to predict influenza outbreaks 1 month earlier than the National Health and Family Planning Commission influenza surveillance system (P = .046). Being younger, not having up-to-date immunizations, and having an underlying health condition were associated with participant-reported influenza-like illness. Digital health applications could supplement traditional influenza surveillance systems in China by providing access to consumers' symptom reporting. Growing popularity and use of commercial digital health applications in China potentially affords opportunities to support disease detection and monitoring and rapid treatment mobilization.

Expanded programme on immunization and primary health care.

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Basu, R N

1982-09-01

surveillance is necessary to mark out priority areas and plan strategies of operation. The government of India supplies all vaccines free of change to the States and the Union territories. At the beginning of the year, on the basis of annual operational vaccination targets, the manufactures are identified to supply different vaccines. Involvement of the community is essential for acceptance of the immunization program. Vaccination coverage assessment surveys are being conducted to determine the immunization of the eligible population. The survey helps to know how many were vaccinated at the right age group and completed the immunization schedule. The surveillance system needs to be strengthened for the collection of data on EPI target diseases for measuring the impact of immunization on reduction of morbidity, mortality, and disability.

Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

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Romain Ballet

2014-12-01

Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

The plays and arts of surveillance: studying surveillance as entertainment

NARCIS (Netherlands)

Albrechtslund, Anders; Dubbeld, L.

2006-01-01

This paper suggests a direction in the development of Surveillance Studies that goes beyond current attention for the caring, productive and enabling aspects of surveillance practices. That is, surveillance could be considered not just as positively protective, but even as a comical, playful,

Conformational occlusion of blockade antibody epitopes, a novel mechanism of GII.4 human norovirus immune evasion

OpenAIRE

Lindesmith, Lisa C.; Mallory, Michael L.; Debbink, Kari; Donaldson, Eric F.; Brewer-Jensen, Paul D.; Swann, Excel W.; Sheahan, Timothy P.; Graham, Rachel L.; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S.

2018-01-01

ABSTRACT Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross-protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by which these epitopes evade immune surveillance are uncertain. Here, we developed a new approach f...

Therapeutic enhancement of protective immunity during experimental leishmaniasis.

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Senad Divanovic

2011-09-01

Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

Natural material adsorbed onto a polymer to enhance immune function

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Reinaque AP

2012-08-01

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

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

Science.gov (United States)

Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

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Neide M. Silva

2017-04-01

Full Text Available Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70. Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for

Severe pediatric influenza in California, 2003-2005: implications for immunization recommendations.

Science.gov (United States)

Louie, Janice K; Schechter, Robert; Honarmand, Somayeh; Guevara, Hugo F; Shoemaker, Trevor R; Madrigal, Nora Y; Woodfill, Celia J I; Backer, Howard D; Glaser, Carol A

2006-04-01

The 2003-2004 influenza season was marked by both the emergence of a new drift "Fujian" strain of influenza A virus and prominent reports of increased influenza-related deaths in children in the absence of baseline data for comparison. In December 2003, the California Department of Health Services initiated surveillance of children who were hospitalized in California with severe influenza in an attempt to measure its impact and to identify additional preventive measures. From December 2003 to May 2005, surveillance of children who were hospitalized in PICUs or dying in the hospital with laboratory evidence of influenza was performed by hospital infection control practitioners and local public health departments using a standardized case definition and reporting form. In the 2003-2004 and 2004-2005 influenza seasons, 125 and 35 cases, respectively, of severe influenza in children were identified in California. The mean and median age of cases were 3.1 years and 1.5 years, with breakdown as follows: AAP) recommendations for immunization, but only 8 had been vaccinated. More than 3 times as many children were reported to be hospitalized in intensive care with influenza in California during the 2003-2004 season compared with the 2004-2005 season. Because children who are younger than 6 months remain at highest risk for severe influenza yet cannot currently be immunized, development and validation of preventive measures for them (eg, maternal immunization, breastfeeding, immunization of young infants and their close contacts) are urgently needed. ACIP's recent recommendation for influenza vaccination of children with conditions that can compromise respiratory function (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders) is further supported by the frequency of underlying neurologic disease in these cases of severe influenza. A significant proportion of children with severe influenza in California, including children who are

The emerging role of immune checkpoint based approaches in AML and MDS.

Science.gov (United States)

Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval

2018-04-01

The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

Science.gov (United States)

Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

2016-01-01

Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Surveillance and Critical Theory

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Christian Fuchs

2015-09-01

Full Text Available In this comment, the author reflects on surveillance from a critical theory approach, his involvement in surveillance research and projects, and the status of the study of surveillance. The comment ascertains a lack of critical thinking about surveillance, questions the existence of something called “surveillance studies” as opposed to a critical theory of society, and reflects on issues such as Edward Snowden’s revelations, and Foucault and Marx in the context of surveillance.

Enhancement of collective immunity in Tokyo metropolitan area by selective vaccination against an emerging influenza pandemic.

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Masaya M Saito

Full Text Available Vaccination is a preventive measure against influenza that does not require placing restrictions on social activities. However, since the stockpile of vaccine that can be prepared before the arrival of an emerging pandemic strain is generally quite limited, one has to select priority target groups to which the first stockpile is distributed. In this paper, we study a simulation-based priority target selection method with the goal of enhancing the collective immunity of the whole population. To model the region in which the disease spreads, we consider an urban area composed of suburbs and central areas connected by a single commuter train line. Human activity is modelled following an agent-based approach. The degree to which collective immunity is enhanced is judged by the attack rate in unvaccinated people. The simulation results show that if students and office workers are given exclusive priority in the first three months, the attack rate can be reduced from [Formula: see text] in the baseline case down to 1-2%. In contrast, random vaccination only slightly reduces the attack rate. It should be noted that giving preference to active social groups does not mean sacrificing those at high risk, which corresponds to the elderly in our simulation model. Compared with the random administration of vaccine to all social groups, this design successfully reduces the attack rate across all age groups.

From habits of attrition to modes of inclusion: enhancing the role of private practitioners in routine disease surveillance.

Science.gov (United States)

Phalkey, Revati K; Butsch, Carsten; Belesova, Kristine; Kroll, Marieke; Kraas, Frauke

2017-08-25

Private practitioners are the preferred first point of care in a majority of low and middle-income countries and in this position, best placed for the surveillance of diseases. However their contribution to routine surveillance data is marginal. This systematic review aims to explore evidence with regards to the role, contribution, and involvement of private practitioners in routine disease data notification. We examined the factors that determine the inclusion of, and the participation thereof of private practitioners in disease surveillance activities. Literature search was conducted using the PubMed, Web of Knowledge, WHOLIS, and WHO-IRIS databases to identify peer-reviewed and gray full-text documents in English with no limits for year of publication or study design. Forty manuscripts were reviewed. The current participation of private practitioners in disease surveillance efforts is appalling. The main barriers to their participation are inadequate knowledge leading to unsatisfactory attitudes and misperceptions that influence their practices. Complicated reporting mechanisms with unclear guidelines, along with unsatisfactory attitudes on behalf of the government and surveillance program managers also contribute to the underreporting of cases. Infrastructural barriers especially the availability of computers and skilled human resources are critical to improving private sector participation in routine disease surveillance. The issues identified are similar to those for underreporting within the Integrated infectious Disease Surveillance and Response systems (IDSR) which collects data mainly from public healthcare facilities. We recommend that surveillance program officers should provide periodic training, supportive supervision and offer regular feedback to the practitioners from both public as well as private sectors in order to improve case notification. Governments need to take leadership and foster collaborative partnerships between the public and private

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

Science.gov (United States)

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

2014-01-01

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

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013.

Science.gov (United States)

Cameron, Ross L; Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G J

2016-01-01

In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009-2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level.

GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

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Carter Steve G

2010-03-01

Full Text Available Abstract Background This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM. In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cultures were grown. The culture supernatant was harvested as a source of metabolites (MTB, and the bacteria were used to isolate cell wall fragments (CW. Both of these fractions were compared in a series of in vitro assays. Results Both MTB and CW inhibited spontaneous and oxidative stress-induced ROS formation in human PMN cells and increased the phagocytic activity of PMN cells in response to bacteria-like carboxylated fluorospheres. Both fractions supported random PMN and f-MLP-directed PMN cell migration, indicating a support of immune surveillance and antibacterial defense mechanisms. In contrast, low doses of both fractions inhibited PMN cell migration towards the inflammatory mediators IL-8 and LTB4. The anti-inflammatory activity was strongest for CW, where the PMN migration towards IL-8 was inhibited down to dilutions of 1010. Both MTB and CW induced the expression of the CD69 activation marker on human CD3- CD56+ NK cells, and enhanced the expression of CD107a when exposed to K562 tumor cells in vitro. The fractions directly modulated cytokine production, inducing production of the Th2 cytokines IL-4, IL-6, and IL-10, and inhibiting production of IL-2. Both fractions further modulated mitogen-induced cytokine production in the following manner: Both fractions enhanced the PHA-induced production of IL-6 and reduced the PHA-induced production of TNF-alpha. Both fractions enhanced the PWM-induced production of TNF-alpha and IFN-gamma. In addition, MTB

GanedenBC30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

Science.gov (United States)

2010-01-01

Background This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM). In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cultures were grown. The culture supernatant was harvested as a source of metabolites (MTB), and the bacteria were used to isolate cell wall fragments (CW). Both of these fractions were compared in a series of in vitro assays. Results Both MTB and CW inhibited spontaneous and oxidative stress-induced ROS formation in human PMN cells and increased the phagocytic activity of PMN cells in response to bacteria-like carboxylated fluorospheres. Both fractions supported random PMN and f-MLP-directed PMN cell migration, indicating a support of immune surveillance and antibacterial defense mechanisms. In contrast, low doses of both fractions inhibited PMN cell migration towards the inflammatory mediators IL-8 and LTB4. The anti-inflammatory activity was strongest for CW, where the PMN migration towards IL-8 was inhibited down to dilutions of 1010. Both MTB and CW induced the expression of the CD69 activation marker on human CD3- CD56+ NK cells, and enhanced the expression of CD107a when exposed to K562 tumor cells in vitro. The fractions directly modulated cytokine production, inducing production of the Th2 cytokines IL-4, IL-6, and IL-10, and inhibiting production of IL-2. Both fractions further modulated mitogen-induced cytokine production in the following manner: Both fractions enhanced the PHA-induced production of IL-6 and reduced the PHA-induced production of TNF-alpha. Both fractions enhanced the PWM-induced production of TNF-alpha and IFN-gamma. In addition, MTB also enhanced both the PHA

Role of Polyamines in Immune Cell Functions

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Rebecca S. Hesterberg

2018-03-01

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

Ideology, Critique and Surveillance

Directory of Open Access Journals (Sweden)

Heidi Herzogenrath-Amelung

2013-11-01

Full Text Available The 2013 revelations concerning global surveillance programmes demonstrate in unprecedented clarity the need for Critical Theory of information and communication technologies (ICTs to address the mechanisms and implications of increasingly global, ubiquitous surveillance. This is all the more urgent because of the dominance of the “surveillance ideology” (the promise of security through surveillance that supports the political economy of surveillance. This paper asks which theoretical arguments and concepts can be useful for philosophically grounding a critique of this surveillance ideology. It begins by examining how the surveillance ideology works through language and introduces the concept of the ‘ideological packaging’ of ICTs to show how rhetoric surrounding the implementation of surveillance technologies reinforces the surveillance ideology. It then raises the problem of how ideology-critique can work if it relies on language itself and argues that Martin Heidegger’s philosophy can make a useful contribution to existing critical approaches to language.

SCM: a practical tool to implement hospital-based syndromic surveillance.

Science.gov (United States)

Ye, Chuchu; Li, Zhongjie; Fu, Yifei; Lan, Yajia; Zhu, Weiping; Zhou, Dinglun; Zhang, Honglong; Lai, Shengjie; Buckeridge, David L; Sun, Qiao; Yang, Weizhong

2016-06-18

Syndromic surveillance has been widely used for the early warning of infectious disease outbreaks, especially in mass gatherings, but the collection of electronic data on symptoms in hospitals is one of the fundamental challenges that must be overcome during operating a syndromic surveillance system. The objective of our study is to describe and evaluate the implementation of a symptom-clicking-module (SCM) as a part of the enhanced hospital-based syndromic surveillance during the 41st World Exposition in Shanghai, China, 2010. The SCM, including 25 targeted symptoms, was embedded in the sentinels' Hospital Information Systems (HIS). The clinicians used SCM to record these information of all the visiting patients, and data were collated and transmitted automatically in daily batches. The symptoms were categorized into seven targeted syndromes using pre-defined criteria, and statistical algorithms were applied to detect temporal aberrations in the data series. SCM was deployed successfully in each sentinel hospital and was operated during the 184-day surveillance period. A total of 1,730,797 patient encounters were recorded by SCM, and 6.1 % (105,352 visits) met the criteria of the seven targeted syndromes. Acute respiratory and gastrointestinal syndromes were reported most frequently, accounted for 92.1 % of reports in all syndromes, and the aggregated time-series presented an obvious day-of-week variation over the study period. In total, 191 aberration signals were triggered, and none of them were identified as outbreaks after verification and field investigation. SCM has acted as a practical tool for recording symptoms in the hospital-based enhanced syndromic surveillance system during the 41st World Exposition in Shanghai, in the context of without a preexisting electronic tool to collect syndromic data in the HIS of the sentinel hospitals.

Glycine does not add to the beneficial effects of perioperative oral immune-enhancing nutrition supplements in high-risk cardiac surgery patients

NARCIS (Netherlands)

Tepaske, Robert; te Velthuis, Henk; Oudemans-van Straaten, Heleen M.; Bossuyt, Patrick M. M.; Schultz, Marcus J.; Eijsman, Leon; Vroom, Margreeth

2007-01-01

Background: Elderly patients and patients with a poor cardiac function have increased morbidity rates when undergoing cardiac surgery. The aim of this study was to determine whether addition of glycine to a standard preoperative oral immune-enhancing nutrition supplement (OIENS) improves outcome.

Immune Evasion, Immunopathology and the Regulation of the Immune System

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Bruno Faivre

2013-02-01

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

Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

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Nicholas Glanville

Full Text Available Human rhinovirus (RV infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2 capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine.

Pleurocidin Peptide Enhances Grouper Anti-Vibrio harveyi Immunity Elicited by Poly(lactide-co-glycolide)-Encapsulated Recombinant Glyceraldehyde-3-phosphate Dehydrogenase.

Science.gov (United States)

Chuang, Shu-Chun; Huang, Wan-Ling; Kau, Sau-Wei; Yang, Yun-Pei; Yang, Chung-Da

2014-05-14

Outer membrane proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are considered immunodominant antigens for eliciting protective immunity against Vibrio harveyi, the main etiological agent of vibriosis in fish. Cationic antimicrobial peptides (AMPs), such as pleurocidin (PLE), play important roles in activating and recruiting immune cells, thereby contributing to subsequent innate and adaptive immune responses. In the present study, we aimed to use PLE peptide as a potent adjuvant to improve the immunogenicity of V. harveyi recombinant GAPDH (rGAPDH). In order to prepare a controlled-release vaccine, PLE peptide and rGAPDH protein were simultaneously encapsulated into polymeric microparticles made from the biodegradable poly(lactide-co-glycolide) (PLG) polymer. The resulting PLG-encapsulated PLE plus rGAPDH (PLG-PLE/rGAPDH) microparticles, 3.21-6.27 μm in diameter, showed 72%-83% entrapment efficiency and durably released both PLE and rGAPDH for a long 30-day period. Following peritoneal immunization in grouper (Epinephelus coioides), PLG-PLE/rGAPDH microparticles resulted in significantly higher (p PLE/rGAPDH microparticles conferred a high survival rate (85%), which was significantly higher (p PLE peptide exhibits an efficacious adjuvant effect to elicit not only improved immunity, but also enhanced protection against V. harveyi in grouper induced by rGAPDH protein encapsulated in PLG microparticles.

Enhanced surveillance of a lymphogranuloma venereum outbreak in Sydney 2010-2012.

Science.gov (United States)

Templeton, David J; Ressler, Kelly-Anne; Hope, Kirsty; Poynten, Isobel M

2016-08-01

To investigate an increase in lymphogranuloma venereum (LGV) notifications in New South Wales (NSW). Enhanced surveillance of notified LGV cases in NSW between May 2010 and April 2012 using doctor and patient questionnaires. Thirty-seven doctors who had diagnosed 67 (76%) of 88 notified anorectal LGV infections were interviewed. The majority (n=33, 89%) of treating doctors were formally trained and accredited in HIV management and prescribing, and most (n=32, 86%) worked in a public sexual health clinic or a general practice with a high caseload of men who have sex with men (MSM). All 67 cases were MSM who resided in inner-city Sydney and all were serovar L2b. Anal symptoms had been present in 64 cases (96%, 95%CI 87-99%) for a median of 8 days (range 2-1,825) prior to presentation. Almost one-third (n=20) had another concurrent STI diagnosed. Most (82%) of the 22 interviewed patients reported being HIV positive and having other STIs diagnosed over the past year. In the preceding month, all 22 men reported condomless anal sex and the median number of casual sexual partners was 5 (range 0-100). Characteristics of LGV cases in NSW are similar to those described worldwide, suggesting that a sexually adventurous subgroup of MSM are at particular risk of infection. Education of non-sexual-health clinicians on LGV risk factors, presentation, testing and management may allow more timely diagnosis and notification of contacts to reduce LGV transmission in the community. © 2016 Public Health Association of Australia.

Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV.

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Nigel J Stevenson

Full Text Available The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV.

A stressful microenvironment: opposing effects of the endoplasmic reticulum stress response in the suppression and enhancement of adaptive tumor immunity.

Science.gov (United States)

Rausch, Matthew P; Sertil, Aparna Ranganathan

2015-03-01

The recent clinical success of immunotherapy in the treatment of certain types of cancer has demonstrated the powerful ability of the immune system to control tumor growth, leading to significantly improved patient survival. However, despite these promising results current immunotherapeutic strategies are still limited and have not yet achieved broad acceptance outside the context of metastatic melanoma. The limitations of current immunotherapeutic approaches can be attributed in part to suppressive mechanisms present in the tumor microenvironment that hamper the generation of robust antitumor immune responses thus allowing tumor cells to escape immune-mediated destruction. The endoplasmic reticulum (ER) stress response has recently emerged as a potent regulator of tumor immunity. The ER stress response is an adaptive mechanism that allows tumor cells to survive in the harsh growth conditions inherent to the tumor milieu such as low oxygen (hypoxia), low pH and low levels of glucose. Activation of ER stress can also alter the cancer cell response to therapies. In addition, the ER stress response promotes tumor immune evasion by inducing the production of protumorigenic inflammatory cytokines and impairing tumor antigen presentation. However, the ER stress response can boost antitumor immunity in some situations by enhancing the processing and presentation of tumor antigens and by inducing the release of immunogenic factors from stressed tumor cells. Here, we discuss the dualistic role of the ER stress response in the modulation of tumor immunity and highlight how strategies to either induce or block ER stress can be employed to improve the clinical efficacy of tumor immunotherapy.

Who is Surveilling Whom?

DEFF Research Database (Denmark)

Mortensen, Mette

2014-01-01

This article concerns the particular form of counter-surveillance termed “sousveillance”, which aims to turn surveillance at the institutions responsible for surveillance. Drawing on the theoretical perspectives “mediatization” and “aerial surveillance,” the article studies WikiLeaks’ publication...

The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree.

Science.gov (United States)

Zhang, Guiqiang; Cheng, Gong; Jia, Peiyuan; Jiao, Siming; Feng, Cui; Hu, Tao; Liu, Hongtao; Du, Yuguang

2017-07-26

Chitosan oligosaccharides (COS), the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2) subunit vaccine to enhance its immunogenicity. The vaccine conjugates were designed by the covalent linkage of COSs to PCV2 molecules and administered to BALB/c mice three times at two-week intervals. The results indicate that, as compared to the PCV2 group, COS-PCV2 conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting lymphocyte proliferation and initiating a mixed T-helper 1 (Th1)/T-helper 2 (Th2) response, including raised levels of PCV2-specific antibodies and an increased production of inflammatory cytokines. Noticeably, with the increasing deacetylation degree, the stronger immune responses to PCV2 were observed in the groups with COS-PCV2 vaccination. In comparison with NACOS (chitin oligosaccharides)-PCV2 and LCOS (chitosan oligosaccharides with low deacetylation degree)-PCV2, HCOS (chitosan oligosaccharides with high deacetylation degree)-PCV2 showed the highest adjuvant effect, even comparable to that of PCV2/ISA206 (a commercialized adjuvant) group. In summary, COS conjugation might be a viable strategy to enhance the immune response to PCV2 subunit vaccine, and the adjuvant effect was positively correlated with the deacetylation degree of COS.

Magnetic resonance imaging surveillance following vestibular schwannoma resection.

Science.gov (United States)

Carlson, Matthew L; Van Abel, Kathryn M; Driscoll, Colin L; Neff, Brian A; Beatty, Charles W; Lane, John I; Castner, Marina L; Lohse, Christine M; Link, Michael J

2012-02-01

To describe the incidence, pattern, and course of postoperative enhancement within the operative bed using serial gadolinium-enhanced magnetic resonance imaging (MRI) following vestibular schwannoma (VS) resection and to identify clinical and radiologic variables associated with recurrence. Retrospective cohort study. All patients who underwent microsurgical resection of VS between January 2000 and January 2010 at a single tertiary referral center were reviewed. Postoperative enhancement patterns were characterized on serial MRI studies. Clinical follow-up and outcomes were recorded. During the last 10 years, 350 patients underwent microsurgical VS resection, and of these, 203 patients met study criteria (mean radiologic follow-up, 3.5 years). A total of 144 patients underwent gross total resection (GTR), 32 received near-total resection (NTR), and the remaining 27 underwent subtotal resection (STR); 98.5% of patients demonstrated enhancement within the operative bed following resection (58.5% linear, 41.5% nodular). Stable enhancement patterns were seen in 24.5% of patients, regression in 66.0%, and resolution in only 3.5% of patients on the most recent postoperative MRI. Twelve patients recurred a mean of 3.0 years following surgery. The average maximum linear diameter growth rate among recurrent tumors was 2.3 mm per year. Those receiving STR were more than nine times more likely to experience recurrence compared to those undergoing NTR or GTR (P assist the clinician in determining an appropriate postoperative MRI surveillance schedule. Future studies using standardized terminology and consistent study metrics are needed to further refine surveillance recommendations. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Information systems to support surveillance for malaria elimination.

Science.gov (United States)

Ohrt, Colin; Roberts, Kathryn W; Sturrock, Hugh J W; Wegbreit, Jennifer; Lee, Bruce Y; Gosling, Roly D

2015-07-01

Robust and responsive surveillance systems are critical for malaria elimination. The ideal information system that supports malaria elimination includes: rapid and complete case reporting, incorporation of related data, such as census or health survey information, central data storage and management, automated and expert data analysis, and customized outputs and feedback that lead to timely and targeted responses. Spatial information enhances such a system, ensuring cases are tracked and mapped over time. Data sharing and coordination across borders are vital and new technologies can improve data speed, accuracy, and quality. Parts of this ideal information system exist and are in use, but have yet to be linked together coherently. Malaria elimination programs should support the implementation and refinement of information systems to support surveillance and response and ensure political and financial commitment to maintain the systems and the human resources needed to run them. National malaria programs should strive to improve the access and utility of these information systems and establish cross-border data sharing mechanisms through the use of standard indicators for malaria surveillance. Ultimately, investment in the information technologies that support a timely and targeted surveillance and response system is essential for malaria elimination. © The American Society of Tropical Medicine and Hygiene.

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

Energy Technology Data Exchange (ETDEWEB)

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

2006-01-15

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

[Different aluminum adjuvants significantly enhances the effect of immunization on Brucella Omp31].

Science.gov (United States)

Qing, Rui; Xiang, Qingke; Liu, Zhongqi; Xiao, Fei; Yang, Fan

2018-02-01

Objective To investigate the effect of aluminum phosphate (AP) and aluminum hydroxide (AH) as adjuvants on Brucella outer membrane protein 31 (Omp31) in inducing humoral and cellular immune responses and immune protection. Methods AP and AH adjuvants were prepared and separately mixed with Brucella Omp31 protein to measure the adsorption rates. The AP- and AH-absorbed Omp31 protein were intraperitoneally injected into BLAB/c mice at 0, 2, and 4 weeks, and meanwhile, unabsorbed Omp31 protein and PBS were used as controls. The levels of serum IgG, IgG1, IgG2a and genital tract secretion sIgA were determined by ELISA at 0, 2, 4 and 6 weeks. Spleen cells were collected for culture at 6 weeks, and the cells were stimulated by Omp31 for 48 hours followed by the analysis of IFN-γ and IL-10 levels in the supernatants by ELISA, and the determination of lymphocyte proliferation by CCK-8 assay. The mice were challenged with Brucella at 6 weeks, and bacterial content in spleen tissue was determined 1 and 2 weeks later. Results AP and AH could absorb over 70% and 85% of the Omp31 protein, respectively, for solutions at all the tested concentrations. ELISA suggested that serum IgG, IgG1, IgG2a and genital tract sIgA levels peaked 2 weeks after the last immunization for both AP and AH groups, and antibody level was higher in the AP and AH groups than the control groups, and higher in the AH group than in the AP group. CCK-8 assay showed that the proliferating rate of lymphocytes induced by the AH group was significantly higher than that by the AP group, and the AH group also showed significantly higher IFN-γ level in the supernatant than the AP group, but no significant difference in IL-10 level. The AH group had remarkably lower bacterial load in the spleen than the AP group 2 weeks after challenged by Brucella 16M strain. Conclusion Both AP and AH adjuvants effectively enhanced immunogenicity and immune protection of the Brucella Omp31 protein, and AH was superior to AP in

SOA-surveillance Nederland

NARCIS (Netherlands)

Rijlaarsdam J; Bosman A; Laar MJW van de; CIE

2000-01-01

In May 1999 a working group was started to evaluate the current surveillance systems for sexually transmitted diseases (STD) and to make suggestions for a renewed effective and efficient STD surveillance system in the Netherlands. The surveillance system has to provide insight into the prevalence

Integrating animal health and food safety surveillance data from slaughterhouse control.

Science.gov (United States)

Lynch, J A; Silva, P

2013-08-01

Surveillance at the slaughterhouse level for animal health and food safety purposes encompasses examination for the presence of pathology, pathogens, drug residues, chemical contaminants and antimicrobial resistance. Government, industry and academia are the primary proponents of such surveillance. A variety of policies and policy instruments from voluntary to legislative may be applied to promote or obligate participation. Efforts to integrate data across such diverse organisations encounter significant legal, logistical and financial challenges. Enhancement of policies to encourage effective integration of animal health and food safety surveillance data from slaughterhouse control should promote: a long-term approach; collaboration among government, industry and academia; application of a risk-based scheme; and transparent public access to data, with generation of consumer-oriented communications derived from the data. A strong case can be made that the complementary pursuit of both sustainable animal health and food safety can continue to be aided by surveillance at the slaughterhouse level.

Verifying influenza and pneumococcal immunization status of children in 2009-2010 from primary care practice records and from the North Carolina Immunization Registry.

Science.gov (United States)

Poehling, Katherine A; Vannoy, Lauren; Peters, Timothy R

2013-01-01

The North Carolina Immunization Registry (NCIR) has been available since 2004. We sought to measure its utilization among practices that provide primary care for children who are enrolled in a prospective influenza surveillance study. This study included children aged 0.5-17 years who presented with fever or acute respiratory symptoms to an emergency department or inpatient setting in Winston-Salem, North Carolina, from September 1, 2009, through May 19, 2010. Study team members verified influenza and pneumococcal immunization status by requesting records from each child's primary care practice and by independently reviewing the NCIR. We assessed agreement of nonregistry immunization medical records with NCIR data using the kappa statistic. Fifty-six practices confirmed the immunization status of 292 study-enrolled children. For most children (238/292, 82%), practices verified the child's immunizations by providing a copy of the NCIR record. For 54 children whose practices verified their immunizations by providing practice records alone, agreement with the NCIR by the kappa statistic was 0.6-0.7 for seasonal and monovalent H1N1 influenza vaccines and 0.8-0.9 for pneumococcal conjugate and polysaccharide vaccines. A total of 221 (98%) of 226 enrolled children younger than 6 years of age had 2 or more immunizations documented in the NCIR. NCIR usage may vary in other regions of North Carolina. More than 95% of children younger than 6 years of age had 2 or more immunizations documented in the NCIR; thus, the Centers for Disease Control and Prevention 2010 goal for immunization information systems was met in this population. We found substantial agreement between practice records and the NCIR for influenza and pneumococcal immunizations in children.

Motivation of health surveillance assistants in Malawi: A qualitative ...

African Journals Online (AJOL)

Background: Motivation of health workers is a critical component of performance and is shaped by multiple factors. This study explored factors that influence motivation of health surveillance assistants (HSAs) in Malawi, with the aim of identifying interventions that can be applied to enhance motivation and performance of ...

Viral Aetiology of Acute Flaccid Paralysis Surveillance Cases, before and after Vaccine Policy Change from Oral Polio Vaccine to Inactivated Polio Vaccine

Directory of Open Access Journals (Sweden)

T. S. Saraswathy Subramaniam

2014-01-01

Full Text Available Since 1992, surveillance for acute flaccid paralysis (AFP cases was introduced in Malaysia along with the establishment of the National Poliovirus Laboratory at the Institute for Medical Research. In 2008, the Ministry of Health, Malaysia, approved a vaccine policy change from oral polio vaccine to inactivated polio vaccine (IPV. Eight states started using IPV in the Expanded Immunization Programme, followed by the remaining states in January 2010. The objective of this study was to determine the viral aetiology of AFP cases below 15 years of age, before and after vaccine policy change from oral polio vaccine to inactivated polio vaccine. One hundred and seventy-nine enteroviruses were isolated from the 3394 stool specimens investigated between 1992 and December 2012. Fifty-six out of 107 virus isolates were polioviruses and the remaining were non-polio enteroviruses. Since 2009 after the sequential introduction of IPV in the childhood immunization programme, no Sabin polioviruses were isolated from AFP cases. In 2012, the laboratory AFP surveillance was supplemented with environmental surveillance with sewage sampling. Thirteen Sabin polioviruses were also isolated from sewage in the same year, but no vaccine-derived poliovirus was detected during this period.

Rebuilding immunity with Remune.

Science.gov (United States)

Whitfield, L

1998-01-01

Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response.

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009–2013

Science.gov (United States)

Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G.J.

2016-01-01

In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009–2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level. PMID:26692336

SCORPIO-VVER core monitoring and surveillance system with advanced capabilities

International Nuclear Information System (INIS)

Molnar, J.; Vocka, R.

2010-01-01

In this work authors present 12 years of operation experience of core monitoring and surveillance system with advanced capabilities on nuclear power plants on 6 unit of VVER-440 type of reactors at two different NPPs. The original version of the SCORPIO (Surveillance of reactor CORe by PIcture On-line display) system was developed for the western type of PWR reactors. The first version of the SCORPIO-VVER Core Monitoring System for Dukovany NPP (VVER-440 type of reactor, Czech Republic) was developed in 1998. For SCORPIO-VVER implementation at Bohunice NPP in Slovakia (2001) the system was enhanced with startup module KRITEX.

Preventing the preventable through effective surveillance: the case of diphtheria in a rural district of Maharashtra, India.

Science.gov (United States)

Phalkey, Revati K; Bhosale, Rajesh V; Joshi, Abhijeet P; Wakchoure, Sushil S; Tambe, Muralidhar P; Awate, Pradip; Marx, Michael

2013-04-08

Epidemic diphtheria is still poorly understood and continues to challenge both developing and developed countries. In the backdrop of poor immunization coverage, non-existent adult boosters, weak case based surveillance and persistence of multiple foci, there is a heightened risk of re-emergence of the disease in epidemic forms in India. Investigating each outbreak to understand the epidemiology of the disease and its current status in the country is therefore necessary. Dhule a predominantly tribal and rural district in Northern Maharashtra has consistently recorded low vaccination coverages alongside sporaidic cases of diphtheria over the last years. This study reports the findings of an onsite survey conducted to assess a recent outbreak of diphtheria in Dhule district and the response mounted to it. Secondary data regarding outbreak detection and response were obtained from the district surveillance office. Clinical data were extracted from hospital records of eleven lab confirmed cases including one death case. Frequency distributions were calculated for each identified clinical and non- clinical variable using Microsoft™ Excel® 2010. Our findings suggest a shift in the median age of disease to adolescents (10-15 years) without gender differences. Two cases (18%) reported disease despite immunization. Clinical symptoms included cough (82%), fever (73%), and throat congestion (64%). About 64% and 36% of the 11 confirmed cases presented with a well defined pseudomembrane and a tonsillar patch respectively. Drug resistance was observed in all three culture positive cases. One death occurred despite the administration of Anti-Diphtheric Serum in a partially immunized case (CFR 9%). Genotyping and toxigenicity of strain was not possible due to specimen contamination during transport as testing facilities were unavailable in the district. The outbreak raises several concerns regarding the epidemiology of diphtheria in Dhule. The reason for shift in the median

In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

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Tânia A Costa

Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection

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Wu Li

2012-01-01

Full Text Available Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis (TB, is one of the world's leading infectious causes of morbidity and mortality. As a mucosal-transmitted pathogen, Mtb infects humans and animals mainly through the mucosal tissue of the respiratory tract. Apart from providing a physical barrier against the invasion of pathogen, the major function of the respiratory mucosa may be to serve as the inductive sites to initiate mucosal immune responses and sequentially provide the first line of defense for the host to defend against this pathogen. A large body of studies in the animals and humans have demonstrated that the mucosal immune system, rather than the systemic immune system, plays fundamental roles in the host’s defense against Mtb infection. Therefore, the development of new vaccines and novel delivery routes capable of directly inducing respiratory mucosal immunity is emphasized for achieving enhanced protection from Mtb infection. In this paper, we outline the current state of knowledge regarding the mucosal immunity against Mtb infection, including the development of TB vaccines, and respiratory delivery routes to enhance mucosal immunity are discussed.

[Immunization with Bifidobacterium bifidum-vectored OprI vaccine of Pseudomonas aeruginosa enhances inhibitory effect on P. aeruginosa in mice].

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Liu, Xiao; Li, Wengui

2017-08-01

Objective To study the pulmonary bacterial loads, splenocyte proliferation, distributions of T cell subsets and cell apoptosis in mice immunized with Bifidobacterium bifidum-vectored OprI (Bb-OprI) vaccine of Pseudomonas aeruginosa and challenged with P. aeruginosa PA01 strain. Methods BALB/c mice were immunized with 5×10 9 CFUs of vaccine by intragastric administration, 3 times a week for 3 weeks, and challenged intranasally with 5×10 6 CFUs of PA01 strain at the fourth week after the first immunization. At the second week after the challenge, all mice were sacrificed to separate their lungs and spleens, and the pulmonary bacterial loads were counted. The proliferation of the splenocytes was determined by MTT assay. The splenic CD4 + , CD8 + T cell subsets and the apoptotic rate of splenocytes were detected by flow cytometry. Results The number of pulmonary bacterial colonies in the mice immunized with the vaccine and challenged with PA01 strain decreased, while the proliferation of splenocytes and the proportion of CD4 + T cells markedly increased, and the apoptosis of splenocytes was notably reduced. Conclusion The intragastric vaccination of recombinant Bb-OprI vaccine can increase the proportion of CD4 + T cells and enhance the inhibitory effect on P. aeruginosa.

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

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Daniel H. Libraty

2014-01-01

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

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

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Viswanathan, Kavitha; Dhabhar, Firdaus S.

2005-04-01

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

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Karen A.O. Martins

2016-01-01

Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Enhancing case definitions for surveillance of human monkeypox in the Democratic Republic of Congo.

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Lynda Osadebe

2017-09-01

Full Text Available Human monkeypox (MPX occurs at appreciable rates in the Democratic Republic of Congo (DRC. Infection with varicella zoster virus (VZV has a similar presentation to that of MPX, and in areas where MPX is endemic these two illnesses are commonly mistaken. This study evaluated the diagnostic utility of two surveillance case definitions for MPX and specific clinical characteristics associated with laboratory-confirmed MPX cases.Data from a cohort of suspect MPX cases (identified by surveillance over the course of a 42 month period during 2009-2014 from DRC were used; real-time PCR diagnostic test results were used to establish MPX and VZV diagnoses. A total of 333 laboratory-confirmed MPX cases, 383 laboratory-confirmed VZV cases, and 36 cases that were determined to not be either MPX or VZV were included in the analyses. Significant (p<0.05 differences between laboratory-confirmed MPX and VZV cases were noted for several signs/symptoms including key rash characteristics. Both surveillance case definitions had high sensitivity and low specificities for individuals that had suspected MPX virus infections. Using 12 signs/symptoms with high sensitivity and/or specificity values, a receiver operator characteristic analysis showed that models for MPX cases that had the presence of 'fever before rash' plus at least 7 or 8 of the 12 signs/symptoms demonstrated a more balanced performance between sensitivity and specificity.Laboratory-confirmed MPX and VZV cases presented with many of the same signs and symptoms, and the analysis here emphasized the utility of including 12 specific signs/symptoms when investigating MPX cases. In order to document and detect endemic human MPX cases, a surveillance case definition with more specificity is needed for accurate case detection. In the absence of a more specific case definition, continued emphasis on confirmatory laboratory-based diagnostics is warranted.

Localized skin changes at the site of immunization with highly irradiated cercariae of Schistosoma mansoni are associated with enhanced resistance to a challenge infection

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Miller, K.L.; Smithers, S.R.

1982-01-01

The level of immunity to a percutaneous cercarial challenge with Schistosoma mansoni was assayed 4-6 weeks after immunization of mice with highly irradiated (20 krad.) cercariae or schistosomula. When immunization and challenge occurred through the same skin site, resistance, particularly that which occurred in the skin, was greater than that observed when immunization and challenge occurred in different sites. The enhanced resistance is believed to be due to localized changes in the skin; 4 weeks after exposure to irradiated cercariae, abdominal skin is characterized by a thickened epidermis, changes in the ground substance and a cellular infiltration of the dermis. A convenient mouse model is described in which one or both ear pinnae are exposed to irradiated cercariae and a percutaneous challenge is given via the abdomen, thus eliminating the effects of local skin changes. In this model, the majority of the challenge infection which succumbs to the immune response appears to be killed in the skin. (author)

Improved embedded non-linear processing of video for camera surveillance

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Cvetkovic, S.D.; With, de P.H.N.

2009-01-01

For a real time imaging in surveillance applications, image fidelity is of primary importance to ensure customer confidence. The fidelity is obtained amongst others via dynamic range expansion and video signal enhancement. The dynamic range of the signal needs adaptation, because the sensor signal

Use of Specialized Security Techniques to Enhance the Authenticity of Surveillance Data

International Nuclear Information System (INIS)

Rocchi, S.; Simlinger, R.; Moeslinger, M.; Murray, J.; Hadfi, G.; John, M.

2015-01-01

In 2013, the IAEA started testing a commercial application-specific integrated circuit (ASIC) from LiveWire technology for its ability to monitor changes in wiring systems in real time. This technology is useful in specific situations where digital video signal authentication cannot be used due to analog cameras used in high radiation level (e.g., hot cells, reading spent fuel identification numbers), dimensional requirements, or when an analog signal has to be shared with a facility's built-in camera. The LiveWire ASIC can be used for tamper indication with resulting cost savings by eliminating the need for specifically manufactured tamper indicating conduits. This technology can also be integrated within the Next Generation Surveillance System (NGSS) camera module, coupled with the upcoming implementation of the analogue video input, for the protection of analog video signals provided by an external camera head. Digital camera identification based on sensor pattern noise analysis is another technique under investigation at the IAEA. Sensor pattern noise is unique to a device and can be used as a distinct identification ''fingerprint''. This technique is increasingly being employed for camera identification and in-image authentication & video forensics by commercial software suites. Interest in this technique for use in safeguards applications is justified by the need to own specific forensic tools and the requirement to verify the authenticity of surveillance streams acquired in analog video input configurations where the camera head is external to the NGSS camera module). Preliminary tests have been performed on surveillance data acquired by NGSS cameras and post-processed with commercial forensic software. The promising results obtained encourage further development efforts and tests to be conducted to fully assess the potential capabilities this technology offers. This paper will focus on these two applications recently addressed by

Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity

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Perdigón Gabriela

2007-09-01

Full Text Available Background Fermented milks containing probiotic bacteria are a way of delivering bioactive constituents to targets in the gastrointestinal tract. We reported previously that the fermentation of milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oral administration of the non-bacterial fraction (FMSpH6 to mice increased total secretory IgA in the intestinal lumen and enhanced the number of IgA and various cytokines producing cells as well as the secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 was effective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied in mice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389 on the gut physiology by measuring parameters such as calcium channels and E-cadherin expression, the activation of the biological signal calcineurin and mast and goblet cells, as a way to determine some mechanisms involved in the immunomodulating effects of the milk fermentation products, observed in previous studies. We analyzed the impact of the supernatant of milk fermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on the reinforcement of the ephitelial barrier, measuring parameters such as calcium channels and E-cadherin expression and in the reinforcement of the non-specific immunity determining mast cells and goblet cells associated to the gut. Results We observed an enhanced expression of TRPV6 channels in the duodenum, indicating an improved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression of calcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNF production, with an increase in the number of these cytokines secreting cells. We determined an increase in the number of mucosal mast cells and goblet cells, which would mean an improved state of mucosal surveillance

T-regulatory cells depletion is the main cause for enhanced antitumor immunity during radio-sensitization of tumors by 2-deoxy-D-glucose

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Farooque, Abdullah; Verma, Amit; Singh, Niharika; Chauhan, Sachin Kumar Singh; Jethani, Jyoti; Adhikari, J.S.; Dwarakanath, B.S.; Afrin, Farhat

2014-01-01

Regulatory T cells (Tregs) are known to have profound effects in blocking anti-tumor immunity. Therefore, Tregs are seen as a major hurdle that must be overcome in order to improve the efficacy of cancer therapy. The glycolytic inhibitor, 2-deoxy-d-glucose (2-DG) enhances radiation and chemotherapeutics induced death of many cancer cells in vitro and local tumor control in vivo, which was found to be associated with the enhanced anti-tumor immunity. Therefore, we investigated the role of Tregs in determining the tumor response to the combined treatment of 2-DG plus ionizing radiation. Ehrlich ascites tumor bearing mice were administered with a single dose of 2-DG (2 gm/Kg/b.wt) intravenously just before focal irradiation (10 Gy). Immuno-phenotyping of Tregs in secondary lymphoid organs was carried out using flow cytometry, while related cytokines were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells and CD4 + CD25 + using real time PCR and Western blot techniques. Results clearly showed depletion (TRAIL mediated apoptosis) of T regs (CD4 + CD25 + FoxP3 + CD39 + FR4 + GITR + CD127 - ), in blood, spleen, lymph node and tumor following the combined treatment. This led to the immune activation in the periphery, secondary lymphoid organs and massive infiltration of CD4 + , CD8 + and NK cells in the tumor, which correlated well with the complete response (cure; tumor free survival). Association of Treg depletion with the tumor response was further confirmed using low doses of cyclophosphamide (which depletes Tegs) and rapamycin (activator of Tregs),wherein the depletor of Tregs enhanced the efficacy of combined treatment, while Tregs enhancer compromised the efficacy. These studies unequivocally established the role of Tregs in determining the therapeutic response and can be used as a target for enhancing the efficacy of this combined treatment, besides establishing the potential of

Jungle Honey Enhances Immune Function and Antitumor Activity

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Miki Fukuda

2011-01-01

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

Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

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Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

2006-01-01

Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

Murine and bovine γδ T cells enhance innate immunity against Brucella abortus infections.

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Jerod A Skyberg

Full Text Available γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ(-/- mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα(-/-, and GMCSF(-/- mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ(-/- mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections.

Migratory and adhesive cues controlling innate-like lymphocyte surveillance of the pathogen-exposed surface of the lymph node.

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Zhang, Yang; Roth, Theodore L; Gray, Elizabeth E; Chen, Hsin; Rodda, Lauren B; Liang, Yin; Ventura, Patrick; Villeda, Saul; Crocker, Paul R; Cyster, Jason G

2016-08-03

Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular sinus (SCS) and associated macrophages for pathogen entry. The factors promoting this surveillance behavior have not been defined. Here, we report that IL7R(hi)Ccr6(+) lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and fungal challenge. We show that these innate-like lymphocytes are mostly LN resident. Ccr6 is required for their accumulation near the SCS and for efficient IL17 induction. Migration into the SCS intrinsically requires S1pr1, whereas movement from the sinus into the parenchyma involves the integrin LFA1 and its ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within the sinus, preventing their loss in lymph flow. These findings establish a role for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens, and they define requirements for cell movement between parenchyma and SCS in what we speculate is a program of immune surveillance that helps achieve LN barrier immunity.

Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant.

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Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J

2015-01-23

Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Combined effect of x irradiation and cell-mediated immune reaction

International Nuclear Information System (INIS)

Song, C.W.; Guertin, D.P.

1978-01-01

The combined effect of radiation and cell-mediated immune reaction on tumor cells was investigated in vitro. Mastocytoma P815-X2 cells of DBA mice either were irradiated first and subjected to immune lysis by immune splenic lymphocytes of C57Bl mice, or the tumor cells were subjected to immune reaction first and then irradiated. Cell survival was quantitated by colony formation in soft agar medium. It was observed that cellular immune damage to tumor cells did not influence the response of tumor cells to subsequent radiation. Irradiation of tumor cells first, followed by subjection of the cells to cellular immune reaction, slightly enhanced the death of the tumor cells. It appears that this enhanced death might have resulted from a relative increase in the ratio of the number of cytotoxic immune cells to the number of target tumor cells in the incubation mixture as a consequence of the decrease in the number of viable tumor cells by radiation

The Stop Transmission of Polio Data Management (STOP DM) assignment and its role in polio eradication and immunization data improvement in Africa.

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Benke, Amalia; Williams, Alford Joseph; MacNeil, Adam

2017-01-01

The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and surveillance data for these countries. Since 2002, Africa has received the majority of support from the STOP DM program, with almost 80% of assignments being placed in African countries. The STOP DM program has played a valuable role in improving the quality and use of data for the GPEI and has increasingly supported other immunization program data needs. In this report we provide an overview of the history, current status, and future of the STOP DM program, with a specific focus on the African continent.

Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.

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Juliane Bremer

Full Text Available The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

Protocatechuic acid (PCA) induced a better antiviral effect by immune enhancement in SPF chickens.

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Guo, Yongxia; Zhang, Qiang; Zuo, Zonghui; Chu, Jun; Xiao, Hongzhi; Javed, M Tariq; He, Cheng

2018-01-01

Protocatechuic acid (PCA) is an antiviral agent against Avian Influenza virus (AIV) and Infectious Bursal Disease (IBD) virus, but its antiviral mechanism is unknown. In this study, we evaluated the humoral and cellular responses to PCA in specific pathogen-free (SPF) chickens. One hundred forty 35-day-old SPF chickens were randomly divided into 7 groups. The birds were inoculated with the commercial, attenuated Newcastle Disease Virus (NDV) vaccine and then received orally with 10, 20 or 40 mg/kg body weight of PCA for 30 days. Immune organ indexes, anti-Newcastle Disease Virus (NDV) antibodies and lymphocyte proliferation, but not body weight, were significantly increased in chicken treated with 40 mg/kg PCA, compared to the control birds treated with Astragalus polysaccharide (ASP). Survival rate was 70% and 60%, respectively, in the chickens with 40 mg/kg PCA, 20 mg/kg PCA while 50% survival was found in the birds treated with 125 mg/kg ASP. PCA treatment resulted in significantly lower viral load and reduced shedding. These results indicate that PCA may improve poultry health by enhancing both the humoral and cellular immune response. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

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Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

1998 annual report Office of Occupational Medicine and Medical Surveillance

International Nuclear Information System (INIS)

Gebus, George R.

1999-01-01

the mission of EH-61 is the prevention of worker illness by fostering outstanding occupational medicine and medical surveillance programs within the DOE complex. The EH-61 annual report for 1998 describes our major activities and achievements as we have worked toward realizing this mission through our main program lines (1) Surveillance; (2) policy(Field SUppOti; (3) Information/Communication; and (4) Research. Some of our major 1998 accomplishments are highlighted below for more details, please consult the corresponding sections of this report. The FORMER BERYLLIUM WORKERS MEDICAL SURVEILLANCE PROGRAM identifies and locates former employees exposed to beryllium and provides enhanced medical monitoring for early identification of chronic beryllium disease (CBD). Over Z0,000 current and former workers have been contacted to date, and there have been about 8,8oo responders. More than 100 cases of CBD have been detected. The DOE FORMER WORKERS PROGRAM (FWP) is targeted primarily to former workers who have either retired or left DOE facilities. In FY 1998, there were 10 pilot projects operating at 9 sites. These pilots will validate approaches for medical screening of former employees and health risk communication efforts. When completed in FY 2002, the information gained from the pilots will serve as a basis for projecting funding and resources needed for the FWP in the years ahead. We have helped develop health-related POLICIES/GUIDANCE, that will promote the health of the contractor workforce by addressing current and emerging issues related to occupational health. The RADIATION EMERGENCY ASSISTANCE CENTER/TRAINING SITE (REAC/TS) is supported by EH-61 and assists DOE by maintaining state-of-the-art expertise in radiation medicine and biodosimetry. This support provides DOE with a national and international 24-hour response capability for evaluating and managing victims of radiation accidents occurring at its facilities or among the general public. In collaboration

Real-time implementations of acoustic signal enhancement techniques for aerial based surveillance and rescue applications

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Ramos, Antonio L. L.; Shao, Zhili; Holthe, Aleksander; Sandli, Mathias F.

2017-05-01

The introduction of the System-on-Chip (SoC) technology has brought exciting new opportunities for the development of smart low cost embedded systems spanning a wide range of applications. Currently available SoC devices are capable of performing high speed digital signal processing tasks in software while featuring relatively low development costs and reduced time-to-market. Unmanned aerial vehicles (UAV) are an application example that has shown tremendous potential in an increasing number of scenarios, ranging from leisure to surveillance as well as in search and rescue missions. Video capturing from UAV platforms is a relatively straightforward task that requires almost no preprocessing. However, that does not apply to audio signals, especially in cases where the data is to be used to support real-time decision making. In fact, the enormous amount of acoustic interference from the surroundings, including the noise from the UAVs propellers, becomes a huge problem. This paper discusses a real-time implementation of the NLMS adaptive filtering algorithm applied to enhancing acoustic signals captured from UAV platforms. The model relies on a combination of acoustic sensors and a computational inexpensive algorithm running on a digital signal processor. Given its simplicity, this solution can be incorporated into the main processing system of an UAV using the SoC technology, and run concurrently with other required tasks, such as flight control and communications. Simulations and real-time DSP-based implementations have shown significant signal enhancement results by efficiently mitigating the interference from the noise generated by the UAVs propellers as well as from other external noise sources.

A targeted and adjuvanted nanocarrier lowers the effective dose of liposomal amphotericin B and enhances adaptive immunity in murine cutaneous leishmaniasis.

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Daftarian, Pirouz M; Stone, Geoffrey W; Kovalski, Leticia; Kumar, Manoj; Vosoughi, Aram; Urbieta, Maitee; Blackwelder, Pat; Dikici, Emre; Serafini, Paolo; Duffort, Stephanie; Boodoo, Richard; Rodríguez-Cortés, Alhelí; Lemmon, Vance; Deo, Sapna; Alberola, Jordi; Perez, Victor L; Daunert, Sylvia; Ager, Arba L

2013-12-01

Amphotericin B (AmB), the most effective drug against leishmaniasis, has serious toxicity. As Leishmania species are obligate intracellular parasites of antigen presenting cells (APC), an immunopotentiating APC-specific AmB nanocarrier would be ideally suited to reduce the drug dosage and regimen requirements in leishmaniasis treatment. Here, we report a nanocarrier that results in effective treatment shortening of cutaneous leishmaniasis in a mouse model, while also enhancing L. major specific T-cell immune responses in the infected host. We used a Pan-DR-binding epitope (PADRE)-derivatized-dendrimer (PDD), complexed with liposomal amphotericin B (LAmB) in an L. major mouse model and analyzed the therapeutic efficacy of low-dose PDD/LAmB vs full dose LAmB. PDD was shown to escort LAmB to APCs in vivo, enhanced the drug efficacy by 83% and drug APC targeting by 10-fold and significantly reduced parasite burden and toxicity. Fortuitously, the PDD immunopotentiating effect significantly enhanced parasite-specific T-cell responses in immunocompetent infected mice. PDD reduced the effective dose and toxicity of LAmB and resulted in elicitation of strong parasite specific T-cell responses. A reduced effective therapeutic dose was achieved by selective LAmB delivery to APC, bypassing bystander cells, reducing toxicity and inducing antiparasite immunity.

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus

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Behar, Samuel M.; Carpenter, Stephen M.; Booty, Matthew G.; Barber, Daniel L.; Jayaraman, Pushpa

2014-01-01

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease – the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810

Anti-tumour immune effect of oral administration of Lactobacillus ...

Indian Academy of Sciences (India)

2015-04-27

Apr 27, 2015 ... Colon cancer; CT26 cells; immunity; Lactobacillus. Abbreviations used: APC ... protect against gastrointestinal disorders, and enhance innate or systemic immunity ...... 2008 Purging metastases in lymphoid organs using a ...

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

Surveillance Culture

DEFF Research Database (Denmark)

2017-01-01

What does it mean to live in a world full of surveillance? In this documentary film, we take a look at everyday life in Denmark and how surveillance technologies and practices influence our norms and social behaviour. Researched and directed by Btihaj Ajana and Anders Albrechtslund....

Emerging infectious diseases in free-ranging wildlife-Australian zoo based wildlife hospitals contribute to national surveillance.

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Keren Cox-Witton

Full Text Available Emerging infectious diseases are increasingly originating from wildlife. Many of these diseases have significant impacts on human health, domestic animal health, and biodiversity. Surveillance is the key to early detection of emerging diseases. A zoo based wildlife disease surveillance program developed in Australia incorporates disease information from free-ranging wildlife into the existing national wildlife health information system. This program uses a collaborative approach and provides a strong model for a disease surveillance program for free-ranging wildlife that enhances the national capacity for early detection of emerging diseases.

Hepatitis A and B immunization for individuals with inherited bleeding disorders.

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Steele, M; Cochrane, A; Wakefield, C; Stain, A-M; Ling, S; Blanchette, V; Gold, R; Ford-Jones, L

2009-03-01

Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders. We reviewed published immunization guidelines from North American immunization advisory bodies and published statements from North American and international haemophilia advisory bodies. A search of the MEDLINE database was performed to find original published literature pertaining to hepatitis A or B immunization of patients with haemophilia or bleeding disorder patients that provided supporting or refuting evidence for advisory body guidelines. Various advisory bodies' immunization guidelines regarding individuals with bleeding disorders have contradictory statements and often did not clarify issues (e.g. post vaccination surveillance). Published literature addressing immunization in bleeding disorder patients is sparse and mostly examines route of vaccine administration, complications and corresponding antibody response. Although the risk of hepatitis A and B infection is low, the use of simple measures such as vaccination is reasonable and advocated by haemophilia advisory bodies. Following our review of the available literature and North American guidelines, we have developed comprehensive and practical recommendations addressing hepatitis A and B immunization for the bleeding disorder population that may be applicable in Bleeding Disorder clinics.

Placental immune editing switch (PIES): learning about immunomodulatory pathways from a unique case report

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Bronchud, Miguel H.; Tresserra, Francesc; Xu, Wenjie; Warren, Sarah; Cusido, Maite; Zantop, Bernat; Zenclussen, Ana Claudia; Cesano, Alessandra

2016-01-01

The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural “placental immune-editing switch” mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue. Our analysis was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman. Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (in the placenta) and pathologically (in the cancer setting). PMID:27852037

Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

Science.gov (United States)

Castano, Ana P.; Hamblin, Michael R.

2006-02-01

, chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.

Enhancement of humoral immunity in mice by coupling pUCpGs10 and aluminium to the HCV recombinant immunogen

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Zhan Na

2011-11-01

Full Text Available Abstract Aim To investigate the enhancement of humoral immunity when CpG ODN (cytidine phosphate guanosine oligodeoxynucleotides and aluminium adjuvants are complexed with the HCV (Hepatitis C virus recombinant immunogen in mice. Methods After immunizing Balb/c mice with the recombination HCV antigen adjuvanted with pUCpGs10 and/or aluminium(antigen+CpG+alum, antigen+CpG, antigen+alum, antigen+PBS, enzyme-linked immunosorbent assay (ELISA was used to measure the specific serum antibody titers of IgG, to determine the neutralization response to various peptide genotypes, and to determine the concentration of IL-6 and IL-10 in supernatants of in vitro cultured splenic lymphocytes. Enzyme-linked immunospot assay (ELISPOT was used to quantify the non-specific and specific splenic antibody-secreting cells (ASCs, and flow cytometry (FCM determined the ratio of different splenic lymphocytes. The serum of rabbits immunized with the recombinant pBVGST/HVR1 antigen immunoprecipitated the HCV isolated from 12 patients' serum. Results The sera antibody titers were 1:51200, 1:9051, 1:18102, 1:6400 respectively after the final immunization and demonstrated good neutralization responses to the six gene peptide containing 1a, 1b, 2a, 3a, 4a and 6a. The aluminum adjuvant increased the population of both specific ASCs (P +CD27+ (P +CD38+ splenic lymphocytes with the aluminum and pUCpGs10 adjuvant present compared to the control group(P Conclusions 1. The aluminum adjuvant induces a potent Th2-biased immune response by increasing both the populations of specific and total ASCs and the ratio of CD19+CD27+ cells. 2. The pUCpGs10 complexed with the aluminum adjuvant boosts the population of plasma cells and increase the efficiency of the immune response. 3. The two adjuvants have synergistic effects on humoral immunity. 4. The recombinant HVR1 protein has the possibility of generating broadly reactive anti-HVR1 antibody.

Enhanced Arabidopsis pattern-triggered immunity by overexpression of cysteine-rich receptor-like kinases.

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Yeh, Yu-Hung; Chang, Yu-Hsien; Huang, Pin-Yao; Huang, Jing-Bo; Zimmerli, Laurent

2015-01-01

Upon recognition of microbe-associated molecular patterns (MAMPs) such as the bacterial flagellin (or the derived peptide flg22) by pattern-recognition receptors (PRRs) such as the FLAGELLIN SENSING2 (FLS2), plants activate the pattern-triggered immunity (PTI) response. The L-type lectin receptor kinase-VI.2 (LecRK-VI.2) is a positive regulator of Arabidopsis thaliana PTI. Cysteine-rich receptor-like kinases (CRKs) possess two copies of the C-X8-C-X2-C (DUF26) motif in their extracellular domains and are thought to be involved in plant stress resistance, but data about CRK functions are scarce. Here, we show that Arabidopsis overexpressing the LecRK-VI.2-responsive CRK4, CRK6, and CRK36 demonstrated an enhanced PTI response and were resistant to virulent bacteria Pseudomonas syringae pv. tomato DC3000. Notably, the flg22-triggered oxidative burst was primed in CRK4, CRK6, and CRK36 transgenics and up-regulation of the PTI-responsive gene FLG22-INDUCED RECEPTOR-LIKE 1 (FRK1) was potentiated upon flg22 treatment in CRK4 and CRK6 overexpression lines or constitutively increased by CRK36 overexpression. PTI-mediated callose deposition was not affected by overexpression of CRK4 and CRK6, while CRK36 overexpression lines demonstrated constitutive accumulation of callose. In addition, Pst DC3000-mediated stomatal reopening was blocked in CRK4 and CRK36 overexpression lines, while overexpression of CRK6 induced constitutive stomatal closure suggesting a strengthening of stomatal immunity. Finally, bimolecular fluorescence complementation and co-immunoprecipitation analyses in Arabidopsis protoplasts suggested that the plasma membrane localized CRK4, CRK6, and CRK36 associate with the PRR FLS2. Association with FLS2 and the observation that overexpression of CRK4, CRK6, and CRK36 boosts specific PTI outputs and resistance to bacteria suggest a role for these CRKs in Arabidopsis innate immunity.

Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine.

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Bukovsky, Antonin; Caudle, Michael R; Carson, Ray J; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M

2009-02-13

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.

Pleurocidin Peptide Enhances Grouper Anti-Vibrio harveyi Immunity Elicited by Poly(lactide-co-glycolide-Encapsulated Recombinant Glyceraldehyde-3-phosphate Dehydrogenase

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Shu-Chun Chuang

2014-05-01

Full Text Available Outer membrane proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH, are considered immunodominant antigens for eliciting protective immunity against Vibrio harveyi, the main etiological agent of vibriosis in fish. Cationic antimicrobial peptides (AMPs, such as pleurocidin (PLE, play important roles in activating and recruiting immune cells, thereby contributing to subsequent innate and adaptive immune responses. In the present study, we aimed to use PLE peptide as a potent adjuvant to improve the immunogenicity of V. harveyi recombinant GAPDH (rGAPDH. In order to prepare a controlled-release vaccine, PLE peptide and rGAPDH protein were simultaneously encapsulated into polymeric microparticles made from the biodegradable poly(lactide-co-glycolide (PLG polymer. The resulting PLG-encapsulated PLE plus rGAPDH (PLG-PLE/rGAPDH microparticles, 3.21–6.27 μm in diameter, showed 72%–83% entrapment efficiency and durably released both PLE and rGAPDH for a long 30-day period. Following peritoneal immunization in grouper (Epinephelus coioides, PLG-PLE/rGAPDH microparticles resulted in significantly higher (p < 0.05, nested design long-lasting GAPDH-specific immunity (serum titers and lymphocyte proliferation than PLG-encapsulated rGAPDH (PLG-rGAPDH microparticles. After an experimental challenge of V. harveyi, PLG-PLE/rGAPDH microparticles conferred a high survival rate (85%, which was significantly higher (p < 0.05, chi-square test than that induced by PLG-rGAPDH microparticles (67%. In conclusion, PLE peptide exhibits an efficacious adjuvant effect to elicit not only improved immunity, but also enhanced protection against V. harveyi in grouper induced by rGAPDH protein encapsulated in PLG microparticles.

Autophagic Mechanism in Anti-Cancer Immunity: Its Pros and Cons for Cancer Therapy.

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Li, Ying-Ying; Feun, Lynn G; Thongkum, Angkana; Tu, Chiao-Hui; Chen, Shu-Mei; Wangpaichitr, Medhi; Wu, Chunjing; Kuo, Macus T; Savaraj, Niramol

2017-06-19

Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial. Accumulated studies have demonstrated that triggering autophagy is able to facilitate anticancer immunity due to an increase in immunogenicity, whereas other studies suggested that autophagy is likely to disarm anticancer immunity mediated by cytotoxic T cells and nature killer (NK) cells. Hence, this contradiction needs to be elucidated. In this review, we discuss the role of autophagy in cancer cells per se and in cancer microenvironment as well as its dual regulatory roles in immune surveillance through modulating presentation of tumor antigens, development of immune cells, and expression of immune checkpoints. We further focus on emerging roles of autophagy induced by current treatments and its impact on anticancer immune response, and illustrate the pros and cons of utilizing autophagy in cancer immunotherapy based on preclinical references.

Enhanced surveillance for tuberculosis among foreign-born persons, Finland, 2014-2016.

Science.gov (United States)

Räisänen, Pirre E; Soini, Hanna; Turtiainen, Pirjo; Vasankari, Tuula; Ruutu, Petri; Nuorti, J Pekka; Lyytikäinen, Outi

2018-05-09

Tuberculosis (TB) in foreign-born residents is increasing in many European countries including Finland. We conducted enhanced TB surveillance to collect supplementary information on TB cases among recent immigrants and their children to provide data for revising TB control policies in Finland to take into account the decrease in native cases and increase in foreign-born cases. TB cases were identified from the National Infectious Diseases Register. Data on foreign-born (if not available, most recent nationality other than Finnish) TB cases notified during 2014-2016 (country of birth, date of arrival to Finland, participation in TB screening, date of first symptoms, and details of possible contact tracing) were requested from physicians responsible for regional communicable disease control through a web-based questionnaire. Questionnaires were returned for 203 (65%) of 314 foreign-born TB cases; 36 (18%) were paediatric cases TB was detected in arrival screening in 42 (21%) and during contact tracing of another TB case in 18 (9%); 143 (70%) cases sought care for symptoms or were identified by chance (e.g. chest x-ray because of an accident). Of cases with data available, 48 (24%) cases were diagnosed within 3 months of arrival to Finland, 55 (27%) cases between 3 months and 2 years from arrival, and 84 (42%) cases after 2 years from arrival. Of all the foreign-born cases, 17% had been in a reception centre in Finland and 15% had been in a refugee camp abroad. In addition to asylum seekers and refugees, TB screening should be considered for immigrants arriving from high TB incidence countries, since the majority of TB cases were detected among persons who immigrated to Finland due to other reasons, presumably work or study. Further evaluation of the target group and timing of TB screening is warranted to update national screening guidance.

Neurovirulent vaccine-derived polioviruses in sewage from highly immune populations.

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Lester M Shulman

Full Text Available BACKGROUND: Vaccine-derived polioviruses (VDPVs have caused poliomyelitis outbreaks in communities with sub-optimal vaccination. Israeli environmental surveillance of sewage from populations with high (>95% documented vaccine coverage of confirmed efficacy identified two separate evolutionary clusters of VDPVs: Group 1 (1998-2005, one system, population 1.6x10(6 and Group 2 (2006, 2 systems, populations 0.7x10(6 and 5x10(4. PRINCIPAL FINDINGS: Molecular analyses support evolution of nine Group 1 VDPVs along five different lineages, starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1 recombinant strain, and independent evolution of three Group 2 VDPVs along one lineage starting from a different recombinant strain. The primary evidence for two independent origins was based on comparison of unique recombination fingerprints, the number and distribution of identical substitutions, and evolutionary rates. Geometric mean titers of neutralizing antibodies against Group 1 VDPVs were significantly lower than against vaccine strains in all age-group cohorts tested. All individuals had neutralizing titers >1:8 against these VDPVs except 7% of the 20-50 year cohort. Group 1 VDPVs were highly neurovirulent in a transgenic mouse model. Intermediate levels of protective immunity against Group 2 VDPVs correlated with fewer (5.0+1.0 amino acid substitutions in neutralizing antigenic sites than in Group 1 VDPV's (12.1+/-1.5. SIGNIFICANCE: VDPVs that revert from live oral attenuated vaccines and reacquire characteristics of wild-type polioviruses not only threaten populations with poor immune coverage, but are also a potential source for re-introduction of poliomyelitis into highly immune populations through older individuals with waning immunity. The presence of two independently evolved groups of VDPVs in Israel and the growing number of reports of environmental VDPV elsewhere make it imperative to determine the global frequency of

Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site.

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Barna Dey

2009-05-01

Full Text Available The human immunodeficiency virus type 1 (HIV-1 exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region.

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies.

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von Kalckreuth, Vera; Konings, Frank; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Breiman, Robert F; Bjerregaard-Andersen, Morten; Clemens, John D; Crump, John A; Cruz Espinoza, Ligia Maria; Deerin, Jessica Fung; Gasmelseed, Nagla; Sow, Amy Gassama; Im, Justin; Keddy, Karen H; Cosmas, Leonard; May, Jürgen; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Rakotozandrindrainy, Raphaël; Schütt-Gerowitt, Heidi; Soura, Abdramane Bassiahi; Warren, Michelle R; Wierzba, Thomas F; Marks, Florian

2016-03-15

New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Advanced digital video surveillance for safeguard and physical protection

International Nuclear Information System (INIS)

Kumar, R.

2002-01-01

Full text: Video surveillance is a very crucial component in safeguard and physical protection. Digital technology has revolutionized the surveillance scenario and brought in various new capabilities like better image quality, faster search and retrieval of video images, less storage space for recording, efficient transmission and storage of video, better protection of recorded video images, and easy remote accesses to live and recorded video etc. The basic safeguard requirement for verifiably uninterrupted surveillance has remained largely unchanged since its inception. However, changes to the inspection paradigm to admit automated review and remote monitoring have dramatically increased the demands on safeguard surveillance system. Today's safeguard systems can incorporate intelligent motion detection with very low rate of false alarm and less archiving volume, embedded image processing capability for object behavior and event based indexing, object recognition, efficient querying and report generation etc. It also demands cryptographically authenticating, encrypted, and highly compressed video data for efficient, secure, tamper indicating and transmission. In physical protection, intelligent on robust video motion detection, real time moving object detection and tracking from stationary and moving camera platform, multi-camera cooperative tracking, activity detection and recognition, human motion analysis etc. is going to play a key rote in perimeter security. Incorporation of front and video imagery exploitation tools like automatic number plate recognition, vehicle identification and classification, vehicle undercarriage inspection, face recognition, iris recognition and other biometric tools, gesture recognition etc. makes personnel and vehicle access control robust and foolproof. Innovative digital image enhancement techniques coupled with novel sensor design makes low cost, omni-directional vision capable, all weather, day night surveillance a reality

An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency.

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Dorostkar, Rohollah; Bamdad, Taravat; Parsania, Masoud; Pouriayevali, Hassan

2012-12-01

Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells. To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model. The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated. The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (pEL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001). The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.

Comprehensive effective and efficient global public health surveillance

Directory of Open Access Journals (Sweden)

McNabb Scott JN

2010-12-01

Full Text Available Abstract At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources. Three movements now set the stage for transformation of surveillance: 1 adoption by Member States of the World Health Organization (WHO of the revised International Health Regulations (IHR[2005]; 2 maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3 consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers. To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners. We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it’s needed, where it’s needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities

Comprehensive effective and efficient global public health surveillance.

Science.gov (United States)

McNabb, Scott J N

2010-12-03

At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources.Three movements now set the stage for transformation of surveillance: 1) adoption by Member States of the World Health Organization (WHO) of the revised International Health Regulations (IHR[2005]); 2) maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3) consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers.To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners.We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it's needed, where it's needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities to the ownership and stewardship

Tumor evasion from immune control: Strategies of a MISS to become a MASS

International Nuclear Information System (INIS)

D'Onofrio, Alberto

2007-01-01

We biologically describe the phenomenon of the evasion of tumors from immune surveillance where tumor cells, initially constrained to exist in a microscopic steady state (MISS) elaborate strategies to evade from the immune control and to reach a macroscopic steady state (MASS). We, then, describe 'evasion' as a long term loss of equilibrium in a framework of prey-predator-like models with adiabatic varying parameters, whose changes reflect the evolutionary adaptation of the tumor in a 'hostile' environment by means of the elaboration of new strategies of survival. Similarities and differences between the present work and the interesting seminal paper [Kuznetsov VA, Knott GD. Modeling tumor regrowth and immunotherapy. Math Comput Model 2001;33:1275-87] are discussed. We also propose and study a model of clonal resistance to the immune control with slowly varying adaptive mutation parameter

Tumor evasion from immune control: Strategies of a MISS to become a MASS

Energy Technology Data Exchange (ETDEWEB)

D' Onofrio, Alberto [Department of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, I-20141 Milan (Italy)]. E-mail: alberto.d' onofrio@ieo.it

2007-01-15

We biologically describe the phenomenon of the evasion of tumors from immune surveillance where tumor cells, initially constrained to exist in a microscopic steady state (MISS) elaborate strategies to evade from the immune control and to reach a macroscopic steady state (MASS). We, then, describe 'evasion' as a long term loss of equilibrium in a framework of prey-predator-like models with adiabatic varying parameters, whose changes reflect the evolutionary adaptation of the tumor in a 'hostile' environment by means of the elaboration of new strategies of survival. Similarities and differences between the present work and the interesting seminal paper [Kuznetsov VA, Knott GD. Modeling tumor regrowth and immunotherapy. Math Comput Model 2001;33:1275-87] are discussed. We also propose and study a model of clonal resistance to the immune control with slowly varying adaptive mutation parameter.

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

Directory of Open Access Journals (Sweden)

Cristina Godinho-Silva

2014-06-01

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

Case based rubella surveillance in Abia State, South East Nigeria, 2007-2011.

Science.gov (United States)

Umeh, Chukwuemeka Anthony; Onyi, Stella Chioma

2014-01-01

Introduction. Rubella infection has the potential of causing severe fetal birth defects collectively called congenital rubella syndrome (CRS) if the mother is infected early in pregnancy. However, little is known about rubella and CRS epidemiology in Nigeria and rubella vaccines are still not part of routine childhood immunization in Nigeria. Methods. Analysis of confirmed cases of rubella in Abia State, Nigeria from 2007 to 2011 detected through Abia State Integrated Disease Surveillance and Response system. Results. Of the 757 febrile rash cases, 81(10.7%) tested positive for rubella immunoglobulin M (IgM). New rubella infection decreased from 6.81/1,000,000 population in 2007 to 2.28/1,000,000 in 2009 and increased to 6.34/1,000,000 in 2011. The relative risk of rubella was 1.5 (CI [0.98-2.28]) times as high in females compared to males and 1.6 times (CI [0.90-2.91]) as high in rural areas compared to urban areas. Eighty six percent of rubella infections occurred in children less than 15 years with a high proportion of cases occurring between 5 and 14 years. Conclusion. Rubella infection in Abia State, Nigeria is predominantly in those who are younger than 15 years old. It is also more prevalent in females and in those living in rural areas of the state. Unfortunately, there is no surveillance of CRS in Nigeria and so the public health impact of rubella infection in the state is not known. Efforts should be made to expand the rubella surveillance in Nigeria to incorporate surveillance for CRS.

SurF: an innovative framework in biosecurity and animal health surveillance evaluation.

Science.gov (United States)

Muellner, Petra; Watts, Jonathan; Bingham, Paul; Bullians, Mark; Gould, Brendan; Pande, Anjali; Riding, Tim; Stevens, Paul; Vink, Daan; Stärk, Katharina Dc

2018-05-16

Surveillance for biosecurity hazards is being conducted by the New Zealand Competent Authority, the Ministry for Primary Industries (MPI) to support New Zealand's biosecurity system. Surveillance evaluation should be an integral part of the surveillance life cycle, as it provides a means to identify and correct problems and to sustain and enhance the existing strengths of a surveillance system. The surveillance evaluation Framework (SurF) presented here was developed to provide a generic framework within which the MPI biosecurity surveillance portfolio, and all of its components, can be consistently assessed. SurF is an innovative, cross-sectoral effort that aims to provide a common umbrella for surveillance evaluation in the animal, plant, environment and aquatic sectors. It supports the conduct of the following four distinct components of an evaluation project: (i) motivation for the evaluation, (ii) scope of the evaluation, (iii) evaluation design and implementation and (iv) reporting and communication of evaluation outputs. Case studies, prepared by MPI subject matter experts, are included in the framework to guide users in their assessment. Three case studies were used in the development of SurF in order to assure practical utility and to confirm usability of SurF across all included sectors. It is anticipated that the structured approach and information provided by SurF will not only be of benefit to MPI but also to other New Zealand stakeholders. Although SurF was developed for internal use by MPI, it could be applied to any surveillance system in New Zealand or elsewhere. © 2018 2018 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

Using Skype to support palliative care surveillance.

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Jones, Jacqueline

2014-02-01

The aim of this article is to demonstrate how a novel yet important tool can facilitate family involvement in person-centred care, despite geographical distance. The author presents a case study as an in-depth example of the use of Skype in the context of palliative care at home. Skype enhanced family surveillance and symptom management, augmented shared decision making, provided a space for virtual bedside vigil, and ultimately provided the rapport necessary for optimal end of life care.

The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket.

Science.gov (United States)

McNamara, K B; van Lieshout, E; Simmons, L W

2014-06-01

Trans-generational immune priming is the transmission of enhanced immunity to offspring following a parental immune challenge. Although within-generation increased investment into immunity demonstrates clear costs on reproductive investment in a number of taxa, the potential for immune priming to impact on offspring reproductive investment has not been thoroughly investigated. We explored the reproductive costs of immune priming in a field cricket, Teleogryllus oceanicus. To assess the relative importance of maternal and paternal immune status, mothers and fathers were immune-challenged with live bacteria or a control solution and assigned to one of four treatments in which one parent, neither or both parents were immune-challenged. Families of offspring were reared to adulthood under a food-restricted diet, and approximately 10 offspring in each family were assayed for two measures of immunocompetence. We additionally quantified offspring reproductive investment using sperm viability for males and ovary mass for females. We demonstrate that parental immune challenge has significant consequences for the immunocompetence and, in turn, reproductive investment of their male offspring. A complex interaction between maternal and paternal immune status increased the antibacterial immune response of male offspring. This increased immune response was associated with a reduction in son's sperm viability, implicating a trans-generational resource trade-off between investment into immunocompetence and reproduction. Our data also show that these costs are sexually dimorphic, as daughters did not demonstrate a similar increase in immunity, despite showing a reduction in ovary mass. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.

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Gupta, Shishir Kumar; Yadav, Pavan Kumar; Tiwari, A K; Gandham, Ravi Kumar; Sahoo, A P

2016-09-01

The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.

U.S. Department of Energy Office of Occupational Medicine and Medical Surveillance 1995--1997 triannual report

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-08-01

From 1995 through 1997 the Office of Occupational Medicine and Medical Surveillance (EH-61) has made numerous achievements that have enhanced the performance of the office and more importantly, the Department of Energy (DOE). This report provides specific information about program activities and accomplishments, as well as individual contacts for each program. The mission of EH-61 is the prevention of worker illness by fostering outstanding occupational medicine and medical surveillance programs within the DOE complex. This mission is being realized as a result of efforts in four main business lines: (1) Surveillance; (2) Research, (3) Policy/Technical Support; and (4) Information/Communication.

Oral administration of Eclipta alba leaf aqueous extract enhances the non-specific immune responses and disease resistance of Oreochromis mossambicus.

Science.gov (United States)

Christybapita, D; Divyagnaneswari, M; Michael, R Dinakaran

2007-10-01

Immunostimulatory effects of the oral administration of the medicinal plant, Eclipta alba leaf extracts was studied in tilapia, Oreochromis mossambicus. For this purpose, fish were fed for 1, 2 or 3 weeks with diets containing E. alba leaf aqueous extract at 0, 0.01, 0.1 or 1% levels. After each week, non-specific humoral (lysozyme, antiprotease and complement) and cellular (myeloperoxidase content, production of reactive oxygen and nitrogen species) responses and disease resistance against Aeromonas hydrophila were determined. The results indicated that E. alba aqueous extract administered as feed supplement significantly enhanced most of the non-specific immune parameters tested. Among the humoral responses, lysozyme activity significantly increased after feeding with aqueous extract for 1, 2 or 3 weeks. No significant modulation was noticed in all the cellular responses tested after 3 weeks of feeding, while reactive oxygen species production and myeloperoxidase content showed significant enhancement after 1 week of feeding with aqueous extract. When challenged with A. hydrophila after 1, 2 or 3 weeks of feeding, the percentage mortality was significantly reduced in the treated fish. The highest dose of 1% gave better protection than the other doses with the relative percentage survival (RPS) values of 64, 75 and 32 after feeding for 1, 2 and 3 weeks respectively. The results indicate that dietary intake of E. alba aqueous leaf extract enhances the non-specific immune responses and disease resistance of O. mossambicus against A. hydrophila.

Limits on surveillance: frictions, fragilities and failures in the operation of camera surveillance.

NARCIS (Netherlands)

Dubbeld, L.

2004-01-01

Public video surveillance tends to be discussed in either utopian or dystopian terms: proponents maintain that camera surveillance is the perfect tool in the fight against crime, while critics argue that the use of security cameras is central to the development of a panoptic, Orwellian surveillance

Handbook of surveillance technologies

CERN Document Server

Petersen, JK

2012-01-01

From officially sanctioned, high-tech operations to budget spy cameras and cell phone video, this updated and expanded edition of a bestselling handbook reflects the rapid and significant growth of the surveillance industry. The Handbook of Surveillance Technologies, Third Edition is the only comprehensive work to chronicle the background and current applications of the full-range of surveillance technologies--offering the latest in surveillance and privacy issues.Cutting-Edge--updates its bestselling predecessor with discussions on social media, GPS circuits in cell phones and PDAs, new GIS s

Exercise and the Regulation of Immune Functions.

Science.gov (United States)

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

2015-01-01

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

Interplay between behavioural thermoregulation and immune response in mealworms.

Science.gov (United States)

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.

Containment and surveillance devices

International Nuclear Information System (INIS)

Campbell, J.W.; Johnson, C.S.; Stieff, L.R.

The growing acceptance of containment and surveillance as a means to increase safeguards effectiveness has provided impetus to the development of improved surveillance and containment devices. Five recently developed devices are described. The devices include one photographic and two television surveillance systems and two high security seals that can be verified while installed

Value of syndromic surveillance within the Armed Forces for early warning during a dengue fever outbreak in French Guiana in 2006

Directory of Open Access Journals (Sweden)

Jefferson Henry

2008-07-01

Full Text Available Abstract Background A dengue fever outbreak occured in French Guiana in 2006. The objectives were to study the value of a syndromic surveillance system set up within the armed forces, compared to the traditional clinical surveillance system during this outbreak, to highlight issues involved in comparing military and civilian surveillance systems and to discuss the interest of syndromic surveillance for public health response. Methods Military syndromic surveillance allows the surveillance of suspected dengue fever cases among the 3,000 armed forces personnel. Within the same population, clinical surveillance uses several definition criteria for dengue fever cases, depending on the epidemiological situation. Civilian laboratory surveillance allows the surveillance of biologically confirmed cases, within the 200,000 inhabitants. Results It was shown that syndromic surveillance detected the dengue fever outbreak several weeks before clinical surveillance, allowing quick and effective enhancement of vector control within the armed forces. Syndromic surveillance was also found to have detected the outbreak before civilian laboratory surveillance. Conclusion Military syndromic surveillance allowed an early warning for this outbreak to be issued, enabling a quicker public health response by the armed forces. Civilian surveillance system has since introduced syndromic surveillance as part of its surveillance strategy. This should enable quicker public health responses in the future.

Sentinel site-enhanced near-real time surveillance documenting West Nile virus circulation in two Culex mosquito species indicating different transmission characteristics, Djibouti City, Djibouti.

Science.gov (United States)

Faulde, Michael K; Spiesberger, Michael; Abbas, Babiker

2012-08-01

The Horn of Africa represents a region formerly known to be highly susceptible to mosquito-borne infectious diseases. In order to investigate whether autochthonous WNV transmission occurs in the Djibouti City area, in how far, and which of, the endemic Culex mosquito species are involved in WNV circulation activity,and whether sentinel site-enhanced near-real time surveillance (SSE-NRTS) may increase WNV detection sensitivity, mosquito vector monitoring was conducted from January 2010 to June 2012. Six monitoring locations, including two identified sentinel sites, considered most probable for potential anthroponotic and zoonotic virus circulation activity, have been continuously employed. Among the 20431 mosquitoes collected, 19069 (93.4%) were Cx. quinquefasciatus, and 1345 (6.6%) Cx. pipiens ssp. torridus. WNV lineage 2 circulation activity was detected between December 20th, 2010 and January 7th, 2011. Overall, 19 WNV RNA-positive mosquito pools were detected. Generally, urban environment-specific WNV-RNA circulation took place in Cx. pipiens ssp. torridus, whereas periurban and rural area-linked circulation was detected only in Cx. quinquefasciatus. Serological investigation data from 10 volunteers employed at the dislocated zoonotic WNV transmission sentinel site suggest that six persons (60%) had an acute, or recent, WNV infection. Results show that WNV should be considered endemic for Djibouti and sentinel site-enhanced near-real time surveillance is an elegant and highly effective epidemiological tool. In Djibouti, the endemicity level, public health impact and transmission modes of vector-borne diseases in concordance with locally optimized monitoring and control regimen deserve further investigation.

An integrated national mortality surveillance system for death registration and mortality surveillance, China.

Science.gov (United States)

Liu, Shiwei; Wu, Xiaoling; Lopez, Alan D; Wang, Lijun; Cai, Yue; Page, Andrew; Yin, Peng; Liu, Yunning; Li, Yichong; Liu, Jiangmei; You, Jinling; Zhou, Maigeng

2016-01-01

In China, sample-based mortality surveillance systems, such as the Chinese Center for Disease Control and Prevention's disease surveillance points system and the Ministry of Health's vital registration system, have been used for decades to provide nationally representative data on health status for health-care decision-making and performance evaluation. However, neither system provided representative mortality and cause-of-death data at the provincial level to inform regional health service needs and policy priorities. Moreover, the systems overlapped to a considerable extent, thereby entailing a duplication of effort. In 2013, the Chinese Government combined these two systems into an integrated national mortality surveillance system to provide a provincially representative picture of total and cause-specific mortality and to accelerate the development of a comprehensive vital registration and mortality surveillance system for the whole country. This new system increased the surveillance population from 6 to 24% of the Chinese population. The number of surveillance points, each of which covered a district or county, increased from 161 to 605. To ensure representativeness at the provincial level, the 605 surveillance points were selected to cover China's 31 provinces using an iterative method involving multistage stratification that took into account the sociodemographic characteristics of the population. This paper describes the development and operation of the new national mortality surveillance system, which is expected to yield representative provincial estimates of mortality in China for the first time.

Digital dashboard design using multiple data streams for disease surveillance with influenza surveillance as an example.

Science.gov (United States)

Cheng, Calvin K Y; Ip, Dennis K M; Cowling, Benjamin J; Ho, Lai Ming; Leung, Gabriel M; Lau, Eric H Y

2011-10-14

Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions.

Immune dysfunction in cirrhosis

Science.gov (United States)

Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

2014-01-01

Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

MIS416 Enhances Therapeutic Functions of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Against Experimental Colitis by Modulating Systemic Immune Milieu

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Byung-Chul Lee

2018-05-01

Full Text Available Human adult stem cells, including umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs, have recently been considered a promising alternative treatment for inflammatory bowel disease (IBD due to their unique immunomodulatory properties and ability to promote tissue regeneration. However, despite many years of research and pre-clinical studies, results from clinical trials using these cells have been diverse and conflicting. This discrepancy is caused by several factors, such as poor engraftment, low survival rate, and donor-dependent variation of the cells. Enhancement of consistency and efficacy of MSCs remains a challenge for the feasibility of cell-based therapy. In this study, we investigated whether administration of MIS416, a novel microparticle that activates NOD2 and TLR9 signaling, could enhance the therapeutic efficacy of hUCB-MSCs against Crohn’s disease, using dextran sulfate sodium (DSS-induced colitis model. Colitis was experimentally induced in mice by using 3% DSS, and mice were administered a retro-orbital injection of MIS416 and subsequent intraperitoneal injection of hUCB-MSCs. Mice were examined grossly, and blood, spleen, and colon tissues were subsequently collected for further ex vivo analyses. To explore the effects of MIS416 on the therapeutic process, hUCB-MSCs and primary isolated immune cells were cultured with MIS416, and in vitro assays were performed. Compared to the single administration of hUCB-MSCs, co-administration with MIS416 improved the therapeutic efficiency of the stem cells by significantly alleviating the symptoms of IBD. Interestingly, MIS416 did not exert any direct effect on the immunomodulatory capacity of hUCB-MSCs. Instead, systemically injected MIS416 altered the immune milieu in the colon which caused hUCB-MSCs to be more readily recruited toward the lesion site and to suppress inflammation more efficiently. In addition, considerable numbers of regulatory immune cells were stimulated

A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and Enhanced Protective Immune Response

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Yao Ma

2018-01-01

Full Text Available Human respiratory syncytial virus (RSV is the most significant cause of acute lower respiratory infection in children. However, there is no licensed vaccine available. Here, we investigated the effect of five or 20 copies of C-Class of CpG ODN (CpG-C motif incorporated into a plasmid DNA vaccine encoding RSV fusion (F glycoprotein on the vaccine-induced immune response. The addition of CpG-C motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified vaccines, especially with the higher 20 copies, resulted in an enhanced shift toward a Th1-biased antibody and T-cell response, a decrease in pulmonary pathology and virus replication, and a decrease in weight loss after RSV challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of improving the efficacy of DNA vaccine against RSV infection.

Influenza surveillance

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Karolina Bednarska

2016-04-01

Full Text Available Influenza surveillance was established in 1947. From this moment WHO (World Health Organization has been coordinating international cooperation, with a goal of monitoring influenza virus activity, effective diagnostic of the circulating viruses and informing society about epidemics or pandemics, as well as about emergence of new subtypes of influenza virus type A. Influenza surveillance is an important task, because it enables people to prepare themselves for battle with the virus that is constantly mutating, what leads to circulation of new and often more virulent strains of influenza in human population. As vaccination is the most effective method of fighting the virus, one of the major tasks of GISRS is developing an optimal antigenic composition of the vaccine for the current epidemic season. European Influenza Surveillance Network (EISN has also developed over the years. EISN is running integrated epidemiological and virological influenza surveillance, to provide appropriate data to public health experts in member countries, to enable them undertaking relevant activities based on the current information about influenza activity. In close cooperation with GISRS and EISN are National Influenza Centres - national institutions designated by the Ministry of Health in each country.

Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial Burden in Mice

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Arshad Khan

2017-12-01

Full Text Available Infection by Mycobacterium tuberculosis (Mtb remains a major global concern and the available Bacillus Calmette-Guerin (BCG vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer, a potent natural killer T (NKT cell agonist. Vaccinated animals exhibited strong antigen-specific CD4 and CD8 T cells responses in the spleen, cervical lymph nodes and lungs. In general, inclusion of the α-GalCer adjuvant significantly enhanced these responses that persisted over 50 days. Furthermore, aerosolized Mtb infection of vaccinated mice resulted in a significant reduction of bacterial load of the lungs and spleens as compared to levels seen in naïve controls or those vaccinated with subunit proteins, adjuvant , or BCG alone. The protection induced by the Mtb antigens and-GalCer vaccine through sublingual route correlated with a TH1-type immunity mediated by antigen-specific IFN-γ and IL-2 producing T cells.

Live Yeast and Yeast Cell Wall Supplements Enhance Immune Function and Performance in Food-Producing Livestock: A Review †,‡

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Paul R. Broadway

2015-08-01

Full Text Available More livestock producers are seeking natural alternatives to antibiotics and antimicrobials, and searching for supplements to enhance growth performance, and general animal health and well-being. Some of the compounds currently being utilized and studied are live yeast and yeast-based products derived from the strain Saccharomyces cerevisiae. These products have been reported to have positive effects both directly and indirectly on the immune system and its subsequent biomarkers, thereby mitigating negative effects associated with stress and disease. These yeast-based products have also been reported to simultaneously enhance growth and performance by enhancing dry matter intake (DMI and average daily gain (ADG perhaps through the establishment of a healthy gastrointestinal tract. These products may be especially useful in times of potential stress such as during birth, weaning, early lactation, and during the receiving period at the feedlot. Overall, yeast supplements appear to possess the ability to improve animal health and metabolism while decreasing morbidity, thereby enhancing profitability of these animals.

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

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

2018-04-18

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

Enhancements of non-specific immune response in Mugil cephlus by seaweed extract against Vibrio alginolyticus (BRTR07

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Rajasekar Thirunavukkarasu

2015-10-01

Full Text Available Objective: To focus on the growth rate and feed utilization of fish by using trash fish feeds supplement with marine seaweeds. Methods: Selected seaweed was extracted using hot-water and its extract was mixed with trash fish feed at different concentrations (0.5%, 1% and 2% for 1-30 days and the nonspecific immune response in fish was studied and challenged with Vibrio alginolyticus at 1 × 106 CFU/fish. The hot-water extract of seaweeds was analysed by gas chromatography-mass spectrometry. Results: The average body weight (5.320 ± 0.018, percent weight gain (227.66 ± 0.28, specific growth rate (2.080 ± 0.015, hepatosomatic index (1.197 ± 0.00 and viscerosomatic index (4.421 ± 0.150 were significantly increased in the fish feed with seaweed containing 5% of Sargassum wightii (S. wightii when compared with other seaweeds and control diet. Hotwater extract of S. wightii (1% was significantly enhanced the immune response in fish when compared with other diets (0.5% and 2%. S. wightii showed good immunostimulation properties. Gas chromatography-mass spectrometry result showed that the hot-water extract of S. wightii seaweed contained fatty acids. Conclusions: Trash fish feed will reduce the production cost and also provide evidence that aqueous leaf extract of S. wightii (1% was added to a formulated fish diet which could activate the non-specific immune response and disease resistance against Vibrio alginolyticus in Mugil cephalus.

Monitoring data quality in syndromic surveillance: Learnings from a resource limited setting

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E Venkatarao

2012-01-01

Full Text Available Background: India is in the process of integrating all disease surveillance systems with the support of a World Bank funded program called the Integrated Disease Surveillance System. In this context the objective of the study was to evaluate the components of the Orissa Multi Disease Surveillance System. Materials and Methods: Multistage sampling was carried out, starting with four districts, followed by sequentially sampling two blocks; and in each block, two sectors and two health sub-centers were selected, all based on the best and worst performances. Two study instruments were developed for data validation, for assessing the components of the surveillance and diagnostic algorithm. The Organizational Ethics Group reviewed and approved the study. Results: In all 178 study subjects participated in the survey. The case definition of suspected meningitis in disease surveillance was found to be difficult, with only 29.94%, who could be correctly identified. Syndromic diagnosis following the diagnostic algorithm was difficult for suspected malaria (28.1%, ′unusual syndrome′ (28.1%, and simple diarrhea (62%. Only 17% could correctly answer questions on follow-up cases, but only 50% prioritized diseases. Our study showed that 54% cross-checked the data before compilation. Many (22% faltered on timeliness even during emergencies. The constraints identified were logistics (56% and telecommunication (41%. The reason for participation in surveillance was job responsibility (34.83%. Conclusions: Most of the deficiencies arose from human errors when carrying out day-to-day processes of surveillance activities, hence, should be improved by retraining. Enhanced laboratory support and electronic transmission would improve data quality and timeliness. Validity of some of the case definitions need to be rechecked. Training Programs should focus on motivating the surveillance personnel.

Enhanced cellular immune response against SIV Gag induced by immunization with DNA vaccines expressing assembly and release-defective SIV Gag proteins

International Nuclear Information System (INIS)

Bu Zhigao; Ye Ling; Compans, Richard W.; Yang Chinglai

2003-01-01

Codon-optimized genes were synthesized for the SIVmac239 Gag, a mutant Gag with mutations in the major homology region, and a chimeric Gag containing a protein destruction signal at the N-terminus of Gag. The mutant and chimeric Gag were expressed at levels comparable to that observed for the wild-type Gag protein but their stability and release into the medium were found to be significantly reduced. Immunization of mice with DNA vectors encoding the mutant or chimeric Gag induced fourfold higher levels of anti-SIV Gag CD4 T cell responses than the DNA vector encoding the wild-type SIV Gag. Moreover, anti-SIV Gag CD8 T cell responses induced by DNA vectors encoding the mutant or chimeric Gag were found to be 5- to 10-fold higher than those induced by the DNA construct for the wild-type Gag. These results indicate that mutations disrupting assembly and/or stability of the SIV Gag protein effectively enhance its immunogenicity when expressed from DNA vaccines

Effect of Immune-Enhancing Enteral Nutrition Enriched with or without Beta-Glucan on Immunomodulation in Critically Ill Patients

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Jae Gil Lee

2016-06-01

Full Text Available We investigated whether high-protein enteral nutrition with immune-modulating nutrients (IMHP enriched with β-glucan stimulates immune function in critically ill patients. In a randomized double-blind placebo-controlled study, 30 patients consumed one of three types of enteral nutrition: a control or IMHP with and without β-glucan. The IMHP with β-glucan group showed increases in natural killer (NK cell activities relative to the baseline, and greater increases were observed in NK cell activities relative to the control group after adjusting for age and gender. The IMHP groups with and without β-glucan had greater increases in serum prealbumin and decreases in high-sensitivity C-reactive protein (hs-CRP than the control group. The control group had a greater decrease in peripheral blood mononuclear cell (PBMC interleukin (IL-12 production than the IMHP with and without β-glucan groups. In all patients, the change (Δ in hs-CRP was correlated with Δ prealbumin and Δ PBMC IL-12, which were correlated with ΔNK cell activity and Δ prealbumin. This study showed beneficial effects of a combination treatment of β-glucan and IMHP on NK cell activity. Additionally, strong correlations among changes in NK cell activity, PBMC IL-12, and hs-CRP suggested that β-glucan could be an attractive candidate for stimulating protective immunity without enhanced inflammation (ClinicalTrials.gov: NCT02569203.

A review of zoonotic disease surveillance supported by the Armed Forces Health Surveillance Center.

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Burke, R L; Kronmann, K C; Daniels, C C; Meyers, M; Byarugaba, D K; Dueger, E; Klein, T A; Evans, B P; Vest, K G

2012-05-01

The Armed Forces Health Surveillance Center (AFHSC), Division of Global Emerging Infections Surveillance and Response System conducts disease surveillance through a global network of US Department of Defense research laboratories and partnerships with foreign ministries of agriculture, health and livestock development in over 90 countries worldwide. In 2010, AFHSC supported zoonosis survey efforts were organized into four main categories: (i) development of field assays for animal disease surveillance during deployments and in resource limited environments, (ii) determining zoonotic disease prevalence in high-contact species which may serve as important reservoirs of diseases and sources of transmission, (iii) surveillance in high-risk human populations which are more likely to become exposed and subsequently infected with zoonotic pathogens and (iv) surveillance at the human-animal interface examining zoonotic disease prevalence and transmission within and between human and animal populations. These efforts have aided in the detection, identification and quantification of the burden of zoonotic diseases such as anthrax, brucellosis, Crimean Congo haemorrhagic fever, dengue fever, Hantaan virus, influenza, Lassa fever, leptospirosis, melioidosis, Q fever, Rift Valley fever, sandfly fever Sicilian virus, sandfly fever Naples virus, tuberculosis and West Nile virus, which are of military and public health importance. Future zoonotic surveillance efforts will seek to develop local capacity for zoonotic surveillance focusing on high risk populations at the human-animal interface. © 2011 Blackwell Verlag GmbH.

Convergence of the innate and adaptive immunity during human aging

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Branca Isabel Pereira

2016-11-01

Full Text Available Aging is associated with profound changes in the human immune system, a phenomenon referred to as immunosenescence. This complex immune remodeling affects the adaptive immune system and the CD8+ T cell compartment in particular, leading to the accumulation of terminally differentiated T cells, which can rapidly exert their effector functions at the expenses of a limited proliferative potential. In this review we will discuss evidence suggesting that senescent αβCD8+ T cells acquire the hallmarks of innate-like T cells and use recently acquired NK cell receptors as an alternative mechanism to mediate rapid effector functions. These cells concomitantly lose expression of co-stimulatory receptors and exhibit decreased TCR signaling suggesting a functional shift away from antigen specific activation. The convergence of innate and adaptive features in senescent T cells challenges the classic division between innate and adaptive immune systems. Innate-like T cells are particularly important for stress and tumor surveillance and we propose a new role for these cells in aging, where the acquisition of innate-like functions may represent a beneficial adaptation to an increased burden of malignancy with age, although it may also pose a higher risk of autoimmune disorders.

Oreochromis mossambicus diet supplementation with Psidium guajava leaf extracts enhance growth, immune, antioxidant response and resistance to Aeromonas hydrophila.

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Gobi, Narayanan; Ramya, Chinnu; Vaseeharan, Baskaralingam; Malaikozhundan, Balasubramanian; Vijayakumar, Sekar; Murugan, Kadarkarai; Benelli, Giovanni

2016-11-01

In this research, we focused on the efficacy of aqueous and ethanol leaf extracts of Psidium guajava L. (guava) based experimental diets on the growth, immune, antioxidant and disease resistance of tilapia, Oreochromis mossambicus following challenge with Aeromonas hydrophila. The experimental diets were prepared by mixing powdered (1, 5 and 10 mg/g) aqueous and ethanol extract of guava leaf with commercial diet. The growth (FW, FCR and SGR), non-specific cellular immune (myeloperoxidase activity, reactive oxygen activity and reactive nitrogen activity) humoral immune (complement activity, antiprotease, alkaline phosphatase activity and lysozyme activity) and antioxidant enzyme responses (SOD, GPX, and CAT) were examined after 30 days of post-feeding. A significant enhancement in the biochemical and immunological parameters of fish were observed fed with experimental diets compared to control. The dietary supplementation of P. guajava leaf extract powder for 30 days significantly reduced the mortality and increased the disease resistance of O. mossambicus following challenge with A. hydrophila at 50 μl (1 × 10 7  cells ml -1 ) compared to control after post-infection. The results suggest that the guava leaf extract could be used as a promising feed additive in aquaculture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Innate and Adaptive Immunity to Mucorales.

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Ghuman, Harlene; Voelz, Kerstin

2017-09-05

Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high mortality rates (50-100%) associated with mucormycosis are reflective of not only the aggressive nature of the infection and the poor therapeutics currently employed, but also the failure of the human immune system to successfully clear the infection. Immune effector interaction with Mucorales is influenced by the developmental stage of the mucormycete spore. In a healthy immune environment, resting spores are resistant to phagocytic killing. Contrarily, swollen spores and hyphae are susceptible to damage and degradation by macrophages and neutrophils. Under the effects of immune suppression, the recruitment and efficacy of macrophage and neutrophil activity against mucormycetes is considerably reduced. Following penetration of the endothelial lining, Mucorales encounter platelets. Platelets adhere to both mucormycete spores and hyphae, and exhibit germination suppression and hyphal damage capacity in vitro. Dendritic cells are activated in response to Mucorales hyphae only, and induce adaptive immunity. It is crucial to further knowledge regarding our immune system's failure to eradicate resting spores under intact immunity and inhibit fungal growth under immunocompromised conditions, in order to understand mucormycosis pathogenicity and enhance therapeutic strategies for mucormycosis.

Surface Environmental Surveillance Procedures Manual

International Nuclear Information System (INIS)

Hanf, Robert W.; Poston, Ted M.

2000-01-01

Shows and explains certain procedures needed for surface environmental surveillance. Hanford Site environmental surveillance is conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy (DOE) under the Surface Environmental Surveillance Project (SESP). The basic requirements for site surveillance are set fourth in DOE Order 5400.1, General Environmental Protection Program Requirements. Guidance for the SESP is provided in DOE Order 5484.1, Environmental Protection, Safety, and Health Protection Information Reporting Requirements and DOE Order 5400.5, Radiation Protection of the Public and Environment. Guidelines for environmental surveillance activities are provided in DOE/EH-0173T, Environmental Regulatory Guide for Radiological Effluent Monitoring and Environmental Surveillance. An environmental monitoring plan for the Hanford Site is outlined in DOE/RL 91-50 Rev. 2, Environmental Monitoring Plan, United States Department of Energy, Richland Operations Office. Environmental surveillance data are used in assessing the impact of current and past site operations on human health and the environment, demonstrating compliance with applicable local, state, and federal environmental regulations, and verifying the adequacy of containment and effluent controls. SESP sampling schedules are reviewed, revised, and published each calendar year in the Hanford Site Environmental Surveillance Master Sampling Schedule. Environmental samples are collected by SESP staff in accordance with the approved sample collection procedures documented in this manual. Personnel training requirements are documented in SESP-TP-01 Rev.2, Surface Environmental Surveillance Project Training Program.

Novel Strategies to Enhance Vaccine Immunity against Coccidioidomycosis

Science.gov (United States)

2013-12-19

Mexico and Central and South America [1]. Coccidioides is a dimorphic ascomycetous fungus with distinct saprobic and parasitic phases and is classified in...lethal spore inoculum. However, sterile immunity was not achieved and pulmonary tissue damage associated with a persistent host inflammatory response...observation will translate to humans. A recent vector-based vaccine against tuberculosis intended to protect by eliciting strong CMI failed in humans despite

Critical Surveillance Studies in the Information Society

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Thomas Allmer

2011-11-01

Full Text Available The overall aim of this paper is to clarify how we can theorize and systemize economic surveillance. Surveillance studies scholars like David Lyon stress that economic surveillance such as monitoring consumers or the workplace are central aspects of surveillance societies. The approach that is advanced in this work recognizes the importance of the role of the economy in contemporary surveillance societies. The paper at hand constructs theoretically founded typologies in order to systemize the existing literature of surveillance studies and to analyze examples of surveillance. Therefore, it mainly is a theoretical approach combined with illustrative examples. This contribution contains a systematic discussion of the state of the art of surveillance and clarifies how different notions treat economic aspects of surveillance. In this work it is argued that the existing literature is insufficient for studying economic surveillance. In contrast, a typology of surveillance in the modern economy, which is based on foundations of a political economy approach, allows providing a systematic analysis of economic surveillance on the basis of current developments on the Internet. Finally, some political recommendations are drawn in order to overcome economic surveillance. This contribution can be fruitful for scholars who want to undertake a systematic analysis of surveillance in the modern economy and who want to study the field of surveillance critically.

Mucosal immunization with the Moraxella catarrhalis porin m35 induces enhanced bacterial clearance from the lung: a possible role for opsonophagocytosis

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Donna eEaston

2011-05-01

Full Text Available Moraxella catarrhalis is a significant cause of respiratory tract infection against which a vaccine is sought. Several outer membrane proteins are currently under investigation as potential vaccine antigens, including the porin M35. We have previously shown that the third external loop of M35 was immunodominant over the remainder of the protein for antibody produced in mice against the refolded recombinant protein. However, as this loop is predicted to fold inside the porin channel we also predicted that it would not be accessible to these antibodies when M35 is expressed on the surface of the bacteria in its native conformation. This study investigated the functional activity of antibodies against M35 and those specific for the loop 3 region of M35 in vitro and in vivo. Antisera from mice immunized with M35 or the loop 3-deletion, M35loop3–, recombinant proteins were not bactericidal but did have enhanced opsonic activity, whereas antibodies raised against the loop 3 peptide were not opsonising indicating that the immunodominant loop 3 of M35 was not accessible to antibody as we had previously predicted. Mucosal immunization with M35, M35 that had an antigenically altered loop 3 (M35(ID78 and M35loop3– enhanced the clearance of M. catarrhalis from the lungs of mice challenged with live M. catarrhalis. The in vivo clearance of bacteria in the mice with the M35-derived protein constructs correlated significantly (p<0.001 with the opsonic activity assessed an in vitro opsonophagocytosis assay. This study has demonstrated that the immunodominat B-cell epitope to loop 3 of the M. catarrhalis outer membrane protein M35 is not associated with immune protection and that M35-specific antibodies are not bactericidal but are opsonising. The opsonising activity correlated with in vivo clearance of the bacteria suggesting that opsonising antibody may be a good correlate of immune protection.

World Alliance for Risk Factor Surveillance White Paper on Surveillance and Health Promotion

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Stefano Campostrini

2015-02-01

Full Text Available This is not a research paper on risk factor surveillance. It is an effort by a key group of researchers and practitioners of risk factor surveillance to define the current state of the art and to identify the key issues involved in the current practice of behavioral risk factor surveillance. Those of us who are the principal authors have worked and carried out research in this area for some three decades. As a result of a series of global meetings beginning in 1999 and continuing every two years since then, a collective working group of the International Union of Health Promotion and Education (IUHPE was formed under the name World Alliance of Risk Factor Surveillance (WARFS. Under this banner the organization sought to write a comprehensive statement on the importance of surveillance to health promotion and public health. This paper, which has been revised and reviewed by established peers in the field, is the result. It provides the reader with a clear summary of the major issues that need to be considered by any and all seeking to carry out behavioral risk factor surveillance.

Immune-enhancing activities of low molecular weight β-glucan depolymerized by gamma irradiation

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Sung, Nak-Yun; Byun, Eui-Hong; Kwon, Sun-Kyu; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Yoo, Young-Choon; Kim, Mee-Ree; Lee, Ju-Woon

2009-07-01

β-glucans are structural cell wall polymers of many microorganisms and cereals which possess immunomodulatory properties and have been used in the food, cosmetic and medical industry. In our previous study, β-glucan was depolymerized by gamma irradiation and leads to improve the solubility and viscosity. This study was carried out to evaluate the functional properties, mainly immune-enhancing activities of low molecular weight β-glucan fragmented by gamma irradiation. The results showed that RAW 264.7 macrophage cell stimulation activities of irradiated β-glucan were higher than that of non-irradiated β-glucan. In addition, the oral administration of gamma-irradiated β-glucan significantly increased the proliferation and cytokine (IFN-γ and IL-2) release of spleen and Peyer's patch cells compared with non-irradiated β-glucan. In conclusion, gamma irradiation could be used as an effective method for the production of depolymerized β-glucan improved functional property such as immunomodulatory activity.

Immune-enhancing activities of low molecular weight β-glucan depolymerized by gamma irradiation

International Nuclear Information System (INIS)

Sung, Nak-Yun; Byun, Eui-Hong; Kwon, Sun-Kyu; Song, Beom-Seok; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Yoo, Young-Choon; Kim, Mee-Ree; Lee, Ju-Woon

2009-01-01

β-glucans are structural cell wall polymers of many microorganisms and cereals which possess immunomodulatory properties and have been used in the food, cosmetic and medical industry. In our previous study, β-glucan was depolymerized by gamma irradiation and leads to improve the solubility and viscosity. This study was carried out to evaluate the functional properties, mainly immune-enhancing activities of low molecular weight β-glucan fragmented by gamma irradiation. The results showed that RAW 264.7 macrophage cell stimulation activities of irradiated β-glucan were higher than that of non-irradiated β-glucan. In addition, the oral administration of gamma-irradiated β-glucan significantly increased the proliferation and cytokine (IFN-γ and IL-2) release of spleen and Peyer's patch cells compared with non-irradiated β-glucan. In conclusion, gamma irradiation could be used as an effective method for the production of depolymerized β-glucan improved functional property such as immunomodulatory activity.

Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

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

2016-01-01

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

Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance.

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Sauvageot, Delphine; Njanpop-Lafourcade, Berthe-Marie; Akilimali, Laurent; Anne, Jean-Claude; Bidjada, Pawou; Bompangue, Didier; Bwire, Godfrey; Coulibaly, Daouda; Dengo-Baloi, Liliana; Dosso, Mireille; Orach, Christopher Garimoi; Inguane, Dorteia; Kagirita, Atek; Kacou-N'Douba, Adele; Keita, Sakoba; Kere Banla, Abiba; Kouame, Yao Jean-Pierre; Landoh, Dadja Essoya; Langa, Jose Paulo; Makumbi, Issa; Miwanda, Berthe; Malimbo, Muggaga; Mutombo, Guy; Mutombo, Annie; NGuetta, Emilienne Niamke; Saliou, Mamadou; Sarr, Veronique; Senga, Raphael Kakongo; Sory, Fode; Sema, Cynthia; Tante, Ouyi Valentin; Gessner, Bradford D; Mengel, Martin A

2016-05-01

Cholera burden in Africa remains unknown, often because of weak national surveillance systems. We analyzed data from the African Cholera Surveillance Network (www.africhol.org). During June 2011-December 2013, we conducted enhanced surveillance in seven zones and four outbreak sites in Togo, the Democratic Republic of Congo (DRC), Guinea, Uganda, Mozambique and Cote d'Ivoire. All health facilities treating cholera cases were included. Cholera incidences were calculated using culture-confirmed cholera cases and culture-confirmed cholera cases corrected for lack of culture testing usually due to overwhelmed health systems and imperfect test sensitivity. Of 13,377 reported suspected cases, 34% occurred in Conakry, Guinea, 47% in Goma, DRC, and 19% in the remaining sites. From 0-40% of suspected cases were aged under five years and from 0.3-86% had rice water stools. Within surveillance zones, 0-37% of suspected cases had confirmed cholera compared to 27-38% during outbreaks. Annual confirmed incidence per 10,000 population was cholera incidence, age distribution, clinical presentation, culture confirmation, and testing frequency. These results can help guide preventive activities, including vaccine use.

rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

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Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

2014-09-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Stimulation of dendritic cells enhances immune response after photodynamic therapy

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Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

2009-02-01

Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

Twitter web-service for soft agent reporting in persistent surveillance systems

Science.gov (United States)

Rababaah, Haroun; Shirkhodaie, Amir

2010-04-01

Persistent surveillance is an intricate process requiring monitoring, gathering, processing, tracking, and characterization of many spatiotemporal events occurring concurrently. Data associated with events can be readily attained by networking of hard (physical) sensors. Sensors may have homogeneous or heterogeneous (hybrid) sensing modalities with different communication bandwidth requirements. Complimentary to hard sensors are human observers or "soft sensors" that can report occurrences of evolving events via different communication devices (e.g., texting, cell phones, emails, instant messaging, etc.) to the command control center. However, networking of human observers in ad-hoc way is rather a difficult task. In this paper, we present a Twitter web-service for soft agent reporting in persistent surveillance systems (called Web-STARS). The objective of this web-service is to aggregate multi-source human observations in hybrid sensor networks rapidly. With availability of Twitter social network, such a human networking concept can not only be realized for large scale persistent surveillance systems (PSS), but also, it can be employed with proper interfaces to expedite rapid events reporting by human observers. The proposed technique is particularly suitable for large-scale persistent surveillance systems with distributed soft and hard sensor networks. The efficiency and effectiveness of the proposed technique is measured experimentally by conducting several simulated persistent surveillance scenarios. It is demonstrated that by fusion of information from hard and soft agents improves understanding of common operating picture and enhances situational awareness.