WorldWideScience

Sample records for activated local immunity

  1. Immunizations: Active vs. Passive

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations: Active vs. Passive Safety & ...

  2. Cupping regulates local immunomodulation to activate neural-endocrine-immune worknet.

    Science.gov (United States)

    Guo, Yang; Chen, Bo; Wang, Dong-Qiang; Li, Ming-Yue; Lim, Calista Hui-Min; Guo, Yi; Chen, Zelin

    2017-08-01

    Research on cupping therapy is lacking at home and abroad. However, cupping and acupuncture therapy are both surface stimulation therapies. This paper suggests the mechanism of cupping therapy and proposes that the same mechanism underlies both cupping and acupuncture therapy. The microenvironment is changed when stimulating the surface of the skin, and physical signals transform into biological signals, which also interact with each other in the body. These signalling cascades activate the neuroendocrine-immune system, which produces the therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. U.S. Immunization program adult immunization activities and resources

    Science.gov (United States)

    Woods, LaDora O.; Bridges, Carolyn B.; Graitcer, Samuel B.; Lamont, Brock

    2016-01-01

    ABSTRACT Adults are recommended to receive vaccines based on their age, medical conditions, prior vaccinations, occupation and lifestyle. However, adult immunization coverage is low in the United States and lags substantially below Healthy People 2020 goals. To assess activities and resources designated for adult immunization programs by state and local health department immunization programs in the United States, we analyzed 2012 and 2013 data from the Centers for Disease Control and Prevention's (CDC) Program Annual Reports and Progress Assessments (PAPA) survey of CDC-funded immunization programs. Fifty-six of 64 funded US immunization programs' responses were included in the analysis. Eighty-two percent of (n = 46) programs reported having a designated adult immunization coordinator in 2012 and 73% (n = 41) in 2013. Of the 46 coordinators reported in 2012, 30% (n = 14) spent more than 50% of their time on adult immunization activities, and only 24% (n = 10) of the 41 adult coordinators in 2013 spent more than 50% of their time on adult immunization activities. In 2012, 23% (n = 13) of the 56 programs had a separate immunization coalition for adults and 68% (n = 38) included adult issues in their overall immunization program coalition. In 2013, 25% (n = 14) had a separate adult immunization coalition while 57% (n = 32) incorporated adult immunizations into their overall immunization program coalition. The results indicate substantial variation across the US in public health infrastructure to support adult immunizations. Continued assessment of adult immunization resources and activities will be important in improving adult immunization coverage levels though program support. With many programs having limited resources dedicated to improving adult immunization rates in the in US, efforts by the health departments to collaborate with providers and other partners in their jurisdictions to increase awareness, increase the use of proven strategies to improve

  4. Local immune mechanisms against parasites

    International Nuclear Information System (INIS)

    Lloyd, S.

    1981-01-01

    The secretory immunological system of the gastrointestinal tract is associated with the production of secretory IgA immunoglobulins. However, despite the fact that secretory IgA antibodies are known to mediate protection against infection with a number of bacteria and viruses, little information is available on their role in protection against infection with parasites. Thus, although elevated levels of IgA immunoglobulins and antibodies are present in the gastrointestinal tract after infection with a number of helminths and protozoa, conclusive evidence that these are associated with protection against infection is often lacking. However, it has now been demonstrated that intestinal IgA antibodies are associated with protection against infection with Taenia taeniaeformis in mice. In addition, secretory IgA antibodies arising from the common mucosal immunological system of the mammary gland are associated with protection against infection with T. taeniaeformis in mice and rats. Thus, since the portal of entry and site of residence of many parasites is the gastrointestinal tract, the secretory immunological system may act as a first line of defence against infection, and it is possible that oral immunization and local stimulation of the gastrointestinal tract may be effective in inducing protection against infection. The use of nuclear techniques (radioisotope-labelled IgA, autoradiography to follow the role of hepatocytes in IgA transport across the liver) are mentioned marginally only in this review

  5. 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.

  6. 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.

  7. Findings from case studies of state and local immunization programs.

    Science.gov (United States)

    Fairbrother, G; Kuttner, H; Miller, W; Hogan, R; McPhillips, H; Johnson, K A; Alexander, E R

    2000-10-01

    As part of its examination of federal support for immunization services during the past decade, the Institute of Medicine (IOM) Committee on Immunization Finance Policies and Practices (IFPP) commissioned eight case studies of the states of Alabama, Maine, Michigan, New Jersey, North Carolina, Texas, and Washington; and a two-county study of Los Angeles and San Diego in California. Specifically, the IOM Committee and these studies reviewed the use of Section 317 grants by the states. Section 317 is a discretionary grant program that supports vaccine purchase and other immunization-related program activities. These studies afforded the Committee an in-depth look at local policy choices, the performance of immunization programs, and federal and state spending for immunization during the past decade. The case-study reports were developed through interviews with state and local health department officials, including immunization program directors, Medicaid agency staff, budget analysts, and Centers for Disease Control and Prevention public health advisors to the jurisdiction. Other sources included state and federal administrative records and secondary sources on background factors and state-level trends. The case studies were supplemented by site visits to Detroit, Houston, Los Angeles, Newark, and San Diego. The nature of immunization "infrastructure" supported by the Section 317 program is shifting from primarily service delivery to a broader set of roles that puts the public effort at the head of a broad immunization partnership among public health, health financing, and other entities in both the public and private sectors. The rate and intensity of transition vary across the case-study areas. In the emerging pattern, service delivery increasingly takes place in the private sector and is related to managed care. "Infrastructure" is moving beyond supporting a core state staff and local health department service delivery to include such activities as immunization

  8. [Local immune and oxidative status in exacerbated chronic apical periodontitis].

    Science.gov (United States)

    Konoplya, A I; Goldobin, D D; Loktionov, A L

    The aim of the study was to define local immune and oxidative changes in patients with exacerbated chronic apical periodontitis. These changes were assessed in saliva of 67 patients with the mean age of 31±2.5 before and after treatment. The study revealed disturbances in cytokines and complement system balance and activation of lipids peroxidation. Combination of Gepon or Vobenzim with Essentiale forte H and Kaskatol proved to be the most effective for correction of this imbalance.

  9. Active Neural Localization

    OpenAIRE

    Chaplot, Devendra Singh; Parisotto, Emilio; Salakhutdinov, Ruslan

    2018-01-01

    Localization is the problem of estimating the location of an autonomous agent from an observation and a map of the environment. Traditional methods of localization, which filter the belief based on the observations, are sub-optimal in the number of steps required, as they do not decide the actions taken by the agent. We propose "Active Neural Localizer", a fully differentiable neural network that learns to localize accurately and efficiently. The proposed model incorporates ideas of tradition...

  10. Local Worlds of Activation

    DEFF Research Database (Denmark)

    Jacobsson, Kerstin; Hollertz, Katarina; Garsten, Christina

    2017-01-01

    arrangements and the role of private services and actors in service delivery differed significantly too, ranging from strictly market-based forms of governance to classical public administration. The article moreover shows how the different activation approaches were reflected in the radically different usages...... from local politics, established local traditions, patterns of networking and modes of collaborating, as the notion of ‘local words of activation’ intends to capture....

  11. Active immunization against renin in normotensive marmoset

    International Nuclear Information System (INIS)

    Michel, J.B.; Guettier, C.; Philippe, M.; Galen, F.X.; Corvol, P.; Menard, J.

    1987-01-01

    Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutneous injections of 30 μg each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of 125 I-labeled human renin at a dilution of ≥ 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly. Plasma renin enzyme activity was undetectable in the animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterize by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney

  12. Injury and subsequent regeneration of muscles for activation of local innate immunity to facilitate the development and relapse of autoimmune myositis in C57BL/6 mice.

    Science.gov (United States)

    Kimura, Naoki; Hirata, Shinya; Miyasaka, Nobuyuki; Kawahata, Kimito; Kohsaka, Hitoshi

    2015-04-01

    To determine whether injury and regeneration of the skeletal muscles induce an inflammatory milieu that facilitates the development and relapse of autoimmune myositis. The quadriceps of C57BL/6 mice were injured with bupivacaine hydrochloride (BPVC) and evaluated histologically. Macrophages and regenerating myofibers in the treated muscles and differentiating C2C12 myotubes were examined for cytokine expression. Mice were immunized with C protein fragments at the base of the tail and in the right hind footpads (day 0) to evoke systemic anti-C protein immunity and to induce local myositis in the right hind limbs. The contralateral quadriceps muscles were injured with BPVC or phosphate buffered saline (PBS) on day 7 or after spontaneous regression of myositis (day 42). The quadriceps muscle in nonimmunized mice was injured with BPVC on day 7. The muscles were examined histologically 14 days after treatment. The BPVC-injured muscles had macrophage infiltration most abundantly at 3 days after the injection, with emergence of regenerating fibers from day 5. The macrophages expressed inflammatory cytokines, including tumor necrosis factor α, interleukin-1β, and CCL2. Regenerating myofibers and C2C12 myotubes also expressed the cytokines. The BPVC-injected muscles from nonimmunized mice had regenerating myofibers with resolved cell infiltration 14 days after treatment. In mice preimmunized with C protein fragments, the muscles injected with BPVC on day 7 as well as on day 42, but not those injected with PBS, had myositis accompanied by CD8+ T cell infiltration. Injury and regeneration could set up an inflammatory milieu in the muscles and facilitate the development and relapse of autoimmune myositis. Copyright © 2015 by the American College of Rheumatology.

  13. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation.

    Science.gov (United States)

    Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W

    2014-09-24

    Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score. Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.

  14. Natural evolution, disease, and localization in the immune system

    Science.gov (United States)

    Deem, Michael

    2004-03-01

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

  15. Local cell-mediated immune reactions in cancer patients

    International Nuclear Information System (INIS)

    Bilynskij, B.T.; Vasil'ev, N.V.; Volod'ko, N.A.; Akademiya Meditsinskikh Nauk SSSR, Tomsk. Onkologicheskij Nauchnyj Tsentr)

    1988-01-01

    The analysis of 178 cases of stage I-II breast cancer showed morphological features of local cell-mediated immune reactions to be of limited prognostic value. A comparative evaluation of some characteristics of cell surface receptors, such as ability to spontaneous rosette formation with sheep erythrocytes and sensitivty to theophylline, was carried out in lymphocyte samples obtained from tumor tissue and peripheral blood of 76 cancer patients subjected to preoperative radiotherapy. The said parameters were studied in breast cancer patients of rosette-forming cell reaction to theophylline were identified, the incidence of some of them being determined by the presence or absence of regional metastases. The level and functional activity of surface receptors of tumor mononuclear cells proved to influence prognosis

  16. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    Chang D

    2014-12-01

    Full Text Available David Chang, Jon Kobashigawa Cedars-Sinai Heart Institute, Los Angeles, CA, USA Abstract: Heart transplant remains the most durable option for end-stage heart disease. Cardiac allograft immune activation and heart transplant rejection remain among the main complications limiting graft and recipient survival. Mediators of the immune system can cause different forms of rejection post-heart transplant. Types of heart transplant rejection include hyperacute rejection, cellular rejection, antibody-mediated rejection, and chronic rejection. In this review, we will summarize the innate and adaptive immune responses which influence the post-heart transplant recipient. Different forms of rejection and their clinical presentation, detection, and immune monitoring will be discussed. Treatment of heart transplant rejection will be examined. We will discuss potential treatment strategies for preventing rejection post-transplant in immunologically high-risk patients with antibody sensitization. Keywords: heart transplant, innate immunity, adaptive immunity, rejection, immunosuppression

  17. Mast cell activators as novel immune regulators.

    Science.gov (United States)

    Johnson-Weaver, Brandi; Choi, Hae Woong; Abraham, Soman N; Staats, Herman F

    2018-05-26

    Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node composition to regulate the induction of adaptive immune responses. The recognition that mast cells play a beneficial role in host responses to microbial infection and induction of adaptive immunity has provided the rationale to evaluate mast cell activators for use as antimicrobials or vaccine adjuvants. This review summarizes the role of mast cell activators in antimicrobial responses while also discussing the use of different classes of mast cell activators as potent vaccine adjuvants that enhance the induction of protective immune responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Global and local targeted immunization in networks with community structure

    International Nuclear Information System (INIS)

    Yan, Shu; Tang, Shaoting; Pei, Sen; Zheng, Zhiming; Fang, Wenyi

    2015-01-01

    Immunization plays an important role in the field of epidemic spreading in complex networks. In previous studies, targeted immunization has been proved to be an effective strategy. However, when extended to networks with community structure, it is unknown whether the superior strategy is to vaccinate the nodes who have the most connections in the entire network (global strategy), or those in the original community where epidemic starts to spread (local strategy). In this work, by using both analytic approaches and simulations, we observe that the answer depends on the closeness between communities. If communities are tied closely, the global strategy is superior to the local strategy. Otherwise, the local targeted immunization is advantageous. The existence of a transitional value of closeness implies that we should adopt different strategies. Furthermore, we extend our investigation from two-community networks to multi-community networks. We consider the mode of community connection and the location of community where epidemic starts to spread. Both simulation results and theoretical predictions show that local strategy is a better option for immunization in most cases. But if the epidemic begins from a core community, global strategy is superior in some cases. (paper)

  19. Experiences from polio supplementary immunization activities in ...

    African Journals Online (AJOL)

    2014-05-31

    May 31, 2014 ... lessons from supplementary immunization activities (SIAs) conducted in the State that will be useful to ... Poliovirus invades the central nervous system and causes ..... The vaccine wastage rate of 6.6% was slightly higher.

  20. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  1. Effect of host nutrition on immunity and local immune response of rabbits to Obeliscoides cuniculi

    International Nuclear Information System (INIS)

    Sinski, E.; Bezubik, B.; Wedrychowicz, H.; Szklarczyk, J.; Doligalska, M.

    1988-01-01

    In a series of experiments carried out on young and adult rabbits the effect of isocaloric low protein diets containing 4% or 8% protein compared with a diet containing 21% protein on Obeliscoides cuniculi infection was studied. The pathogenesis, resistance and local immunity were assessed after single infections with 10,000 larvae or reinfection with 5000 larvae. Live weight gain was reduced in young and adult rabbits fed the low protein diets, but the establishment of parasites was not substantially influenced by protein deprivation. However, development of worms in the histotrophic phase and parasite fecundity were impaired in association with the low protein diet. Moreover, mild anaemia as well as changes in the mucosal immune response as a result of infection were related to the level of dietary protein. (author). 30 refs, 6 figs, 5 tabs

  2. Global efficiency of local immunization on complex networks.

    Science.gov (United States)

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J

    2013-01-01

    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, rumours and diseases spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in 17 empirical networks of diverse nature using 2 epidemic models. We find that a judicious choice of local measures, based either on the network's connectivity at a microscopic scale or on its community structure at a mesoscopic scale, compares favorably to global measures, such as betweenness centrality, in terms of efficiency, practicality and robustness. We also develop an analytical framework that highlights a transition in the characteristic scale of different epidemic regimes. This allows to decide which local measure should govern immunization in a given scenario.

  3. Global efficiency of local immunization on complex networks

    Science.gov (United States)

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J.

    2013-07-01

    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, rumours and diseases spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in 17 empirical networks of diverse nature using 2 epidemic models. We find that a judicious choice of local measures, based either on the network's connectivity at a microscopic scale or on its community structure at a mesoscopic scale, compares favorably to global measures, such as betweenness centrality, in terms of efficiency, practicality and robustness. We also develop an analytical framework that highlights a transition in the characteristic scale of different epidemic regimes. This allows to decide which local measure should govern immunization in a given scenario.

  4. Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids

    Science.gov (United States)

    2008-08-01

    SUBJECT TERMS Cancer therapy by localized immune response, Magneto -rehological Fluids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...Metastasized Breast Cancer by Localized Therapy utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit Evrensel...2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy utilizing

  5. Active and passive immunity, vaccine types, excipients and licensing.

    Science.gov (United States)

    Baxter, David

    2007-12-01

    Abstract Immunity is the state of protection against infectious disease conferred either through an immune response generated by immunization or previous infection or by other non-immunological factors. This article reviews active and passive immunity and the differences between them: it also describes the four different commercially available vaccine types (live attenuated, killed/inactivated, subunit and toxoid): it also looks at how these different vaccines generate an adaptive immune response.

  6. HIV-1 Reservoir Association with Immune Activation

    Directory of Open Access Journals (Sweden)

    Alejandro Vallejo

    2015-09-01

    Full Text Available In this issue of EBioMedicine, Ruggiero and colleagues describe immune activation biomarkers associated with the size of the HIV reservoir in a carefully designed cross-sectional study. The cohort consists of a homogeneous sample of HIV-1-infected patients with long-term plasma HIV-1 RNA suppression under antiretroviral treatment (ART. It is crucial to explore the potential utility of biomarkers that are easier (less labor intensive, less expensive to measure than integrated HIV DNA load, in order to quickly and accurately quantify cellular reservoirs of HIV.

  7. AVIDITY EVALUATION OF LOCAL IgA ANTIBODIES IN PERSONS IMMUNIZED WITH LIVE INFLUENZA VACCINE

    Directory of Open Access Journals (Sweden)

    S. A. Donina

    2008-01-01

    Full Text Available Abstract. At present, immunogenicity evaluation of influenza vaccines is performed by quantitative assessment of increased serum antibodies. It was, however, shown that the degree of human defense against influenza is mostly related to their qualitative characteristics, i.e., avidity (functional activity. Leading role of local immunity is demonstrated in protection against influenza. Such immunity is mediated by IgA antibodies from mucosal airways. Meanwhile, the avidity issues for local antibodies still remain open.In present study, an attempt was undertaken to evaluate post-vaccination local immunological memory for influenza A virus, according to IgA antibodies from upper respiratory secretions. Two techniques were used to evaluate antibody avidity, that were previously applied for studying this phenomenon with serum imunoglobulins, i.e., a dynamic test (measurement of antigen-antibody reaction rates, and a test with urea, a chaotropic agent (avidity is determined as a strength of antigen-antibody complex. A total of 202 persons (18 to 20 years old were enrolled into the study.With both tests, a broad range of individual avidity values was observed for the antibodies. A significant cohort (up to 30 per cent of persons immunized with live influenza vaccine, showed sharply increased avidity of secretory IgA antibodies by both methods, along with accumulation of these immunoglobulins after vaccination. A reverse relationship is revealed between avidity levels of these antibodies before vaccination, and increase of this parameter post-immunization. The data present convincing arguments for specific renewal of local humoral immunological memory, as induced by live influenza vaccine. The study substantiates a necessity for application of the both tests in parallel, when determining avidity of secretory IgA antibodies. (Med. Immunol., vol. 10, N 4-5, pp 423-430.

  8. Antigen localization controls T cell-mediated tumor immunity.

    Science.gov (United States)

    Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

    2011-08-01

    Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

  9. Passive and active immunity against parvovirus infection in piglets ...

    African Journals Online (AJOL)

    On the basis of the given results, we conclude that colostral immunity to parvovirus infection in swine lasts for about one month and that antibodies found in the blood serum of piglets after the first month of life are a result of the activation of the immune system. Keywords: Porcine parvovirus, colostral immunity, reproductive ...

  10. Immunization Dropout Rates in Ihe, Awgu Local Government Area ...

    African Journals Online (AJOL)

    Background: Immunization against childhood diseases is one of the most important ways of preventing childhood morbidity and mortality. Aims: The objective of this study is to review the dropout rates of immunization of children in a health center using a single dose of diphtheria‑pertussis‑tetanus (DPT1) and three doses of ...

  11. Anatomical localization of commensal bacteria in immune cell homeostasis and disease.

    Science.gov (United States)

    Fung, Thomas C; Artis, David; Sonnenberg, Gregory F

    2014-07-01

    The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in the intestine, including the surface of intestinal epithelial cells (IECs) and the interior of gut-associated lymphoid tissues. These distinct tissue localization patterns permit unique interactions with the mammalian immune system and collectively influence intestinal immune cell homeostasis. Conversely, dysregulated localization of commensal bacteria can lead to inappropriate activation of the immune system and is associated with numerous chronic infectious, inflammatory, and metabolic diseases. Therefore, regulatory mechanisms that control proper anatomical containment of commensal bacteria are essential to maintain tissue homeostasis and limit pathology. In this review, we propose that commensal bacteria associated with the mammalian GI tract can be anatomically defined as (i) luminal, (ii) epithelial-associated, or (iii) lymphoid tissue-resident, and we discuss the role and regulation of these microbial populations in health and disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis.

    Science.gov (United States)

    Talabér, Gergely; Jondal, Mikael; Okret, Sam

    2013-11-05

    Systemic glucocorticoids (GCs) mainly originate from de novo synthesis in the adrenal cortex under the control of the hypothalamus-pituitary-adrenal (HPA)-axis. However, research during the last 1-2 decades has revealed that additional organs express the necessary enzymes and have the capacity for de novo synthesis of biologically active GCs. This includes the thymus, intestine, skin and the brain. Recent research has also revealed that locally synthesized GCs most likely act in a paracrine or autocrine manner and have significant physiological roles in local homeostasis, cell development and immune cell activation. In this review, we summarize the nature, regulation and known physiological roles of extra-adrenal GC synthesis. We specifically focus on the thymus in which GC production (by both developing thymocytes and epithelial cells) has a role in the maintenance of proper immunological function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Immunization Dropout Rates in Ihe, Awgu Local Government Area ...

    African Journals Online (AJOL)

    vaccine. Subjects and Methods: This is a cross sectional study where immunization dropout rate of ... especially with the addition of other vaccines such as yellow fever in endemic areas and tetanus toxoid (injections for the pregnant women.

  14. Local and systemic humoral immune response in farmed Atlantic salmon (Salmo salar L.) under a natural amoebic gill disease outbreak.

    Science.gov (United States)

    Marcos-López, Mar; Espinosa Ruiz, Cristóbal; Rodger, Hamish D; O'Connor, Ian; MacCarthy, Eugene; Esteban, M Ángeles

    2017-07-01

    Amoebic gill disease (AGD), caused by the protozoan parasite Neoparamoeba perurans, is one of the most significant infectious diseases for Atlantic salmon (Salmo salar L.) mariculture. The present study investigated the humoral immune response (both local in gill mucus and systemic in serum) of farmed Atlantic salmon naturally infected with N. perurans in commercial sea pens, at two different stages of the disease and after freshwater treatment. Parameters analysed included activity of immune related enzymes (i.e. lysozyme, peroxidase, protease, anti-protease, esterase, alkaline phosphatase), IgM levels, and the terminal carbohydrate profile in the gill mucus. Overall, greater variations between groups were noted in the immune parameters determined in gill mucus than the equivalent in the serum. In gill mucus, IgM levels and peroxidase, lysozyme, esterase and protease activities were decreased in fish showing longer exposure time to the infection and higher disease severity, then showed a sequential increase after treatment. Results obtained highlight the capacity of gills to elicit a local response to the infection, indicate an impaired immune response at the later stages of the disease, and show partial reestablishment of the host immune status after freshwater treatment. In addition to providing data on the humoral response to AGD, this study increases knowledge on gill mucosal humoral immunity, since some of the parameters were analysed for the first time in gill mucus. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-03-01

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

  16. Effect of immunomodifier on radiation-induced antitumor immunity following local irradiation to tumor, 2

    International Nuclear Information System (INIS)

    Mukae, Shiro; Norimura, Toshiyuki; Tsuchiya, Takehiko

    1988-01-01

    This study was carried out to clarify whether or not the antitumor cell-mediated immunity of host is more effectively induced by the combined use of mouse interferon-α/β (MuIFN-α/β) with local irradiation than by simple local irradiation to tumor. C3H/He female mice, MM46 tumor cells and mouse interferon-α/β (MuIFN-α/β) were used in the experiment. Antitumor activity in mice was evaluated by the inhibition of tumor growth and mean survival days after treatment. Spleen cell killing activity to MM46 tumor cells was measured to evaluate the antitumor activity in vitro. In the case of single use of MuIFN-α/β, tumor growth was more rapid than in the non-treated group (control) in vivo. The mean survival days were also reduced. There was no siginificant difference in tumor growth inhibition between combined therapy using X-irradiation and MuIFN-α/β, and single therapy by local irradiation. However, in the case of administration of MuIFN-α/β after irradiation, the mean survival days was significantly increased compared with the group receiving X-ray irradiation only. (author)

  17. Combined local and systemic immunization is essential for durable T-cell mediated heterosubtypic immunity against influenza A virus

    DEFF Research Database (Denmark)

    Uddbäck, Ida Elin Maria; Pedersen, Line M I; Pedersen, Sara R

    2016-01-01

    nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. Local......The threat from unpredictable influenza virus pandemics necessitates the development of a new type of influenza vaccine. Since the internal proteins are highly conserved, induction of T cells targeting these antigens may provide the solution. Indeed, adenoviral (Ad) vectors expressing flu...... (intranasal (i.n.)) immunization elicited delayed, but more lasting protection despite relatively inefficient immunization. However, by far, the most robust protection was induced by simultaneous, combined (i.n. + s.c.) vaccination, and, notably, in this case clinical protection lasted at least 8 months...

  18. Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

    Science.gov (United States)

    Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

    2017-08-01

    Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (Psinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

  19. Proteflazid® and local immunity in diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections.

    Science.gov (United States)

    Kaminsky, Vjacheslav; Chernyshov, Viktor; Grynevych, Oleksandr; Benyuk, Vasil; Kornatskaya, Alla; Shalko, Miroslava; Usevich, Igor; Revenko, Oleg; Shepetko, Maxim; Solomakha, Ludmila

    2017-03-21

    Reporting of clinical trials results for Proteflazid® in the drug formulation suppositories and vaginal swabs soaked in the solution of the drug to the local immunity of the female reproductive tract. The aim of study was to examine the state of local immunity in the reproductive tract of women with sexually transmitted diseases caused by human papillomavirus, herpes viruses (Type 1, 2) and mixed infection (herpes viruses + chlamydia). The trials involved 216 women with viral sexually transmitted diseases: Cervical Dysplasia associated with papillomavirus infection (HPV) (Group 1); Herpes genitalis type 1 (HSV- 1) and type 2 (HSV-1) (Group 2); mixed infection - HSV-1, HSV-2 and chlamydia (Group 3). Treatment results have confirmed that Proteflazid® contributes to sustainable performance improvement of basic factors of local immunity - sIgA, lysozyme and complement component C3 in the cervical mucus for all three groups of women. Proteflazid® enhances level of local immunity markers (sIgA, lysozyme, C3 complement component) and improves their ratios. Also it intensifies anticontagious activity of mucosal protection and female reproductive system as whole, during treatment diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections (herpesvirus and chlamydia).

  20. Assessment of Routine Immunization Coverage in Nyala Locality, Reasons behind Incomplete Immunization in South Darfur State, Sudan

    OpenAIRE

    Ismail, Ismail Tibin Adam; El-Tayeb, Elsadeg Mahgoob; Omer, Mohammed Diaaeldin F.A.; Eltahir, Yassir Mohammed; El-Sayed, El-Tayeb Ahmed; Deribe, Kebede

    2014-01-01

    Little is known about the coverage of routine immunization service in South Darfur state, Sudan. Therefore, this study was conducted to determine the vaccination rate and barriers for vaccination. A cross-sectional community-based study was undertaken in Nyala locality, south Darfur, Sudan, including urban, rural and Internal Displaced Peoples (IDPs) population in proportional representation. Survey data were collected by a questionnaire which was applied face to face to parents of 213 childr...

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

    Science.gov (United States)

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

    2016-01-26

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

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

    Directory of Open Access Journals (Sweden)

    Anne-Constance Franz

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peter Liehl

    2006-06-01

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

  4. Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain.

    Science.gov (United States)

    Xie, Wenrui; Chen, Sisi; Strong, Judith A; Li, Ai-Ling; Lewkowich, Ian P; Zhang, Jun-Ming

    2016-08-17

    Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a "microsympathectomy" by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory

  5. Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids. Addendum

    Science.gov (United States)

    2009-08-01

    Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit A. Evrensel...AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible... Magneto -rheological Fluid (MRF) iron nano-particles were synthesized using the reverse micelle technique and coated with poly(NIPAAm). The size

  6. Japan's nuclear PA activity in local governments

    International Nuclear Information System (INIS)

    Fujii, Nobuyuki

    1995-01-01

    This presentation emphasises some points of PA activities, based on the experience of 'cooperation projects for local governments'. Local governments distribute the public information directly to the residents. This is very important because officers of the local government can be the opinion leaders of the region. Local government exist very close to the residents, while the central government is a distant and faceless existence for the local people. It is believed that the local governments play an imperative role in PA activities. In other words, we must further utilize the organizations and functions of the local governments to implement PA activities. In conclusion, three recommendations are offered. Firstly, enough budget and authority should be given to the local governments as far as PA activities in their areas are concerned, and most of such activities should be entrusted to the local governments. Local governments should place more public relations officers, and continue the manpower development. Second, with regard to highly technical or specialized issues which a local governments cannot treat alone, related organizations like JAERO should support their PA activities. Third, such related organizations should also cooperate with local government including assistance in providing know-how, when their public information activities focus on educators, journalists, or the women. These three points should be given due consideration in our cooperation projects for the local governments, and JAERO is doing its best every day

  7. Transcriptomic variation of locally-infected skin of Epinephelus coioides reveals the mucosal immune mechanism against Cryptocaryon irritans.

    Science.gov (United States)

    Hu, Yazhou; Li, Anxing; Xu, Yang; Jiang, Biao; Lu, Geling; Luo, Xiaochun

    2017-07-01

    Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system. Comparative analyses of infected skin (group Isk) and uninfected skin (group Nsk) from the same challenged fish and control skin (group C) from uninfected control fish were conducted. As a result, a total of 91,082 unigenes with an average length of 2880 base pairs were obtained and among them, 38,704 and 48,617 unigenes were annotated based on homology with matches in the non-redundant and zebrafish database, respectively. Pairwise comparison resulted in 10,115 differentially-expressed genes (DEGs) in the Isk/C group comparison (4,983 up-regulated and 5,132 down-regulated), 2,275 DEGs in the Isk/Nsk group comparison (1,319 up-regulated and 956 down-regulated) and 4,566 DEGs in the Nsk/C group comparison (1,534 up-regulated and 3,032 down-regulated). Seven immune-related categories including 91 differentially-expressed immune genes (86 up-regulated and 5 down-regulated) were scrutinized. Both DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and immune-related gene expression analysis were used, and both analyses showed that the genes were more significantly altered in the locally-infected skin than in the uninfected skin of the same challenged fish. This suggests the skin's local immune response is important for host defense against this ectoparasite infection. Innate immune molecules, including hepcidin, C-type lectin, transferrin, transferrin receptor protein, serum amyloid A

  8. Factors of Innate and Adaptive Local Immunity in Children with Primary Deficiencies of Antibody Formation

    Directory of Open Access Journals (Sweden)

    L.I. Chernyshova

    2013-10-01

    Full Text Available In 40 children with various types of primary immunodeficiencies (PID of antibody formation we examined factors of local immunity in saliva. It is found that in the saliva of children with PID of antibody formation in comparison with immunocompetent children the concentration of factors of adaptive immunity is significantly reduced. Lack of adaptive immunity in the PID of antibody formation to some extent is compensated by increased concentrations of innate immune factors on the mucous membranes — the free Sc, as well as lactoferrin in selective immunodeficiency of IgA. At PID of antibody formation we observed increased TNF-α level in the saliva, which may indicate the persistence of local inflammation on the membranes of the respiratory tract.

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

    Science.gov (United States)

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

    1994-01-01

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

  10. Physical activity influences the immune system of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Thorsten Schmidt

    2017-01-01

    Full Text Available It has been suggested that physical activity in breast cancer patients can not only improve quality of life. Influences on physical and psychological levels have been evaluated, but effects on the immune system of breast cancer patients are hardly known. A PubMed search identified relevant trials and meta-analyses from 1970 to 2013. This review summarizes the results of international studies and the current discussion of effects of physical activity on the immune system of breast cancer patients. Highlighted are effects of physical activity on the immune system. Seven original articles and 14 reviews included in this review. Two original and the review articles includes other tumor entities besides breast cancer.Evaluated methods such as dose-response relationships for exercise in oncology, hardly exist. Increased immunological anti-cancer activity due to physical activity is probably mediated via an increase in number and cytotoxicity of monocytes and natural killer cells and cytokines.

  11. Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats.

    Science.gov (United States)

    Talbman, M A; Smith, D J

    1974-06-01

    The effect of local immunization with Streptococcus mutans on dental caries in conventional and gnotobiotic rats was studied. Injection of these animals with S. mutans strain 6715 incorporated into complete Freund adjuvant consistently resulted in the presence of antibody in saliva directed to this organism. This antibody was primarily of the immunoglobulin A class as demonstrated by specific antiglobulin augmentation and gel filtration of antibody activity. Serum antibody was also present. Five experiments have been completed in conventional rats and two in gnotobiotic animals. The immunized group of animals always had lower mean caries scores than comparably sham-immunized or nonimmunized control groups. The numbers of lesions were also always lower in the immunized animals, suggesting a possible interference with the formation of new lesions in immunized animals. The reductions in dental caries and lesions were greater on smooth surfaces than on occlusal surfaces. which might be explained as interference with adherence phenomena demonstrated by S. mutans. It is proposed that salivary immunoglobulin A antibody may be viewed as an ecological determinant in the oral cavity by affecting oral microorganisms and possibly their by-products.

  12. Assessment of Routine Immunization Coverage in Nyala Locality, Reasons behind Incomplete Immunization in South Darfur State, Sudan.

    Science.gov (United States)

    Ismail, Ismail Tibin Adam; El-Tayeb, Elsadeg Mahgoob; Omer, Mohammed Diaaeldin F A; Eltahir, Yassir Mohammed; El-Sayed, El-Tayeb Ahmed; Deribe, Kebede

    2014-02-25

    Little is known about the coverage of routine immunization service in South Darfur state, Sudan. Therefore, this study was conducted to determine the vaccination rate and barriers for vaccination. A cross-sectional community-based study was undertaken in Nyala locality, south Darfur, Sudan, including urban, rural and Internal Displaced Peoples (IDPs) population in proportional representation. Survey data were collected by a questionnaire which was applied face to face to parents of 213 children 12-23 months. The collected data was then analyzed with SPSS software package. Results showed that vaccination coverage as revealed by showed vaccination card alone was 63.4% while it was increased to 82.2% when both history and cards were used. Some (5.6%) of children were completely non-vaccinated. The factors contributing to the low vaccination coverage were found to be knowledge problems of mothers (51%), access problems (15%) and attitude problems (34%). Children whose mother attended antenatal care and those from urban areas were more likely to complete their immunization schedule. In conclusion, the vaccination coverage in the studied area was low compared to the national coverage. Efforts to increase vaccination converge and completion of the scheduled plan should focus on addressing concerns of caregivers particularly side effects and strengthening the Expanded Programmer on Immunization services in rural areas.

  13. [Immune regulation activity and mechanism of Tibetan Kefir exopolysaccharide fractions].

    Science.gov (United States)

    Meng, Li; Zhang, Lanwei

    2009-12-01

    To investigate the effects and mechanism on immune regulation activity in mice of two Tibetan Kefir exoploysaccharides (EPS) with different molecular weight of 0.1 x 10(5) - 3 x 10(5) (fraction 1) and 1.8 x 10(3) (fraction 2). The immune regulation activity experiment was carried out in vitro based on the Functional Assessment Procedure and Test Methods of Health Food, which was issued by Ministry of Health of China. First, we treated mice subjects with EPS at doses of 40 mg/kg, 80 mg/kg, 120 mg/kg through ig. Then we detected the index of immune organs, the ability of antibody production (tested by HC50), activity of NK cell, delayed type hypersensitivity (DTH) and phagocytosis of macrophage in mice. Finally, we examined the expression of Erk protein in Macrophages by Western Blot assay. Fraction 1 could promote HC50, activity of NK cell and DTH in mice which low dose showed better. Fraction 2 could promote DTH, phagocytosis of macrophage which high dose showed better. The expression of Erk and COX-2 had the same trend with Phagocytic index. We verified the two fractions of Tibetan Kefir EPS could enhance immune functions in mice. Fraction 1 regulated immune function through NK cell and B cell while fraction 2 through macrophage cell and T cell. The effects to macrophage of Tibetan Kefir EPS in mice may realize through extra cellular signal-regulated kinase Erk pathway.

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

    Science.gov (United States)

    Canetta, Sarah E; Brown, Alan S

    2012-12-01

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

  15. Characterization of innate immune activity in Phrynops geoffroanus (Testudines: Chelidae

    Directory of Open Access Journals (Sweden)

    Bruno O. Ferronato

    2009-12-01

    Full Text Available The innate immune activity of the freshwater turtle Phrynops geoffroanus (Schweigger, 1812 was investigated, using a sheep-red-blood cell hemolysis assay. The time- and concentration-dependent hemolytic activity of the turtle plasma was low compared to that reported for other reptiles. However the plasma of P. geoffroanus exhibited higher activity at elevated temperatures, resulting in temperature-dependent hemolysis. The sensitivity of turtle plasma to temperature could be interpreted as a mechanism by which freshwater turtles use basking behavior to elevate body temperature, thus enhancing the innate immune response. However, we cannot discard the possibility that environmental contaminants could be affecting the turtle's immune response, since the animals in this investigation were captured in a polluted watercourse.

  16. Immunization

    Science.gov (United States)

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

  17. Long-Range Activation of Systemic Immunity through Peptidoglycan Diffusion in Drosophila

    Science.gov (United States)

    Gendrin, Mathilde; Welchman, David P.; Poidevin, Mickael; Hervé, Mireille; Lemaitre, Bruno

    2009-01-01

    The systemic immune response of Drosophila is known to be induced both by septic injury and by oral infection with certain bacteria, and is characterized by the secretion of antimicrobial peptides (AMPs) into the haemolymph. To investigate other possible routes of bacterial infection, we deposited Erwinia carotovora (Ecc15) on various sites of the cuticle and monitored the immune response via expression of the AMP gene Diptericin. A strong response was observed to deposition on the genital plate of males (up to 20% of a septic injury response), but not females. We show that the principal response to genital infection is systemic, but that some AMPs, particularly Defensin, are induced locally in the genital tract. At late time points we detected bacteria in the haemolymph of immune deficient RelishE20 flies, indicating that the genital plate can be a route of entry for pathogens, and that the immune response protects flies against the progression of genital infection. The protective role of the immune response is further illustrated by our observation that RelishE20 flies exhibit significant lethality in response to genital Ecc15 infections. We next show that a systemic immune response can be induced by deposition of the bacterial elicitor peptidoglycan (PGN), or its terminal monomer tracheal cytotoxin (TCT), on the genital plate. This immune response is downregulated by PGRP-LB and Pirk, known regulators of the Imd pathway, and can be suppressed by the overexpression of PGRP-LB in the haemolymph compartment. Finally, we provide strong evidence that TCT can activate a systemic response by crossing epithelia, by showing that radiolabelled TCT deposited on the genital plate can subsequently be detected in the haemolymph. Genital infection is thus an intriguing new model for studying the systemic immune response to local epithelial infections and a potential route of entry for naturally occurring pathogens of Drosophila. PMID:20019799

  18. Activation of Innate Immunity by Bacterial Ligands of Toll-like Receptors

    Directory of Open Access Journals (Sweden)

    Nelli K. Akhmatova

    2014-03-01

    Full Text Available Tγδ and B1 lymphocytes are essential components of the mucosal immune system, activating different bacterial and viral ligands without costimulatory signals and preprocessing of other immune effectors. This ability enables the immune system to provide rapid protection against pathogens and contributes to the decoding mechanism of the sensitizing activity of mucosal antigens, because the interaction of these cells produces antibodies for immunoglobulin M (IgM and IgA, but not for IgE. We studied 3 routes of introducing antigens for opportunistic microorganisms to activate Tγδ and B1 lymphocytes: subcutaneous, intranasal, and oral. The subcutaneous and intranasal routes produced a significant increase of these cells in lymph nodes associated with the nasal cavity (NALT and in those associated with bronchial tissue (BALT. The oral route significantly increased levels of these cells in the spleen, in NALT, BALT, and in nodes associated with the gut (GALT. We found that mucosal application of the immunomodulator Immunovac-VP-4 (contains antigens of conditionally pathogenic microorganisms, in conjunction with the activation of Tγδ and B1, induces adaptive immune mechanisms not only in the lymphoid formations associated with the respiratory system and with GALT, but also in the spleen (increased expression of cluster of differentiation 3 [CD3], CD4, CD8, CD19, and CD25. This indicates that there is migration of lymphoid cells from the regional lymph nodes and mucosal lymphoid tissues via the lymph and blood to distant organs, lymphoid development, and both local and systemic immunity. Mucosal application of Immunovac-VP-4 in mice potentiates the cytotoxic activity of NK cells in the NALT, BALT and GALT. The highest cytotoxicity was observed in cells, derived from lymphoid tissue of the intestine after oral immunization. Although we found that cytokine production was increased by all 3 immunization routes, it was most intensive after subcutaneous

  19. Pathogen-secreted proteases activate a novel plant immune pathway.

    Science.gov (United States)

    Cheng, Zhenyu; Li, Jian-Feng; Niu, Yajie; Zhang, Xue-Cheng; Woody, Owen Z; Xiong, Yan; Djonović, Slavica; Millet, Yves; Bush, Jenifer; McConkey, Brendan J; Sheen, Jen; Ausubel, Frederick M

    2015-05-14

    Mitogen-activated protein kinase (MAPK) cascades play central roles in innate immune signalling networks in plants and animals. In plants, however, the molecular mechanisms of how signal perception is transduced to MAPK activation remain elusive. Here we report that pathogen-secreted proteases activate a previously unknown signalling pathway in Arabidopsis thaliana involving the Gα, Gβ, and Gγ subunits of heterotrimeric G-protein complexes, which function upstream of an MAPK cascade. In this pathway, receptor for activated C kinase 1 (RACK1) functions as a novel scaffold that binds to the Gβ subunit as well as to all three tiers of the MAPK cascade, thereby linking upstream G-protein signalling to downstream activation of an MAPK cascade. The protease-G-protein-RACK1-MAPK cascade modules identified in these studies are distinct from previously described plant immune signalling pathways such as that elicited by bacterial flagellin, in which G proteins function downstream of or in parallel to an MAPK cascade without the involvement of the RACK1 scaffolding protein. The discovery of the new protease-mediated immune signalling pathway described here was facilitated by the use of the broad host range, opportunistic bacterial pathogen Pseudomonas aeruginosa. The ability of P. aeruginosa to infect both plants and animals makes it an excellent model to identify novel immunoregulatory strategies that account for its niche adaptation to diverse host tissues and immune systems.

  20. Location of tumor affects local and distant immune cell type and number.

    Science.gov (United States)

    Hensel, Jonathan A; Khattar, Vinayak; Ashton, Reading; Lee, Carnellia; Siegal, Gene P; Ponnazhagan, Selvarangan

    2017-03-01

    Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid-derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia. In addition, immune cells from the spleen were examined from animals of both tumor locations by flow cytometry. The study demonstrates that location of tumor, and not simply the tumor itself, has a definitive role in regulating immune effectors. Among all immune cells characterized, macrophages were decreased and myeloid dendritic cell were increased in both tumor locations. This difference was more evident in subcutaneous tumors. Additionally, spleens from mice with subcutaneous tumors contained greater increases in both macrophages and myeloid dendritic cells than in mice with bone tumors. Furthermore, in subcutaneous tumors there was an increase in CD4 + and CD8 + T-cell numbers, which was also observed in their spleens. These data indicate that alterations in tumor-reactive immune cells are more pronounced at the primary site, and exert a similar change at the major secondary lymphoid organ than in the bone TME. These findings could provide translational insight into designing therapeutic strategies that account for location of metastatic foci.

  1. Innate immune recognition and activation during HIV infection

    Directory of Open Access Journals (Sweden)

    Larsen Carsten S

    2010-06-01

    Full Text Available Abstract The pathogenesis of HIV infection, and in particular the development of immunodeficiency, remains incompletely understood. Whichever intricate molecular mechanisms are at play between HIV and the host, it is evident that the organism is incapable of restricting and eradicating the invading pathogen. Both innate and adaptive immune responses are raised, but they appear to be insufficient or too late to eliminate the virus. Moreover, the picture is complicated by the fact that the very same cells and responses aimed at eliminating the virus seem to play deleterious roles by driving ongoing immune activation and progressive immunodeficiency. Whereas much knowledge exists on the role of adaptive immunity during HIV infection, it has only recently been appreciated that the innate immune response also plays an important part in HIV pathogenesis. In this review, we present current knowledge on innate immune recognition and activation during HIV infection based on studies in cell culture, non-human primates, and HIV-infected individuals, and discuss the implications for the understanding of HIV immunopathogenesis.

  2. The Verticillium-specific protein VdSCP7 localizes to the plant nucleus and modulates immunity to fungal infections.

    Science.gov (United States)

    Zhang, Lisha; Ni, Hao; Du, Xuan; Wang, Sheng; Ma, Xiao-Wei; Nürnberger, Thorsten; Guo, Hui-Shan; Hua, Chenlei

    2017-07-01

    Fungal pathogens secrete effector proteins to suppress plant basal defense for successful colonization. Resistant plants, however, can recognize effectors by cognate R proteins to induce effector-triggered immunity (ETI). By analyzing secretomes of the vascular fungal pathogen Verticillium dahliae, we identified a novel secreted protein VdSCP7 that targets the plant nucleus. The green fluorescent protein (GFP)-tagged VdSCP7 gene with either a mutated nuclear localization signal motif or with additional nuclear export signal was transiently expressed in Nicotiana benthamiana, and investigated for induction of plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized by gene knockout and complementation, and GFP labeling. Expression of the VdSCP7 gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and altered the plant's susceptibility to the pathogens Botrytis cinerea and Phytophthora capsici. The immune response activated by VdSCP7 was highly dependent on its initial extracellular secretion and subsequent nuclear localization in plants. Knockout of the VdSCP7 gene significantly enhanced V. dahliae aggressiveness on cotton. GFP-labeled VdSCP7 is secreted by V. dahliae and accumulates in the plant nucleus. We conclude that VdSCP7 is a novel effector protein that targets the host nucleus to modulate plant immunity, and suggest that plants can recognize VdSCP7 to activate ETI during fungal infection. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  3. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Brian J. [Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Pollack, Ian F. [Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Okada, Hideho, E-mail: okadah@upmc.edu [Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States); Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 (United States)

    2013-11-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas.

  4. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    International Nuclear Information System (INIS)

    Ahn, Brian J.; Pollack, Ian F.; Okada, Hideho

    2013-01-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas

  5. Immune activation is associated with decreased thymic function in ...

    African Journals Online (AJOL)

    Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

  6. Histone deacetylase inhibitors suppress immune activation in primary mouse microglia

    NARCIS (Netherlands)

    Kannan, Vishnu; Brouwer, Nieske; Hanisch, Uwe-Karsten; Regen, Tommy; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    Neuroinflammation is required for tissue clearance and repair after infections or insults. To prevent excessive damage, it is crucial to limit the extent of neuroinflammation and thereby the activation of its principal effector cell, microglia. The two main major innate immune cell types in the CNS

  7. Source localization of rhythmic ictal EEG activity

    DEFF Research Database (Denmark)

    Beniczky, Sándor; Lantz, Göran; Rosenzweig, Ivana

    2013-01-01

    Although precise identification of the seizure-onset zone is an essential element of presurgical evaluation, source localization of ictal electroencephalography (EEG) signals has received little attention. The aim of our study was to estimate the accuracy of source localization of rhythmic ictal...... EEG activity using a distributed source model....

  8. The role of rare innate immune cells in Type 2 immune activation against parasitic helminths.

    Science.gov (United States)

    Webb, Lauren M; Tait Wojno, Elia D

    2017-09-01

    The complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles - located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understand how the host protects itself during helminth infection.

  9. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus

    2017-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future...... vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally...... primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via...

  10. Chicken Immune Response after In Ovo Immunization with Chimeric TLR5 Activating Flagellin of Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Katarzyna A Radomska

    Full Text Available Campylobacter jejuni is the main cause of bacterial food-borne diseases in developed countries. Chickens are the most important source of human infection. Vaccination of poultry is an attractive strategy to reduce the number of C. jejuni in the intestinal tract of chickens. We investigated the immunogenicity and protective efficacy of a recombinant C. jejuni flagellin-based subunit vaccine with intrinsic adjuvant activity. Toll-like receptor activation assays demonstrated the purity and TLR5 stimulating (adjuvant activity of the vaccine. The antigen (20-40 μg was administered in ovo to 18 day-old chicken embryos. Serum samples and intestinal content were assessed for antigen-specific systemic and mucosal humoral immune responses. In ovo vaccination resulted in the successful generation of IgY and IgM serum antibodies against the flagellin-based subunit vaccine as determined by ELISA and Western blotting. Vaccination did not induce significant amounts of flagellin-specific secretory IgA in the chicken intestine. Challenge of chickens with C. jejuni yielded similar intestinal colonization levels for vaccinated and control animals. Our results indicate that in ovo delivery of recombinant C. jejuni flagellin subunit vaccine is a feasible approach to yield a systemic humoral immune response in chickens but that a mucosal immune response may be needed to reduce C. jejuni colonization.

  11. Activating transcription factor 3 regulates immune and metabolic homeostasis.

    Science.gov (United States)

    Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

    2012-10-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

  12. Effects of radiotherapy on immunity in patients with localized carcinoma of the cervix uteri

    International Nuclear Information System (INIS)

    Hancock, B.W.; Bruce, L.; Heath, J.; Sugden, P.; Ward, A.M.

    1979-01-01

    To assess the effects of radiotherapy on immune status, a wide range of assessments have been performed on patients with localized carcinoma of the cervix uteri undergoing and initially responding clinically to radical pelvic radiotherapy. neutrophil function was essentially unchanged by treatment. Absolute neutrophil and lymphocyte counts fell after treatment and remained depressed 3 and 12 months following treatment. The proportions of T and B cells dropped with treatment but recovered to near-presentation levels during the follow-up period even though absolute counts remained depressed. In vitro tests of cellular immunity were depressed by treatment and remained so 3 and 12 months following treatment whereas skin test responses remained normal throughout the assessments. Inhibitory plasma effects were observed in photohaemagglutinin lymphocyte transformation studies on 4 untreated patients; at follow-up these effects were not evident. A variable response in immune indices has therefore been observed in patients in remission after treatment of localized carcinoma cervix stressing the importance of assessing several aspects of immune function and implying that persistent depression of certain indices does not adversely affect the host tumor response. In two patients relapsing after apparently good initial response, all aspects of immunological assessment (except serum immunoglobulin levels and neutrophil function) deteriorated

  13. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Directory of Open Access Journals (Sweden)

    Rasmus Mortensen

    Full Text Available Streptococcus pyogenes (group A streptococcus, GAS is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  14. Prostaglandin E and the local immune response in chronic periodontal disease

    International Nuclear Information System (INIS)

    Loening, T.; Albers, H.-K.; Lisboa, B.P.; Burkhardt, A.; Caselitz, J.

    1980-01-01

    The local immune reaction of progressive chronic periodontal disease may be particularly influenced by macrophages and macrophage-derived factors. Among these substances the prostaglandins and lysosomal enzymes may play an important pathogenetic role. Parallel immunohistochemical and radioimmunological studies were done to investigate the relatiships of the immune-competent cells and the inflammatory mediators in gingival tissues. The radioimmunological analysis revealed that prostaglandin E increases markedly in the established gingival lesions. Immunohistochemically prostaglandin E was mainly localized within macrophage-like cells. Cytoplasmic lysozyme could be detected in these cells, too. On the other hand, the B-cell response is the prominent feature in established chronic periodontal disease. However, there is apparently a disturbed B-cell reaction as indicated by the irregular IgG-subclass pattern and by the production of mainly monomeric IgA. The possible interactions of macrophages and especially B-cells via prostaglandin E-mediated mechanisms are discussed. (author)

  15. 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.

  16. Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

    Science.gov (United States)

    Spencer, LaShonda Y; Christiansen, Shawna; Wang, Chia-Hao H; Mack, Wendy J; Young, Mary; Strickler, Howard D; Anastos, Kathryn; Minkoff, Howard; Cohen, Mardge; Geenblatt, Ruth M; Karim, Roksana; Operskalski, Eva; Frederick, Toni; Homans, James D; Landay, Alan; Kovacs, Andrea

    2016-02-01

    Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV

  17. Monitoring of local CD8 β-expressing cell populations during Eimeria tenella infection of naïve and immune chickens

    DEFF Research Database (Denmark)

    Wattrang, Eva; Thebo, Per; Lunden, Anna

    2016-01-01

    The purpose of this study was to monitor abundance and activation of local CD8β-expressing T-cell populations during Eimeria tenella infections of naïve chickens and chickens immune by previous infections. Chickens were infected with E. tenella up to three times. Caecal T-cell receptor (TCR) γ...

  18. Palmitoylation of the immunity related GTPase, Irgm1: impact on membrane localization and ability to promote mitochondrial fission.

    Directory of Open Access Journals (Sweden)

    Stanley C Henry

    Full Text Available The Immunity-Related GTPases (IRG are a family of large GTPases that mediate innate immune responses. Irgm1 is particularly critical for immunity to bacteria and protozoa, and for inflammatory homeostasis in the intestine. Although precise functions for Irgm1 have not been identified, prior studies have suggested roles in autophagy/mitophagy, phagosome remodeling, cell motility, and regulating the activity of other IRG proteins. These functions ostensibly hinge on the ability of Irgm1 to localize to intracellular membranes, such as those of the Golgi apparatus and mitochondria. Previously, it has been shown that an amphipathic helix, the αK helix, in the C-terminal portion of the protein partially mediates membrane binding. However, in absence of αK, there is still substantial binding of Irgm1 to cellular membranes, suggesting the presence of other membrane binding motifs. In the current work, an additional membrane localization motif was found in the form of palmitoylation at a cluster of cysteines near the αK. An Irgm1 mutant possessing alanine to cysteine substitutions at these amino acids demonstrated little residual palmitoylation, yet it displayed only a small decrease in localization to the Golgi and mitochondria. In contrast, a mutant containing the palmitoylation mutations in combination with mutations disrupting the amphipathic character of the αK displayed a complete loss of apparent localization to the Golgi and mitochondria, as well as an overall loss of association with cellular membranes in general. Additionally, Irgm1 was found to promote mitochondrial fission, and this function was undermined in Irgm1 mutants lacking the palmitoylation domain, and to a greater extent in those lacking the αK, or the αK and palmitoylation domains combined. Our data suggest that palmitoylation together with the αK helix firmly anchor Irgm1 in the Golgi and mitochondria, thus facilitating function of the protein.

  19. Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

    Science.gov (United States)

    Aznar, Aude; Chen, Nicolas W.G.; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

    2014-01-01

    Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H2O2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001

  20. Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Masaki Shimono

    Full Text Available Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of

  1. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Streeter, P.R.

    1985-01-01

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

  3. HIV-induced immune activation - pathogenesis and clinical relevance

    Directory of Open Access Journals (Sweden)

    Stellbrink HJ

    2010-01-01

    Full Text Available Abstract This manuscript is communicated by the German AIDS Society (DAIG http://www.daignet.de. It summarizes a series of presentations and discussions during a workshop on immune activation due to HIV infection. The workshop was held on November 22nd 2008 in Hamburg, Germany. It was organized by the ICH Hamburg under the auspices of the German AIDS Society (DAIG e.V..

  4. A Review of Immune Checkpoint Inhibitors for the Management of Locally Advanced or Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Hanna, Kirollos S

    2017-11-01

    Urothelial carcinoma (UC) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable. Stage IV metastatic disease is associated with only a 5% survival rate at 5 years. Gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin are the preferred regimens for individuals with advance, metastatic disease and a good performance status and organ function. Second-line therapies in this setting are limited. During the course of 1 year, five immune checkpoint inhibitors were approved for treatment of cancers in the locally advanced or metastatic setting: atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for UC. Based on the limited data, pembrolizumab and atezolizumab may be the drugs of choice, as they are supported by the most influential data to date; however, further research is warranted. Ongoing clinical trials will further assess the benefits of inducing cellular immunity in the treatment of UC. These therapies mark a new landscape in the treatment of UC. In this article, the available data on immune checkpoint inhibitors for the treatment of locally advanced or metastatic UC and their place in therapy are reviewed. © 2017 Pharmacotherapy Publications, Inc.

  5. Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment.

    Science.gov (United States)

    Salinas-Carmona, Mario Cesar; Rosas-Taraco, Adrian Geovanni; Welsh, Oliverio

    2012-10-01

    Human diseases produced by pathogenic actinomycetes are increasing because they may be present as opportunistic infections. Some of these microbes cause systemic infections associated with immunosuppressive conditions, such as chemotherapy for cancer, immunosuppressive therapy for transplant, autoimmune conditions, and AIDS; while others usually cause localized infection in immunocompetent individuals. Other factors related to this increase in incidence are: antibiotic resistance, not well defined taxonomy, and a delay in isolation and identification of the offending microbe. Examples of these infections are systemic disease and brain abscesses produced by Nocardia asteroides or the located disease by Nocardia brasiliensis, named actinomycetoma. During the Pathogenic Actinomycetes Symposium of the 16th International Symposium on Biology of Actinomycetes (ISBA), held in Puerto Vallarta, Mexico, several authors presented recent research on the mechanisms by which N. brasiliensis modulates the immune system to survive in the host and advances in medical treatment of human actinomycetoma. Antibiotics and antimicrobials that are effective against severe actinomycetoma infections with an excellent therapeutic outcome and experimental studies of drugs that show promising bacterial inhibition in vivo and in vitro were presented. Here we demonstrate a systemic strong acquired immune response in humans and experimental mice at the same time of a local dominance of anti inflammatory cytokines environment. The pathogenic mechanisms of some actinomycetes include generation of an immunosuppressive micro environment to evade the protective immune response. This information will be helpful in understanding pathogenesis and to design new drugs for treatment of actinomycetoma.

  6. Candesartan ameliorates impaired fear extinction induced by innate immune activation.

    Science.gov (United States)

    Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T

    2016-02-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 h after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Characterization of the early local immune response to Ixodes ricinus tick bites in human skin.

    Science.gov (United States)

    Glatz, Martin; Means, Terry; Haas, Josef; Steere, Allen C; Müllegger, Robert R

    2017-03-01

    Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick-bite skin lesions (skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Scintigraphic diagnosis and computed tomographic localization of an accessory spleen following relapse of chronic immune thrombocytopaenia

    International Nuclear Information System (INIS)

    Cardaci, G.T.; Blake, M.P.

    1992-01-01

    Chronic immune thrombocytopaenia is an immunologically mediated disorder resulting in disordered platelet kinetics and potentially life-threatening disease. Failure of medical therapy is an indication for splenectomy, and responses are seen in 80% of patients following this procedure. An important cause of relapse following splenectomy is the presence of an accessory spleen. A patient with Hodgkin's Disease developed chronic immune thrombocytopaenia despite previous splenectomy. A remission was induced with immunosuppressive therapy, but he later relapsed. An accessory spleen was detected using 99 m Tc denatured red blood cells and localized using computed tomography. Resection of the accessory spleen resulted in clinical remission. As accessory spleens are often small in size, combined modality imaging is recommended in the evaluation of this disorder. 15 refs., 2 figs

  9. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

    Directory of Open Access Journals (Sweden)

    Mones M. Abu Shady

    2015-07-01

    Conclusion: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

  10. Human Ebola virus infection results in substantial immune activation.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  11. Modification of glomerular immune complex deposition in mice by activation of the reticuloendothelial system.

    OpenAIRE

    Barcelli, U; Rademacher, R; Ooi, Y M; Ooi, B S

    1981-01-01

    To determine the effect of activation of the reticuloendothelial system on the localization of immune complexes in the kidney, a model of passive serum sickness nephritis in the mouse was used, with activation of the reticuloendothelial system with Corynebacterium parvum. Groups of mice, control and C. parvum-treated animals, were injected with BSA-125I-anti-BSA complexes containing 3 mg 125I-anti-BSA. Blood was obtained at 5 min, at 3 h, and at 12 h, when the animals were killed. Blood conce...

  12. Liver restores immune homeostasis after local inflammation despite the presence of autoreactive T cells.

    Science.gov (United States)

    Béland, Kathie; Lapierre, Pascal; Djilali-Saiah, Idriss; Alvarez, Fernando

    2012-01-01

    The liver must keep equilibrium between immune tolerance and immunity in order to protect itself from pathogens while maintaining tolerance to food antigens. An imbalance between these two states could result in an inflammatory liver disease. The aims of this study were to identify factors responsible for a break of tolerance and characterize the subsequent restoration of liver immune homeostasis. A pro-inflammatory environment was created in the liver by the co-administration of TLR ligands CpG and Poly(I:C) in presence or absence of activated liver-specific autoreactive CD8(+) T cells. Regardless of autoreactive CD8(+) T cells, mice injected with CpG and Poly(I:C) showed elevated serum ALT levels and a transient liver inflammation. Both CpG/Poly(I:C) and autoreactive CD8(+)T cells induced expression of TLR9 and INF-γ by the liver, and an up-regulation of homing and adhesion molecules CXCL9, CXCL10, CXCL16, ICAM-1 and VCAM-1. Transferred CFSE-labeled autoreactive CD8(+) T cells, in presence of TLR3 and 9 ligands, were recruited by the liver and spleen and proliferated. This population then contracted by apoptosis through intrinsic and extrinsic pathways. Up-regulation of FasL and PD-L1 in the liver was observed. In conclusion, TLR-mediated activation of the innate immune system results in a pro-inflammatory environment that promotes the recruitment of lymphocytes resulting in bystander hepatitis. Despite this pro-inflammatory environment, the presence of autoreactive CD8(+) T cells is not sufficient to sustain an autoimmune response against the liver and immune homeostasis is rapidly restored through the apoptosis of T cells.

  13. Liver restores immune homeostasis after local inflammation despite the presence of autoreactive T cells.

    Directory of Open Access Journals (Sweden)

    Kathie Béland

    Full Text Available The liver must keep equilibrium between immune tolerance and immunity in order to protect itself from pathogens while maintaining tolerance to food antigens. An imbalance between these two states could result in an inflammatory liver disease. The aims of this study were to identify factors responsible for a break of tolerance and characterize the subsequent restoration of liver immune homeostasis. A pro-inflammatory environment was created in the liver by the co-administration of TLR ligands CpG and Poly(I:C in presence or absence of activated liver-specific autoreactive CD8(+ T cells. Regardless of autoreactive CD8(+ T cells, mice injected with CpG and Poly(I:C showed elevated serum ALT levels and a transient liver inflammation. Both CpG/Poly(I:C and autoreactive CD8(+T cells induced expression of TLR9 and INF-γ by the liver, and an up-regulation of homing and adhesion molecules CXCL9, CXCL10, CXCL16, ICAM-1 and VCAM-1. Transferred CFSE-labeled autoreactive CD8(+ T cells, in presence of TLR3 and 9 ligands, were recruited by the liver and spleen and proliferated. This population then contracted by apoptosis through intrinsic and extrinsic pathways. Up-regulation of FasL and PD-L1 in the liver was observed. In conclusion, TLR-mediated activation of the innate immune system results in a pro-inflammatory environment that promotes the recruitment of lymphocytes resulting in bystander hepatitis. Despite this pro-inflammatory environment, the presence of autoreactive CD8(+ T cells is not sufficient to sustain an autoimmune response against the liver and immune homeostasis is rapidly restored through the apoptosis of T cells.

  14. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    Science.gov (United States)

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  15. Differential Effects of Naja naja atra Venom on Immune Activity

    Directory of Open Access Journals (Sweden)

    Jian-Qun Kou

    2014-01-01

    Full Text Available Previous studies reported that Naja naja atra venom (NNAV inhibited inflammation and adjuvant arthritis. Here we investigated the role of NNAV in regulation of immune responses in mice. Oral administration of NNAV to normal mice showed significant increase in natural killer cell activity, B lymphocyte proliferation stimulated by lipopolysaccharides, and antibody production in response to sheep red blood cells. Meanwhile, NNAV markedly decreased T lymphocyte proliferation stimulated by concanavalin A, arrested the cell cycle at G0/G1 phase, and suppressed CD4 and CD8 T cell divisions. Furthermore, NNAV inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reaction. This modulation of immune responses may be partly attributed to the selective increase in Th1 and Th2 cytokines (IFN-γ, IL-4 secretion and inhibition of Th17 cytokine (IL-17 production. In dexamethasone-induced immunosuppressed mice, NNAV restored the concentration of serum IgG and IgM, while decreasing the percentage of CD4 and CD8 T-cell subsets. These results indicate that NNAV enhances the innate and humoral immune responses while inhibiting CD4 Th17 and CD8 T cell actions, suggesting that NNAV could be a potential therapeutic agent for autoimmune diseases.

  16. The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity.

    Science.gov (United States)

    Leonhardt, Ines; Spielberg, Steffi; Weber, Michael; Albrecht-Eckardt, Daniela; Bläss, Markus; Claus, Ralf; Barz, Dagmar; Scherlach, Kirstin; Hertweck, Christian; Löffler, Jürgen; Hünniger, Kerstin; Kurzai, Oliver

    2015-03-17

    Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and macrophage inflammatory protein 1 alpha [MIP-1α]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance. Farnesol is a quorum-sensing molecule which controls morphological plasticity of the pathogenic yeast Candida albicans. As such, it is a major mediator of intraspecies communication. Here, we investigated the impact of farnesol on human innate immune cells known to be

  17. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

    Science.gov (United States)

    Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

    2014-10-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive. © 2014 Wiley Periodicals, Inc.

  18. Go local: morality and international activism

    Directory of Open Access Journals (Sweden)

    Aleksandar Jokic

    2013-03-01

    Full Text Available A step towards constructing an ethics of international activism is proposed by formulating a series of constraints on what would constitute morally permissible agency in the context that involves delivering services abroad, directly or indirectly. Perhaps surprisingly, in this effort the author makes use of the concept of ‘force multiplier’. This idea and its official applications have explanatory importance in considering the correlation between the post-Cold War phenomenal growth in the number of international non-governmental organizations and the emergence of the US as the sole, unchallenged superpower. Four moral constraints useful for morally assessing international activism are formulated and defended. The final outcome is an argument in favor of an overarching duty for any activist-minded Westerner to go local, while developing nations are urged to closely regulate, even criminalize, activities by international activists and ‘human rights organizations’ on their territory when not in solidarity or in support of local movements. The position defended, urging the normative primacy of local over international activism, also finds support in Immanuel Kant's Third Definitive Article for A Perpetual Peace.

  19. Planning and Implementing Immunization Billing Programs at State and Local Health Departments: Barriers and Possible Solutions.

    Science.gov (United States)

    Corriero, Rosemary; Redmon, Ginger

    Before participating in a project funded by the Centers for Disease Control and Prevention, most state and local health departments (LHDs) were not seeking reimbursement or being fully reimbursed by insurance plans for the cost of immunization services (including vaccine costs and administration fees) they provided to insured patients. Centers for Disease Control and Prevention's Billables Project was designed to enable state and LHDs to bill public and private insurance plans for immunization services provided to insured patients. Identify and describe key barriers state and LHDs may encounter while planning and implementing a billing program, as well as possible solutions for overcoming those barriers. This study used reports from Billables Project participants to explore barriers they encountered when planning and implementing a billing program and steps taken to address those barriers. Thirty-eight state immunization programs. Based on project participants' reports, barriers were noted in 7 categories: (1) funding and costs, (2) staff, (3) health department characteristics, (4) third-party payers and insurance plans, (5) software, (6) patient insurance status, and (7) other barriers. Possible solutions for overcoming those barriers included hiring or seeking external help, creating billing guides and training modules, streamlining workflows, and modifying existing software systems. Overcoming barriers during planning and implementation of a billing program can be challenging for state and LHDs, but the experiences and suggestions of past Billables Project participants can help guide future billing program efforts.

  20. Use of the local lymph node assay in assessment of immune function

    International Nuclear Information System (INIS)

    Berg, Femke A. van den; Baken, Kirsten A.; Vermeulen, Jolanda P.; Gremmer, Eric R.; Steeg, Harry van; Loveren, Henk van

    2005-01-01

    The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene (B[a]P). Subsequently, cell proliferation and interferon-γ (IFN-γ) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse

  1. Use of the local lymph node assay in assessment of immune function.

    Science.gov (United States)

    van den Berg, Femke A; Baken, Kirsten A; Vermeulen, Jolanda P; Gremmer, Eric R; van Steeg, Harry; van Loveren, Henk

    2005-07-01

    The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene, (B[a]P). Subsequently, cell proliferation and interferon-gamma (IFN-gamma) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse.

  2. Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

    Science.gov (United States)

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-01-01

    Neuroblastoma is the most common extra cranial solid tumour of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumour cells suppress T cell proliferation, through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34+ progenitor proliferation. Finally we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1 specific TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

  3. Evaluation of local immune response to Fasciola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigen

    Directory of Open Access Journals (Sweden)

    Ricardo E Mendes

    2010-08-01

    Full Text Available Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14 was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN. The goats used consisted of group 1 (unimmunized and uninfected, group 2 [infected control - immunized with Quillaia A (Quil A] and group 3 (immunized with rSm14 in Quil A and infected, each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6% (p < 0.001 and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05. This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.

  4. EXPENSES FOR ECONOMIC ACTIVITIES FROM LOCAL BUDGETS

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    CRISTINEL ICHIM

    2015-04-01

    Full Text Available In the present article we propose to analyze and deepen significant categories of costs funded from the local budgets, namely the expenditure for economic activities. Our scientific approach begins with determining the place occupied by such expenses in local public expenditure by specifying their content and role. The center of gravity of the study is to treat and deepen the three subgroups of expenses that we consider representative: "The expenses for production, transportation, distribution and supply of heat in a centralized system", "Transport Costs" and Expenditure for agriculture and forestry ". The reaserch is based on the quantitative analysis of the expenses for economic actions, in local budgets, based on the existing data from the Statistical Yearbook of Romania, and highlights the structure of this type of expenses as well as the place they hold in the expediture of local budgets.The study includes an analysis of the dynamics of the share held by economic costs within total expenses from local budgets. From the reaserch carried out, it is shown that the evolution and structure of the expenditures for economic actions from local budgets is determined by the action of certain economical and social factors that vary from one administrative teritorial unit to another: the ray of economical develpoment of the administrative ter itorial unit, urbanization, the number and social structure of the population. The reaserch shows that in the field of expenses for economic actions, the largest share is held by expenditures for transportation (almost 80%, far away from the expenses for fuel and energy (13,66%. During the 1999-2013 the dynamic of expenses for economical actions in the total of expenditures of local budgets, is sinusoidal due to the intervention of certain legislative changes.

  5. Local and systemic immune responses following infection of broiler-type chickens with avian Metapneumovirus subtypes A and B.

    Science.gov (United States)

    Rautenschlein, Silke; Aung, Ye Htut; Haase, Christine

    2011-03-15

    Infections with avian Metapneumovirus (aMPV) are often associated with swollen head syndrome in meat type chickens. Previous studies in turkeys have demonstrated that local humoral and cell-mediated immunity plays a role in aMPV-infection. Previous experimental and field observations indicated that the susceptibility of broilers and their immune reactions to aMPV may differ from turkeys. In the presented study local and systemic immune reactions of broilers were investigated after experimental infections with subtypes A and B aMPV of turkey origin. Both virus subtypes induced a mild respiratory disease. The recovery from respiratory signs correlated with the induction of local and systemic aMPV virus-neutralizing antibodies, which began to rise at 6 days post infection (dpi), when the peak of clinical signs was observed. In a different manner to the virus neutralizing (VN) and IgG-ELISA serum antibody titres, which showed high levels until the end of the experiments between 24 and 28 dpi, the specific IgA-ELISA and VN-antibody levels in tracheal washes decreased by 10 and 14 dpi, respectively, which may explain the recurring aMPV-infections in the field. Ex vivo cultured spleen cells from aMPV-infected broilers released at 3 and 6 dpi higher levels of IFN-γ after stimulation with Concanavalin A as compared to virus-free birds. In agreement with studies in turkeys, aMPV-infected broilers showed a clear CD4+ T cell accumulation in the Harderian gland (HG) at 6 dpi (P<0.05). In contrast to other investigations in turkeys aMPV-infected broilers showed an increase in the number of CD8alpha+ cells at 6 dpi compared to virus-free birds (P<0.05). The numbers of local B cells in the Harderian gland were not affected by the infection. Both aMPV A and B induced up-regulation of interferon (IFN)-γ mRNA-expression in the nasal turbinates, while in the Harderian gland only aMPV-A induced enhanced IFN-γ expression at 3 dpi. The differences in systemic and local T cell and

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

    OpenAIRE

    Nurmasitoh, Titis

    2015-01-01

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

  7. Immune activation by histones: plusses and minuses in inflammation.

    Science.gov (United States)

    Pisetsky, David S

    2013-12-01

    Histones are highly cationic proteins that are essential components of the cell nucleus, interacting with DNA to form the nucleosome and regulating transcription. Histones, however, can transit from the cell nucleus during cell death and, once in an extracellular location, can serve as danger signals and activate immune cells. An article in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 3336-3342] reports that histones can activate monocyte-derived DCs via the NRLP3 inflammasome to induce the production of IL-1β. As such, histones, which can also stimulate TLRs, may drive events in the immunopathogenesis of a wide range of acute and chronic diseases marked by sterile inflammation. While the mechanism of this stimulation is not known, the positive charge of histones may provide a structural element to promote interaction with cells and activation of downstream signaling systems. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Systemic and local immune response in pigs intradermally and intramuscularly injected with inactivated Mycoplasma hyopneumoniae vaccines.

    Science.gov (United States)

    Martelli, P; Saleri, R; Cavalli, V; De Angelis, E; Ferrari, L; Benetti, M; Ferrarini, G; Merialdi, G; Borghetti, P

    2014-01-31

    The systemic and respiratory local immune response induced by the intradermal administration of a commercial inactivated Mycoplasma hyopneumoniae whole-cell vaccine (Porcilis(®) MHYO ID ONCE - MSD AH) in comparison with two commercial vaccines administered via the intramuscular route and a negative control (adjuvant only) was investigated. Forty conventional M. hyopneumoniae-free pigs were randomly assigned to four groups (ten animals each): Group A=intradermal administration of the test vaccine by using the needle-less IDAL(®) vaccinator at a dose of 0.2 ml; Group B=intramuscular administration of a commercially available vaccine (vaccine B); Group C=intramuscular administration of the adjuvant only (2 ml of X-solve adjuvant); Group D=intramuscular administration of a commercially available vaccine (vaccine D). Pigs were vaccinated at 28 days of age. Blood and bronchoalveolar lavage (BAL) fluid samples were collected at vaccination (blood only), 4 and 8 weeks post-vaccination. Serum and BAL fluid were tested for the presence of antibodies by ELISA test. Peripheral blood monomorphonuclear cells (PBMC) were isolated to quantify the number of IFN-γ secreting cells by ELISpot. Moreover, cytokine gene expression from the BAL fluid was performed. Total antibodies against M. hyopneumoniae and specific IgG were detected in serum of intradermally and intramuscularly (vaccine B only) vaccinated pigs at 4 and 8 weeks post-vaccination. M. hyopneumoniae specific IgA were detected in BAL fluid from vaccinated animals (Groups A and B) but not from controls and animals vaccinated with the bacterin D (padministration of an adjuvanted bacterin induces both systemic and mucosal immune responses. Moreover, the intramuscularly administered commercial vaccines each had a different ability to stimulate the immune response both systemically and locally. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Early Subretinal Allograft Rejection Is Characterized by Innate Immune Activity.

    Science.gov (United States)

    Kennelly, Kevin P; Holmes, Toby M; Wallace, Deborah M; O'Farrelly, Cliona; Keegan, David J

    2017-06-09

    Successful subretinal transplantation is limited by considerable early graft loss despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a nonimmunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation, and the neutrophil chemoattractant KC/GRO/CINC was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, nonimmunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7, and 28 days postoperatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b and F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ɛ) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using the Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p < 0.001) reduced between postoperative day (POD) 3 (90 ± 4%) and POD 7 (20 ± 7%). CD11b+, F4/80+, and Gr1 Ly-6G+ cells increased significantly (p < 0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Colabeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7, and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ɛ was low and did not differ significantly between time points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal, for the first time, a critical role for innate immune mechanisms early in subretinal graft rejection. The future success

  10. Immune activation by nucleic acids: A role in pregnancy complications.

    Science.gov (United States)

    Konečná, B; Lauková, L; Vlková, B

    2018-04-01

    Cell-free self-DNA or RNA may induce an immune response by activating specific sensing receptors. During pregnancy, placental nucleic acids present in the maternal circulation further activate these receptors due to the presence of unmethylated CpG islands. A higher concentration of cell-free foetal DNA is associated with pregnancy complications and a higher risk for foetal rejection. Cell-free foetal DNA originates from placental trophoblasts. It appears in different forms: free, bound to histones in nucleosomes, in neutrophil extracellular traps (NETs) and in extracellular vesicles (EVs). In several pregnancy complications, cell-free foetal DNA triggers the production of proinflammatory cytokines, and this production results in a cellular and humoral immune response. This review discusses preeclampsia, systemic lupus erythematosus, foetal growth restriction, gestational diabetes, rheumatoid arthritis and obesity in pregnancy from an immunological point of view and closely examines the different pathways that result in maternal inflammation. Understanding the role of cell-free nucleic acids, as well as the biogenesis of NETs and EVs, will help us to specify their functions or targets, which seem to be important in pregnancy complications. It is still not clear whether higher concentrations of cell-free nucleic acids in the maternal circulation are the cause or consequence of various complications. Therefore, further clinical studies and, even more importantly, animal experiments that focus on the involved immunological pathways are needed. © 2018 The Foundation for the Scandinavian Journal of Immunology.

  11. Liposomal α-galactosylceramide is taken up by gut-associated lymphoid tissue and stimulates local and systemic immune responses.

    Science.gov (United States)

    Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

    2017-12-01

    α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration. Fluorescently labelled cationic liposomes incorporating α-GalCer were prepared, characterized and administered by oral gavage to fasted mice. Liposomes were detected inside the Peyer's patches (PPs), in the subepithelial dome just under the follicle-associated epithelium. CD11b + cells and CD11c + were shown to have taken up the formulation in a higher proportion compared to the total cell proportion in the PPs, suggesting that cells with these markers may be the prominent antigen-presenting cells involved in selective uptake. Finally, the liposomal formulation demonstrated a higher degree of immune stimulation compared to the DMSO/Tween 80 solubilized α-GalCer in the PPs, mesenteric lymph nodes and spleen as shown by the increased expression of IL-4 mRNA expression and increased proportion of NKT cells at 6 h and 3 days after administration. These results show that oral delivery of a liposomal α-GalCer can stimulate local and systemic immune responses to a different degree compared to the non-liposomal form. © 2017 Royal Pharmaceutical Society.

  12. Metabolic signals and innate immune activation in obesity and exercise.

    Science.gov (United States)

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

  13. Regulation of NO synthesis, local inflammation, and innate immunity to pathogens by BET family proteins.

    Science.gov (United States)

    Wienerroither, Sebastian; Rauch, Isabella; Rosebrock, Felix; Jamieson, Amanda M; Bradner, James; Muhar, Matthias; Zuber, Johannes; Müller, Mathias; Decker, Thomas

    2014-02-01

    Transcriptional activation of the Nos2 gene, encoding inducible nitric oxide synthase (iNOS), during infection or inflammation requires coordinate assembly of an initiation complex by the transcription factors NF-κB and type I interferon-activated ISGF3. Here we show that infection of macrophages with the intracellular bacterial pathogen Listeria monocytogenes caused binding of the BET proteins Brd2, Brd3, and, most prominently, Brd4 to the Nos2 promoter and that a profound reduction of Nos2 expression occurred in the presence of the BET inhibitor JQ1. RNA polymerase activity at the Nos2 gene was regulated through Brd-mediated C-terminal domain (CTD) phosphorylation at serine 5. Underscoring the critical importance of Brd for the regulation of immune responses, application of JQ1 reduced NO production in mice infected with L. monocytogenes, as well as innate resistance to L. monocytogenes and influenza virus. In a murine model of inflammatory disease, JQ1 treatment increased the colitogenic activity of dextran sodium sulfate (DSS). The data presented in our study suggest that BET protein inhibition in a clinical setting poses the risk of altering the innate immune response to infectious or inflammatory challenge.

  14. Advantages of laparoscopic compared to conventional surgery are not related to an innate immune response of peritoneal immune activation: an animal study in rats.

    Science.gov (United States)

    Lingohr, Philipp; Dohmen, Jonas; Matthaei, Hanno; Schwandt, Timo; Stein, Kathy; Hong, Gun-Soo; Steitz, Julia; Longerich, Thomas; Bölke, Edwin; Wehner, Sven; Kalff, Jörg C

    2017-06-01

    Laparoscopic surgery (LS) has proved superior compared to conventional surgery (CS) regarding morbidity, length of hospital stay, rate of wound infection and time until recovery. An improved preservation of the postoperative immune function is assumed to contribute to these benefits though the role of the local peritoneal immune response is still poorly understood. Our study investigates the peritoneal immune response subsequent to abdominal surgery and compares it between laparoscopic and conventional surgery to find an immunological explanation for the clinically proven benefits of LS. Wistar rats (N = 140) underwent laparoscopic cecum resection (LCR; N = 28), conventional cecum resection (CCR; N = 28), laparoscopic sham operation (LSO; N = 28), conventional sham operation (CSO; N = 28), or no surgical treatment (CTRL; N = 28). Postoperatively, peritoneal lavages were performed, leukocytes isolated and analyzed regarding immune function and phagocytosis activity. Immune function was inhibited postoperatively in animals undergoing LCR or CCR compared to CTRL reflected by a lower TNF-α (CTRL 3956.65 pg/ml, LCR 2018.48 pg/ml (p = 0.023), CCR 2793.78 pg/ml (n.s.)) and IL-6 secretion (CTRL 625.84 pg/ml, LCR 142.84 pg/ml (p = 0.009), CCR 169.53 pg/ml (p = 0.01)). Phagocytosis was not affected in rats undergoing any kind of surgery compared to CTRL. Neither cytokine secretion nor phagocytosis activity differed significantly between laparoscopic and conventional surgery. According to our findings the benefits associated with LS compared to CS cannot be explained by differences in the postoperative peritoneal innate immune response. Further studies are needed to elucidate the causes for a more favorable postoperative outcome in patients after LS compared to CS.

  15. Active surveillance for localized prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Berg, Kasper D; Røder, M Andreas

    2015-01-01

    and costs of AS in patients with localized PCa. MATERIALS AND METHODS: In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications......OBJECTIVE: Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory...

  16. Active surveillance for localized prostate cancer

    DEFF Research Database (Denmark)

    Thostrup, Mathias; Thomsen, Frederik B; Iversen, Peter

    2018-01-01

    risk of biochemical recurrence were investigated and compared in men with very low-risk, low-risk and intermediate-risk PCa in the cohort. MATERIALS AND METHODS: In total, 451 men were followed on AS and monitored with prostate-specific antigen (PSA) tests, digital rectal examinations and rebiopsies......OBJECTIVE: The purpose of active surveillance (AS) is to reduce overtreatment of men with localized prostate cancer (PCa) without compromising survival. The objective of this study was to update a large Scandinavian single-center AS cohort. Furthermore, the use of curative treatment and subsequent...

  17. PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

    Science.gov (United States)

    Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

    2017-11-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be

  18. Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study.

    Science.gov (United States)

    Mirjolet, C; Charon-Barra, C; Ladoire, S; Arbez-Gindre, F; Bertaut, A; Ghiringhelli, F; Leroux, A; Peiffert, D; Borg, C; Bosset, J F; Créhange, G

    2018-01-01

    Introduction : Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods : We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impact of infiltration of the tumor or tumor site after preopRT on progression-free survival (PFS) and overall survival (OS). Secondary endpoints were the impact of dose fractionation scheme on TILs. Results : In univariate analysis, several factors significantly correlated (pguide physicians in adjuvant treatment decision-making.

  19. No evidence of local adaptation of immune responses to Gyrodactylus in three-spined stickleback (Gasterosteus aculeatus).

    Science.gov (United States)

    Robertson, Shaun; Bradley, Janette E; MacColl, Andrew D C

    2017-01-01

    Parasitism represents one of the most widespread lifestyles in the animal kingdom, with the potential to drive coevolutionary dynamics with their host population. Where hosts and parasites evolve together, we may find local adaptation. As one of the main host defences against infection, there is the potential for the immune response to be adapted to local parasites. In this study, we used the three-spined stickleback and its Gyrodactylus parasites to examine the extent of local adaptation of parasite infection dynamics and the immune response to infection. We took two geographically isolated host populations infected with two distinct Gyrodactylus species and performed a reciprocal cross-infection experiment in controlled laboratory conditions. Parasite burdens were monitored over the course of the infection, and individuals were sampled at multiple time points for immune gene expression analysis. We found large differences in virulence between parasite species, irrespective of host, and maladaptation of parasites to their sympatric host. The immune system responded to infection, with a decrease in expression of innate and Th1-type adaptive response genes in fish infected with the less virulent parasite, representing a marker of a possible resistance mechanism. There was no evidence of local adaptation in immune gene expression levels. Our results add to the growing understanding of the extent of host-parasite local adaptation, and demonstrate a systemic immune response during infection with a common ectoparasite. Further immunological studies using the stickleback-Gyrodactylus system can continue to contribute to our understanding of the function of the immune response in natural populations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

    Directory of Open Access Journals (Sweden)

    Alexandra E Folias

    Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

  1. The Immune Pathogenesis of Immune Reconstitution Inflammatory Syndrome Associated with Highly Active Antiretroviral Therapy in AIDS

    Science.gov (United States)

    Zhou, Huaying; He, Yan; Chen, Zi; He, Bo; He, Mei

    2014-01-01

    Abstract The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4+ and CD8+ naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4+CD25+Foxp3+ regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-γ levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD+CD25+Fox3+ percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART. PMID:25131160

  2. Mechanisms and pathways of innate immune activation and regulation in health and cancer.

    Science.gov (United States)

    Cui, Jun; Chen, Yongjun; Wang, Helen Y; Wang, Rong-Fu

    2014-01-01

    Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer.

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

    Directory of Open Access Journals (Sweden)

    Arunita Chatterjee

    2016-06-01

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

  4. A study of the localized humoral immune response to implicated microorganisms in juvenile periodontitis

    International Nuclear Information System (INIS)

    Hall, E.R.

    1988-01-01

    A study was undertaken using an in vitro explant culture system to determine the presence of immunoglobulins (IgG, IgA, and IgM) in the supernatant fluids (SF) of disease gingival tissue explant cultures. Studies were also undertaken to determine if the de novo biosynthesis of 14 C-immunoglobulins could be observed in the explant cultures of diseased tissues from juvenile periodontitis (JP) patients. Radiolabeled proteins were detected in the SF and immunodiffusion studies using goat antihuman gamma, alpha or mu chain serum revealed the presence of IgG and IgA but no IgM present in the SF of the JP gingival tissue explant cultures. Immunodiffusion studies using goat anti-human gamma chain serum with Staph protein A isolated IgG fractions of the SF, followed by autoradiography of the IgG precipitation lines demonstrated the biosynthesis of IgG by the JP gingival tissue explant cultures. The serological studies suggested that local immune response in JP was to a polymicrobic infection. The SF of JP showed significantly higher levels of antibody reactivity to B. intermedius, C. ochracea, E. nodatum and P. micros as compared to healthy tissues. The local antibody response to the microorganisms tested differed from that observed in the sera of the patients

  5. A study of the localized humoral immune response to implicated microorganisms in juvenile periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Hall, E.R.

    1988-01-01

    A study was undertaken using an in vitro explant culture system to determine the presence of immunoglobulins (IgG, IgA, and IgM) in the supernatant fluids (SF) of disease gingival tissue explant cultures. Studies were also undertaken to determine if the de novo biosynthesis of {sup 14}C-immunoglobulins could be observed in the explant cultures of diseased tissues from juvenile periodontitis (JP) patients. Radiolabeled proteins were detected in the SF and immunodiffusion studies using goat antihuman gamma, alpha or mu chain serum revealed the presence of IgG and IgA but no IgM present in the SF of the JP gingival tissue explant cultures. Immunodiffusion studies using goat anti-human gamma chain serum with Staph protein A isolated IgG fractions of the SF, followed by autoradiography of the IgG precipitation lines demonstrated the biosynthesis of IgG by the JP gingival tissue explant cultures. The serological studies suggested that local immune response in JP was to a polymicrobic infection. The SF of JP showed significantly higher levels of antibody reactivity to B. intermedius, C. ochracea, E. nodatum and P. micros as compared to healthy tissues. The local antibody response to the microorganisms tested differed from that observed in the sera of the patients.

  6. 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.

  7. 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

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

    Science.gov (United States)

    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.

  9. Immune-suppressive activity of punicalagin via inhibition of NFAT activation

    International Nuclear Information System (INIS)

    Lee, Sang-Ik; Kim, Byoung-Soo; Kim, Kyoung-Shin; Lee, Samkeun; Shin, Kwang-Soo; Lim, Jong-Soon

    2008-01-01

    Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies

  10. Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

    Science.gov (United States)

    Zhou, Haoming; Wang, Han; Ni, Ming; Yue, Shi; Xia, Yongxiang; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2018-02-13

    Glycogen synthase kinase 3β (Gsk3β [Gsk3b]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo. We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model. Compared with controls, myeloid Gsk3b KO mice were protected from IRI, with diminished proinflammatory but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages, Gsk3β deficiency resulted in an early reduction of Tnf gene transcription but sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation in vitro. These effects were associated with enhanced AMP-activated protein kinase (AMPK) activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP [Nr0b2]). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β Ser9 phosphorylation and the phosphoinositide 3-kinase-Akt signalling pathway. In vivo, myeloid Gsk3β deficiency facilitated SHP upregulation by ischaemia-reperfusion in liver macrophages. Treatment of Gsk3b KO mice with either AMPK inhibitor or SHP small interfering RNA before the onset of liver ischaemia restored liver proinflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected wild-type mice from liver IRI, with reduced proinflammatory immune activation. Inhibition of the AMPK-SHP pathway by liver ischaemia was demonstrated in tumour resection

  11. Effect of ionizing radiation on active thyroid immunity

    International Nuclear Information System (INIS)

    Ibrahim, I.I.; Abdelaal, A.E.; AL-Gachari, A.I.; Hindy, O.W.; Abdalla, M.I.; Said, M.M.; Shoucha, M.A.; and Salama, F.M.

    1988-01-01

    The present study was carried out to explore the effect of exposure to ionizing radiation on the immune system in cocks. A total number of 36 mature Fayoumi cocks were randomly assigned to: control, 300 R and 600 r groups. Whole body irradiation was carried out in co-60 unit 24 hours. Prior to induction of immunity. Thyroglobulin (T G) immunity was induced in all birds and sera were collected before, 1, 2, 4, 6, 8 and 16 weeks. After immunization. T G antibodies were evaluated by using radioisotopic techniques: i- Ammonium sulphate method, ii-polyethylene glycol method and iii-The circulating thyroid hormones. The results obtained indicated the formation of thyroglobulin antibodies in all immunized birds at 6 weeks. After immunization and thereafter, although it was detected in some birds at 4 weeks. after immunization. The antibody titer increased sharply after the sixth Th week reaching its peak value at the sixteenth week interval. The suppressive effect of ionizing radiation on the immune response was evident in the irradiated groups, particularly the 600 r group. Some birds in the 600 r group were not able to respond appropriately to the challenge and did not survive until the end of observation period

  12. Immune adjuvant activity of the olive, soybean and corn oils

    Directory of Open Access Journals (Sweden)

    Ana Claudia Marinho da Silva

    2016-08-01

    Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

  13. Immune algorithm based active PID control for structure systems

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  14. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

    Science.gov (United States)

    Shan, Liang; Siliciano, Robert F.

    2014-01-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  15. Local Immune Homeostasis of Gastric Mucosa in Chronic CagA-positive Hр-associated Gastritis in Children

    Directory of Open Access Journals (Sweden)

    O.Ye. Abaturov

    2012-04-01

    Full Text Available The article deal with study of lymphocyte-macrophage link of the gastric mucosa local immunity in Hр-associated chronic gastritis, taking into account the presence of the cytotoxin-associated gene A (CagA Hр through a standard morphological examination according to the Modified Sydney System and immunohistochemical studies of biopsy specimens.

  16. Immune activation affects chemical sexual ornaments of male Iberian wall lizards

    Science.gov (United States)

    López, Pilar; Gabirot, Marianne; Martín, José

    2009-01-01

    Many animals use chemical signals in sexual selection, but it is not clear how these sexual traits might have evolved to signal honestly male condition. It is possible that there is a trade-off between maintaining the immune system and the elaboration of ornaments. We experimentally challenged the immune system of male Iberian wall lizards, Podarcis hispanica, with a bacterial antigen (lipopolysaccharide), without pathogenic effects, to explore whether the immune activation affected chemical ornaments. Immune activation resulted in decreased proportions of a major chemical in femoral secretions (cholesta-5,7-dien-3-ol = provitamin D3) known to be selected in scent of males by females and which active form (vitamin D) has a variety of important effects on immune system function. This result suggests the existence of a potential trade-off between physiological regulation of the immune system and the allocation of essential nutrients (vitamins) to sexual chemical ornaments in male lizards.

  17. Functional Bowel Disorders Are Associated with a Central Immune Activation

    Directory of Open Access Journals (Sweden)

    Per G. Farup

    2017-01-01

    Full Text Available Background. Subjects with depression and unexplained neurological symptoms have a high prevalence of gastrointestinal comorbidity probably related to the brain-gut communication. This study explored associations between functional gastrointestinal disorders (FGID and inflammatory markers in subjects with these disorders. Methods. The FGID, including irritable bowel syndrome (IBS, were classified according to the Rome III criteria, and degree of symptoms was assessed with IBS symptom severity score (IBS-SSS. A range of interleukins (IL, chemokines and growth factors, tryptophan, and kynurenine were analysed in serum and the cerebrospinal fluid (CSF, and short-chain fatty acids (SCFA were analysed in the faeces. The results are reported as partial correlation (pc and p values. Results. Sixty-six subjects were included. IBS was associated with high levels of tryptophan (p=0.048 and kynurenine (p=0.019 and low level of IL-10 (p=0.047 in the CSF. IBS-SSS was associated with high tumor necrosis factor and low IL-10 in the CSF; pc=0.341 and p=0.009 and pc=−0.299 and p=0.023, respectively. Propionic minus butyric acid in faeces was negatively associated with IL-10 in the CSF (pc=−0.416, p=0.005. Conclusions. FGID were associated with a proinflammatory immune activation in the central nervous system and a disturbed tryptophan metabolism that could have been mediated by the faecal microbiota.

  18. Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

    Directory of Open Access Journals (Sweden)

    Barbara Ensoli

    2010-11-01

    Full Text Available Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002. Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002, served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+ and CD8(+ cellular activation (CD38 and HLA-DR together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+ T cells and B cells with reduction of CD8(+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+ and CD8(+ T cells were accompanied by increases of CD4(+ and CD8(+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite

  19. Localization of cortical areas activated by thinking.

    Science.gov (United States)

    Roland, P E; Friberg, L

    1985-05-01

    These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work in the form of operations on internal information, done by an awake subject. The rCBF was measured in 254 cortical regions in 11 subjects with the intracarotid 133Xe injection technique. In normal man, changes in the regional cortical metabolic rate of O2 leads to proportional changes in rCBF. One control study was taken with the subjects at rest. Then the rCBF was measured during three different simple algorithm tasks, each consisting of retrieval of a specific memory followed by a simple operation on the retrieved information. Once started, the information processing went on in the brain without any communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined that they started at their front door and then walked alternatively to the left or the right each time they reached a corner. The rCBF increased only in homotypical cortical areas during thinking. The areas in the superior prefrontal cortex increased their rCBF equivalently during the three types of thinking. In the remaining parts of the prefrontal cortex there were multifocal increases of rCBF. The localizations and intensities of these rCBF increases depended on the type of internal operation occurring. The rCBF increased bilaterally in the angular cortex during 50-3 thinking. The rCBF increased in the right midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and

  20. Mechanisms and kinetics for platelet and neutrophil localization in immune complex nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, R.J.; Alpers, C.E.; Pruchno, C.; Schulze, M.; Baker, P.J.; Pritzl, P.; Couser, W.G. (Univ. of Washington, Seattle (USA))

    1989-11-01

    We have previously reported that both neutrophils (PMNs) and platelets mediate proteinuria in a model of subendothelial immune complex (IC) nephritis (GN) in the rat. In order to understand the interaction of PMNs and platelets in this model, we quantitated the uptake of {sup 111}In-labelled platelets in glomeruli and correlated this with the number of PMNs observed histologically at 10 and 30 minutes, 1, 4 and 24 hours following induction of GN. Platelet accumulation was biphasic with a major peak at 10 minutes and a minor peak at four hours. Early platelet accumulation was complement dependent, and PMN-independent. PMN accumulation occurred after the initial platelet influx, peaking at one and four hours, was complement dependent, but was not affected by platelet depletion. Complement depletion significantly reduced proteinuria. This is the first documentation that platelet accumulation in glomeruli in IC GN is complement dependent. In addition, the enhancement of PMN-mediated injury by the platelet in this model does not involve effects of platelets on PMN localization, thus implying a functional interaction between these cells within the glomerulus.

  1. Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma.

    Science.gov (United States)

    Higashi-Kuwata, Nobuyo; Makino, Takamitsu; Inoue, Yuji; Takeya, Motohiro; Ihn, Hironobu

    2009-08-01

    Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.

  2. Linalool Exhibits Cytotoxic Effects by Activating Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Mei-Yin Chang

    2014-05-01

    Full Text Available According to recent studies, the Plantaginaceae, which are traditional Chinese herbal remedies, have potential for use in viral infection treatment and cancer therapy. Linalool and p-coumaric acid are two of the biologically active compounds that can be isolated from the Plantaginaceae. This study mainly focused on investigating the bioactivity of linalool as well as the bioactivity of p-coumaric acid in terms of their cytotoxic effects on cancer cells. Whether the mechanisms of such effects are generated through apoptosis and immunoregulatory activity were also investigated. By using WST-1 analysis, it was shown that linalool and p-coumaric acid have good inhibitory effects against breast, colorectal and liver cancer cells. The IC50 values of linalool for those cancer cell types were 224 μM, 222 μM, and 290 μM, respectively, and the IC50 values of p-coumaric acid were 693 μM, 215 μM and 87 μM, respectively. Cell cycle analysis also confirmed that linalool and p-coumaric acid can lead to apoptosis. By using flow cytometry, it was determined that treatment with linalool rather than p-coumaric acid significantly increased the sub-G1 phase and that there were more cells concentrated in the G1 phase. Furthermore, by using cytokine array analysis, we found that linalool can stimulate IFN-γ, IL-13, IL-2, IL-21, IL-21R, IL-4, IL-6sR and TNF-α secretion. This demonstrated that in addition to the bidirectional regulation capabilities found in linalool, it also induces Th1 cellular immune response in T-47D cells. These results showed that linalool holds great potential for use in cancer therapy, and we believe that it could provide an alternative way to take action against tumors.

  3. Nutrition, Physical Activity, and Obesity - National Immunization Survey (Breastfeeding)

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes breastfeeding data from the National Immunization Survey (NIS). This data is used for DNPAO's Data, Trends, and Maps database, which provides...

  4. Immune activation by casein dietary antigens in bipolar disorder

    NARCIS (Netherlands)

    Severance, E.G.; Dupont, D.; Dickerson, F.B.; Stallings, C.R.; Origoni, A.E.; Krivogorsky, B.; Yang, S.; Haasnoot, W.; Yolken, R.H.

    2010-01-01

    Objectives: Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized

  5. Characterization of the local immune response to cyst antigens during the acute and elimination phases of primary murine giardiasis.

    Science.gov (United States)

    Abdul-Wahid, Aws; Faubert, Gaétan

    2008-05-01

    . Regardless of the Ag tested, a trend was consistently observed where the concentration of local antibodies was found to be slightly increased by the acute phase, where we detected approximately 200microg/mg of specific IgA and approximately 300ng/ml of specific IgG in intestinal lavage of infected mice. By the elimination phase, the amount of specific antibodies was found to increase to approximately 600microg/mg of specific IgA and approximately 1300ng/ml of specific IgG antibodies. Finally, we tested the biological activity of these antibodies and found that they were able to reduce the ability of trophozoites to differentiate into cysts in vitro. Collectively, we believe these results demonstrate for the first time the existence of significant cellular and humoral immune responses against Giardia cyst Ags that may contribute to the reduction of cyst shedding in infected animals.

  6. Activation of glioma cells generates immune tolerant NKT cells.

    Science.gov (United States)

    Tang, Bo; Wu, Wei; Wei, Xiaowei; Li, Yang; Ren, Gang; Fan, Wenhai

    2014-12-12

    Therapeutic outcomes of glioma are currently not encouraging. Tumor tolerance plays an important role in the pathogenesis of glioma. It is reported that micro RNAs (miR) are associated with tumor development. This study aims to investigate the role of miR-92a in the development of tolerant natural killer T (NKT) cells. In this study, U87 cells (a human glioma cell line) and primary glioma cells were prepared. The assessment of miR-92a was performed by real time RT-PCR. The expression of interleukin (IL)-10 and IL-6 in NKT cells was evaluated by flow cytometry. Results showed that abundant IL-6(+) IL-10(+) NKT cells were detected in glioma tissue. Cultures of glioma cells and NKT cells induced the expression of IL-6 and IL-10 in NKT cells. Glioma cells expressed miR-92a; the latter played a critical role in the induction of IL-6 and IL-10 expression in NKT cells. The expression of the antitumor molecules, including perforin, Fas ligand, and interferon-γ, was significantly attenuated compared with control NKT cells. The IL-6(+) IL-10(+) NKT cells showed less capability in the induction of apoptosis in glioma cells, but showed the immune suppressor functions on CD8(+) T cell activities. We conclude that glioma-derived miR-92a induces IL-6(+) IL-10(+) NKT cells; this fraction of NKT cells can suppress cytotoxic CD8(+) T cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity.

    Directory of Open Access Journals (Sweden)

    Manikandan Subramanian

    Full Text Available Obesity-induced inflammation in visceral adipose tissue (VAT is a major contributor to insulin resistance and type 2 diabetes. Whereas innate immune cells, notably macrophages, contribute to visceral adipose tissue (VAT inflammation and insulin resistance, the role of adaptive immunity is less well defined. To address this critical gap, we used a model in which endogenous activation of T cells was suppressed in obese mice by blocking MyD88-mediated maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T cells in vitro, and VAT T and B cell activation was markedly reduced in Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice, thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting blood glucose, plasma insulin, and the glucose response to glucose and insulin were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus, CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this process does not have a discernible effect on macrophage-mediated VAT inflammation or systemic glucose homeostasis.

  8. Effect of balanced low pressure drying of curcuma longa leaf on skin immune activation activities.

    Science.gov (United States)

    Choi, Wooseok; Lim, Hye Won; Lee, Hyeon Yong

    2014-01-01

    The effect of balanced low pressure drying pretreatment associated with ultrasonication extraction (BU) on the enhancement of skin immune modulatory activities of Curcuma longa leaf was studied by comparing with conventional hot air drying (HE), freeze drying (FE) and balanced low pressure drying (BE) pretreatment processes. In considering skin immune activation activities such as the inhibition of hyaluronidase activity, the BU extract showed ca. 10% higher than those of HE, and even higher than that of the FE extract. Nitric oxide production from macrophage of the BU extract in adding 1.0 mg/mL was increased up to 16.5 μM. When measuring inhibition of IL-6 and TNF-a production from the human T lymphocytes (T cell), the BU extract also showed 53% and 78% of inhibition effect, respectively. It is found that the BU extract could effectively suppress the expression levels of skin inflammation related genes such as Cox-2 and iNOS, down to 80% and 85% compared to the control, respectively. Balanced low pressure drying process was especially active on dehydration of the leaves with minimizing the destruction and making easier elution of the bioactive substances, which resulted in higher extraction yield and better biological activities.

  9. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans

    NARCIS (Netherlands)

    Kox, M.; Eijk, L.T.G.J. van; Zwaag, J.; Wildenberg, J. van den; Sweep, F.C.; Hoeven, J.G. van der; Pickkers, P.

    2014-01-01

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot

  10. Mothers’ Characteristics and Immunization Status of Under-Five Children in Ojo Local Government Area, Lagos State, Nigeria

    Directory of Open Access Journals (Sweden)

    John Lekan Oyefara

    2014-08-01

    Full Text Available Immunization is a key element of public health, a pre-requisite to social and economic development, and a crucial element that enables every child to reach his or her full physical and intellectual potential. It is a prevention against various child killer diseases such as tuberculosis (Bacillus Calmette Gurine [BCG], tetanus, whooping cough, diphtheria, poliomyelitis, hepatitis B, yellow fever, and measles. The main objective of this study is to examine the relationships between household characteristics, social mobilization, and immunization status of under-5 children in Lagos metropolis, Nigeria. To achieve this objective, a non-experimental research design was adopted. The research method utilized in the design is cross-sectional survey. The sampled study location is Ojo local government area of Lagos State. A total of 265 respondents were randomly sampled for the survey using multistage random sampling technique. Generated data were analyzed using univariate, bivariate, and multivariate statistical techniques. The findings of the study reveal significant relationship between women’s level of education and full immunization of their children. Specifically, 38.9% of women without any formal education had fully immunized their children compared with 86.9% of women with secondary education. In addition, 90.9% of women who assessed themselves to be average on wealth assessment compared with 45.3% of the poor had fully immunized their children. On the basis of the study’s findings, there is a need for a holistic approach that will involve all social classes and communities on child immunization to have 100% immunization coverage and minimal child morbidity and mortality in all areas of the city.

  11. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition.

    Science.gov (United States)

    Reitz, M U; Gifford, M L; Schäfer, P

    2015-04-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth-immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth-immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth-immunity cross-talk. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Active or passive immunization in unexplained recurrent miscarriage

    DEFF Research Database (Denmark)

    Christiansen, Ole B; Nielsen, Henriette Svarre; Pedersen, Bjorn

    2004-01-01

    placebo-controlled trials since 1986 in which greater doses than used in other trials have been administered, and both treatments are now used for routine therapy. Our results have convinced us that using the correct immunization protocols on the right subsets of RM patients is effective, but we admit...

  13. Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes

    NARCIS (Netherlands)

    van der Wal, A. C.; Piek, J. J.; de Boer, O. J.; Koch, K. T.; Teeling, P.; van der Loos, C. M.; Becker, A. E.

    1998-01-01

    OBJECTIVE: To discriminate between chronic inflammation and acute activation of the plaque immune response in culprit lesions of patients with acute coronary syndromes. DESIGN: Retrospective study. SETTING: Tertiary referral centre. SUBJECTS: 71 patients having coronary atherectomy were classified

  14. Evaluation of an In Vitro of Human Immune Activation Induced by Freeze-Thaw Tissue Damage

    National Research Council Canada - National Science Library

    DuBose, D

    2002-01-01

    In training and in combat, soldiers are under the constant threat of injury. Injury that results in tissue necrosis can activate the immune system and ultimately enhance disturbances in organ function...

  15. Bronchoalveolar lavage is an ideal tool in evaluation of local immune response of pigs vaccinated with Pasteurella multocida bacterin vaccine

    Directory of Open Access Journals (Sweden)

    Shiney George

    2015-04-01

    Full Text Available Aim: The aim was to study the bronchoalveolar lavage (BAL technique in evaluating the local immune response of pig immunized with Pasteurella multocida bacterin vaccine. Materials and Methods: Weaned piglets were immunized with formalin-inactivated P52 strain of P. multocida bacterin and evaluated for pulmonary immune response in BAL fluid. BAL was performed before vaccination and at different post vaccination days. The BAL fluid was assayed using enzyme-linked immunosorbent assay to study the development of P. multocida specific antibody isotypes and also evaluated for different cell populations using standard protocol. Results: The average recovery percentage of BAL fluid varies from 58.33 to 61.33 in vaccinated and control group of piglets. The BAL fluid of vaccinated pigs showed increase in antibody titer up to 60th days post vaccination (8.98±0.33, IgG being the predominant isotype reached maximum titer of 6.12±0.20 on 45th days post vaccination, followed by IgM and a meager concentration of IgA could be detected. An increased concentration of the lymphocyte population and induction of plasma cells was detected in the BAL fluid of vaccinated pigs. Conclusion: Though intranasal vaccination with P. multocida plain bacterin vaccine could not provoke a strong immune response, but is promising as lymphocyte population was increased and plasma cells were detected. BAL can be performed repeatedly up to 3/4 months of age in pigs to study pulmonary immune response without affecting their health.

  16. On the Discrete Kinetic Theory for Active Particles. Modelling the Immune Competition

    Directory of Open Access Journals (Sweden)

    I. Brazzoli

    2006-01-01

    Full Text Available This paper deals with the application of the mathematical kinetic theory for active particles, with discrete activity states, to the modelling of the immune competition between immune and cancer cells. The first part of the paper deals with the assessment of the mathematical framework suitable for the derivation of the models. Two specific models are derived in the second part, while some simulations visualize the applicability of the model to the description of biological events characterizing the immune competition. A final critical outlines some research perspectives.

  17. Activation of cutaneous immune responses in complex regional pain syndrome

    Science.gov (United States)

    Birklein, Frank; Drummond, Peter D.; Li, Wenwu; Schlereth, Tanja; Albrecht, Nahid; Finch, Philip M.; Dawson, Linda F.; Clark, J. David; Kingery, Wade S.

    2014-01-01

    The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but TNF-α and IL-6 are elevated in experimental skin blister fluid from CRPS affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS exaggerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The current investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid. Skin biopsies were collected from the affected skin and the contralateral mirror site in 55 CRPS patients and the biopsy sections were immunostained for keratinocyte, cell proliferation, mast cell markers, TNF-α, and IL-6. In early CRPS keratinocytes were activated in the affected skin, resulting in proliferation, epidermal thickening, and up-regulated TNF-α and IL-6 expression. In chronic CRPS there was reduced keratinocyte proliferation with epidermal thinning in the affected skin. Acute CRPS patients also had increased mast cell accumulation in the affected skin, but there was no increase in mast cell numbers in chronic CRPS. PMID:24462502

  18. Immune and hormonal activity in adults suffering from depression

    Directory of Open Access Journals (Sweden)

    S.O.V. Nunes

    2002-05-01

    Full Text Available An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5% were females and 11 (27.5% were males (2.6:1 ratio. The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and ß-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05. The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05. These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation.

  19. Evaluation of local anesthetic and antipyretic activities of Cinchona ...

    African Journals Online (AJOL)

    Purpose: To evaluate the local anesthetic and antipyretic activities of an aqueous extract of Cinchona officinalis (C. officinalis) in experimental animal models. Methods: Various doses of the aqueous extract was tested for its local anesthetic activity in guinea pigs and frogs using intracutaneous and plexus anesthesia, ...

  20. Fluorescent dye labeled influenza virus mainly infects innate immune cells and activated lymphocytes and can be used in cell-mediated immune response assay

    OpenAIRE

    Xie, Dongxu

    2009-01-01

    Early results have recognized that influenza virus infects the innate and adaptive immune cells. The data presented in this paper demonstrated that influenza virus labeled with fluorescent dye not only retained the ability to infect and replicate in host cells, but also stimulated a similar human immune response as did unlabeled virus. Influenza virus largely infected the innate and activated adaptive immune cells. Influenza B type virus was different from that of A type virus. B type virus w...

  1. Active surveillance for clinically localized prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Klotz, Laurence H

    2014-01-01

    Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS stra......Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection...

  2. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Science.gov (United States)

    Kato, Kazuki; Ishii, Ryohei; Goto, Eiji; Ishitani, Ryuichiro; Tokunaga, Fuminori; Nureki, Osamu

    2013-01-01

    The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  3. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Directory of Open Access Journals (Sweden)

    Kazuki Kato

    Full Text Available The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING, resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  4. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    International Nuclear Information System (INIS)

    Meng Jie; Yang Man; Jia Fumin; Kong Hua; Zhang Weiqi; Xu Haiyan; Wang Chaoying; Xie Sishen; Xing Jianmin

    2010-01-01

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  5. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    Science.gov (United States)

    Meng, Jie; Yang, Man; Jia, Fumin; Kong, Hua; Zhang, Weiqi; Wang, Chaoying; Xing, Jianmin; Xie, Sishen; Xu, Haiyan

    2010-04-01

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  6. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    Energy Technology Data Exchange (ETDEWEB)

    Jie, Meng; Man, Yang; Fumin, Jia; Hua, Kong; Weiqi, Zhang; Haiyan, Xu [Department of Biomedical Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005 (China); Chaoying, Wang; Sishen, Xie [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, 8 Nan San Jie, Zhongguancun, Beijing100080 (China); Xing Jianmin, E-mail: xuhy@pumc.edu.cn [Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029 (China)

    2010-04-09

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  7. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

    International Nuclear Information System (INIS)

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

    2004-01-01

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

  8. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    Science.gov (United States)

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  9. Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

    Science.gov (United States)

    Kelesidis, T; Jackson, N; McComsey, GA; Wang, X; Elashoff, D; Dube, MP; Brown, TT; Yang, OO; Stein, JH; Currier, JS

    2016-01-01

    Objective The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. Study In the AIDS Clinical Trials Group (ACTG) A5260, 234 HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravir and had HIV-1 RNA lipoproteins may contribute to persistent immune activation on ART. PMID:27603288

  10. Deposition of idiotype-anti-idiotype immune complexes in renal glomeruli after polyclonal B cell activation

    International Nuclear Information System (INIS)

    Goldman, M.; Rose, L.M.; Hochmann, A.; Lambert, P.H.

    1982-01-01

    We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC-15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions

  11. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

    Directory of Open Access Journals (Sweden)

    Mones M. Abu Shady

    2015-08-01

    Full Text Available OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27. Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb, erythrocyte sedimentation rate (ESR, and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a, interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p 0.05. Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05.CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

  12. Danger Signals Activating the Immune Response after Trauma

    Directory of Open Access Journals (Sweden)

    Stefanie Hirsiger

    2012-01-01

    Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  13. Intermittent Metronomic Drug Schedule Is Essential for Activating Antitumor Innate Immunity and Tumor Xenograft Regression

    Directory of Open Access Journals (Sweden)

    Chong-Sheng Chen

    2014-01-01

    Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.

  14. Localization of cortical areas activated by thinking

    DEFF Research Database (Denmark)

    Roland, P E; Friberg, L

    1985-01-01

    midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and posterior superior parietal cortex, increased their rCBF exclusively during route-finding thinking. We observed no decreases in rCBF. All r......These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work...... communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined...

  15. Porcine models for the study of local and systemic regulation of innate immune factors in obesity

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard

    state of low-grade inflammation in the adipose tissues, which involves several factors of the innate immune response having a range of systemic effects and which has been implicated in the development of the metabolic syndrome. To investigate the impact of obesity and obesity-related diseases good...... translational animal models are needed, and as such pigs have been proposed as relevant models for human obesity-induced inflammation as pigs share many genetic, anatomical and physiological features with humans. In this project the up- and downregulation of genes and proteins involved in the innate immune...... the number of animals to be used in a trial to obtain statistical power. For the gene regulation analysis, two platforms for quantitative real-time PCR (qPCR) were employed: The Rotor-Gene Q instrument and the microfluidics-based high-throughput Bio-Mark. For the serum protein concentrations analysis several...

  16. Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect - a histopathological and immunohistochemical study

    International Nuclear Information System (INIS)

    Nagtegaal, Iris D; Marijnen, Corrie AM; Kranenbarg, Elma Klein; Mulder-Stapel, Adri; Hermans, Jo; Velde, Cornelis JH van de; Krieken, J Han JM van

    2001-01-01

    Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer

  17. Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.

    Science.gov (United States)

    Yuen, Grace J; Ausubel, Frederick M

    2018-12-31

    The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

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

    2017-05-17

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

  20. Serum bactericidal activity as indicator of innate immunity in pacu Piaractus mesopotamicus (Holmberg, 1887

    Directory of Open Access Journals (Sweden)

    J.D. Biller-Takahashi

    2013-12-01

    Full Text Available The immune system of teleost fish has mechanisms responsible for the defense against bacteria through protective proteins in several tissues. The protein action can be evaluated by serum bactericidal activity and this is an important tool to analyze the immune system. Pacu, Piaractus mesopotamicus, is one of the most important fish in national aquaculture. However there is a lack of studies on its immune responses. In order to standardize and assess the accuracy of the serum bactericidal activity assay, fish were briefly challenged with Aeromonas hydrophila and sampled one week after the challenge. The bacterial infection increased the concentration of protective proteins, resulting in a decrease of colony-forming unit values expressed as well as an enhanced serum bactericidal activity. The protocol showed a reliable assay, appropriate to determine the serum bactericidal activity of pacu in the present experimental conditions.

  1. EFFECT OF POLYPHENOLIC COMPOUNDS ISOLATED FROM CARTHAMUS TINCTORIUS AND CALENDULA OFFICINALIS L., ON FUNCTIONAL ACTIVITY OF IMMUNE CELLS UNDER CONDITIONS OF CYTOSTATIC IMMUNOSUPPRESSION

    Directory of Open Access Journals (Sweden)

    N. V. Masnaya

    2013-01-01

    Full Text Available The purpose of the study – to study the effect of polyphenolic compounds extracted from the flowers of safflower oil and calendula, the functional activity of immune cells in cytotoxic immune suppression.Conventional methods determined the total number of splenocytes, relative (% and absolute (106, the number of antibody-forming cells (AFC in the spleen of mice by local hemolysis by Cunningham.Evaluated the effect of compounds of natural origin on the cellular immune response in the delayed-type hypersensitivity (DTH. Phagocytic activity of peritoneal macrophages was determined by the method based on the intensity of their capture ink particles. We studied the functional activity of peritoneal macrophages by NBT test (spontaneous and stimulated. Studies were conducted on male mice Category 1 (conventional linear mouse line CBA/CaLac aged 2–2.5 months, weighing 20–22 g. After the introduction mice line CBA/CaLac of polyphenolic compounds derived from flowers of Carthamus tinctorius and flowers of Calendula officinalis L. during the 5-day course in dose 50 mg/kg was observed stimulation of the humoral immune response (total number of splenocytes, the number of antibodies in the spleen cells and the functional activity of macrophages and Immunomodulating effect on the humoral immunity and the functional activity of macrophages after a single injection of cyclophosphamide in dose 250 mg/kg. Immunotropic activity of polyphenolic compounds is higher than that those of the reference product of tincture of Echinacea purpurea.

  2. Influence of physical activity on the immune system in breast cancer patients during chemotherapy.

    Science.gov (United States)

    Schmidt, Thorsten; Jonat, Walter; Wesch, Daniela; Oberg, Hans-Heinrich; Adam-Klages, Sabine; Keller, Lisa; Röcken, Christoph; Mundhenke, Christoph

    2018-03-01

    Physical activity can impact the immune system in different ways, e.g. by alteration of the humoral and cellular immune response. Physical activity at medium intensity enhances numbers of cytotoxic T cells, NK cells and macrophages in healthy people. The aim of this study was to compare the effects of endurance and resistance training on the immune system in breast cancer patients during adjuvant chemotherapy. In a prospective, controlled and randomized intervention exploratory trial, 12-week supervised endurance or resistance training were compared with usual care twice a week. Endpoints were the absolute numbers of the immune cells such as CD3 + T lymphocytes including CD4 + - and CD8 + , αβ T cells, γδT cells, CD3 - /CD16 + /56 + NK cells and CD19 + B cells, before and after 12 weeks of treatment. Cell numbers were analyzed using fluorescence-activated cell sorting. Despite different physical interventions in all groups immune cell count decreased in CD3 T cells including TCR αβ and CD4 T cells, NK cells and CD19 B cells 12 weeks after initiation of chemotherapy and start of the physical intervention program, while the reduction of γδ T cells and CD8 T cells is less prominent in the RT and UC group. Chemotherapy led to a decrease in nearly all measured immune cells. In this study, physical intervention with endurance or resistance training did not suppress cellular immunity any further. Larger multicenter trials are needed to evaluate the exact impact of sports intervention on immune cell subpopulations.

  3. TU-CD-303-03: Localized Radiation Can Induce Systemic Anti-Cancer Immune and Non-Immune Responses and How We Might Utilize It

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, M. [National Institutes of Health (United States)

    2015-06-15

    Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of

  4. TU-CD-303-03: Localized Radiation Can Induce Systemic Anti-Cancer Immune and Non-Immune Responses and How We Might Utilize It

    International Nuclear Information System (INIS)

    Ahmed, M.

    2015-01-01

    Recent advances in cancer research have shed new light on the complex processes of how therapeutic radiation initiates changes at cellular, tissue, and system levels that may lead to clinical effects. These new advances may transform the way we use radiation to combat certain types of cancers. For the past two decades many technological advancements in radiation therapy have been largely based on the hypothesis that direct radiation-induced DNA double strand breaks cause cell death and thus tumor control and normal tissue damage. However, new insights have elucidated that in addition to causing cellular DNA damage, localized therapeutic radiation also initiates cascades of complex downstream biological responses in tissue that extend far beyond where therapeutic radiation dose is directly deposited. For instance, studies show that irradiated dying tumor cells release tumor antigens that can lead the immune system to a systemic anti-cancer attack throughout the body of cancer patient; targeted irradiation to solid tumor also increases the migration of tumor cells already in bloodstream, the seeds of potential metastasis. Some of the new insights may explain the long ago discovered but still unexplained non-localized radiation effects (bystander effect and abscopal effect) and the efficacy of spatially fractionated radiation therapy (microbeam radiation therapy and GRID therapy) where many “hot” and “cold” spots are intentionally created throughout the treatment volume. Better understanding of the mechanisms behind the non-localized radiation effects creates tremendous opportunities to develop new and integrated cancer treatment strategies that are based on radiotherapy, immunology, and chemotherapy. However, in the multidisciplinary effort to advance new radiobiology, there are also tremendous challenges including a lack of multidisciplinary researchers and imaging technologies for the microscopic radiation-induced responses. A better grasp of the essence of

  5. Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome.

    Science.gov (United States)

    Matricon, J; Meleine, M; Gelot, A; Piche, T; Dapoigny, M; Muller, E; Ardid, D

    2012-12-01

    Irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. To determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. Immune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. The changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology. © 2012 Blackwell Publishing Ltd.

  6. Local expression of vaginal Th1 and Th2 cytokines in murine vaginal candidiasis under different immunity conditions.

    Science.gov (United States)

    Chen, Shanjuan; Li, Shaohua; Wu, Yan; Liu, Zhixiang; Li, Jiawen

    2008-08-01

    To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 (IL-2)/Th2 (IL-4, IL-10, TGF-beta1) cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-beta1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-beta1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans (C. albicans), and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.

  7. Liver X receptor and peroxisome proliferator-activated receptor as integrators of lipid homeostasis and immunity.

    Science.gov (United States)

    Kidani, Yoko; Bensinger, Steven J

    2012-09-01

    Lipid metabolism has emerged as an important modulator of innate and adaptive immune cell fate and function. The lipid-activated transcription factors peroxisome proliferator-activated receptor (PPAR) α, β/δ, γ and liver X receptor (LXR) are members of the nuclear receptor superfamily that have a well-defined role in regulating lipid homeostasis and metabolic diseases. Accumulated evidence over the last decade indicates that PPAR and LXR signaling also influence multiple facets of inflammation and immunity, thereby providing important crosstalk between metabolism and immune system. Herein, we provide a brief introduction to LXR and PPAR biology and review recent discoveries highlighting the importance of PPAR and LXR signaling in the modulation of normal and pathologic states of immunity. We also examine advances in our mechanistic understanding of how nuclear receptors impact immune system function and homeostasis. Finally, we discuss whether LXRs and PPARs could be pharmacologically manipulated to provide novel therapeutic approaches for modulation of the immune system under pathologic inflammation or in the context of allergic and autoimmune disease. © 2012 John Wiley & Sons A/S.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  9. [Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].

    Science.gov (United States)

    Karal'nik, B V; Ponomareva, T S; Deriabin, P N; Denisova, T G; Mel'nikova, N N; Tugambaev, T I; Atshabar, B B; Zakarian, S B

    2014-01-01

    Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments. Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs. Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine. The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,

  10. [Proteolytic activity of IgG-antibodies of mice, immunized by calf thymus histones].

    Science.gov (United States)

    Kit, Iu Ia; Korniĭ, N; Kril', I Ĭ; Mahorivs'ka, I B; Tkachenko, V; Bilyĭ, R O; Stoĭka, R S

    2014-01-01

    The main goal of the study was to determine the ability of histones to induce production of the proteolytically active IgG-antibodies in BALB/c mice. In order to perform this study 8 mice were immunized with the fraction of total calf thymus histones. IgGs were isolated from the serum of the immunized and not immunized animals by means of precipitation with 33% ammonium sulfate, followed by affinity chromatography on protein G-Sepharose column. Histones, myelin basic protein (MBP), lysozyme, BSA, ovalbumin, macroglobulin, casein and cytochrome c served as substrates for determining the proteolytic activity. It was found that IgGs from the blood serum of immunized mice are capable of hydrolyzing histone H1, core histone and MBP. On the contrary, the proteolytic activity of IgGs from the blood serum of not immunized mice was not detected. The absence of proteolytical enzymes in the fraction of IgGs was proven by HPLC chromatography. High levels of proteolytic activity toward histones have been also detected in affinity purified IgGs from blood serum of patients with rheumatoid arthritis, but not in healthy donors. These data indicate that eukaryotic histones may induce production of protabzymes in mammals. The possible origin of these protabzymes and their potential biological role in mammalians is discussed.

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

    Science.gov (United States)

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

    2014-07-01

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

  12. Vaginal immunization to elicit primary T-cell activation and dissemination.

    Directory of Open Access Journals (Sweden)

    Elena Pettini

    Full Text Available Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4(+ T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4(+ T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.

  13. Active Immunization and Evaluation Against Luteinizing Hormone for Radioimmunoassay Technique in Human Serum

    International Nuclear Information System (INIS)

    Ebeid, N.H.; Shafik, H.M.; Ayoub, S.M.; Mehany, N.L.

    2014-01-01

    This study evaluated the antigenicity of luteinizing hormone conjugate with Bovine Serum Albumin (LH-BSA). The conjugation of LH- BSA was carried out by 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide HCl (ECDI). Three rabbits were immunized against LH-BSA. Two rabbits were immunized against nonconjugated LH and two rabbits against BSA only. Immunization was carried out through primary injection and 4 boosters. The preparation of the radioiodinated 125 I-LH was carried out using N- Bromo-Succinimide as oxidizing agent. The preparation of LH standards was carried out. The obtained LH antisera were characterized of titer, immuno response and displacement profile formulation, optimization and validation of the local liquid phase LH- Radioimmunoassay (RIA) system was carried out. The results provide a highly sensitive and accurate RIA system of LH-BSA. This technique could be used in measuring LH in human serum to investigate fertility especially disorders of the hypothalamic / pituitary / gonadal axis

  14. Differential effects of active and passive coping on secretory immunity

    NARCIS (Netherlands)

    Bosch, JA; de Geus, E.J.C.; Kelder, A.; Veerman, E.C.I.; Hoogstraten, J.; van Nieuw Amerongen, A.

    2001-01-01

    This study examined the acute immunological effects of two laboratory stressors, expected to evoke distinct patterns of cardiac autonomic activity; namely an "active coping" time-paced memory test, and a "passive coping" stressful video showing surgical operations. We measured salivary S-IgA,

  15. Phenoloxidase activity in the infraorder Isoptera: unraveling life-history correlates of immune investment

    Science.gov (United States)

    Rosengaus, Rebeca B.; Reichheld, Jennifer L.

    2016-02-01

    Within the area of ecological immunology, the quantification of phenoloxidase (PO) activity has been used as a proxy for estimating immune investment. Because termites have unique life-history traits and significant inter-specific differences exist regarding their nesting and foraging habits, comparative studies on PO activity can shed light on the general principles influencing immune investment against the backdrop of sociality, reproductive potential, and gender. We quantified PO activity across four termite species ranging from the phylogenetically basal to the most derived, each with their particular nesting/foraging strategies. Our data indicate that PO activity varies across species, with soil-dwelling termites exhibiting significantly higher PO levels than the above-ground wood nester species which in turn have higher PO levels than arboreal species. Moreover, our comparative approach suggests that pathogenic risks can override reproductive potential as a more important driver of immune investment. No gender-based differences in PO activities were recorded. Although termite PO activity levels vary in accordance with a priori predictions made from life-history theory, our data indicate that nesting and foraging strategies (and their resulting pathogenic pressures) can supersede reproductive potential and other life-history traits in influencing investment in PO. Termites, within the eusocial insects, provide a unique perspective for inferring how different ecological pressures may have influenced immune function in general and their levels of PO activity, in particular.

  16. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    Science.gov (United States)

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  17. Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy

    NARCIS (Netherlands)

    Verhage, R. J. J.; Boone, J.; Rijkers, G. T.; Cromheecke, G. J.; Kroese, A. C.; Weijs, T. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

    2014-01-01

    Background. Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This

  18. Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

    Science.gov (United States)

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2018-03-01

    Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  19. Corticosterone suppresses immune activity in territorial Galápagos marine iguanas during reproduction.

    Science.gov (United States)

    Berger, Silke; Martin, Lynn B; Wikelski, Martin; Romero, L Michael; Kalko, Elisabeth K V; Vitousek, Maren N; Rödl, Thomas

    2005-04-01

    Individuals that display elaborate sexually selected characters often show reduced immune function. According to the immunocompetence handicap hypothesis, testosterone (T) is responsible for this result as it drives the development and maintenance of sexual characters and causes immunosuppression. But glucocorticoids also have strong influences on immune function and may also be elevated in reproductively active males. Here, we compared immune activity using the phytohemagglutinin (PHA) skin test in three discrete groups of male marine iguanas (Amblyrhynchus cristatus): territorials, satellites, and bachelors. Males of these three reproductive phenotypes had indistinguishable T concentrations during the height of the breeding season, but their corticosterone (cort) concentrations, body condition and hematocrit were significantly different. Territorial males, the animals with the most elaborate sexual ornaments and behaviors, had lower immune responses and body condition but higher cort concentrations and hematocrit than satellites or bachelors. To test directly cort's immunosuppressive role, we elevated cort by either restraining animals or additionally injecting cort and compared their PHA swelling response with the response of free-roaming animals. Such experimental elevation of cort significantly decreased immune activity in both restrained and cort-injected animals. Our data show that cort can induce immunosuppression, but they do not support the immunocompetence handicap hypothesis in its narrow sense because T concentrations were not related to immunosuppression.

  20. Posttransplant Immune Activation: Innocent Bystander or Insidious Culprit of Posttransplant Accelerated Atherosclerosis.

    Science.gov (United States)

    Ducloux, Didier; Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

    2017-09-01

    Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8 + T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8 + T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.

  1. Activation of antitumor immune responses by Ganoderma formosanum polysaccharides in tumor-bearing mice.

    Science.gov (United States)

    Wang, Cheng-Li; Lu, Chiu-Ying; Hsueh, Ying-Chao; Liu, Wen-Hsiung; Chen, Chun-Jen

    2014-11-01

    Fungi of the genus Ganoderma are basidiomycetes that have been used as traditional medicine in Asia and have been shown to exhibit various pharmacological activities. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the maturation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response in vivo. In this study, we investigated whether the immune adjuvant function of PS-F2 can stimulate antitumor immune responses in tumor-bearing mice. Continuous intraperitoneal or oral administration of PS-F2 effectively suppressed the growth of colon 26 (C26) adenocarcinoma, B16 melanoma, and sarcoma 180 (S180) tumor cells in mice without adverse effects on the animals' health. PS-F2 did not cause direct cytotoxicity on tumor cells, and it lost the antitumor effect in mice with severe combined immunodeficiency (SCID). CD4(+) T cells, CD8(+) T cells, and serum from PS-F2-treated tumor-bearing mice all exhibited antitumor activities when adoptively transferred to naïve animals, indicating that PS-F2 treatment stimulates tumor-specific cellular and humoral immune responses. These data demonstrate that continuous administration of G. formosanum polysaccharide PS-F2 can activate host immune responses against ongoing tumor growth, suggesting that PS-F2 can potentially be developed into a preventive/therapeutic agent for cancer immunotherapy.

  2. Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues

    DEFF Research Database (Denmark)

    Jørgensen, P E; Erlandsen, E J; Poulsen, Steen Seier

    2000-01-01

    the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest...

  3. Activity Recognition and Localization on a Truck Parking Lot

    NARCIS (Netherlands)

    Andersson, M.; Patino, L.; Burghouts, G.J.; Flizikowski, A.; Evans, M.; Gustafsson, D.; Petersson, H.; Schutte, K.; Ferryman, J.

    2013-01-01

    In this paper we present a set of activity recognition and localization algorithms that together assemble a large amount of information about activities on a parking lot. The aim is to detect and recognize events that may pose a threat to truck drivers and trucks. The algorithms perform zone-based

  4. Preliminary comparison of different immune and production components in local and imported Saanen goats reared under a sub-tropical environment.

    Science.gov (United States)

    Barbour, Elie K; Itani, Houssam H; Sleiman, Fawwak T; Saade, Maya F; Harakeh, Steve; Nour, Afif M Abdel; Shaib, Houssam A

    2012-01-01

    Three objectives were included in this research work. The first objective compared different immune components in healthy mature males, mature females, and female kids of local and imported Saanen goats, reared under a sub-tropical environment. The significantly differing immune components were the blood monocyte percent, blood CD8 count, and the total white blood cell count. The second objective compared the performance of Saanen versus local does. The means of the milk yield and prolificacy of the imported Saanen does were significantly higher than those of the local does (pgoats on protection potential against prevalent diseases in the sub-tropical zone of the eastern Mediterranean countries is discussed.

  5. 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.

  6. Local IL-23 expression in murine vaginal candidiasis and its relationship with infection and immune status.

    Science.gov (United States)

    Wu, Yan; Tan, Zhijian; Liu, Zhixiang; Xia, Dechao; Li, Jiawen

    2006-01-01

    To investigate the expression of vaginal IL-23 and its role in experimental murine vaginal candidiasis and its relationship with infection and immune status, immuno-competent (group A) and immuno-suppressed (group B) murine models of vaginal candidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls (group C). The level of IL-23 p19 mRNA in murine vaginal tissue was determined by RT-PCR. Significantly increased levels of IL-23p19mRNA were observed on the 4th, the 7th and 14th day after inoculation in immuno-competent group when compared with that in control group (Pvaginal candidiasis and has a protective function during infection. Low vaginal IL-23 level may correlate with the increased susceptibility to Candida albicans in immuno-suppressed group.

  7. Design of Immune-Algorithm-Based Adaptive Fuzzy Controllers for Active Suspension Systems

    Directory of Open Access Journals (Sweden)

    Ming-Yuan Shieh

    2014-04-01

    Full Text Available The aim of this paper is to integrate the artificial immune systems and adaptive fuzzy control for the automobile suspension system, which is regarded as a multiobjective optimization problem. Moreover, the fuzzy control rules and membership controls are then introduced for identification and memorization. It leads fast convergence in the search process. Afterwards, by using the diversity of the antibody group, trapping into local optimum can be avoided, and the system possesses a global search capacity and a faster local search for finding a global optimal solution. Experimental results show that the artificial immune system with the recognition and memory functions allows the system to rapidly converge and search for the global optimal approximate solutions.

  8. Immune activation in multiple sclerosis and interferon-beta therapy

    DEFF Research Database (Denmark)

    Krakauer, Martin

    2007-01-01

    The PhD dissertation emanated from the Danish MS Research Centre, Rigshosptalet, Copenhagen. Multiple sclerosis (MS) is an inflammatory disease of the CNS. Inflammatory responses by T helper (Th)-lymphocytes are characterised by distinct cytokine expression profiles. In MS, activated Th1...... of inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset...

  9. Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases

    DEFF Research Database (Denmark)

    Xanthoulea, Sofia; Pasparakis, Manolis; Kousteni, Stavroula

    2004-01-01

    Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses. Due to its pleiotropic activities, the amplitude and duration of TNF function must be tightly regulated. One of the mechanisms that may have evolved...... to modulate TNF function is the proteolytic cleavage of its cell surface receptors. In humans, mutations affecting shedding of the p55TNF receptor (R) have been linked with the development of the TNFR-associated periodic syndromes, disorders characterized by recurrent fever attacks and localized inflammation....... Here we show that knock-in mice expressing a mutated nonsheddable p55TNFR develop Toll-like receptor-dependent innate immune hyperreactivity, which renders their immune system more efficient at controlling intracellular bacterial infections. Notably, gain of function for antibacterial host defenses...

  10. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.

    Science.gov (United States)

    Fairfax, Benjamin P; Humburg, Peter; Makino, Seiko; Naranbhai, Vivek; Wong, Daniel; Lau, Evelyn; Jostins, Luke; Plant, Katharine; Andrews, Robert; McGee, Chris; Knight, Julian C

    2014-03-07

    To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.

  11. Starvation stress affects the interplay among shrimp gut microbiota, digestion and immune activities.

    Science.gov (United States)

    Dai, Wen-Fang; Zhang, Jin-Jie; Qiu, Qiong-Fen; Chen, Jiong; Yang, Wen; Ni, Sui; Xiong, Jin-Bo

    2018-05-24

    Aquatic animals are frequently suffered from starvation due to restricted food availability or deprivation. It is currently known that gut microbiota assists host in nutrient acquisition. Thus, exploring the gut microbiota responses would improve our understanding on physiological adaptation to starvation. To achieve this, we investigated how the gut microbiota and shrimp digestion and immune activities were affected under starvation stress. The results showed that the measured digestion activities in starved shrimp were significantly lower than in normal cohorts; while the measured immune activities exhibited an opposite trend. A structural equation modeling (SEM) revealed that changes in the gut bacterial community were directly related to digestive and immune enzyme activities, which in turn markedly affected shrimp growth traits. Notably, several gut bacterial indicators that characterized the shrimp nutrient status were identified, with more abundant opportunistic pathogens in starved shrimp, although there were no statistical differences in the overall diversity and the structures of gut bacterial communities between starved and normal shrimp. Starved shrimp exhibited less connected and cooperative interspecies interaction as compared with normal cohorts. Additionally, the functional pathways involved in carbohydrate and protein digestion, glycan biosynthesis, lipid and enzyme metabolism remarkably decreased in starved shrimp. These attenuations could increase the susceptibility of starved shrimp to pathogens infection. In summary, this study provides novel insights into the interplay among shrimp digestion, immune activities and gut microbiota in response to starvation stress. Copyright © 2018. Published by Elsevier Ltd.

  12. Quantification of local morphodynamics and local GTPase activity by edge evolution tracking.

    Directory of Open Access Journals (Sweden)

    Yuki Tsukada

    2008-11-01

    Full Text Available Advances in time-lapse fluorescence microscopy have enabled us to directly observe dynamic cellular phenomena. Although the techniques themselves have promoted the understanding of dynamic cellular functions, the vast number of images acquired has generated a need for automated processing tools to extract statistical information. A problem underlying the analysis of time-lapse cell images is the lack of rigorous methods to extract morphodynamic properties. Here, we propose an algorithm called edge evolution tracking (EET to quantify the relationship between local morphological changes and local fluorescence intensities around a cell edge using time-lapse microscopy images. This algorithm enables us to trace the local edge extension and contraction by defining subdivided edges and their corresponding positions in successive frames. Thus, this algorithm enables the investigation of cross-correlations between local morphological changes and local intensity of fluorescent signals by considering the time shifts. By applying EET to fluorescence resonance energy transfer images of the Rho-family GTPases Rac1, Cdc42, and RhoA, we examined the cross-correlation between the local area difference and GTPase activity. The calculated correlations changed with time-shifts as expected, but surprisingly, the peak of the correlation coefficients appeared with a 6-8 min time shift of morphological changes and preceded the Rac1 or Cdc42 activities. Our method enables the quantification of the dynamics of local morphological change and local protein activity and statistical investigation of the relationship between them by considering time shifts in the relationship. Thus, this algorithm extends the value of time-lapse imaging data to better understand dynamics of cellular function.

  13. Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

    Directory of Open Access Journals (Sweden)

    G. K. Chimal-Ramírez

    2013-01-01

    Full Text Available Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system’s regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining; these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion. Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies.

  14. Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

    Directory of Open Access Journals (Sweden)

    Chun-Jung Huang

    2013-01-01

    Full Text Available Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation.

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

    Science.gov (United States)

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

    2008-10-01

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

  16. Self-reported parenting style is associated with children's inflammation and immune activation.

    Science.gov (United States)

    Byrne, Michelle L; Badcock, Paul B; Simmons, Julian G; Whittle, Sarah; Pettitt, Adam; Olsson, Craig A; Mundy, Lisa K; Patton, George C; Allen, Nicholas B

    2017-04-01

    Family environments and parenting have been associated with inflammation and immune activation in children and adolescents; however, it remains unclear which specific aspects of parenting drive this association. In this study, we cross-sectionally examined the association between 5 discrete parenting styles and inflammation and immune activation in late childhood. Data were drawn from 102 families (55 with female children, mean age 9.50 years, SD = 0.34) participating in the Imaging Brain Development in the Childhood to Adolescence Transition Study. Children provided saliva samples from which inflammation (C-reactive protein) and immune competence/activation (secretory immunoglobulin A) were measured. Parents completed the Alabama Parenting Questionnaire, which measures 5 aspects of parenting style-positive parental involvement, positive disciplinary techniques, consistency in disciplinary techniques, corporal punishment, and monitoring and supervision. Results showed that higher scores on the poor parental monitoring scale were associated with higher levels of both inflammation and immune activation in children. This study highlights parental monitoring and supervision as a specific aspect of parenting behavior that may be important for children's physical and mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Association of sex work with reduced activation of the mucosal immune system.

    Science.gov (United States)

    Lajoie, Julie; Kimani, Makubo; Plummer, Francis A; Nyamiobo, Francis; Kaul, Rupert; Kimani, Joshua; Fowke, Keith R

    2014-07-15

    Unprotected intercourse and seminal discharge are powerful activators of the mucosal immune system and are important risk factors for transmission of human immunodeficiency virus (HIV). This study was designed to determine if female sex work is associated with changes in the mucosal immunity. Cervicovaginal lavage and plasma from 122 HIV-uninfected female sex workers (FSW) and 44 HIV-uninfected low-risk non-FSW from the same socioeconomic district of Nairobi were analyzed for evidence of immune activation (IA). The cervico-mononuclear cells (CMC) were analyzed for cellular activation by flow cytometry. Lower IA was observed in FSW compared to the low-risk women as demonstrated by the lower level of MIP-3α (P sex work and increased with duration of sex work. This study showed that sex work is associated with important changes in the mucosal immune system. By analyzing chemokine/cytokine levels and CMC activation, we observed a lower mucosal IA in HIV-uninfected FSW compared to low-risk women. © 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.

  18. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

    Science.gov (United States)

    Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

    2016-01-01

    The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression. PMID:26700461

  19. Attenuation fluctuations and local dermal reflectivity are indicators of immune cell infiltrate and epidermal hyperplasia in skin inflammation

    Science.gov (United States)

    Phillips, Kevin G.; Wang, Yun; Choudhury, Niloy; Levitz, David; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven

    2012-02-01

    Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses responsible for skin homeostasis. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of psoriasis remains under investigated. To elucidate the spatial-temporal morphological evolution of psoriasis we undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to non-invasively document dermal alterations due to immune cell infiltration and epidermal hyperplasia in an Imiquimod (IMQ) induced model of psoriasis-like inflammation in DBA2/C57Bl6 hybrid mice. Quantitative appraisal of dermal architectural changes was achieved through a three parameter fit of OCT axial scans in the dermis of the form A(z) = ρ exp(-mu;z +ɛ(z)). Ensemble averaging of the fit parameters over 2000 axial scans per mouse in each treatment arm revealed that the local dermal reflectivity ρ, decreased significantly in response to 6 day IMQ treatment (p = 0.0001), as did the standard deviation of the attenuation fluctuation std(ɛ(z)), (p = 0.04), in comparison to cream controls and day 1 treatments. No significant changes were observed in the average dermal attenuation rate, μ. Our results suggest these label-free OCT-based metrics can be deployed to investigate new therapeutic targets in animal models as well as aid in clinical staging of psoriasis in conjunction with the psoriasis area and severity index.

  20. Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE.

    Science.gov (United States)

    Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Abu-Asab, Mones S; Tsokos, Maria; Morris, John C; Kalle, Wouter H J

    2007-04-01

    We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined. Animals treated with the AL complexes had significantly lower levels of beta-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P<0.05). The tumor to non-tumor ratio of beta-galactosidase marker expression was significantly higher for the AL complex treated animals. NA induced significantly higher titers of adenoviral-specific antibodies compared to the AL complexes (P<0.05). The AL complexes provided protection (immunoshielding) to the adenovirus from neutralizing antibody. Forty-seven percent more beta-galactosidase expression was detected following intratumoral injection with AL complexes compared to the NA in animals pre-immunized with adenovirus. Complexing of adenovirus with liposomes provides a simple method to enhance tumor localization of the vector, decrease the immunogenicity of adenovirus, and provide protection of the virus from pre-existing neutralizing antibodies.

  1. Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia.

    Science.gov (United States)

    Tommola, Päivi; Bützow, Ralf; Unkila-Kallio, Leila; Paavonen, Jorma; Meri, Seppo

    2015-04-01

    Localized provoked vulvodynia (LPV) may have inflammatory etiology. We wanted to find out whether the cell-mediated immune system becomes activated in the vestibular mucosa in LPV. This was a controlled cross-sectional study. Vestibular mucosal specimens were obtained from 27 patients with severe LPV and 15 controls. Detailed clinical history of the patients was obtained. For immunohistochemistry, antibodies against CD3 (T cells), CD20 (B cells), IgA (mucosal plasma cells), CD163 (dendritic cells [DCs]), CD68 (macrophages), and CD117 (mast cells) were employed. Mann-Whitney U test and χ(2) test were used for statistical analyses. More B lymphocytes and mature mucosal IgA-plasma cells were found in patients than in controls (P associated lymphoid tissue analogous to mucosa-associated lymphoid tissue. Vestibule-associated lymphoid tissue may emerge as a response to local infection or inflammation in LPV. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection

    DEFF Research Database (Denmark)

    Shinde, Prashant V; Xu, Haifeng C; Maney, Sathish Kumar

    2018-01-01

    Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169(+) cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169(+) cells during viral infections remain...... stomatitis virus infection, phagocytes produce tumor necrosis factor (TNF) which signals via TNFR1 and promote "enforced virus replication" in CD169(+) macrophages. Consequently, lack of TNF or TNFR1 resulted in defective immune activation and VSV clearance....

  3. Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

    Directory of Open Access Journals (Sweden)

    Daisuke Ibi

    2015-11-01

    Full Text Available Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.

  4. Understanding Internal Accountability in Nigeria’s Routine Immunization System: Perspectives From Government Officials at the National, State, and Local Levels

    Directory of Open Access Journals (Sweden)

    Daniel J. Erchick

    2017-07-01

    Full Text Available Background Routine immunization coverage in Nigeria has remained low, and studies have identified a lack of accountability as a barrier to high performance in the immunization system. Accountability lies at the heart of various health systems strengthening efforts recently launched in Nigeria, including those related to immunization. Our aim was to understand the views of health officials on the accountability challenges hindering immunization service delivery at various levels of government. Methods A semi-structured questionnaire was used to interview immunization and primary healthcare (PHC officials from national, state, local, and health facility levels in Niger State in north central Nigeria. Individuals were selected to represent a range of roles and responsibilities in the immunization system. The questionnaire explored concepts related to internal accountability using a framework that organizes accountability into three axes based upon how they drive change in the health system. Results Respondents highlighted accountability challenges across multiple components of the immunization system, including vaccine availability, financing, logistics, human resources, and data management. A major focus was the lack of clear roles and responsibilities both within institutions and between levels of government. Delays in funding, especially at lower levels of government, disrupted service delivery. Supervision occurred less frequently than necessary, and the limited decision space of managers prevented problems from being resolved. Motivation was affected by the inability of officials to fulfill their responsibilities. Officials posited numerous suggestions to improve accountability, including clarifying roles and responsibilities, ensuring timely release of funding, and formalizing processes for supervision, problem solving, and data reporting. Conclusion Weak accountability presents a significant barrier to performance of the routine immunization

  5. Induction of potent local cellular immunity with low dose X4 SHIVSF33A vaginal exposure

    International Nuclear Information System (INIS)

    Tasca, Silvana; Tsai, Lily; Trunova, Nataliya; Gettie, Agegnehu; Saifuddin, Mohammed; Bohm, Rudolf; Chakrabarti, Lisa; Cheng-Mayer, Cecilia

    2007-01-01

    Intravaginal inoculation of rhesus macaques with varying doses of the CXCR4 (X4)-tropic SHIV SF33A isolate revealed a threshold inoculum for establishment of systemic virus infection and a dose dependency in overall viral burden and CD4+ T cell depletion. While exposure to inoculum size of 1000 or greater 50% tissue infectious dose (TCID 50 ) resulted in high viremia and precipitous CD4+ T cell loss, occult infection was observed in seven of eight macaques exposed to 500 TCID 50 of the same virus. The latter was characterized by intermittent detection of low level virus with no evidence of seroconversion or CD4+ T cell decline, but with signs of an ongoing antiviral T cell immune response. Upon vaginal re-challenge with the same limiting dose 11-12 weeks after the first, classic pathogenic X4 SHIV SF33A infection was established in four of the seven previously exposed seronegative macaques, implying enhanced susceptibility to systemic infection with prior exposure. Pre-existing peripheral SIV gag-specific CD4+ T cells were more readily demonstrable in macaques that became systemically infected following re-exposure than those that were not. In contrast, early presence of circulating polyfunctional cytokine secreting CD8+ T cells or strong virus-specific proliferative responses in draining lymph nodes and in the gut associated lymphoid tissue (GALT) following the first exposure was associated with protection from systemic re-infection. These studies identify the gut and lymphoid tissues proximal to the genital tract as sites of robust CD8 T lymphocyte responses that contribute to containment of virus spread following vaginal transmission

  6. Low-dose radiation induces drosophila innate immunity through toll pathway activation

    International Nuclear Information System (INIS)

    Seong, Ki Moon; Kim, Cha Soon; Lee, Byung-Sub; Nam, Seon Young; Yang, Kwang Hee; Kim, Ji-Young; Jin, Young-Woo; Park, Joong-Jean; Min, Kyung-Jin

    2012-01-01

    Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and N-terminal kinase (JNK). These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila. (author)

  7. Immune reconstitution inflammatory syndrome after initiating highly active antiretroviral therapy in HIV-infected children

    International Nuclear Information System (INIS)

    Kilborn, Tracy; Zampoli, Marco

    2009-01-01

    The outcome of HIV infection has improved since the widespread availability of highly active antiretroviral therapy (HAART). Some patients, however, develop a clinical and radiological deterioration following initiation of HAART due to either the unmasking of occult subclinical infection or an enhanced inflammatory response to a treated infection. This phenomenon is believed to result from the restored ability to mount an immune response and is termed immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease. IRIS is widely reported in the literature in adult patients, most commonly associated with mycobacterial infections. There is, however, a paucity of data documenting the radiological findings of IRIS in children. Radiologists need to be aware of this entity. As a diagnosis of exclusion it is essential that the radiological findings be assessed in the context of the clinical presentation. This article reviews the common clinical and radiological manifestations of IRIS in HIV-infected children. (orig.)

  8. [Immune mechanisms of the active ingredients of Chinese medicinal herbs for chronic prostatitis].

    Science.gov (United States)

    Wang, Hao; Zhou, Yu-chun; Xue, Jian-guo

    2016-01-01

    Chronic prostatitis is a common male disease, and its pathogenesis is not yet clear. Most scholars believe that oxidative stress and immune imbalance are the keys to the occurrence and progression of chronic prostatitis. Currently immunotherapy of chronic prostatitis remains in the exploratory stage. This article relates the active ingredients of 5 Chinese medicinal herbs (total glucosides of paeony, tripterigium wilfordii polglycosidium, curcumin, geniposide, and quercetin) for the treatment of chronic prostatitis and their possible action mechanisms as follows: 1) inhibiting the immune response and activation and proliferation of T-cells, and adjusting the proportion of Th1/Th2 cells; 2) upregulating the expression of Treg and enhancing the patient's tolerability; 3) suppressing the activation of the NF-kB factor, reducing the release of iNOS, and further decreasing the release of NO, IL-2 and other inflammatory cytokines, which contribute to the suppression of the immune response; 4) inhibiting the production of such chemokines as MCP-1 and MIP-1α in order to reduce their induction of inflammatory response. Studies on the immune mechanisms of Chinese medicinal herbs in the treatment of chronic prostatitis are clinically valuable for the development of new drugs for this disease.

  9. The role of medicaments, exosomes and miRNA molecules in modulation of macrophage immune activity

    Directory of Open Access Journals (Sweden)

    Katarzyna Nazimek

    2015-01-01

    Full Text Available Macrophages play an important role in innate immunity, in induction and orchestration of acquired immune response as well as in the maintenance of tissue homeostasis. Macrophages as antigen presenting cells induce or inhibit the development of immune response and as effector cells play an important role in innate immunity to infectious agents and in delayed--type hypersensitivity as well. Thus, either up- or down-regulation of their activity leads to the impairment of different biological processes. This often results in the development of immunological diseases or inflammatory response associated with metabolic, cardiovascular or neuroendocrine disorders. Therefore, the possibility of modulation of macrophage function should allow for elaboration of new effective therapeutic strategies. Noteworthy, interaction of medicaments with macrophages may directly mediate their therapeutic activity or is an additional beneficial effect increasing efficacy of treatment. Further, macrophage differentiation is regulated by miRNA-223, while expression of miRNA-146 and miRNA-155 may modulate and/or be a result of the current cell phenotype. Present review is focused on the current knowledge about the action of medicaments, microRNA molecules, exosomes and related vesicles on macrophages leading to modulation of their biological activity.

  10. Localization of urease activity in ureaplasma urealyticum cells

    International Nuclear Information System (INIS)

    Vinther, O.

    1976-01-01

    Measurements of the urease activity of various cell fractions of U. urealyticum showed that this activity was confined to the soluble fraction of the cytoplasm. An attempt was made to devise a method for electron microscopic detection of the sites of urease activity based on precipitation of electron-dense MnO 2 at the alkaline pH created by the hydrolysis of urea. The results obtained supported the previous results indicating a cytoplasmatic localization of the urease activity in the cells. Helical ribosome patterns were observed when glutaraldehyde-fixed cells were treated with cytochemical test solutions. (author)

  11. Localization of urease activity in Ureaplasma urealyticum cells

    Energy Technology Data Exchange (ETDEWEB)

    Vinther, O [Aarhus Univ. (Denmark)

    1976-01-01

    Measurements of the urease activity of various cell fractions of U. urealyticum showed that this activity was confined to the soluble fraction of the cytoplasm. An attempt was made to devise a method for electron microscopic detection of the sites of urease activity based on precipitation of electron-dense MnO/sub 2/ at the alkaline pH created by the hydrolysis of urea. The results obtained supported the previous results indicating a cytoplasmatic localization of the urease activity in the cells. Helical ribosome patterns were observed when glutaraldehyde-fixed cells were treated with cytochemical test solutions.

  12. Inorganic nanoparticles and the immune system: detection, selective activation and tolerance

    Science.gov (United States)

    Bastús, Neus G.; Sánchez-Tilló, Ester; Pujals, Silvia; Comenge, Joan; Giralt, Ernest; Celada, Antonio; Lloberas, Jorge; Puntes, Victor F.

    2012-03-01

    The immune system is the responsible for body integrity and prevention of external invasion. On one side, nanoparticles are no triggers that the immune system is prepared to detect, on the other side it is known that foreign bodies, not only bacteria, viruses and parasites, but also inorganic matter, can cause various pathologies such as silicosis, asbestosis or inflammatory reactions. Therefore, nanoparticles entering the body, after interaction with proteins, will be either recognized as self-agents or detected by the immune system, encompassing immunostimulation or immunosuppression responses. The nature of these interactions seems to be dictated not specially by the composition of the material but by modifications of NP coating (composition, surface charge and structure). Herein, we explore the use of gold nanoparticles as substrates to carry multifunctional ligands to manipulate the immune system in a controlled manner, from undetection to immunostimulation. Murine bone marrow macrophages can be activated with artificial nanometric objects consisting of a gold nanoparticle functionalized with peptides. In the presence of some conjugates, macrophage proliferation was stopped and pro-inflammatory cytokines were induced. The biochemical type of response depended on the type of conjugated peptide and was correlated with the degree of ordering in the peptide coating. These findings help to illustrate the basic requirements involved in medical NP conjugate design to either activate the immune system or hide from it, in order to reach their targets before being removed by phagocytes. Additionally, it opens up the possibility to modulate the immune response in order to suppress unwanted responses resulting from autoimmunity, or allergy or to stimulate protective responses against pathogens.

  13. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yi, E-mail: yihooyi@gmail.com; Ericsson, Ida, E-mail: ida.ericsson@ntnu.no; Doseth, Berit, E-mail: berit.doseth@ntnu.no; Liabakk, Nina B., E-mail: nina.beate.liabakk@ntnu.no; Krokan, Hans E., E-mail: hans.krokan@ntnu.no; Kavli, Bodil, E-mail: bodil.kavli@ntnu.no

    2014-03-10

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.

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

    Science.gov (United States)

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

    2012-12-11

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

  15. Human immunodeficiency virus-like particles activate multiple types of immune cells

    International Nuclear Information System (INIS)

    Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo

    2007-01-01

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

  16. Childhood immunization rates in rural Intibucá, Honduras: an analysis of a local database tool and community health center records for assessing and improving vaccine coverage.

    Science.gov (United States)

    He, Yuan; Zarychta, Alan; Ranz, Joseph B; Carroll, Mary; Singleton, Lori M; Wilson, Paria M; Schlaudecker, Elizabeth P

    2012-12-07

    Vaccines are highly effective at preventing infectious diseases in children, and prevention is especially important in resource-limited countries where treatment is difficult to access. In Honduras, the World Health Organization (WHO) reports very high immunization rates in children. To determine whether or not these estimates accurately depict the immunization coverage in non-urban regions of the country, we compared the WHO data to immunization rates obtained from a local database tool and community health center records in rural Intibucá, Honduras. We used data from two sources to comprehensively evaluate immunization rates in the area: 1) census data from a local database and 2) immunization data collected at health centers. We compared these rates using logistic regression, and we compared them to publicly available WHO-reported estimates using confidence interval inclusion. We found that mean immunization rates for each vaccine were high (range 84.4 to 98.8 percent), but rates recorded at the health centers were significantly higher than those reported from the census data (p ≤ 0.001). Combining the results from both databases, the mean rates of four out of five vaccines were less than WHO-reported rates (p 0.05), except for diphtheria/tetanus/pertussis vaccine (p=0.02) and oral polio vaccine (p Honduras were high across data sources, though most of the rates recorded in rural Honduras were less than WHO-reported rates. Despite geographical difficulties and barriers to access, the local database and Honduran community health workers have developed a thorough system for ensuring that children receive their immunizations on time. The successful integration of community health workers and a database within the Honduran decentralized health system may serve as a model for other immunization programs in resource-limited countries where health care is less accessible.

  17. The potential impact of low dose ionizing γ-radiation on immune response activity up-regulated by Ikaros in IM-9 B lymphocytes

    International Nuclear Information System (INIS)

    Kim Sung Jn; Jang, Seon A; Yang, Kwang Hee; Kim, Ji Young; Kim, Cha Soon; Nam, Seon Young; Jeong, Mee Seon; Jin, Young Woo

    2011-01-01

    The biological effects of low dose ionizing radiation (LDIR) remain insufficiently understood. We examined for the scientific evidence to show the biological effects of LDIR using radiation-sensitive immune cells. We found that Ikaros protein was responded to low dose-dependent effects of gamma radiation in IM-9 B lymphocytes. Ikaros encodes zinc finger transcription factors that is important regulators of a hematopoietic stem cells (HSCs) progression to the B lymphoid lineage development, differentiation and proliferation. In this study, we observed that cell proliferation was enhanced from 10% to 20% by LDIR (0.05 Gy) in IM-9 B lymphocytes. The Ikaros protein was phosphorylated in its serine/threonine (S/T) region and decreased its DNA binding activity in the cells exposed to LDIR. We found that Ikaros phosphorylation was up-regulated by CK2/AKT pathway and the residues of ser-304 and ser-306 in Ikaros was phosphorylated by LDIR. We also observed that Ikaros protein was localized from the nucleus to the cytoplasm after LDIR and bound with Autotaxin (ENPP2, ATX) protein, stimulating proliferation, migration and survival of immune cells. In addition, we found that the lysoPLD activity of ATX was dependent on Ikaros-ATX binding activity. These results indicate that the Ikaros is an important regulator of immune activation. Therefore, we suggest that low dose ionizing radiation can be considered as a beneficial effects, stimulating the activation of immune cells.

  18. A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.

    Science.gov (United States)

    Yang, Yuqi; Li, Shuli; Zhu, Guannan; Zhang, Qian; Wang, Gang; Gao, Tianwen; Li, Chunying; Wang, Lin; Jian, Zhe

    2017-07-01

    Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood. The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response. Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry. Enzyme-linked immunosorbent assay was performed to analyze the expressions of chemokines in the serum samples and cytotoxic markers secreted by CD8 + T cells which were sorted from the peripheral blood mononuclear cells in healthy donors, vitiligo and halo nevus patients. Tissue levels of chemokine receptors and CXCR3 ligands in healthy controls, vitiligo patients and halo nevus patients were determined by qRT-PCR analysis. The percentages of CXCR3 + CD4 + T and CXCR3 + CD8 + T cells from the peripheral blood samples were examined by flow cytometry. Tissue and serum hydrogen peroxide (H 2 O 2 ) concentrations were measured using H 2 O 2 assay kit. Immunohistochemistry revealed a significant T-cell response, with pronounced dermal infiltrates of CD8 + T cells in vitiligo and halo nevus. The inflammatory cytotoxic markers such as Granzyme B and Perforin were also elevated in vitiligo and halo nevus, suggesting inflammatory responses in situ. By qRT-PCR and ELISA assay, we found significantly increased expressions of the chemokine receptor CXCR3 and its ligands, especially the accumulated CXCL10 in the skin lesions of vitiligo and halo nevus. Moreover, the level of H 2 O 2 , a key player involved in regulation of the immune response was significantly upregulated in the skin lesions of vitiligo and halo nevus. In addition, the increased H 2 O 2 concentration correlated positively with CXCL10 level in skin

  19. 21 CFR 346.10 - Local anesthetic active ingredients.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... ingredient: (a) Benzocaine 5 to 20 percent. (b) Benzyl alcohol 1 to 4 percent. (c) Dibucaine 0.25 to 1...

  20. Antimicrobial Activity of Sabulun Salo a Local Traditional Medicated ...

    African Journals Online (AJOL)

    The antimicrobial activity of Sabulun salo; a local traditional medicated soap widely used by different tribes in Nigeria such as Hausa, Yoruba and Nupe against skin infections was examined against some clinical isolates of pathogenic microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans) using ...

  1. Antihypertensive Activity of Residue From “Gebto Arekei”. Locally ...

    African Journals Online (AJOL)

    Antihypertensive Activity of Residue From “Gebto Arekei”. Locally Distilled Medicinal Spirit From a Brew Containing Lupinus albus Seeds in Renovascular Hypertensive Guines-Pigs. Cherinet Ambaye, Tesfaye Tolessa, Abebe Abera, Hassen Taha Sherief, Dawit Abebe, Kelbessa Urga ...

  2. Finer discrimination of brain activation with local multivariate distance

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The organization of human brain function is diverse on different spatial scales.Various cognitive states are alwavs represented as distinct activity patterns across the specific brain region on fine scales.Conventional univariate analysis of functional MRI data seeks to determine how a particular cognitive state is encoded in brain activity by analyzing each voxel separately without considering the fine-scale patterns information contained in the local brain regions.In this paper,a local multivariate distance mapping(LMDM)technique is proposed to detect the brain activation and to map the fine-scale brain activity patterns.LMDM directly represents the local brain activity with the patterns across multiple voxels rather than individual voxels,and it employs the multivariate distance between different patterns to discriminate the brain state on fine scales.Experiments with simulated and real fMRI data demonstrate that LMDM technique can dramatically increase the sensitivity of the detection for the fine-scale brain activity pettems which contain the subtle information of the experimental conditions.

  3. Polysaccharide-Containing Macromolecules in a Kampo (Traditional Japanese Herbal Medicine, Hochuekkito: Dual Active Ingredients for Modulation of Immune Functions on Intestinal Peyer's Patches and Epithelial cells

    Directory of Open Access Journals (Sweden)

    Hiroaki Kiyohara

    2011-01-01

    Full Text Available A traditional Japanese herbal (Kampo medicine, Hochuekkito (Bu-Zhong-Yi-Qi-Tang in Chinese, TJ-41 is a well-known Kampo formula, and has been found to enhance antigen-specific antibody response in not only local mucosal immune system in upper respiratory tract, but also systemic immune system through upper respiratory mucosal immune system. Although this immunopharmacological effect has been proposed to express by modulation of intestinal immune system including Peyer's patches and intestinal epithelial cells, active ingredients are not known. TJ-41 directly affected the production of bone marrow cell-proliferative growth factors from murine Peyer's patch immunocompetent cells in vitro. Among low molecular, intermediate size and macromolecular weight fractions prepared from TJ-41, only fraction containing macromolecular weight ingredients showed Peyer's patch-mediated bone marrow cell-proliferation enhancing activity. Anion-exchange chromatography and gel filtration gave 17 subfractions comprising polysaccharides and lignins from the macromolecular weight fraction of TJ-41, and some of the subfractions showed significant enhancing activities having different degrees. Some of the subfractions also expressed stimulating activity on G-CSF-production from colonic epithelial cells, and statistically significant positive correlation was observed among enhancing activities of the subfractions against Peyer's patch immunocompetent cells and epithelial cells. Among the fractions from TJ-41 oral administration of macromolecular weight ingredient fraction to mice succeeded to enhance antigen-specific antibody response in systemic immune system through upper respiratory mucosal immune system, but all the separated fractions failed to enhance the in vivo antibody response in upper respiratory tract.

  4. Immune activity, body condition and human-associated environmental impacts in a wild marine mammal.

    Directory of Open Access Journals (Sweden)

    Patrick M Brock

    Full Text Available Within individuals, immunity may compete with other life history traits for resources, such as energy and protein, and the damage caused by immunopathology can sometimes outweigh the protective benefits that immune responses confer. However, our understanding of the costs of immunity in the wild and how they relate to the myriad energetic demands on free-ranging organisms is limited. The endangered Galapagos sea lion (Zalophus wollebaeki is threatened simultaneously by disease from domestic animals and rapid changes in food availability driven by unpredictable environmental variation. We made use of this unique ecology to investigate the relationship between changes in immune activity and changes in body condition. We found that during the first three months of life, changes in antibody concentration were negatively correlated with changes in mass per unit length, skinfold thickness and serum albumin concentration, but only in a sea lion colony exposed to anthropogenic environmental impacts. It has previously been shown that changes in antibody concentration during early Galapagos sea lion development were higher in a colony exposed to anthropogenic environmental impacts than in a control colony. This study allows for the possibility that these relatively large changes in antibody concentration are associated with negative impacts on fitness through an effect on body condition. Our findings suggest that energy availability and the degree of plasticity in immune investment may influence disease risk in natural populations synergistically, through a trade-off between investment in immunity and resistance to starvation. The relative benefits of such investments may change quickly and unpredictably, which allows for the possibility that individuals fine-tune their investment strategies in response to changes in environmental conditions. In addition, our results suggest that anthropogenic environmental impacts may impose subtle energetic costs on

  5. Distinct regions of the Phytophthora essential effector Avh238 determine its function in cell death activation and plant immunity suppression.

    Science.gov (United States)

    Yang, Bo; Wang, Qunqing; Jing, Maofeng; Guo, Baodian; Wu, Jiawei; Wang, Haonan; Wang, Yang; Lin, Long; Wang, Yan; Ye, Wenwu; Dong, Suomeng; Wang, Yuanchao

    2017-04-01

    Phytophthora pathogens secrete effectors to manipulate host innate immunity, thus facilitating infection. Among the RXLR effectors highly induced during Phytophthora sojae infection, Avh238 not only contributes to pathogen virulence but also triggers plant cell death. However, the detailed molecular basis of Avh238 functions remains largely unknown. We mapped the regions responsible for Avh238 functions in pathogen virulence and plant cell death induction using a strategy that combines investigation of natural variation and large-scale mutagenesis assays. The correlation between cellular localization and Avh238 functions was also evaluated. We found that the 79 th residue (histidine or leucine) of Avh238 determined its cell death-inducing activity, and that the 53 amino acids in its C-terminal region are responsible for promoting Phytophthora infection. Transient expression of Avh238 in Nicotiana benthamiana revealed that nuclear localization is essential for triggering cell death, while Avh238-mediated suppression of INF1-triggered cell death requires cytoplasmic localization. Our results demonstrate that a representative example of an essential Phytophthora RXLR effector can evolve to escape recognition by the host by mutating one nucleotide site, and can also retain plant immunosuppressive activity to enhance pathogen virulence in planta. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  6. Teollisuuden Voima Oy - Industrial Power Company Ltd. Local information activity

    International Nuclear Information System (INIS)

    Engros, Taina

    1989-01-01

    There are two nuclear power producers in Finland - the state-owned power company Imatran Voima Oy which operates two 440 MW Soviet-made PWR units in southern Finland, east of Helsinki and the Teollisuuden Voima Oy - Industrial Power Company Ltd, or TVO, owned by Finnish industrial companies. TVO operates two 710 MW ABB ATOM BWR units producing about one fifth of the country's electricity consumption. Operating experiences are extremely good from all Finnish nuclear power plants. The Finns' attitude towards nuclear power has changed into a positive direction in recent times. This can probably be noted as an international trend now that the Chernobyl accident is becoming an incident of the past. The Finnish citizens and politicians are facing two questions; first, what is their attitude towards nuclear power as a source of energy, in other words, do they approve of the plants currently in operation. The second question is how they stand on the building of new plants. It is probably another universal phenomenon that the attitudes of people living in the vicinity of nuclear power plants are less critical than the attitudes of those living farther away. This does not, by any means, result in local information activity being easier or less important than nationwide information activity. On the contrary, local decision-makers, local media and inhabitants are those who can, and through whom we can, influence also wider circles. The Nuclear Energy Act, which became effective in Finland last year, defines that the final decision on whether nuclear power plants can be built inside a municipality, is made at local level. As far as TVO is concerned one factor making local information activity easier is the small size of the locality. The difficulty TVO has to face is the people's suspicion of information activity. All information is considered propaganda, regardless of its form, and only negative news are considered information. Also, a large proportion of people are passive

  7. Teollisuuden Voima Oy - Industrial Power Company Ltd. Local information activity

    Energy Technology Data Exchange (ETDEWEB)

    Engros, Taina [Department of Information, TVO, Olkiluoto FIN-27160 (Finland)

    1989-07-01

    There are two nuclear power producers in Finland - the state-owned power company Imatran Voima Oy which operates two 440 MW Soviet-made PWR units in southern Finland, east of Helsinki and the Teollisuuden Voima Oy - Industrial Power Company Ltd, or TVO, owned by Finnish industrial companies. TVO operates two 710 MW ABB ATOM BWR units producing about one fifth of the country's electricity consumption. Operating experiences are extremely good from all Finnish nuclear power plants. The Finns' attitude towards nuclear power has changed into a positive direction in recent times. This can probably be noted as an international trend now that the Chernobyl accident is becoming an incident of the past. The Finnish citizens and politicians are facing two questions; first, what is their attitude towards nuclear power as a source of energy, in other words, do they approve of the plants currently in operation. The second question is how they stand on the building of new plants. It is probably another universal phenomenon that the attitudes of people living in the vicinity of nuclear power plants are less critical than the attitudes of those living farther away. This does not, by any means, result in local information activity being easier or less important than nationwide information activity. On the contrary, local decision-makers, local media and inhabitants are those who can, and through whom we can, influence also wider circles. The Nuclear Energy Act, which became effective in Finland last year, defines that the final decision on whether nuclear power plants can be built inside a municipality, is made at local level. As far as TVO is concerned one factor making local information activity easier is the small size of the locality. The difficulty TVO has to face is the people's suspicion of information activity. All information is considered propaganda, regardless of its form, and only negative news are considered information. Also, a large proportion of people are passive

  8. The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity

    OpenAIRE

    Bowen, David G.; Zen, Monica; Holz, Lauren; Davis, Thomas; McCaughan, Geoffrey W.; Bertolino, Patrick

    2004-01-01

    Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for prima...

  9. Effects of local Polynesian plants and algae on growth and expression of two immune-related genes in orbicular batfish (Platax orbicularis).

    Science.gov (United States)

    Reverter, Miriam; Saulnier, Denis; David, Rarahu; Bardon-Albaret, Agnès; Belliard, Corinne; Tapissier-Bontemps, Nathalie; Lecchini, David; Sasal, Pierre

    2016-11-01

    The emerging orbicular batfish (Platax orbicularis) aquaculture is the most important fish aquaculture industry in French Polynesia. However, bacterial infections are causing severe mortality episodes. Therefore, there is an urgent need to find an effective management solution. Besides the supplying difficulty and high costs of veterinary drugs in French Polynesia, batfish aquaculture takes place close to the coral reef, where use of synthetic persistent drugs should be restricted. Medicinal plants and bioactive algae are emerging as a cheaper and more sustainable alternative to chemical drugs. We have studied the effect of local Polynesian plants and the local opportunistic algae Asparagopsis taxiformis on batfish when orally administered. Weight gain and expression of two immune-related genes (lysozyme g - Lys G and transforming growth factor beta - TGF-β1) were studied to analyze immunostimulant activity of plants on P. orbicularis. Results showed that several plants increased Lys G and TGF-β1 expression on orbicular batfish after 2 and 3 weeks of oral administration. A. taxiformis was the plant displaying the most promising results, promoting a weight gain of 24% after 3 weeks of oral administration and significantly increasing the relative amount of both Lys G and TGF-β1 transcripts in kidney and spleen of P. orbicularis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Reinforcement active learning in the vibrissae system: optimal object localization.

    Science.gov (United States)

    Gordon, Goren; Dorfman, Nimrod; Ahissar, Ehud

    2013-01-01

    Rats move their whiskers to acquire information about their environment. It has been observed that they palpate novel objects and objects they are required to localize in space. We analyze whisker-based object localization using two complementary paradigms, namely, active learning and intrinsic-reward reinforcement learning. Active learning algorithms select the next training samples according to the hypothesized solution in order to better discriminate between correct and incorrect labels. Intrinsic-reward reinforcement learning uses prediction errors as the reward to an actor-critic design, such that behavior converges to the one that optimizes the learning process. We show that in the context of object localization, the two paradigms result in palpation whisking as their respective optimal solution. These results suggest that rats may employ principles of active learning and/or intrinsic reward in tactile exploration and can guide future research to seek the underlying neuronal mechanisms that implement them. Furthermore, these paradigms are easily transferable to biomimetic whisker-based artificial sensors and can improve the active exploration of their environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Immune Aspects of Female Infertility

    Directory of Open Access Journals (Sweden)

    Andrea Brazdova

    2016-05-01

    Full Text Available Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility.

  12. Basic study on low dose radiation effect: SOD activity of immune organs and hemogram in rats

    International Nuclear Information System (INIS)

    Yamaoka, Kiyonori; Kaneko, Ichiro; Mizutani, Takeo; Nakano, Kazushiro; Edamatsu, Rei; Mori, Akitane.

    1989-01-01

    We examined the effect of low dose radiation on SOD activities of immune organs such as thymus, spleen, bone marrow in rats and hematological findings changes. Animals were exposed to radiation in a wholebody fashion, 4 hours before sacrifice. SOD activities in thymus and bone marrow cells from the rats X-ray irradiated at doses of 0.25∼0.50 Gy/10 min were enhanced in comparison with those of non-irradiated rats. The enhancement was also observed in spleen cells obtained from group of rats irradiated at 0.05 Gy/10 min. Radiation exposure with over 0.50 Gy/10 min gave rats inhibitory responses in those immune organs. The changes in homogram were not observed with γ-ray exposure of less than 0.10 Gy/10 min. (author)

  13. Prenatal programing: at the intersection of maternal stress and immune activation.

    Science.gov (United States)

    Howerton, Christopher L; Bale, Tracy L

    2012-08-01

    Exposure to prenatal insults such as maternal stress and pathogenic infections has been associated with an increased risk for neurodevelopmental disorders. The mechanisms by which these programing events occur likely involve complex interactions between the maternal hormonal milieu, the placenta, and the developing fetus, in addition to compounding factors such as fetal sex and gestational stage of development. Despite the diverse biological processes involved, examination of common pathways in maternal stress and immune activation offers intriguing possibilities for elucidation of mechanistic insight. Further, the endocrine and sex-specific placenta is a tissue poised to be a key mediator in fetal programing, located at the intersection of the maternal and embryonic environments. In this review, we will discuss the potential shared mechanisms of maternal stress and immune pathway activation, with a particular focus on the important contribution and role of the placenta. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Leukocytes respiratory burst activity as indicator of innate immunity of pacu Piaractus mesopotamicus

    Directory of Open Access Journals (Sweden)

    JD Biller-Takahashi

    Full Text Available The present study evaluated the assay to quantify the respiratory burst activity of blood leukocytes of pacu as an indicator of the innate immune system, using the reduction of nitroblue tetrazolium (NBT to formazan as a measure of the production of reactive oxygen species (ROS. In order to assess the accuracy of the assay, fish were challenged by Aeromonas hydrophila and sampled one week after challenge. The A. hydrophila infection increased the leukocyte respiratory burst activity. The protocol showed a reliable and easy assay, appropriate to determine the respiratory burst activity of blood leukocytes of pacu, a neotropical fish, in the present experimental conditions.

  15. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

    International Nuclear Information System (INIS)

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-01-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy

  16. Adenosine can thwart antitumor immune responses elicited by radiotherapy. Therapeutic strategies alleviating protumor ADO activities

    Energy Technology Data Exchange (ETDEWEB)

    Vaupel, Peter [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Multhoff, Gabriele [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Helmholtz Zentrum Muenchen, Institute for innovative Radiotherapy (iRT), Experimental Immune Biology, Neuherberg (Germany)

    2016-05-15

    By studying the bioenergetic status we could show that the development of tumor hypoxia is accompanied, apart from myriad other biologically relevant effects, by a substantial accumulation of adenosine (ADO). ADO has been shown to act as a strong immunosuppressive agent in tumors by modulating the innate and adaptive immune system. In contrast to ADO, standard radiotherapy (RT) can either stimulate or abrogate antitumor immune responses. Herein, we present ADO-mediated mechanisms that may thwart antitumor immune responses elicited by RT. An overview of the generation, accumulation, and ADO-related multifaceted inhibition of immune functions, contrasted with the antitumor immune effects of RT, is provided. Upon hypoxic stress, cancer cells release ATP into the extracellular space where nucleotides are converted into ADO by hypoxia-sensitive, membrane-bound ectoenzymes (CD39/CD73). ADO actions are mediated upon binding to surface receptors, mainly A2A receptors on tumor and immune cells. Receptor activation leads to a broad spectrum of strong immunosuppressive properties facilitating tumor escape from immune control. Mechanisms include (1) impaired activity of CD4 + T and CD8 + T, NK cells and dendritic cells (DC), decreased production of immuno-stimulatory lymphokines, and (2) activation of Treg cells, expansion of MDSCs, promotion of M2 macrophages, and increased activity of major immunosuppressive cytokines. In addition, ADO can directly stimulate tumor proliferation and angiogenesis. ADO mechanisms described can thwart antitumor immune responses elicited by RT. Therapeutic strategies alleviating tumor-promoting activities of ADO include respiratory hyperoxia or mild hyperthermia, inhibition of CD39/CD73 ectoenzymes or blockade of A2A receptors, and inhibition of ATP-release channels or ADO transporters. (orig.) [German] Untersuchungen des bioenergetischen Status ergaben, dass Tumorhypoxie neben vielen anderen bedeutsamen biologischen Effekten zu einem starken

  17. Regulation of intestinal immune responses through TLR activation: implications for pro- and prebiotics

    Directory of Open Access Journals (Sweden)

    Sander eDe Kivit

    2014-02-01

    Full Text Available The intestinal mucosa is constantly facing a high load of antigens including bacterial antigens derived from the microbiota and food. Despite this, the immune cells present in the gastrointestinal tract do not initiate a pro-inflammatory immune response. Toll-like receptors (TLRs are pattern recognition receptors expressed by various cells in the gastrointestinal tract, including intestinal epithelial cells (IEC and resident immune cells in the lamina propria. Many diseases, including chronic intestinal inflammation (e.g. inflammatory bowel disease, irritable bowel syndrome (IBS, allergic gastroenteritis (e.g. eosinophilic gastroenteritis and allergic IBS and infections are nowadays associated with a deregulated microbiota. The microbiota may directly interact with TLR. In addition, differences in intestinal TLR expression in health and disease may suggest that TLR play an essential role in disease pathogenesis and may be novel targets for therapy. TLR signaling in the gut is involved in either maintaining intestinal homeostasis or the induction of an inflammatory response. This mini review provides an overview of the current knowledge regarding the contribution of intestinal epithelial TLR signaling in both tolerance induction or promoting intestinal inflammation, with a focus on food allergy. We will also highlight a potential role of the microbiota in regulating gut immune responses, especially through TLR activation.

  18. Altered biomarkers of mucosal immunity and reduced vaginal Lactobacillus concentrations in sexually active female adolescents.

    Directory of Open Access Journals (Sweden)

    Rebecca Pellett Madan

    Full Text Available Genital secretions collected from adult women exhibit in vitro activity against herpes simplex virus (HSV and Escherichia coli (E. coli, but prior studies have not investigated this endogenous antimicrobial activity or its mediators in adolescent females.Anti-HSV and anti-E.coli activity were quantified from cervicovaginal lavage (CVL specimens collected from 20 sexually active adolescent females (15-18 years. Soluble immune mediators that may influence this activity were measured in CVL, and concentrations of Lactobacillus jensenii and crispatus were quantified by PCR from vaginal swabs. Results for adolescents were compared to those obtained from 54 healthy, premenopausal adult women. Relative to specimens collected from adults, CVL collected from adolescent subjects had significantly reduced activity against E. coli and diminished concentrations of protein, IgG, and IgA but significantly increased anti-HSV activity and concentrations of interleukin (IL-1α, IL-6 and IL-1 receptor antagonist. Vaginal swabs collected from adolescent subjects had comparable concentrations of L. crispatus but significantly reduced concentrations of L. jensenii, relative to adult swabs.Biomarkers of genital mucosal innate immunity may differ substantially between sexually active adolescents and adult women. These findings warrant further study and may have significant implications for prevention of sexually transmitted infections in adolescent females.

  19. Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4

    Directory of Open Access Journals (Sweden)

    Bo Yoon Chang

    2015-10-01

    Full Text Available Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE. MFE stimulated the production of cytokines, nitric oxide (NO and tumor necrosis factor-α (TNF-α and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase and nuclear factor-κB (NF-κB signaling pathways downstream from toll-like receptor (TLR 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK cell activity, cytotoxic T lymphocyte (CTL activity and IFN-γ production. Immunoglobulin G (IgG antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

  20. Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4.

    Science.gov (United States)

    Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

    2015-10-13

    Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

  1. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Directory of Open Access Journals (Sweden)

    Genevieve E Martin

    Full Text Available Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001, soluble CD163 (sCD163, p = 0.001, sCD14 (p = 0.022, neopterin (p = 0.029 and an increased proportion of CD16(+ monocytes (p = 0.009 compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002 suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+ T lymphocytes.Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  2. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Science.gov (United States)

    Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

    2013-01-01

    Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  3. Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue

    International Nuclear Information System (INIS)

    Imanaka, Kazufumi; Tanaka, Koji; Sasai, Keisuke

    1984-01-01

    We have already reported the effectiveness of active specific immunotherapy based on the immune reaction of low-dose irradiated tumor tissue. In the present study, three kinds of immunotherapeutic methods subdivided by used cells were performed in order to compare each effectiveness. C3H/He mice bearing MM 46 tumor transplanted in the right hind paws received local irradiation with the dose of 3,000 rad on the 6th day, and the above-mentioned three methods, using tumor cells, lymphocytes, and tumor cells combining lymphocytes which were all separated from the topical tumor tissue exposed to 2,000 rad, were applied respectively on the 14 th day. The most effective data were obtained from two groups treated by the immunotherapy with tumor cells combining lymphocytes, which virtually caused the longest survival and best tumor growth control. (author)

  4. NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

    DEFF Research Database (Denmark)

    Iversen, Marie Beck; Jensen, Simon Kok; Hansen, Anne Louise

    2015-01-01

    . The marine sponge derived lipid αGalCer has recently been demonstrated as a specific agonist for activation of human and murine NKT cells. In the present study we investigated the applicability of αGalCer pre-treatment for immune protection against intra-vaginal HSV-2 infection. We found that C57BL/6 WT mice...... that received local pre-treatment with αGalCer prior to intra-vaginal HSV-2 infection had a lower mean disease score, mortality and viral load in the vagina following infection, compared to mice that did not receive αGalCer pre-treatment. Further, we found increased numbers of CD45 and NK1.1 positive cells...... in vaginal tissue and elevated levels of IFN-γ in the vaginal tissue and in vaginal fluids 24h after αGalCer pre-treatment. Collectively our data demonstrate a protective effect of αGalCer induced activation of NKT cells in the innate immune protection against viral infection....

  5. T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

    Science.gov (United States)

    Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

    2017-03-01

    Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

  6. Quantitative evaluation of blood elements by neutron activation analysis in mice immunized with Bothrops snake venoms

    International Nuclear Information System (INIS)

    Zamboni, C.B.; Metairon, S.; Suzuki, M.F.; Furtado, M.F.; Sant'Anna, O.A.; Tambourgi, D.V.

    2009-01-01

    Mice genetically selected for high antibody responsiveness (HIII) were immunized against different Bothrops species snake venoms from distinct region of Brazil. The Neutron Activation Analysis technique was used to evaluate the whole blood concentrations of elements of clinical relevance [Ca, Cl, K, Mg and Na] in order to establish a potential correlation between antibody response and blood constituents after Bothrops venom administration for clinical screening of envenomed patients. (author)

  7. Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells

    OpenAIRE

    Swaims, Alison Y.; Khani, Francesca; Zhang, Yingyu; Roberts, Arthur I.; Devadas, Satish; Shi, Yufang; Rabson, Arnold B.

    2010-01-01

    Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulate...

  8. Maternal immune activation during pregnancy in rats impairs working memory capacity of the offspring.

    Science.gov (United States)

    Murray, Brendan G; Davies, Don A; Molder, Joel J; Howland, John G

    2017-05-01

    Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring. Pregnant Long Evans rats were treated with either saline or polyI:C (4mg/kg; i.v.) on gestational day 15. Male offspring of the litters (2-3months of age) were subsequently trained on a nonmatching-to-sample task with odors. After a criterion was met, the rats were tested on the odor span task, which requires rats to remember an increasing span of different odors to receive food reward. Rats were tested using delays of approximately 40s during the acquisition of the task. Importantly, polyI:C- and saline-treated offspring did not differ in performance of the nonmatching-to-sample task suggesting that both groups could perform a relatively simple working memory task. In contrast, polyI:C-treated offspring had reduced span capacity in the middle and late phases of odor span task acquisition. After task acquisition, the rats were tested using the 40s delay and a 10min delay. Both groups showed a delay-dependent decrease in span, although the polyI:C-treated offspring had significantly lower spans regardless of delay. Our results support the validity of the maternal immune activation model for studying the cognitive symptoms of neurodevelopmental disorders such as schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

    NARCIS (Netherlands)

    van der Lee, Saskia; Kemmeren, Jeanet M; de Rond, Lia G H; Öztürk, Kemal; Westerhof, Anneke; de Melker, Hester E; Sanders, Elisabeth A M; Berbers, Guy A M; van der Maas, Nicoline A T; Rümke, Hans C; Buisman, Anne-Marie

    In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the

  10. STUDY OF THE INFLUENCE OF COMPLEX TREATMENT USING IMMUNOMODULATORS ON THE STATE OF LOCAL IMMUNITY IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS I-II SEVERITY ON ENTEROBIASIS

    Directory of Open Access Journals (Sweden)

    Savel’eva NN

    2016-12-01

    used toothpaste and rinse "Forest Balsam" for the duration of treatment and 1 month after the end of therapy. The effect of the proposed and conventional therapy on local immunity judged on the content of lysozyme, sIgA, mIgA, IgG, total protein, extracellular peroxidase activity and bactericidal oral secretions. Statistical processing of materials made using mathematical statistical methods for data analysis. Results & discussion. Under the influence of the proposed therapy in patients of the group increases the activity of local immunity factors and attenuates the inflammatory process in the periodontium. On the 1st day of the end of therapy in this group of patients significantly increases the content of lysozyme in the oral secretions and sIgA to normal values, with elevated levels of IgG and mIgA, which differed before treatment, reduced to normal values (p˂0,05 and remain so the entire period of observation for 6 months. Patients comparison group in the application of traditional therapy of total protein content in the oral secretions to the 6-month observation is not reduced to normal, but there was a positive trend in the growth of the content of sIgA and lysozyme and decreased total protein levels in the oral secretions. The level in the oral secretions mIgA and IgG in patients with the comparison group were not significantly changed the whole period of study. Patients of the main group under the influence of the therapy took place dynamic normalization of extracellular peroxidase activity, whereas in patients with comparison groups to restore the values of the rate of extracellular peroxidase activity did not occur. Between indicators peroxidase activity of patients of the main group and the comparison group, respectively, in all periods of the study were significant differences (p˂0,05. Study of the bactericidal activity of saliva showed that the study group patients who received the combined treatment immunokorregirujushchej therapy by the end of the

  11. Influence of immune activation and inflammatory response on cardiovascular risk associated with the human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Beltrán LM

    2015-01-01

    Full Text Available Luis M Beltrán,1 Alfonso Rubio-Navarro,2 Juan Manuel Amaro-Villalobos,2 Jesús Egido,2–4 Juan García-Puig,1 Juan Antonio Moreno21Metabolic-Vascular Unit, Fundación IdiPAZ-Hospital Universitario La Paz, Madrid, Spain; 2Vascular, Renal, and Diabetes Research Lab, IIS-Fundación Jiménez Díaz, Madrid, Spain; 3Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM, Madrid, Spain; 4Fundación Renal Iñigo Alvarez de Toledo-Instituto Reina Sofía de Investigaciones Nefrológicas (FRIAT-IRSIN, Madrid, SpainAbstract: Patients infected with the human immunodeficiency virus (HIV have an increased cardiovascular risk. Although initially this increased risk was attributed to metabolic alterations associated with antiretroviral treatment, in recent years, the attention has been focused on the HIV disease itself. Inflammation, immune system activation, and endothelial dysfunction facilitated by HIV infection have been identified as key factors in the development and progression of atherosclerosis. In this review, we describe the epidemiology and pathogenesis of cardiovascular disease in patients with HIV infection and summarize the latest knowledge on the relationship between traditional and novel inflammatory, immune activation, and endothelial dysfunction biomarkers on the cardiovascular risk associated with HIV infection.Keywords: HIV, cardiovascular disease, immune activation, inflammation, antiretroviral therapy

  12. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects.

    Directory of Open Access Journals (Sweden)

    Ece A Mutlu

    2014-02-01

    Full Text Available HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

  13. Impact of Hot Environment on Fluid and Electrolyte Imbalance, Renal Damage, Hemolysis, and Immune Activation Postmarathon

    Directory of Open Access Journals (Sweden)

    Rodrigo Assunção Oliveira

    2017-01-01

    Full Text Available Previous studies have demonstrated the physiological changes induced by exercise exposure in hot environments. We investigated the hematological and oxidative changes and tissue damage induced by marathon race in different thermal conditions. Twenty-six male runners completed the São Paulo International Marathon both in hot environment (HE and in temperate environment (TE. Blood and urine samples were collected 1 day before, immediately after, 1 day after, and 3 days after the marathon to analyze the hematological parameters, electrolytes, markers of tissue damage, and oxidative status. In both environments, the marathon race promotes fluid and electrolyte imbalance, hemolysis, oxidative stress, immune activation, and tissue damage. The marathon runner’s performance was approximately 13.5% lower in HE compared to TE; however, in HE, our results demonstrated more pronounced fluid and electrolyte imbalance, renal damage, hemolysis, and immune activation. Moreover, oxidative stress induced by marathon in HE is presumed to be related to protein/purine oxidation instead of other oxidative sources. Fluid and electrolyte imbalance and protein/purine oxidation may be important factors responsible for hemolysis, renal damage, immune activation, and impaired performance after long-term exercise in HE. Nonetheless, we suggested that the impairment on performance in HE was not associated to the muscle damage and lipoperoxidation.

  14. Drug Trafficking Organizations and Local Economic Activity in Mexico.

    Science.gov (United States)

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000-2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations.

  15. The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor

    NARCIS (Netherlands)

    Townsend, Philip D.; Dixon, Christopher H.; Slootweg, Erik J.; Sukarta, Octavina C.A.; Yang, Ally W.H.; Hughes, Timothy R.; Sharples, Gary J.; Palsson, Lars-Olof; Takken, Frank L.W.; Goverse, Aska; Cann, Martin J.

    2018-01-01

    Plant NLR proteins enable the immune system to recognise and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming and some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato is further

  16. Apoplastic Venom Allergen-like Proteins of Cyst Nematodes Modulate the Activation of Basal Plant Innate Immunity by Cell Surface Receptors

    Science.gov (United States)

    Lozano-Torres, Jose L.; Wilbers, Ruud H. P.; Warmerdam, Sonja; Finkers-Tomczak, Anna; Diaz-Granados, Amalia; van Schaik, Casper C.; Helder, Johannes; Bakker, Jaap; Goverse, Aska; Schots, Arjen; Smant, Geert

    2014-01-01

    Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes most likely utilize

  17. Apoplastic venom allergen-like proteins of cyst nematodes modulate the activation of basal plant innate immunity by cell surface receptors.

    Science.gov (United States)

    Lozano-Torres, Jose L; Wilbers, Ruud H P; Warmerdam, Sonja; Finkers-Tomczak, Anna; Diaz-Granados, Amalia; van Schaik, Casper C; Helder, Johannes; Bakker, Jaap; Goverse, Aska; Schots, Arjen; Smant, Geert

    2014-12-01

    Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes most likely utilize

  18. Apoplastic venom allergen-like proteins of cyst nematodes modulate the activation of basal plant innate immunity by cell surface receptors.

    Directory of Open Access Journals (Sweden)

    Jose L Lozano-Torres

    2014-12-01

    Full Text Available Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes

  19. A Force-Activated Trip Switch Triggers Rapid Dissociation of a Colicin from Its Immunity Protein

    Science.gov (United States)

    Farrance, Oliver E.; Hann, Eleanore; Kaminska, Renata; Housden, Nicholas G.; Derrington, Sasha R.; Kleanthous, Colin; Radford, Sheena E.; Brockwell, David J.

    2013-01-01

    Colicins are protein antibiotics synthesised by Escherichia coli strains to target and kill related bacteria. To prevent host suicide, colicins are inactivated by binding to immunity proteins. Despite their high avidity (Kd≈fM, lifetime ≈4 days), immunity protein release is a pre-requisite of colicin intoxication, which occurs on a timescale of minutes. Here, by measuring the dynamic force spectrum of the dissociation of the DNase domain of colicin E9 (E9) and immunity protein 9 (Im9) complex using an atomic force microscope we show that application of low forces (force-triggered increase in off-rate a trip bond. Using mutational analysis, we elucidate the mechanism of this switch in affinity. We show that the N-terminal region of E9, which has sparse contacts with the hydrophobic core, is linked to an allosteric activator region in E9 (residues 21–30) whose remodelling triggers immunity protein release. Diversion of the force transduction pathway by the introduction of appropriately positioned disulfide bridges yields a force resistant complex with a lifetime identical to that measured by ensemble techniques. A trip switch within E9 is ideal for its function as it allows bipartite complex affinity, whereby the stable colicin:immunity protein complex required for host protection can be readily converted to a kinetically unstable complex whose dissociation is necessary for cellular invasion and competitor death. More generally, the observation of two force phenotypes for the E9:Im9 complex demonstrates that force can re-sculpt the underlying energy landscape, providing new opportunities to modulate biological reactions in vivo; this rationalises the commonly observed discrepancy between off-rates measured by dynamic force spectroscopy and ensemble methods. PMID:23431269

  20. Local Helioseismology of Emerging Active Regions: A Case Study

    Science.gov (United States)

    Kosovichev, Alexander G.; Zhao, Junwei; Ilonidis, Stathis

    2018-04-01

    Local helioseismology provides a unique opportunity to investigate the subsurface structure and dynamics of active regions and their effect on the large-scale flows and global circulation of the Sun. We use measurements of plasma flows in the upper convection zone, provided by the Time-Distance Helioseismology Pipeline developed for analysis of solar oscillation data obtained by Helioseismic and Magnetic Imager (HMI) on Solar Dynamics Observatory (SDO), to investigate the subsurface dynamics of emerging active region NOAA 11726. The active region emergence was detected in deep layers of the convection zone about 12 hours before the first bipolar magnetic structure appeared on the surface, and 2 days before the emergence of most of the magnetic flux. The speed of emergence determined by tracking the flow divergence with depth is about 1.4 km/s, very close to the emergence speed in the deep layers. As the emerging magnetic flux becomes concentrated in sunspots local converging flows are observed beneath the forming sunspots. These flows are most prominent in the depth range 1-3 Mm, and remain converging after the formation process is completed. On the larger scale converging flows around active region appear as a diversion of the zonal shearing flows towards the active region, accompanied by formation of a large-scale vortex structure. This process occurs when a substantial amount of the magnetic flux emerged on the surface, and the converging flow pattern remains stable during the following evolution of the active region. The Carrington synoptic flow maps show that the large-scale subsurface inflows are typical for active regions. In the deeper layers (10-13 Mm) the flows become diverging, and surprisingly strong beneath some active regions. In addition, the synoptic maps reveal a complex evolving pattern of large-scale flows on the scale much larger than supergranulation

  1. Bacterial Infection of Fly Ovaries Reduces Egg Production and Induces Local Hemocyte Activation

    Science.gov (United States)

    Brandt, Stephanie M.; Schneider, David S.

    2009-01-01

    Summary Morbidity, the state of being diseased, is an important aspect of pathogenesis that has gone relatively unstudied in fruit flies. Our interest is in characterizing how bacterial pathogenesis affects various physiologies of the fly. We chose to examine the fly ovary because we found bacterial infection had a striking effect on fly reproduction. We observed decreased egg laying after bacterial infection that correlated with increased bacterial virulence. We also found that bacteria colonized the ovary in a previously undescribed manner; bacteria were found in the posterior of the ovary, adjacent to the lateral oviduct. This local infection in the ovary resulted in melanization and activation of the cellular immune response at the site of infection. PMID:17400292

  2. Cetuximab Enhanced the Cytotoxic Activity of Immune Cells during Treatment of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Lin Wang

    2017-11-01

    Full Text Available Background/Aims: Cetuximab is a chimeric IgG1 monoclonal antibody which targets the extracellular domain of epidermal growth factor receptor. This antibody is widely used for colorectal cancer (CRC treatment but its influence on the immune system is incompletely understood. Methods: The immune influence of cetuximab therapy in CRC patients was investigated by analyzing peripheral blood mononuclear cells using flow cytometry. We undertook in vitro cytotoxicity and cytokine-profile assays to ascertain the immunomodulatory effect of cetuximab treatment. Results: The number of CD3+ T, CD8+ T, and natural killer (NK cells was increased significantly and T-regulatory cells reduced gradually after cetuximab treatment. Percentage of CD4+ T, natural killer T (NKT-like, invariant NKT, and dendritic cells was similar between baseline patients and cetuximab patients. Expression of CD137 on NK and CD8+ T cells was increased significantly after 4 weeks of cetuximab therapy. In vitro cetuximab treatment markedly increased expression of CD137 and CD107a on NK and CD8+ T cells. Cetuximab treatment promoted the cytotoxic activity of NK and CD8+ T cells against tumor cells. Conclusion: Cetuximab treatment promotes activation of the immune response but alleviates immunosuppression: this might be the underlying anti-CRC effect of cetuximab.

  3. Fibroblast activation protein is dispensable in the anti-influenza immune response in mice.

    Directory of Open Access Journals (Sweden)

    Sioh-Yang Tan

    Full Text Available Fibroblast activation protein alpha (FAP is a unique dual peptidase of the S9B serine protease family, being capable of both dipeptidyl peptidase and endopeptidase activities. FAP is expressed at low level in healthy adult organs including the pancreas, cervix, uterus, submaxillary gland and the skin, and highly upregulated in embryogenesis, chronic inflammation and tissue remodelling. It is also expressed by cancer-associated stromal fibroblasts in more than 90% of epithelial tumours. FAP has enzymatic and non-enzymatic functions in the growth, immunosuppression, invasion and cell signalling of tumour cells. FAP deficient mice are fertile and viable with no gross abnormality, but little data exist on the role of FAP in the immune system. FAP is upregulated in association with microbial stimulation and chronic inflammation, but its function in infection remains unknown. We showed that major populations of immune cells including CD4+ and CD8+ T cells, B cells, dendritic cells and neutrophils are generated and maintained normally in FAP knockout mice. Upon intranasal challenge with influenza virus, FAP mRNA was increased in the lungs and lung-draining lymph nodes. Nonetheless, FAP deficient mice showed similar pathologic kinetics to wildtype controls, and were capable of supporting normal anti-influenza T and B cell responses. There was no evidence of compensatory upregulation of other DPP4 family members in influenza-infected FAP-deficient mice. FAP appears to be dispensable in anti-influenza adaptive immunity.

  4. 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

  5. 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

  6. The mitogen-activated protein kinase (MAPK pathway: role in immune evasion by trypanosomatids

    Directory of Open Access Journals (Sweden)

    Mercedes Carolina Soares-Silva

    2016-02-01

    Full Text Available Leishmania spp and Trypanosoma cruzi are the causative agents of leishmaniasis and Chagas' disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. These parasites belong to the family Trypanosomatidae and are both obligate intracellular parasites that manipulate host signaling pathways to establish the infection, and also subvert the host innate immune system. Mitogen-activated protein kinases (MAPKs are serine and threonine protein kinases, highly conserved in eukaryotes, and are involved in signal transduction pathways that are related to modulation of physiological and pathophysiological cell responses. This mini-review highlights the current knowledge about the mechanisms that Leishmania spp and T. cruzi have evolved to target host MAPK signaling pathway, highjack immune response, and in this manner, promote parasite maintenance in the host.

  7. Changes in proHB-EGF expression after functional activation of the immune system cells

    Directory of Open Access Journals (Sweden)

    T. O. Chudina

    2017-12-01

    Full Text Available The level of proHB-EGF expression on J774, Raji, KG-1 cells derived from different types of human and mouse immune system cells under the standard in vitro culture conditions and during functional activation of these cells was investigated. Changes in the proHB-EGF expression on the cell surface were found to depend on the density of cell population, the content of fetal bovine serum in the culture medium, the effect of mitogenic factors – bacterial lipopolysaccharide, an inactive full-size form of diphtheria toxin (CRM197 and recombinant soluble HB-EGF – rsHB-EGF. The results obtained are important for the understanding of the functional role of proHB-EGF receptor on the surface of macrophage-like cells and B lymphocytes and indicate the involvement of this receptor in immune response regulation in an organism.

  8. Creating leptin-like biofunctions by active immunization against chicken leptin receptor in growing chickens.

    Science.gov (United States)

    Lei, M M; Wu, S Q; Shao, X B; Li, X W; Chen, Z; Ying, S J; Shi, Z D

    2015-01-01

    In this study, immunization against chicken leptin receptor (cLEPR) extracellular domain (ECD) was applied to investigate leptin regulation and LEPR biofunction in growing chicken pullets. A recombinant protein (cLEPR ECD) based on the cLEPR complemenary DNA sequence corresponding to the 582nd to 796th amino acid residues of cLEPR mature peptide was prepared and used as antigen. Immunization against cLEPR ECD in growing chickens increased anti-cLEPR ECD antibody titers in blood, enhanced proportions of phosphorylated janus kinase 2 (JAK2) and served as signal transducer and activator of transcription 3 (STAT3) protein in liver tissue. Chicken live weight gain and abdominal fat mass were significantly decreased (P chickens. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Production of interferon-gamma by in vivo tumor-sensitized T cells: Association with active antitumor immunity

    International Nuclear Information System (INIS)

    Bursuker, I.; Pearce, M.T.

    1990-01-01

    The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma

  10. Transcriptome profiling indicating canine parvovirus type 2a as a potential immune activator.

    Science.gov (United States)

    Fan, Xu-Xu; Gao, Yuan; Shu, Long; Wei, Yan-Quan; Yao, Xue-Ping; Cao, Sui-Zhong; Peng, Guang-Neng; Liu, Xiang-Tao; Sun, Shi-Qi

    2016-12-01

    Canine parvovirus type 2a (CPV-2a) is a variant of CPV-2, which is a highly contagious pathogen causing severe gastroenteritis and death in young dogs. However, how CPV-2 participates in cell regulation and immune response remains unknown. In this study, persistently infected MDCK cells were generated through culture passage of the CPV-2a-infected cells for ten generations. Our study showed that CPV-2a induces cell proliferation arrest and cell morphology alternation before the fourth generation, whereas, the cell morphology returns to normal after five times of passages. PCR detection of viral VP2 gene demonstrated that CPV-2a proliferate with cell passage. An immunofluorescence assay revealed that CPV-2a particles were mainly located in the cell nuclei of MDCK cell. Then transcriptome microarray revealed that gene expression pattern of MDCK with CPV-2a persistent infection is distinct compared with normal cells. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genome pathway analysis demonstrated that CPV-2a infection induces a series of membrane-associated genes expression, including many MHC protein or MHC-related complexes. These genes are closely related to signaling pathways of virus-host interaction, including antigen processing and presentation pathway, intestinal immune network, graft-versus-host disease, and RIG-I-like helicases signaling pathway. In contrast, the suppressed genes mediated by CPV-2a showed low enrichment in any category, and were only involved in pathways linking to synthesis and metabolism of amino acids, which was confirmed by qPCR analysis. Our studies indicated that CPV-2a is a natural immune activator and has the capacity to activate host immune responses, which could be used for the development of antiviral strategy and biomaterial for medicine.

  11. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.

    Science.gov (United States)

    Kox, Matthijs; van Eijk, Lucas T; Zwaag, Jelle; van den Wildenberg, Joanne; Sweep, Fred C G J; van der Hoeven, Johannes G; Pickkers, Peter

    2014-05-20

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.

  12. Activation of immunity, immune response, antioxidant ability, and resistance against Vibrio alginolyticus in white shrimp Litopenaeus vannamei decrease under long-term culture at low pH.

    Science.gov (United States)

    Chen, Yu-Yuan; Chen, Jiann-Chu; Tseng, Kuei-Chi; Lin, Yong-Chin; Huang, Chien-Lun

    2015-10-01

    The growth, activation of immunity, immune parameters, and transcript levels of cytMnSOD, mtMnSOD, ecCuZnSOD, glutathione peroxidase (GPx), catalase, lysozyme, and penaeidin 3a were examined in white shrimp Litopenaeus vannamei reared at pH 6.8 and 8.1 after 24 weeks. No significant difference in growth was observed between the two groups. An in vitro study indicated that phenoloxidase activity and respiratory bursts (RB, release of the superoxide anion) were significantly higher in the haemocytes of pH 8.1 shrimp (shrimp reared at pH 8.1) than in pH 6.8 shrimp (shrimp reared at pH 6.8). An in vivo study indicated that the levels of immune parameters of pH 8.1 shrimp were significantly higher than in pH 6.8 shrimp, and the transcript levels of cytMnSOD, ecCuZnSOD, glutathione peroxidase, lysozyme, and penaeidin 3a were down-regulated in pH 6.8 shrimp. In another experiment, shrimp reared at pH 6.8 and 8.1 for 24 weeks were challenged with Vibrio alginolyticus. The mortality rate of pH 6.8 shrimp was significantly higher than in pH 8.1 shrimp over 12-168 h. Phagocytic activity, phagocytic index, and clearance efficiency to V. alginolyticus were significantly lower in pH 6.8 shrimp. We concluded that shrimp under long-term culture at pH 6.8 exhibited decreased resistance against V. alginolyticus as evidenced by reductions in the activation of immunity and immune parameters together with decreased transcript levels of cytMnSOD, ecCuZnSOD, GPx, lysozyme, and penaeidin 3a. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort

    Directory of Open Access Journals (Sweden)

    Colebunders Robert

    2011-02-01

    Full Text Available Abstract Background Antiretroviral therapy (ART partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. Methods T-cell activation (CD38+HLA-DR+ and immune exhaustion (PD-1+ were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199 cells/μl], N = 34 ], optimal [282 (200-415 cells/μl, N = 64] and super-optimal [528 (416-878 cells/μl, N = 30]. Results Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+ was higher among suboptimal relative to optimal (P P = 0.022]. Conclusion T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.

  14. Pharmacological evaluation for anticancer and immune activities of a novel polysaccharide isolated from Boletus speciosus Frost.

    Science.gov (United States)

    Hou, Yiling; Ding, Xiang; Hou, Wanru; Song, Bo; Wang, Ting; Wang, Fang; Li, Jian; Zeng, Yichun; Zhong, Jie; Xu, Ting; Zhu, Hongqing

    2014-04-01

    The fungal polysaccharides have been revealed to exhibit a variety of biological activities, including antitumor, immune-stimulation and antioxidation activities. In the present study, the immune and anticancer activities of a novel polysaccharide, BSF-A, isolated from Boletus speciosus Frost was investigated. The inhibitory rate of S180 tumors in mice treated with 40 mg/kg BSF-A reached 62.449%, which was the highest rate from the three doses administered; this may be comparable to mannatide. The antitumor activity of BSF-A is commonly considered to be a consequence of the stimulation of the cell-mediated immune response, as it may significantly promote the macrophage cells in the dose range of 100-400 µg/ml in vitro. The levels of the cytokines, IL-6, IL-1β and TNF-α, and nitric oxide, induced by BSF-A treatment at varying concentrations in the macrophage cells were similar to the levels in the cells treated with lipopolysaccharide. There was weak expression of the TNF-α, IL-6, IL-1β and inducible nitric oxide synthase mRNA in the untreated macrophages, but this increased significantly in a dose-dependent manner in the BSF-A-treated cells. BSF-A also had a time- and dose-dependent effect on the growth inhibition of the Hep-2 cells, with the concentration of 400 µg/ml having the highest inhibitory rate. A quantitative PCR array analysis of the gene expression profiles indicated that BSF-A had anticancer activities that affected cell apoptosis in the Hep-2 cells. The results obtained in the present study indicated that the purified polysaccharide of Boletus speciosus Frost is a potential source of natural anticancer substances.

  15. Local seismic activity monitored at King Sejong Station, Antarctica

    OpenAIRE

    Lee,Duk Kee; Kim,Yea Dong; Nam,Sang Heon; Jin,Young Keun

    1998-01-01

    Source location estimation from single station earthquake data collected at King Sejong Station (62°13'3l"N, 58°47'07"W) from 1995 to 1996 provides seismic activity around King Sejong Station. Analysis of local events, less than 1.5°in angular epicentral distance, finds epicenters located near the Shackleton Fracture Zone, the South Shetland Platform, Deception Island, and North Bransfield Basin. Estimated magnitudes range from 2.2 to 4.5 on the Richter scale, averaging 4.0 in North Bransfiel...

  16. Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

    Directory of Open Access Journals (Sweden)

    Dan Ehninger

    2014-01-01

    Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

  17. Controlling measles using supplemental immunization activities: a mathematical model to inform optimal policy.

    Science.gov (United States)

    Verguet, Stéphane; Johri, Mira; Morris, Shaun K; Gauvreau, Cindy L; Jha, Prabhat; Jit, Mark

    2015-03-03

    The Measles & Rubella Initiative, a broad consortium of global health agencies, has provided support to measles-burdened countries, focusing on sustaining high coverage of routine immunization of children and supplementing it with a second dose opportunity for measles vaccine through supplemental immunization activities (SIAs). We estimate optimal scheduling of SIAs in countries with the highest measles burden. We develop an age-stratified dynamic compartmental model of measles transmission. We explore the frequency of SIAs in order to achieve measles control in selected countries and two Indian states with high measles burden. Specifically, we compute the maximum allowable time period between two consecutive SIAs to achieve measles control. Our analysis indicates that a single SIA will not control measles transmission in any of the countries with high measles burden. However, regular SIAs at high coverage levels are a viable strategy to prevent measles outbreaks. The periodicity of SIAs differs between countries and even within a single country, and is determined by population demographics and existing routine immunization coverage. Our analysis can guide country policymakers deciding on the optimal scheduling of SIA campaigns and the best combination of routine and SIA vaccination to control measles. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

    Directory of Open Access Journals (Sweden)

    A. G. Rybka

    2016-01-01

    Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

  19. Local oral immunization with synthetic peptides induces a dual mucosal IgG and salivary IgA antibody response and prevents colonization of Streptococcus mutans.

    Science.gov (United States)

    Lehner, T; Haron, J; Bergmeier, L A; Mehlert, A; Beard, R; Dodd, M; Mielnik, B; Moore, S

    1989-01-01

    A small cell surface antigen of Streptococcus mutans was partially sequenced and the amino terminal peptides of 11, 15 and 20 amino acid residues and a dimer of the 15 and 20 residues peptides were synthesized. The synthetic peptides (SP) were used in topical oral immunization of the gingivomucosal epithelium of macaque monkeys. Sequential examination for antibodies over a period of up to 30 weeks revealed that six applications of the linear or cyclized SP11 and a random SP11 induced negligible or very low antibody levels. In contrast, the SP17 (SP15 with added cysteine at each terminus), SP21 (SP20 with one cysteine) and the dimer (SP35) induced significant anti-SP as well as anti-native streptococcal antibodies in the gingival fluid and in saliva. The functional significance of this immune response was examined by studying its effect on oral colonization of S. mutans following feeding of a carbohydrate-rich diet. Whereas control animals, sham-immunized with a random SP of 11 residues, showed increased colonization of the teeth by S. mutans, there was no colonization or a significant reduction in colonization of animals immunized with the cyclized SP17, linear SP21 or dimerized SP35. These experiments suggest that local immunization with SP derived from the sequences of a streptococcal cell surface antigen induce a dual local immune response of gingival IgG and salivary IgA antibodies against the SP and native SA. These antibodies may be involved in preventing colonization of S. mutans, which is the principal agent in the development of dental caries. PMID:2759661

  20. Subcellular Localization of Large Yellow Croaker ( Larimichthys crocea) TLR21 and Expression Profiling of Its Gene in Immune Response

    Science.gov (United States)

    Sun, Qingxue; Fan, Zejun; Yao, Cuiluan

    2018-04-01

    Toll-like receptor 21 (TLR21) is a non-mammalian type TLR, and plays an important role in innate immune response in fish. In this paper, the full-length cDNA sequence of TLR21 gene was identified and characterized from large yellow croaker, Larimichthys crocea and was termed as LcTLR21. It consists of 3365 bp, including a 5'-terminal untranslated region (UTR) of 97 bp, a 3'-terminal UTR of 331 bp, and an open reading frame (ORF) of 2937 bp encoding a polypeptide of 978 amino acid residues. The deduced LcTLR21 contains a signal peptide domain at N-terminal, 12 leucine-rich repeats (LRRs) at the extracellular region, a transmembrane domain and a cytoplasmic toll-interleukin-1 receptor (TIR) domain at the C-terminal. Subcellular localization analysis revealed that the LcTLR21-GFP was constitutively expressed in cytoplasm. Tissue expression analysis indicated that LcTLR21 gene broadly expressed in most of the examined tissues, with the most predominant abundance in spleen, followed by head-kidney and liver, while the weakest expression was detected in brain. The expression level of LcTLR21 after LPS, poly I:C and Vibrio parahaemolyticus challenges was investigated in spleen, head-kidney and liver. LcTLR21 gene transcripts increased significantly in all examined tissues after the challenges, and the highest expression level was detected in liver at 24 h after poly I:C stimulation ( P < 0.05), suggesting that LcTLR21 might play a crucial role in fish resistance to viral and bacterial infections.

  1. Spherical loudspeaker array for local active control of sound.

    Science.gov (United States)

    Rafaely, Boaz

    2009-05-01

    Active control of sound has been employed to reduce noise levels around listeners' head using destructive interference from noise-canceling sound sources. Recently, spherical loudspeaker arrays have been studied as multiple-channel sound sources, capable of generating sound fields with high complexity. In this paper, the potential use of a spherical loudspeaker array for local active control of sound is investigated. A theoretical analysis of the primary and secondary sound fields around a spherical sound source reveals that the natural quiet zones for the spherical source have a shell-shape. Using numerical optimization, quiet zones with other shapes are designed, showing potential for quiet zones with extents that are significantly larger than the well-known limit of a tenth of a wavelength for monopole sources. The paper presents several simulation examples showing quiet zones in various configurations.

  2. Variations in epidermal cytochrome oxidase activity after local irradiation

    International Nuclear Information System (INIS)

    Itoiz, M.E.; Rey, B.M. de; Cabrini, R.L.

    1982-01-01

    Cytochrome oxidase activity was evaluated histochemically as an index of mitochondrial damage after local irradiation with X-rays. It was determined by microphotometry on the tail skin of newly born Wistar rats four days after irradiation with doses ranging from 2 to 16krad. The enzyme activity of the whole epidermis increased after irradiation, the increases being related to the increase in thickness of the epithelium which was observed as a response to irradiation injury. Within the dose range tested, the enzyme concentration (expressed per unit volume of tissue) decreased in relation to the dose applied. At the electron microscopy level, the cytochemical demonstration of cytochrome oxidase revealed an irregular reaction over the cristae, intramitochondrial vacuolization and partial homogenization of the matrix. Positive membrane fragments were seen around lipid droplets. This reaction confirms the mitochondrial origin of these previously observed radiation-induced vacuoles. (author)

  3. Cellular immune responses and phagocytic activity of fishes exposed to pollution of volcano mud.

    Science.gov (United States)

    Risjani, Yenny; Yunianta; Couteau, Jerome; Minier, Christophe

    2014-05-01

    Since May 29, 2006, a mud volcano in the Brantas Delta of the Sidoarjo district has emitted mud that has inundated nearby villages. Pollution in this area has been implicated in detrimental effects on fish health. In fishes, leukocyte and phagocytic cells play a vital role in body defenses. We report for the first time the effect of "LUSI" volcano mud on the immune systems of fish in the Brantas Delta. The aim of this study was to find biomarkers to allow the evaluation of the effects of volcanic mud and anthropogenic pollution on fish health in the Brantas Delta. The study took places at the Brantas Delta, which was polluted by volcano mud, and at reference sites in Karangkates and Pasuruan. Leukocyte numbers were determined using a Neubauer hemocytometer and a light microscope. Differential leukocyte counts were determined using blood smears stained with May Grunwald-Giemsa, providing neutrophil, lymphocyte and monocyte counts. Macrophages were taken from fish kidney, and their phagocytic activity was measured. In vitro analyses revealed that leukocyte and differential leukocyte counts (DLC) were higher in Channa striata and Chanos chanos caught from the polluted area. Macrophage numbers were higher in Oreochromis mossambicus than in the other species, indicating that this species is more sensitive to pollution. In areas close to volcanic mud eruption, all specimens had lower phagocytic activity. Our results show that immune cells were changed and phagocytic activity was reduced in the polluted area indicating cytotoxicity and alteration of the innate immune system in fishes exposed to LUSI volcano mud and anthropogenic pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Salicylic Acid and Jasmonic Acid Pathways are Activated in Spatially Different Domains Around the Infection Site During Effector-Triggered Immunity in Arabidopsis thaliana.

    Science.gov (United States)

    Betsuyaku, Shigeyuki; Katou, Shinpei; Takebayashi, Yumiko; Sakakibara, Hitoshi; Nomura, Nobuhiko; Fukuda, Hiroo

    2018-01-01

    The innate immune response is, in the first place, elicited at the site of infection. Thus, the host response can be different among the infected cells and the cells surrounding them. Effector-triggered immunity (ETI), a form of innate immunity in plants, is triggered by specific recognition between pathogen effectors and their corresponding plant cytosolic immune receptors, resulting in rapid localized cell death known as hypersensitive response (HR). HR cell death is usually limited to a few cells at the infection site, and is surrounded by a few layers of cells massively expressing defense genes such as Pathogenesis-Related Gene 1 (PR1). This virtually concentric pattern of the cellular responses in ETI is proposed to be regulated by a concentration gradient of salicylic acid (SA), a phytohormone accumulated around the infection site. Recent studies demonstrated that jasmonic acid (JA), another phytohormone known to be mutually antagonistic to SA in many cases, is also accumulated in and required for ETI, suggesting that ETI is a unique case. However, the molecular basis for this uniqueness remained largely to be solved. Here, we found that, using intravital time-lapse imaging, the JA signaling pathway is activated in the cells surrounding the central SA-active cells around the infection sites in Arabidopsis thaliana. This distinct spatial organization explains how these two phythormone pathways in a mutually antagonistic relationship can be activated simultaneously during ETI. Our results re-emphasize that the spatial consideration is a key strategy to gain mechanistic insights into the apparently complex signaling cross-talk in immunity. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  5. Design parameters for measurements of local catalytic activity on surfaces

    DEFF Research Database (Denmark)

    Johansson, Martin; Johannessen, Tue; Jørgensen, Jan Hoffmann

    2006-01-01

    Computational fluid dynamics in combination with experiments is used to characterize a gas sampling device for measurements of the local catalytic activity on surfaces. The device basically consists of a quartz capillary mounted concentrically inside an aluminum tube. Reactant gas is blown toward......, the limits of the range in reaction rate, which can be Studied are estimated. (c) 2005 Elsevier B.V. All rights reserved.......Computational fluid dynamics in combination with experiments is used to characterize a gas sampling device for measurements of the local catalytic activity on surfaces. The device basically consists of a quartz capillary mounted concentrically inside an aluminum tube. Reactant gas is blown toward...... limit for the lateral resolution of the measurement, and that a flow rate of the order of 240 (ml/min)(n) is sufficient to achieve this resolution. The sensitivity is reasonable also with high flow rates, due to the presence of a pocket of stagnant gas under the tip of the capillary. Furthermore...

  6. Enhancing cancer immunotherapy through nanotechnology-mediated tumor infiltration and activation of immune cells.

    Science.gov (United States)

    Shen, Haifa; Sun, Tong; Hoang, Hanh H; Burchfield, Jana S; Hamilton, Gillian F; Mittendorf, Elizabeth A; Ferrari, Mauro

    2017-12-01

    Cancer immunotherapy has become arguably the most promising advancement in cancer research and therapy in recent years. The efficacy of cancer immunotherapy is critically dependent on specific physiological and physical processes - collectively referred to as transport barriers - including the activation of T cells by antigen presenting cells, T cells migration to and penetration into the tumor microenvironment, and movement of nutrients and other immune cells through the tumor microenvironment. Nanotechnology-based approaches have great potential to help overcome these transport barriers. In this review, we discuss the ways that nanotechnology is being leveraged to improve the efficacy and potency of various cancer immunotherapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bingfen Yang

    Full Text Available CD244 (2B4 is a member of the signaling lymphocyte activation molecule (SLAM family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+ T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+ T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M. tuberculosis antigen-specific CD4(+ T cells compared with latent infection individuals. The frequencies of CD244/2B4-expressing antigen-specific CD4(+ T cells were significantly higher in retreatment active TB patients than in new active TB patients. Compared with CD244/2B4-dull and -middle CD4(+ T cells, CD244/2B4-bright CD4(+ T cell subset had significantly reduced expression of IFN-γ, suggesting that CD244/2B4 expression may modulate IFN-γ production in M. tuberculosis antigen-responsive CD4(+ T cells. Activation of CD244/2B4 signaling by cross-linking led to significantly decreased production of IFN-γ. Blockage of CD244/2B4 signaling pathway of T cells from patients with active TB resulted in significantly increased production of IFN-γ, compared with isotype antibody control. In conclusion, CD244/2B4 signaling pathway has an inhibitory role on M. tuberculosis antigen-specific CD4(+ T cell function.

  8. Engineering blood meal-activated systemic immunity in the yellow fever mosquito, Aedes aegypti.

    Science.gov (United States)

    Kokoza, V; Ahmed, A; Cho, W L; Jasinskiene, N; James, A A; Raikhel, A

    2000-08-01

    Progress in molecular genetics makes possible the development of alternative disease control strategies that target the competence of mosquitoes to transmit pathogens. We tested the regulatory region of the vitellogenin (Vg) gene of Aedes aegypti for its ability to express potential antipathogen factors in transgenic mosquitoes. Hermes-mediated transformation was used to integrate a 2.1-kb Vg-promoter fragment driving the expression of the Defensin A (DefA) coding region, one of the major insect immune factors. PCR amplification of genomic DNA and Southern blot analyses, carried out through the ninth generation, showed that the Vg-DefA transgene insertion was stable. The Vg-DefA transgene was strongly activated in the fat body by a blood meal. The mRNA levels reached a maximum at 24-h postblood meal, corresponding to the peak expression time of the endogenous Vg gene. High levels of transgenic defensin were accumulated in the hemolymph of bloodfed female mosquitoes, persisting for 20-22 days after a single blood feeding. Purified transgenic defensin showed antibacterial activity comparable to that of defensin isolated from bacterially challenged control mosquitoes. Thus, we have been able to engineer the genetically stable transgenic mosquito with an element of systemic immunity, which is activated through the blood meal-triggered cascade rather than by infection. This work represents a significant step toward the development of molecular genetic approaches to the control of vector competence in pathogen transmission.

  9. IDO chronic immune activation and tryptophan metabolic pathway: A potential pathophysiological link between depression and obesity.

    Science.gov (United States)

    Chaves Filho, Adriano José Maia; Lima, Camila Nayane Carvalho; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Maes, Michael; Macedo, Danielle

    2018-01-03

    Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity. This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation.

    Science.gov (United States)

    Hellmuth, Joanna; Colby, Donn; Valcour, Victor; Suttichom, Duanghathai; Spudich, Serena; Ananworanich, Jintanat; Prueksakaew, Peeriya; Sailasuta, Napapon; Allen, Isabel; Jagodzinski, Linda L; Slike, Bonnie; Ochi, Derek; Paul, Robert

    2017-11-01

    This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm 3 , t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

  11. Interrelation secretory activity of stomach and immunes changes of peripheral blood when ulcerogenesis stomach.

    Science.gov (United States)

    Matveeva, L V; Mosina, L M

    2016-01-01

    Incidence of gastric ulcer is high in almost all countries of the world. On the development and course of the disease affect the state acid- and enzymes production stomach, immune status. The purpose was to determine the presence and power of correlative links secretory activity of the stomach and immune changes in the peripheral blood during exacerbation of ulcer disease stomach. Surveyed in obtaining informed consent 42 patients with gastric ulcer in the acute phase prior to the eradication and antisecretory therapy and 40 healthy volunteers. On the state of function acid- and enzymes production of the gastric mucosa judged by the results of a 2-hour intragastric pH-metry and serum concentration pepsinogen, gastrin before the start of active treatment. Immunophenotype lymphocytes on CD-antigens (CD3, CD4, CD8, CD16, CD19, CD45, CD56) was measured by immunofluorescence, levels immunoglobulin isotype M, G, A, E - ELISA method. When short-term intragastric pH-metry of the stomach hyperacidity patients recorded 6.7 times more likely than healthy, normacidity - 12.3 times less. Reduction of acid production was observed up to 8.6 times more, indicating the development of mucosal atrophy. Basal pH in the antrum was lower by 54.5% than in the control group, with stimulation increased by 33.6%, but remained lower than the values of healthy individuals by 48.7%. When ELISA amount pepsinogen patients showed significant increase in serum levels of PG-I relative to the control group at 33.4%, PG-II - 52%. In assessing the immune status of patients were identified changes in system phagocytes, cellular and humoral links, most pronounced for severe current peptic ulcer disease. The results indicate the presence of positive and negative correlative links mild to moderate force between indicators of secretory activity of gastric mucosal innate and adaptive immunity in patients with acute exacerbation of peptic ulcer disease. The presence and nature of these relationships should

  12. Effect of low doses of ionizing radiation on the thymus-dependent humoral immune response and the polyclonal activation of B-lymphocytes

    International Nuclear Information System (INIS)

    Sharetskij, A.N.; Surinov, B.P.; Abramova, M.R.

    2000-01-01

    The results of studies on the effect of the low-dose (10 cGy with the dose rate of 1cGy/min) γ-radiation on the indices of the mice system and local immune response are presented. The sheep erythrocytes were used as a thymus-dependent antigen. It is shown that the total irradiation with the above dose rate induced the increase in the primary thymus-dependent humoral immune response on the sheep erythrocytes and polyclonal activation of the B-lymphocytes. The sharp oppression of the antibody formation was observed in the immune response dynamics after the phase of the radiation-induced elevation. The injection of hydroquinone right after the irradiation resulted in elimination of the radiation stimulation of the polyclonal response of the B-cells. The essential decrease in the immunoantilogarithmic radiation effect took place in the animals treated with thymogen. The possible negative consequences of the low-dose ionizing radiation impact on the body immune system are discussed [ru

  13. HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon.

    Science.gov (United States)

    Mutz, Pascal; Metz, Philippe; Lempp, Florian A; Bender, Silke; Qu, Bingqian; Schöneweis, Katrin; Seitz, Stefan; Tu, Thomas; Restuccia, Agnese; Frankish, Jamie; Dächert, Christopher; Schusser, Benjamin; Koschny, Ronald; Polychronidis, Georgios; Schemmer, Peter; Hoffmann, Katrin; Baumert, Thomas F; Binder, Marco; Urban, Stephan; Bartenschlager, Ralf

    2018-05-01

    Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B virus (HBV) infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in coinfected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level. PHHs were isolated from liver resection tissues from HBV-, HCV-, and human immunodeficiency virus-negative patients. Differentiated HepaRG cells overexpressing the HBV receptor sodium taurocholate cotransporting polypeptide (dHepaRGNTCP) and PHHs were infected with HBV. Huh7.5 cells were transfected with circular HBV DNA genomes resembling viral covalently closed circular DNA (cccDNA), and subsequently infected with HCV; this served as a model of HBV and HCV coinfection. Cells were incubated with IFN inducers, or IFNs, and antiviral response and viral replication were analyzed by immune fluorescence, reverse-transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and flow cytometry. HBV infection of dHepaRGNTCP cells and PHHs neither activated nor inhibited signaling via pattern recognition receptors. Incubation of dHepaRGNTCP cells and PHHs with IFN had little effect on HBV replication or levels of cccDNA. HBV infection of these cells did not inhibit JAK-STAT signaling or up-regulation of IFN-stimulated genes. In coinfected cells, HBV did not prevent IFN-induced suppression of HCV replication. In dHepaRGNTCP cells and PHHs, HBV evades the induction of IFN and IFN-induced antiviral effects. HBV infection does not rescue HCV from the IFN-mediated response. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Variable activation of immune response by quinoa (Chenopodium quinoa Willd.) prolamins in celiac disease.

    Science.gov (United States)

    Zevallos, Victor F; Ellis, H Julia; Suligoj, Tanja; Herencia, L Irene; Ciclitira, Paul J

    2012-08-01

    Celiac disease is an enteropathy triggered by dietary gluten found in wheat, barley, and rye. The current treatment is a strict gluten-free diet. Quinoa is a highly nutritive plant from the Andes, with low concentrations of prolamins, that has been recommended as part of a gluten-free diet; however, few experimental data support this recommendation. We aimed to determine the amount of celiac-toxic prolamin epitopes in quinoa cultivars from different regions of the Andes and the ability of these epitopes to activate immune responses in patients with celiac disease. The concentration of celiac-toxic epitopes was measured by using murine monoclonal antibodies against gliadin and high-molecular-weight glutenin subunits. Immune response was assessed by proliferation assays of celiac small intestinal T cells/interferon-γ (IFN-γ) and production of IFN-γ/IL-15 after organ culture of celiac duodenal biopsy samples. Fifteen quinoa cultivars were tested: 4 cultivars had quantifiable concentrations of celiac-toxic epitopes, but they were below the maximum permitted for a gluten-free food. Cultivars Ayacuchana and Pasankalla stimulated T cell lines at levels similar to those for gliadin and caused secretion of cytokines from cultured biopsy samples at levels comparable with those for gliadin. Most quinoa cultivars do not possess quantifiable amounts of celiac-toxic epitopes. However, 2 cultivars had celiac-toxic epitopes that could activate the adaptive and innate immune responses in some patients with celiac disease. These findings require further investigation in the form of in vivo studies, because quinoa is an important source of nutrients for patients with celiac disease.

  15. Effect of steroids on the activation status of platelets in patients with Immune thrombocytopenia (ITP).

    Science.gov (United States)

    Bhoria, Preeti; Sharma, Saniya; Varma, Neelam; Malhotra, Pankaj; Varma, Subhash; Luthra-Guptasarma, Manni

    2015-01-01

    The activation status of platelets in Immune Thrombocytopenia (ITP) patients--which is still somewhat controversial--is of potential interest, because activated platelets tend to aggregate (leading to excessive clotting or thromboembolic events) but cannot do so when platelet numbers are low, as in ITP. Although corticosteroids are the first line of therapy in ITP, the effect of steroids on activation of platelets has not been evaluated so far. We examined the status of platelet activation (with and without stimulation with ADP) in ITP patients, at the start of therapy (pre-steroid treatment, naive) and post-steroid treatment (classified on the basis of steroid responsiveness). We used flow cytometry to evaluate the levels of expression of P-selectin, and PAC-1 binding to platelets of 55 ITP patients and a similar number of healthy controls, treated with and without ADP. We found that platelets in ITP patients exist in an activated state. In patients who are responsive to steroids, the treatment reverses this situation. Also, the fold activation of platelets upon treatment with ADP is more in healthy controls than in ITP patients; treatment with steroids causes platelets in steroid-responsive patients to become more responsive to ADP-activation, similar to healthy controls. Thus steroids may cause changes in the ability of platelets to get activated with an agonist like ADP. Our results provide new insights into how, and why, steroid therapy helps in the treatment of ITP.

  16. The role of the local microenvironment in regulating susceptibility and immune responses to sexually transmitted viruses in the female genital tract.

    Science.gov (United States)

    Kaushic, Charu

    2009-12-01

    Sexually transmitted viruses cause chronic infections that have serious long-term health consequences. Based on the evidence from clinical and epidemiological studies, women carry a disproportionately higher burden of sexually transmitted diseases. The reasons for this are not well understood and possibly relate to a variety of social, behavioral and economic factors. In addition to these factors there are biological reasons that contribute to the higher prevalence in women. In this context it is critical to focus on and understand the local microenvironment of the female genital tract, since the majority of viral infections in women occur by heterosexual transmission. The genital tract is also the target site for initiation and maintenance of protective immune responses that could prevent or eliminate viral infections. The epithelial cells of the genital tract provide the first line of defense against viral entry. The interactions between each sexually transmitted virus and the genital epithelium are distinct and determine the outcome of exposure. They are also influenced by a number of factors in the local genital milieu. Among these factors are the female sex hormones that regulate both the susceptibility as well as immune responses to viral infections in the genital tract. Better understanding of the interactions of viruses with the local environment in the female genital tract will lead to development of novel methods to prevent sexually transmitted infections as well as to enhance innate and adaptive immunity.

  17. Forms of Supporting Local Innovative Business Activity in European Countries

    Directory of Open Access Journals (Sweden)

    Oleksandr Fedirko

    2017-04-01

    Full Text Available The article investigates contemporary trends of innovation policy of European countries, describes the essence of contemporary mechanisms and tools for supporting local innovative development. The following most powerful tools for facilitating scientific and technical and innovative business activity are discovered: direct support of private R&D, financing of innovative enterprises, governmental and private cooperative scientific and research projects. A trend is identified for decreasing the share of institutional financing of R&D, and increasing of weight of competitive financing of academic institutions. A conclusion is made as for spreading of technologies commercialization processes support, especially on final stages thereof; the share of these has increased in respect of governmental programs focused on early stages of scientific and research projects. An insight is that within the last two decades the tools for facilitating local innovative business activities have been diversified in the EU: alongside with long-term collaborative governmental and private R&D and initiatives for developing innovative science intensive clusters, short-term tools have been significantly spread, such as innovation projects vouchers and science intensive start-ups support. Given that, it is established that traditionally developed toolkit for supporting small and medium enterprises is being complimented with scaled programs of large companies direct financing. A general trend is identified for increasing the weight of collaborative programs, while the share of individual subsidies and grants for R&D and that of companies innovative activity has substantially decreased. Higher effectiveness of start-ups facilitation measures is concluded, as well as that of venture investments, in comparison with individual subsidies. The leading role of start-ups in EU economy is determined by a range of advantages originating from dynamic process of formation thereof

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

    Science.gov (United States)

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

    2018-04-01

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

  19. Experimental Salmonella typhimurium infections in rats. II. Active and passive immunization as protection against a lethal bacterial dose

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1990-01-01

    Immunization against a lethal dose of Salmonella typhimurium was studied in athymic and thymus-bearing LEW rats. Active immunization was performed with formalin-killed whole cell vaccine or sublethal infection prior to the lethal infection. After vaccination with killed bacteria the euthymic...... from immunized thymus grafted animals provided only limited protective effect, and treatment with cells from athymic animals had no effect. The study shows that although isogeneic thymus-grafted nude rats become resistent to reinfection with S. typhimurium, only large doses of spleen cells from...

  20. Systemic Immune Activation Leads to Neuroinflammation and Sickness Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Steven Biesmans

    2013-01-01

    Full Text Available Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.

  1. Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors.

    Science.gov (United States)

    Bhattacharyya, Suchita; Zagórska, Anna; Lew, Erin D; Shrestha, Bimmi; Rothlin, Carla V; Naughton, John; Diamond, Michael S; Lemke, Greg; Young, John A T

    2013-08-14

    Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate immune responses initiated by Toll-like receptors and type I interferons (IFNs). Many enveloped viruses display the phospholipid phosphatidylserine on their membranes, through which they bind Gas6 and Protein S and engage TAM receptors. We find that ligand-coated viruses activate TAM receptors on dendritic cells (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses that are elevated in comparison to wild-type cells. As a consequence, TAM-deficient DCs are relatively resistant to infection by flaviviruses and pseudotyped retroviruses, but infection can be restored with neutralizing type I IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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

  3. Innate immunity

    African Journals Online (AJOL)

    Ronnie Anderson is Director of the Medical Research Council Unit for Inflammation and Immunity. ... field have included macrophage, T cell, cytokine and cytokine activated killer cell interactions .... monocytes, mast cells, lymphocytes, eccrine.

  4. Localizing Brain Activity from Multiple Distinct Sources via EEG

    Directory of Open Access Journals (Sweden)

    George Dassios

    2014-01-01

    Full Text Available An important question arousing in the framework of electroencephalography (EEG is the possibility to recognize, by means of a recorded surface potential, the number of activated areas in the brain. In the present paper, employing a homogeneous spherical conductor serving as an approximation of the brain, we provide a criterion which determines whether the measured surface potential is evoked by a single or multiple localized neuronal excitations. We show that the uniqueness of the inverse problem for a single dipole is closely connected with attaining certain relations connecting the measured data. Further, we present the necessary and sufficient conditions which decide whether the collected data originates from a single dipole or from numerous dipoles. In the case where the EEG data arouses from multiple parallel dipoles, an isolation of the source is, in general, not possible.

  5. Effects of polio eradication activities on routine immunization: lessons from the 2013 outbreak response in Somali region of Ethiopia

    OpenAIRE

    Tafesse, Belete; Tekle, Ephrem; Wondwossen, Liya; Bogale, Mengistu; Fiona, Braka; Nsubuga, Peter; Tomas, Karengera; Kassahun, Aron; Kathleen, Gallagher; Teka, Aschalew

    2017-01-01

    Introduction Ethiopia experienced several WPV importations with a total of 10 WPV1 cases confirmed during the 2013 outbreak alone before it is closed in 2015. We evaluated supplemental immunization activities (SIAs), including lessons learned for their effect on the routine immunization program during the 2013 polio outbreak in Somali regional state. Methods We used descriptive study to review documents and analyse routine health information system reports from the polio outbreak affected Som...

  6. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

    OpenAIRE

    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood do...

  7. The effects of the local environment on active galactic nuclei

    International Nuclear Information System (INIS)

    Manzer, L. H.; De Robertis, M. M.

    2014-01-01

    There continues to be significant controversy regarding the mechanism(s) responsible for the initiation and maintenance of activity in galactic nuclei. In this paper we will investigate possible environmental triggers of nuclear activity through a statistical analysis of a large sample of galaxy groups. The focus of this paper is to identify active galactic nuclei (AGNs) and other emission-line galaxies in these groups and to compare their frequency with a sample of over 260,000 isolated galaxies from the same catalog. The galaxy groups are taken from the catalog of Yang et al., in which over 20,000 virialized groups of galaxies (2 ≤ N ≤ 20) with redshifts between 0.01 and 0.20 are from the Sloan Digital Sky Survey. We first investigate the completeness of our data set and find, though biases are a concern particularly at higher redshift, that our data provide a fair representation of the local universe. After correcting emission-line equivalent widths for extinction and underlying Balmer stellar absorption, we classify galaxies in the sample using traditional emission-line ratios, while incorporating measurement uncertainties. We find a significantly higher fraction of AGNs in groups compared with the isolated sample. Likewise, a significantly higher fraction of absorption-line galaxies are found in groups, while a higher fraction of star-forming galaxies prefer isolated environments. Within grouped environments, AGNs and star-forming galaxies are found more frequently in small- to medium-richness groups, while absorption-line galaxies prefer groups with larger richnesses. Groups containing only emission-line galaxies have smaller virial radii, velocity dispersions, and masses compared with those containing only absorption-line galaxies. Furthermore, the AGN fraction increases with decreasing distance to the group centroid, independent of galaxy morphology. Using properties obtained from Galaxy Zoo, there is an increased fraction of AGNs within merging systems

  8. The effects of the local environment on active galactic nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Manzer, L. H.; De Robertis, M. M., E-mail: liannemanzer@gmail.com, E-mail: mmdr@yorku.ca [Department of Physics and Astronomy, York University, Toronto, ON M3J 1P3 (Canada)

    2014-06-20

    There continues to be significant controversy regarding the mechanism(s) responsible for the initiation and maintenance of activity in galactic nuclei. In this paper we will investigate possible environmental triggers of nuclear activity through a statistical analysis of a large sample of galaxy groups. The focus of this paper is to identify active galactic nuclei (AGNs) and other emission-line galaxies in these groups and to compare their frequency with a sample of over 260,000 isolated galaxies from the same catalog. The galaxy groups are taken from the catalog of Yang et al., in which over 20,000 virialized groups of galaxies (2 ≤ N ≤ 20) with redshifts between 0.01 and 0.20 are from the Sloan Digital Sky Survey. We first investigate the completeness of our data set and find, though biases are a concern particularly at higher redshift, that our data provide a fair representation of the local universe. After correcting emission-line equivalent widths for extinction and underlying Balmer stellar absorption, we classify galaxies in the sample using traditional emission-line ratios, while incorporating measurement uncertainties. We find a significantly higher fraction of AGNs in groups compared with the isolated sample. Likewise, a significantly higher fraction of absorption-line galaxies are found in groups, while a higher fraction of star-forming galaxies prefer isolated environments. Within grouped environments, AGNs and star-forming galaxies are found more frequently in small- to medium-richness groups, while absorption-line galaxies prefer groups with larger richnesses. Groups containing only emission-line galaxies have smaller virial radii, velocity dispersions, and masses compared with those containing only absorption-line galaxies. Furthermore, the AGN fraction increases with decreasing distance to the group centroid, independent of galaxy morphology. Using properties obtained from Galaxy Zoo, there is an increased fraction of AGNs within merging systems

  9. Induced prion protein controls immune-activated retroviruses in the mouse spleen.

    Directory of Open Access Journals (Sweden)

    Marius Lötscher

    Full Text Available The prion protein (PrP is crucially involved in transmissible spongiform encephalopathies (TSE, but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP.

  10. Consumer available permanent hair dye products cause major allergic immune activation in an animal model

    DEFF Research Database (Denmark)

    Bonefeld, C M; Larsen, J M; Dabelsteen, S

    2010-01-01

    Background p-Phenylenediamine (PPD) and related substances are ingredients of more than two-thirds of oxidative (permanent) hair dyes currently used. Although PPD is a potent skin sensitizer in predictive assays, the extent to which permanent hair dyes sensitize humans has been questioned due...... to the in-use conditions, e.g. the presence of couplers in the hair dye gel and rapid oxidation using a developer. Objectives To study the skin sensitizing potential of permanent hair dyes in mice. Methods Two different permanent hair dye products containing PPD were studied in CBA mice using a modified......-cell proliferation within the draining lymph nodes. Treatment with the mixture induced at least 20% more skin inflammation, cytokine production and CD4+ T-cell activation compared with the colour gel alone. Conclusions Consumer available PPD-containing permanent hair dyes can be potent and rapid immune activators...

  11. The Effects of the Local Environment on Active Galactic Nuclei

    Science.gov (United States)

    Manzer, L. H.; De Robertis, M. M.

    2014-06-01

    There continues to be significant controversy regarding the mechanism(s) responsible for the initiation and maintenance of activity in galactic nuclei. In this paper we will investigate possible environmental triggers of nuclear activity through a statistical analysis of a large sample of galaxy groups. The focus of this paper is to identify active galactic nuclei (AGNs) and other emission-line galaxies in these groups and to compare their frequency with a sample of over 260,000 isolated galaxies from the same catalog. The galaxy groups are taken from the catalog of Yang et al., in which over 20,000 virialized groups of galaxies (2 universe. After correcting emission-line equivalent widths for extinction and underlying Balmer stellar absorption, we classify galaxies in the sample using traditional emission-line ratios, while incorporating measurement uncertainties. We find a significantly higher fraction of AGNs in groups compared with the isolated sample. Likewise, a significantly higher fraction of absorption-line galaxies are found in groups, while a higher fraction of star-forming galaxies prefer isolated environments. Within grouped environments, AGNs and star-forming galaxies are found more frequently in small- to medium-richness groups, while absorption-line galaxies prefer groups with larger richnesses. Groups containing only emission-line galaxies have smaller virial radii, velocity dispersions, and masses compared with those containing only absorption-line galaxies. Furthermore, the AGN fraction increases with decreasing distance to the group centroid, independent of galaxy morphology. Using properties obtained from Galaxy Zoo, there is an increased fraction of AGNs within merging systems, unlike star-forming galaxies. These results provide some indication that the local environment does play a role in initiating activity in galactic nuclei, but it is by no means simple or straightforward.

  12. Tanshinone IIA attenuates neuropathic pain via inhibiting glial activation and immune response.

    Science.gov (United States)

    Cao, Fa-Le; Xu, Min; Wang, Yan; Gong, Ke-Rui; Zhang, Jin-Tao

    2015-01-01

    Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord. Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    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

  14. Dominant effects of the diet on the microbiome and the local and systemic immune response in mice.

    Directory of Open Access Journals (Sweden)

    Jot Hui Ooi

    Full Text Available Outside the nutrition community the effects of diet on immune-mediated diseases and experimental outcomes have not been appreciated. Investigators that study immune-mediated diseases and/or the microbiome have overlooked the potential of diet to impact disease phenotype. We aimed to determine the effects of diet on the bacterial microbiota and immune-mediated diseases. Three different laboratory diets were fed to wild-type mice for 2 weeks and resulted in three distinct susceptibilities to dextran sodium sulfate (DSS-induced colitis. Examination of the fecal microbiota demonstrated a diet-mediated effect on the bacteria found there. Broad-spectrum antibiotics disturbed the gut microbiome and partially eliminated the diet-mediated changes in DSS susceptibility. Dietary changes 2 days after DSS treatment were protective and suggested that the diet-mediated effect occurred quickly. There were no diet-mediated effects on DSS susceptibility in germ-free mice. In addition, the diet-mediated effects were evident in a gastrointestinal infection model (Citrobacter rodentium and in experimental autoimmune encephalomyelitis. Taken together, our study demonstrates a dominant effect of diet on immune-mediated diseases that act rapidly by changing the microbiota. These findings highlight the potential of using dietary manipulation to control the microbiome and prevent/treat immune-mediated disease.

  15. Effects of polio eradication activities on routine immunization: lessons from the 2013 outbreak response in Somali region of Ethiopia.

    Science.gov (United States)

    Tafesse, Belete; Tekle, Ephrem; Wondwossen, Liya; Bogale, Mengistu; Fiona, Braka; Nsubuga, Peter; Tomas, Karengera; Kassahun, Aron; Kathleen, Gallagher; Teka, Aschalew

    2017-01-01

    Ethiopia experienced several WPV importations with a total of 10 WPV1 cases confirmed during the 2013 outbreak alone before it is closed in 2015. We evaluated supplemental immunization activities (SIAs), including lessons learned for their effect on the routine immunization program during the 2013 polio outbreak in Somali regional state. We used descriptive study to review documents and analyse routine health information system reports from the polio outbreak affected Somali regional state. All data and technical reports of the 15 rounds of polio SIAs from June 2013 through June 2015 and routine immunization coverages for DPT-Hib-HepB 3 and measles were observed. More than 93% of the SIAs were having administrative coverage above 95%. The trend of routine immunization for the two antigens, over the five years (2011 through 2015) did not show a consistent pattern against the number of SIAs. Documentations showed qualitative positive impacts of the SIAs strengthening the routine immunization during all courses of the campaigns. The quantitative impact of polio SIAs on routine immunization remained not so impressive in this study. Clear planning, data consistencies and completeness issues need to be cleared for the impact assessment in quantitative terms, in polio legacy planning as well as for the introduction of injectable polio vaccine through the routine immunization.

  16. Human Activity Recognition Supported on Indoor Localization: A Systematic Review.

    Science.gov (United States)

    Cerón, Jesús; López, Diego M

    2018-01-01

    The number of older adults is growing worldwide. This has a social and economic impact in all countries because of the increased number of older adults affected by chronic diseases, health emergencies, and disabilities, representing at the end high cost for the health system. To face this problem, the Ambient Assisted Living (AAL) domain has emerged. Its main objective is to extend the time that older adults can live independently in their homes. AAL is supported by different fields and technologies, being Human Activity Recognition (HAR), control of vital signs and location tracking the three of most interest during the last years. To perform a systematic review about Human Activity Recognition (HAR) approaches supported on Indoor Localization (IL) and vice versa, describing the methods they have used, the accuracy they have obtained and whether they have been directed towards the AAL domain or not. A systematic review of six databases was carried out (ACM, IEEE Xplore, PubMed, Science Direct and Springer). 27 papers were found. They were categorised into three groups according their approach: paper focus on 1. HAR, 2. IL, 3. HAR and IL. A detailed analysis of the following factors was performed: type of methods and technologies used for HAR, IL and data fusion, as well as the precision obtained for them. This systematic review shows that the relationship between HAR and IL has been very little studied, therefore providing insights of its potential mutual support to provide AAL solutions.

  17. Role of immune activation in CD4+ T-cell depletion in HIV-1 infected Indian patients.

    Science.gov (United States)

    Vajpayee, M; Kaushik, S; Sreenivas, V; Mojumdar, K; Mendiratta, S; Chauhan, N K

    2009-01-01

    The correlation of immune activation with CD4(+) depletion and HIV-1 disease progression has been evidenced by several studies involving mainly clade B virus. However, this needs to be investigated in developing countries such as India predominately infected with clade C virus. In a cross-sectional study of 68 antiretroviral treatment naïve, HIV-1 infected Indian patients, we studied the association between CD4(+) T cells, plasma HIV-1 RNA levels, and immune activation markers using unadjusted and adjusted correlative analyses. Significant negative correlations of higher magnitude were observed between the CD4(+) T cell percentages and plasma HIV-1 RNA levels in the study population when adjusted for the effects of immune activation markers. However, the negative association of CD4(+) T cells with immune activation markers remained unaffected when controlled for the effects of plasma HIV-1 RNA levels. Our results support the important role of immune activation in CD4(+) T cell depletion and disease progression during untreated HIV-1 infection.

  18. The Ustilago maydis effector Pep1 suppresses plant immunity by inhibition of host peroxidase activity.

    Directory of Open Access Journals (Sweden)

    Christoph Hemetsberger

    Full Text Available The corn smut Ustilago maydis establishes a biotrophic interaction with its host plant maize. This interaction requires efficient suppression of plant immune responses, which is attributed to secreted effector proteins. Previously we identified Pep1 (Protein essential during penetration-1 as a secreted effector with an essential role for U. maydis virulence. pep1 deletion mutants induce strong defense responses leading to an early block in pathogenic development of the fungus. Using cytological and functional assays we show that Pep1 functions as an inhibitor of plant peroxidases. At sites of Δpep1 mutant penetrations, H₂O₂ strongly accumulated in the cell walls, coinciding with a transcriptional induction of the secreted maize peroxidase POX12. Pep1 protein effectively inhibited the peroxidase driven oxidative burst and thereby suppresses the early immune responses of maize. Moreover, Pep1 directly inhibits peroxidases in vitro in a concentration-dependent manner. Using fluorescence complementation assays, we observed a direct interaction of Pep1 and the maize peroxidase POX12 in vivo. Functional relevance of this interaction was demonstrated by partial complementation of the Δpep1 mutant defect by virus induced gene silencing of maize POX12. We conclude that Pep1 acts as a potent suppressor of early plant defenses by inhibition of peroxidase activity. Thus, it represents a novel strategy for establishing a biotrophic interaction.

  19. The innate immune response in fetal lung mesenchymal cells targets VEGFR2 expression and activity.

    Science.gov (United States)

    Medal, Rachel M; Im, Amanda M; Yamamoto, Yasutoshi; Lakhdari, Omar; Blackwell, Timothy S; Hoffman, Hal M; Sahoo, Debashis; Prince, Lawrence S

    2017-06-01

    In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). With the use of Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines. The transcriptional response was different between cells from E11, E15, and E18 mouse lungs. In all cells tested, LPS inhibited expression of a small core group of genes including the VEGF receptor Vegfr2 Although best characterized in vascular endothelial populations, we demonstrated here that fetal mouse lung mesenchymal cells express Vegfr2 and respond to VEGF-A stimulation. In mesenchymal cells, VEGF-A increased cell migration, activated the ERK/AKT pathway, and promoted FOXO3A nuclear exclusion. With the use of an experimental coculture model of epithelial-mesenchymal interactions, we also showed that VEGFR2 inhibition prevented formation of three-dimensional structures. Both LPS and tyrosine kinase inhibition reduced three-dimensional structure formation. Our data suggest a novel mechanism for inflammation-mediated defects in lung development involving reduced VEGF signaling in lung mesenchyme. Copyright © 2017 the American Physiological Society.

  20. In Vitro Evaluation of Colloidal Silver on Immune Function: Anti lymphoproliferative Activity

    International Nuclear Information System (INIS)

    Franco-Molina, M. A.; Mendoza-Gamboa, E.; Zarate-Trivino, D. G.; Coronado-Cerda, E.E.; Alcocer-Gonzalez, J. M.; Resendez-Perez, D.; Rodriguez-Salazar, M.C.; Rivera-Morales, L.G.; Tamez-Guerra, R.; Rodriguez-Padilla, C.

    2016-01-01

    Colloidal silver (AgC) is currently used by humans and it can be internalized through inhalation, injection, ingestion, and dermal contact. However, there is limited information about immunological activity; more investigations using colloidal silver are needed. In the present study, the effects of AgC (17.5 ng/m L) on immunological parameters (proliferation and immuno phenotyping) using human peripheral blood mononuclear cells (PBMC) and macrophages (phagocytosis) and cytotoxicity on leukemia and lymphoma cancer cell lines (1.75 to 17.5 ng/m L) were investigated. AgC was observed to significantly ρ) decrease interleukin-2 (I L-2) production and proliferation induced by phytohemagglutinin or concanavalin A in PBMC without affecting its cell viability but with cytotoxic effect on cancer cells. IL-2, IL-4, IL-6, IL-10, INF-γ, and IL_-17 A cytokines production and CD3"+, CD3"-CD19"+, CD3"+CD4"+, CD3"+CD8"+, and CD16"+CD56"+ PBMC phenotypes were not affected by AgC. The present study demonstrates that colloidal silver is harmless and nontoxic to the immune system cells and its ability to interfere with the immune response by decreasing cell proliferation when stimulated with mitogens demonstrated the anti lymphoproliferative potential of AgC

  1. The potential for castration of domestic animals by active immunization against GnRH

    International Nuclear Information System (INIS)

    Gonzalez, A.; Allen, A.F.; Murphy, B.D.; Mapletoft, R.J.; Cohen, R.

    1990-01-01

    Trials have been carried out in sheep and beef cattle in attempts to induce immunity against gonadotropin releasing hormone (GnRH), with the objective of using immunocastration as a replacement for surgical castration. Of the protein carriers used, ovalbumin and horse albumin yielded highest responses, with keyhole limpet haemocyanin (KLH) being a potent substitute for both. Different adjuvants were also used. In these trials, highest titre responses were obtained using Freund's complete (FCA) or Freund's incomplete (FIA) adjuvant in cattle and sheep. Although no adjuvant was found to yield as high a response as FCA and Alhydrogel, an aluminium hydroxide adjuvant generally yielded a high response in cattle and sheep. The results from the trials in beef calves indicate that active immunization against GnRH does not affect average daily gains, total body weight gain or carcass dressing percentage. The results suggest the potential of immunocastration as a substitute for surgical castration in cattle and sheep. (author). 30 refs, 8 figs, 2 tabs

  2. In Vitro Evaluation of Colloidal Silver on Immune Function: Antilymphoproliferative Activity

    Directory of Open Access Journals (Sweden)

    M. A. Franco-Molina

    2016-01-01

    Full Text Available Colloidal silver (AgC is currently used by humans and it can be internalized through inhalation, injection, ingestion, and dermal contact. However, there is limited information about immunological activity; more investigations using colloidal silver are needed. In the present study, the effects of AgC (17.5 ng/mL on immunological parameters (proliferation and immunophenotyping using human peripheral blood mononuclear cells (PBMC and macrophages (phagocytosis and cytotoxicity on leukemia and lymphoma cancer cell lines (1.75 to 17.5 ng/mL were investigated. AgC was observed to significantly (p<0.05 decrease interleukin-2 (IL-2 production and proliferation induced by phytohemagglutinin or concanavalin A in PBMC without affecting its cell viability but with cytotoxic effect on cancer cells. IL-2, IL-4, IL-6, IL-10, INF-γ, and IL-17A cytokines production and CD3+, CD3−CD19+, CD3+CD4+, CD3+CD8+, and CD16+CD56+ PBMC phenotypes were not affected by AgC. The present study demonstrates that colloidal silver is harmless and nontoxic to the immune system cells and its ability to interfere with the immune response by decreasing cell proliferation when stimulated with mitogens demonstrated the antilymphoproliferative potential of AgC.

  3. The impact of inflammation and immune activation on B cell differentiation during HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Nicolas eRuffin

    2012-01-01

    Full Text Available HIV-1 infection is characterized by continuous antigenic stimulation, chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells has previously been reported to occur in both children and adults infected with HIV-1; these cells are responsible for mounting and maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development which are impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.

  4. Digital quantification of gene expression in sequential breast cancer biopsies reveals activation of an immune response.

    Directory of Open Access Journals (Sweden)

    Rinath M Jeselsohn

    Full Text Available Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. A useful approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy and the definitive surgery. These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define the biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention using the Nanostring nCounter platform. We found that while the majority of the transcripts did not vary between the two biopsies, there was evidence of activation of immune related genes in response to the first biopsy and further investigations of the immune changes after a biopsy in early breast cancer seem warranted.

  5. Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation.

    Science.gov (United States)

    Cox, D; Kerrigan, S W; Watson, S P

    2011-06-01

    It has become clear that platelets are not simply cell fragments that plug the leak in a damaged blood vessel; they are, in fact, also key components in the innate immune system, which is supported by the presence of Toll-like receptors (TLRs) on platelets. As the cells that respond first to a site of injury, they are well placed to direct the immune response to deal with any resulting exposure to pathogens. The response is triggered by bacteria binding to platelets, which usually triggers platelet activation and the secretion of antimicrobial peptides. The main platelet receptors that mediate these interactions are glycoprotein (GP)IIb-IIIa, GPIbα, FcγRIIa, complement receptors, and TLRs. This process may involve direct interactions between bacterial proteins and the receptors, or can be mediated by plasma proteins such as fibrinogen, von Willebrand factor, complement, and IgG. Here, we review the variety of interactions between platelets and bacteria, and look at the potential for inhibiting these interactions in diseases such as infective endocarditis and sepsis. © 2011 International Society on Thrombosis and Haemostasis.

  6. Childhood life events, immune activation and the development of mood and anxiety disorders: the TRAILS study.

    Science.gov (United States)

    Jonker, I; Rosmalen, J G M; Schoevers, R A

    2017-05-02

    The experience of childhood life events is associated with higher vulnerability to develop psychiatric disorders. One of the pathways suggested to lead to this vulnerability is activation of the immune system. The aim of this study is to find out whether the association between childhood life events and the development of mood and anxiety disorders is predicted by the activation of the immune system. This study was performed in TRAILS, a large prospective population cohort, from which a subgroup was selected (N=1084, 54.3% female, mean age 19.0 (s.d., 0.6)). Childhood life events before age 16 were assessed using questionnaires at age 12, 14, 16 and 19. Immune activation was assessed at age 16 by elevated high-sensitive C-reactive protein (hsCRP) and by levels of immunoglobulin G antibodies against the herpes viruses herpes simplex virus 1, cytomegalovirus and Epstein-Barr virus. At age 19, the presence of mood and anxiety disorders was determined using the World Health Organization Composite International Diagnostic Interview Version 3.0. Regression analyses were used to study the association between life events, the inflammatory markers and mental health. We found that childhood life events score was associated with risk of mood disorders (B=0.269, P<0.001) and anxiety disorders (B=0.129, P<0.001). Childhood life events score was marginally associated with elevated hsCRP (B=0.076, P=0.006), but not with the antibody levels. This was especially due to separation trauma (P=0.015) and sexual abuse (P=0.019). Associations lost significance after correcting for lifestyle factors such as body mass index and substance abuse (P=0.042). None of the inflammatory markers were associated with development of anxiety disorders or mood disorders. In conclusion, the life event scores predicted the development of anxiety disorders and mood disorders at age 19. Life event scores were associated with elevated hsCRP, which was partly explained by lifestyle factors. Elevated hs

  7. Induction of local and systemic immune reactions following infection of turkeys with avian Metapneumovirus (aMPV) subtypes A and B.

    Science.gov (United States)

    Liman, Martin; Rautenschlein, Silke

    2007-02-15

    Most of the studies regarding the immunopathogenesis of avian Metapneumovirus (aMPV) have been done with subtype C of aMPV. Not much is known about the immunopathogenesis of aMPV subtypes A and B in turkeys. Specifically, local immune reactions have not been investigated yet. We conducted two experiments in commercial turkeys. We investigated local and systemic humoral and cell mediated immune reactions following infection with an attenuated vaccine strain of aMPV subtype B (Experiment I) and virulent strains of aMPV subtypes A and B (Experiment II). Turkeys infected with virulent aMPV strains developed mild respiratory signs while birds inoculated with the attenuated aMPV did not show any clinical signs. Virus neutralizing antibodies were detected locally in tracheal washes and systemically in serum as soon as 5-7 days post aMPV infection (PI) independent of the strain used. Virus neutralizing antibody titres peaked at 7 days PI and then antibody levels declined. The peak of serum ELISA antibody production varied between infected groups and ranged from 14 and 28 days PI. All aMPV strains induced an increase in the percentage of CD4+ T cell populations in spleen and Harderian gland at days 7 or 14 PI. Furthermore, as shown in Experiment I, infection with the attenuated aMPV-B strain stimulated spleen leukocytes to release significantly higher levels of interferons (IFNs), interleukin-6 and nitric oxide in ex vivo culture in comparison to virus-free controls up to 7 days PI (P<0.05). As detected by quantitative real time RT-PCR in Experiment II, infection with virulent aMPV induced an increased IFNgamma expression in the Harderian gland in comparison to virus-free controls. IFNgamma expression in the spleen varied between aMPV strains and days PI. Overall, our study demonstrates that aMPV subtypes A and B infection induced humoral and cell mediated immune reactions comparable to subtype C infections. We observed only temporary stimulation of serum virus neutralizing

  8. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

    Science.gov (United States)

    Yamamoto, N; Naraparaju, V R

    1998-06-01

    Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.

  9. A leukocyte activation test identifies food items which induce release of DNA by innate immune peripheral blood leucocytes.

    Science.gov (United States)

    Garcia-Martinez, Irma; Weiss, Theresa R; Yousaf, Muhammad N; Ali, Ather; Mehal, Wajahat Z

    2018-01-01

    Leukocyte activation (LA) testing identifies food items that induce a patient specific cellular response in the immune system, and has recently been shown in a randomized double blinded prospective study to reduce symptoms in patients with irritable bowel syndrome (IBS). We hypothesized that test reactivity to particular food items, and the systemic immune response initiated by these food items, is due to the release of cellular DNA from blood immune cells. We tested this by quantifying total DNA concentration in the cellular supernatant of immune cells exposed to positive and negative foods from 20 healthy volunteers. To establish if the DNA release by positive samples is a specific phenomenon, we quantified myeloperoxidase (MPO) in cellular supernatants. We further assessed if a particular immune cell population (neutrophils, eosinophils, and basophils) was activated by the positive food items by flow cytometry analysis. To identify the signaling pathways that are required for DNA release we tested if specific inhibitors of key signaling pathways could block DNA release. Foods with a positive LA test result gave a higher supernatant DNA content when compared to foods with a negative result. This was specific as MPO levels were not increased by foods with a positive LA test. Protein kinase C (PKC) inhibitors resulted in inhibition of positive food stimulated DNA release. Positive foods resulted in CD63 levels greater than negative foods in eosinophils in 76.5% of tests. LA test identifies food items that result in release of DNA and activation of peripheral blood innate immune cells in a PKC dependent manner, suggesting that this LA test identifies food items that result in release of inflammatory markers and activation of innate immune cells. This may be the basis for the improvement in symptoms in IBS patients who followed an LA test guided diet.

  10. Histologic characteristics and local cellular immunity of the gland of the third eyelid after topical ophthalmic administration of 2% cyclosporine for treatment of dogs with keratoconjunctivitis sicca.

    Science.gov (United States)

    Izci, Celal; Celik, Ilhami; Alkan, Fahrettin; Ogurtan, Zeki; Ceylan, Cengiz; Sur, Emrah; Ozkan, Yasemin

    2002-05-01

    To evaluate the efficacy of topical administration of a 2% solution of cyclosporine (CsA) for treatment of dogs with keratoconjunctivitis sicca (KCS) and to correlate results with histopathologic characteristics and local cellular immunity of the gland of the third eyelid. 24 dogs with bilateral KCS. Lacrimal secretion was measured, using Schirmer tear test (STT) strips. Leukocyte and T-lymphocyte subsets were determined in blood samples. Histopathologic changes as well as CD4+, CD8+, and alpha-naphthyl-acetate esterase-positive (ANAE+) lymphocytes were evaluated. Clinical signs resolved at the end of 1 month in conjunction with significantly increased STT values, compared with baseline values. Fifteen and 30 days after discontinuation of CsA treatment, a decrease was observed in STT values in both eyes; however, only values for the right eye were significantly different. There was a significant decrease in the number of lymphocytes and ANAE+ lymphocytes 15 and 30 days after discontinuation of CsA treatment, compared with baseline values. Differences were not observed in number of CD4+ lymphocytes among treatment groups. However, there was a significant decrease in number of CD8+ lymphocytes with reversal of the CD4+:CD8+ in both eyes after CsA treatment for 30 days, compared with the control group. Increased secretory activity and decreased lymphocyte infiltration were characteristic histopathologic findings. Topical administration of a 2% solution of CsA was effective for the treatment of dogs with KCS. Strict follow-up monitoring is required after the cessation of treatment because of the possibility of recurrence of KCS.

  11. Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

    International Nuclear Information System (INIS)

    Doloff, Joshua C; Waxman, David J

    2015-01-01

    Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune activation. Increased expression of many host (mouse) immune networks was also seen in both tumor models, including complement components, toll-like receptors, interferons, and cytolysis pathways. Key upstream regulators activated by metronomic cyclophosphamide include members of the interferon, toll-like receptor, inflammatory response, and PPAR signaling pathways, whose activation may contribute to anti-tumor immunity. Many upstream regulators inhibited by metronomic cyclophosphamide, including hypoxia-inducible factors and MAP kinases, have glioma-promoting activity; their inhibition may contribute to the therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide schedule. Large numbers of responsive cytokines, chemokines and immune regulatory genes linked to innate immune cell recruitment and tumor regression were identified, as were several immunosuppressive factors that may contribute to the observed escape of some tumors from metronomic CPA

  12. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement

    DEFF Research Database (Denmark)

    Frederiksen, Pernille Dorthea; Thiel, Steffen; Larsen, Claus Bindslev

    2005-01-01

    Ficolins play a role in the innate immune defence as pathogen-associated molecular pattern recognition molecules. Three ficolins are found in humans: H-ficolin, L-ficolin and M-ficolin. L-ficolin and H-ficolin circulate in blood in complexes with mannan-binding lectin-associated serine proteases...... (MASPs) and are capable of activating the complement system. L-ficolin shows affinity for acetylated compounds and binds to various capsulated strains of bacteria. H-ficolin has been shown to bind Aerococcus viridans. Less is known about M-ficolin, but it is thought to be present only on monocytes. We...... system. We developed a monoclonal rat anti-human-M/L-ficolin antibody and verified by flow cytometric analysis the presence of ficolin on the surface of peripheral blood monocytes....

  13. Potential use of local and systemic humoral immune response parameters to forecast Mycoplasma hyopneumoniae associated lung lesions.

    Directory of Open Access Journals (Sweden)

    Beatriz Garcia-Morante

    Full Text Available Immunopathological events are key for the development of enzootic pneumonia (EP, which is macroscopically observed as cranioventral pulmonary consolidation (CVPC. This study aimed to investigate the putative association between the humoral immune response against Mycoplasma hyopneumoniae (M. hyopneumoniae and prevalence and extension of CVPC in 1 experimentally infected pigs, 2 slaughtered pigs and 3 sequentially necropsied pigs in a longitudinal study. CVPC was scored by means of the European Pharmacopoeia recommended methodology. Specific IgG, IgG1 and IgG2 antibodies were assessed in serum. In addition, mucosal IgG and IgA antibodies were analyzed in broncho-alveolar lavage fluid (BALF from experimentally challenged pigs. The systemic humoral immune response in experimentally infected pigs was delayed in onset whereas humoral respiratory mucosal immune response appeared more rapidly but declined earlier. Although low, BALF IgG antibodies showed the highest correlation with CVPC scores (r = 0.49, p<0.05. In slaughter-aged pigs, both percentage of lungs with CVPC and mean lung lesion score were significantly higher in M. hyopneumoniae seropositive farms compared to the seronegative ones (p<0.001. Similarly, seropositive sequentially necropsied pigs showed more severe CVPC than seronegative ones. Overall, mean serological values might help to forecast prevalence and severity of EP-like lung lesions using a population based approach. Remarkably, the specific systemic humoral immune response was found to be predominated by the IgG2 subclass, suggesting a dominant Th1-mediated immune response to M. hyopneumoniae.

  14. A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity

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    Kaname Nosaki

    2016-01-01

    Full Text Available Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, both in vitro and in vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPL in vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.

  15. The effect of active immunization against vasoactive intestinal peptide (VIP) and inhibin on reproductive performance of aging White Leghorn roosters.

    Science.gov (United States)

    Avital-Cohen, N; Heiblum, R; Argov, N; Rosenstrauch, A; Chaiseha, Y; Mobarkey, N; Rozenboim, I

    2012-01-01

    Decreasing fertility in aging domestic roosters is a well-known phenomenon. Aging is manifested by a decrease in plasma testosterone level, testis function, and spermatogenesis, resulting in a low level of fertility. The roles of vasoactive intestinal peptide (VIP) and testicular inhibin in this aging process are not clear. The effects of active immunization against VIP, inhibin, or the combination of both hormones on the reproduction of aging White Leghorn (WL) roosters were assayed. In experiment 1a, 60 White Leghorn roosters (67 wk of age) were divided into 4 groups (n = 15/group). The first group was actively immunized against VIP, the second against inhibin, the third against VIP and inhibin, and the fourth served as a control. Active immunization against VIP decreased semen quality parameters, plasma steroid levels, and gene expression of gonadotropin-releasing hormone-I (GnRH-I), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH receptor, VIP, and prolactin (Prl). Immunization against inhibin increased some of the semen quality parameters and FSH mRNA gene expression but decreased inhibin gene expression. In experiment 1b, at 94 wk of age, we took the actively immunized against VIP group and the control group and divided them into 2 subgroups (n = 7 or 8): the first group was injected with 1 mg of ovine Prl (oPrl) daily for 7 d, and the second group served as a control. Administration of oPrl to previously VIP-immunized birds significantly elevated semen quality parameters. We suggest that VIP, Prl, and inhibin have an important effect on the reproductive axis in aging roosters. Active immunization against VIP-depressed reproductive activity and Prl administration restored their reproduction, indicating that both VIP and Prl are essential for reproduction in aging roosters. Immunization against inhibin improved FSH mRNA gene expression, suggesting a negative role of inhibin on FSH secretion in aging roosters. Not all semen quality parameters

  16. Modelling the Immune Response to Cancer: An Individual-Based Approach Accounting for the Difference in Movement Between Inactive and Activated T Cells.

    Science.gov (United States)

    Macfarlane, Fiona R; Lorenzi, Tommaso; Chaplain, Mark A J

    2018-06-01

    A growing body of experimental evidence indicates that immune cells move in an unrestricted search pattern if they are in the pre-activated state, whilst they tend to stay within a more restricted area upon activation induced by the presence of tumour antigens. This change in movement is not often considered in the existing mathematical models of the interactions between immune cells and cancer cells. With the aim to fill such a gap in the existing literature, in this work we present a spatially structured individual-based model of tumour-immune competition that takes explicitly into account the difference in movement between inactive and activated immune cells. In our model, a Lévy walk is used to capture the movement of inactive immune cells, whereas Brownian motion is used to describe the movement of antigen-activated immune cells. The effects of activation of immune cells, the proliferation of cancer cells and the immune destruction of cancer cells are also modelled. We illustrate the ability of our model to reproduce qualitatively the spatial trajectories of immune cells observed in experimental data of single-cell tracking. Computational simulations of our model further clarify the conditions for the onset of a successful immune action against cancer cells and may suggest possible targets to improve the efficacy of cancer immunotherapy. Overall, our theoretical work highlights the importance of taking into account spatial interactions when modelling the immune response to cancer cells.

  17. Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism.

    Science.gov (United States)

    Hasan, Maroof; Gonugunta, Vijay K; Dobbs, Nicole; Ali, Aktar; Palchik, Guillermo; Calvaruso, Maria A; DeBerardinis, Ralph J; Yan, Nan

    2017-01-24

    Three-prime repair exonuclease 1 knockout (Trex1 -/- ) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1 -/- mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism. We also genetically separated the inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1 -/- background, and many metabolic defects persist in Trex1 -/- Irf3 -/- cells and mice. We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prolonged survival of Trex1 -/- mice without dampening inflammation. Mechanistically, we identified TBK1 as a key regulator of mTORC1 activity in Trex1 -/- cells. Together, our data demonstrate that chronic innate immune activation of TBK1 suppresses mTORC1 activity, leading to dysregulated cellular metabolism.

  18. MiRNA-548ah, a Potential Molecule Associated with Transition from Immune Tolerance to Immune Activation of Chronic Hepatitis B

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    Tong-Jing Xing

    2014-08-01

    Full Text Available Objective: The present study aims to identify the differently expressed microRNA (miRNA molecules and target genes of miRNA in the immune tolerance (IT and immune activation (IA stages of chronic hepatitis B (CHB. Methods: miRNA expression profiles of peripheral blood mononuclear cells (PBMCs at the IT and IA stages of CHB were screened using miRNA microarrays and authenticated using a quantitative real-time polymerase chain reaction (RT-PCR. Gene ontology (GO and the Kyoto encyclopedia of genes and genomes (KEGG were used to analyze the significant functions and pathways of possible target genes of miRNAs. Assays of the gain and loss of function of the miRNAs were performed to verify the target genes in THP-1 cell lines. The luciferase reporter test was used on 293T cells as direct targets. Results: Significantly upregulated miR-548 and miR-4804 were observed in the miRNA microarrays and confirmed by RT-PCR in PBMCs at the IT and IA stages of CHB. GO and KEGG analysis revealed that MiR-548 and miR-4804 could be involved in numerous signaling pathways and protein binding activity. IFNγR1 was predicted as a target gene and validated as the direct gene of MiR-548. Significant negative correlation was found between the miR-548ah and mRNA levels of IFN-γR1 in CHB patients. Conclusions: The abnormal expression profiles of miRNA in PBMCs could be closely associated with immune activation of chronic HBV infection. miR-548, by targeting IFN-γR1, may represent a mechanism that can facilitate viral pathogenesis and help determine new therapeutic molecular targets.

  19. Machine learning of molecular properties: Locality and active learning

    Science.gov (United States)

    Gubaev, Konstantin; Podryabinkin, Evgeny V.; Shapeev, Alexander V.

    2018-06-01

    In recent years, the machine learning techniques have shown great potent1ial in various problems from a multitude of disciplines, including materials design and drug discovery. The high computational speed on the one hand and the accuracy comparable to that of density functional theory on another hand make machine learning algorithms efficient for high-throughput screening through chemical and configurational space. However, the machine learning algorithms available in the literature require large training datasets to reach the chemical accuracy and also show large errors for the so-called outliers—the out-of-sample molecules, not well-represented in the training set. In the present paper, we propose a new machine learning algorithm for predicting molecular properties that addresses these two issues: it is based on a local model of interatomic interactions providing high accuracy when trained on relatively small training sets and an active learning algorithm of optimally choosing the training set that significantly reduces the errors for the outliers. We compare our model to the other state-of-the-art algorithms from the literature on the widely used benchmark tests.

  20. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules

    International Nuclear Information System (INIS)

    Teschendorff, Andrew E; Gomez, Sergio; Arenas, Alex; El-Ashry, Dorraya; Schmidt, Marcus; Gehrmann, Mathias; Caldas, Carlos

    2010-01-01

    Elucidating the activation pattern of molecular pathways across a given tumour type is a key challenge necessary for understanding the heterogeneity in clinical response and for developing novel more effective therapies. Gene expression signatures of molecular pathway activation derived from perturbation experiments in model systems as well as structural models of molecular interactions ('model signatures') constitute an important resource for estimating corresponding activation levels in tumours. However, relatively few strategies for estimating pathway activity from such model signatures exist and only few studies have used activation patterns of pathways to refine molecular classifications of cancer. Here we propose a novel network-based method for estimating pathway activation in tumours from model signatures. We find that although the pathway networks inferred from cancer expression data are highly consistent with the prior information contained in the model signatures, that they also exhibit a highly modular structure and that estimation of pathway activity is dependent on this modular structure. We apply our methodology to a panel of 438 estrogen receptor negative (ER-) and 785 estrogen receptor positive (ER+) breast cancers to infer activation patterns of important cancer related molecular pathways. We show that in ER negative basal and HER2+ breast cancer, gene expression modules reflecting T-cell helper-1 (Th1) and T-cell helper-2 (Th2) mediated immune responses play antagonistic roles as major risk factors for distant metastasis. Using Boolean interaction Cox-regression models to identify non-linear pathway combinations associated with clinical outcome, we show that simultaneous high activation of Th1 and low activation of a TGF-beta pathway module defines a subtype of particularly good prognosis and that this classification provides a better prognostic model than those based on the individual pathways. In ER+ breast cancer, we find that

  1. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    Science.gov (United States)

    2012-01-01

    Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD). Methods In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I

  2. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    Directory of Open Access Journals (Sweden)

    Cribbs David H

    2012-07-01

    Full Text Available Abstract Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD. Methods In a well-powered microarray study of young (20 to 59 years, aged (60 to 99 years, and AD (74 to 95 years cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%. In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets, with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc receptors and human

  3. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

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    Mones M. Abu Shady

    2015-07-01

    Full Text Available Objective: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA and correlate them with disease activity. Methods: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27. Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb, erythrocyte sedimentation rate (ESR, and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, and neopterin were measured. Results: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-α, IL-6, and MCP-1 (p  0.05. Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p  0,05. A análise de regressão linear múltipla mostrou que o JADAS-27 e a TSE foram as principais variáveis associadas à neopterina sérica em pacientes com AIJ (p < 0,05. Conclusão: A elevação das concentrações plasmáticas de neopterina em pacientes com AIJ precoce pode indicar um estímulo de resposta imune. A neopterina sérica pode ser usada como um indicador sensível para analisar o histórico de inflamações e o escore de atividade da doença em pacientes com AIJ. Keywords: MCP-1, TNF-α, Rheumatoid arthritis, Palavras-chave: MCP-1, FNT-α, Artrite reumatoide

  4. Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization.

    Science.gov (United States)

    Saito, Misa; Kondo, Masahiro; Ohshima, Motohiro; Deguchi, Kazuki; Hayashi, Hideki; Inoue, Kazuyuki; Tsuji, Daiki; Masuko, Takashi; Itoh, Kunihiko

    2014-04-01

    A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody-derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98-expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope-immunized mouse spleen-derived antibody Fab library showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an undetectable minor population in mimotope-induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co-administration of adjuvant compounds such as T-cell epitope peptides and Toll-like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  5. Interleukin-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium

    Science.gov (United States)

    Liu, Rebecca; Lauridsen, Holly M.; Amezquita, Robert A.; Pierce, Richard W.; Jane-wit, Dan; Fang, Caodi; Pellowe, Amanda S.; Kirkiles-Smith, Nancy C.; Gonzalez, Anjelica L.; Pober, Jordan S.

    2016-01-01

    A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multi-step process that involves sequential cell-cell interactions of circulating leukocytes with interleukin (IL)-1- or tumor necrosis factor-α (TNF)-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a pro-inflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, while neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA-seq analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media (CM) from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and also stimulate neutrophil production of pro-inflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs but not ECs can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondria outer membrane permeabilization and caspase 9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by CM from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

  6. Immune-enhancing activities of low molecular weight β-glucan depolymerized by gamma irradiation

    Science.gov (United States)

    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.

  7. 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.

  8. Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation.

    Science.gov (United States)

    Moons, Wesley G; Shields, Grant S

    2015-08-01

    Psychological stressors reliably trigger systemic inflammatory activity as indexed by levels of proinflammatory cytokines. This experiment demonstrates that one's specific emotional reaction to a stressor may be a significant determinant of whether an inflammatory reaction occurs in response to that stressor. Based on extant correlational evidence and theory, a causal approach was used to determine whether an avoidant emotion (anxiety) triggers more inflammatory activity than an approach emotion (anger). In an experimental design (N = 40), a 3-way Emotion Condition × Time × Analyte interaction revealed that a writing-based anxiety induction, but not a writing-based anger induction, increased mean levels of interferon-γ (IFN- γ) and interleukin-1β (IL-1β), but not interleukin-6 (IL-6) in oral mucous, F(2, 54) = 4.64, p = .01, ηp(²) = .15. Further, self-reported state anxiety predicted elevated levels of proinflammatory cytokines, all ΔR(²) >.06, ps emotions can differentially cause inflammatory activity and support a theoretical model explaining these effects based on the avoidance or approach motivations associated with emotions. (c) 2015 APA, all rights reserved).

  9. Radionuclide activity and the immune system functioning in residents of radiation contaminated areas

    Directory of Open Access Journals (Sweden)

    V. L. Sokolenko

    2015-09-01

    Full Text Available The objective of this research is to assess the relation of radioactive contamination degree to immune system functioning, in the absence or presence of additional potential immunosuppressants. To achieve the objective, during the period of 1995–2015 we examined 250 people, students of Cherkasy State University, who lived in the areas of enhanced radiation monitoring before. Also we evaluated the additional impact of the emotional stress caused by examinations on examined students. Indicators of cellular immunity were determined by immunophenotyping and dyeing using Romanowsky-Giemsa method. The level of immunoglobulins in blood serum was determined by radial immunodiffusion (Mancini method. The level of cortisol in blood serum was determined by immunoenzyme method. We have found that in absence of the emotional stress among residents of the areas contaminated with radionuclides, cortisol level remained at the upper limit of homeostatic norm. There is an average positive correlation between the activity of radionuclides in the territories of residence and the level of cortisol. There are marked average positive correlations between the activity of radionuclides and the level of neutrophils, and low positive correlations with the levels of IgG and IgM in blood serum. Average negative correlations between the activity of radionuclides and the following parameters are also observed: absolute and relative number of functionally mature T-lymphocytes with phenotype CD3+, absolute and relative number of their helper subpopulation CD4+, absolute and relative number of natural killer cells with phenotype CD16+; and strong negative correlations with immunoregulatory index CD4+/CD8+. Cortisol level shows the similar correlation with the same parameters, but correlation coefficient is lower. Under conditions of additional stress, caused by emotional load during the examinations, cortisol level significantly increases. This enhanced previously discovered

  10. Localization of Glucose Oxidase and Catalase Activities in Aspergillus niger

    NARCIS (Netherlands)

    Witteveen, Cor F.B.; Veenhuis, Marten; Visser, Jaap

    The subcellular localization of glucose oxidase (EC 1.1.3.4) in Aspergillus niger N400 (CBS 120.49) was investigated by (immuno)cytochemical methods. By these methods, the bulk of the enzyme was found to be localized in the cell wall. In addition, four different catalases (EC 1.11.1.6) were

  11. Potential use of local and systemic humoral immune response parameters to forecast Mycoplasma hyopneumoniae associated lung lesions.

    Science.gov (United States)

    Garcia-Morante, Beatriz; Segalés, Joaquim; Fraile, Lorenzo; Llardén, Gemma; Coll, Teresa; Sibila, Marina

    2017-01-01

    Immunopathological events are key for the development of enzootic pneumonia (EP), which is macroscopically observed as cranioventral pulmonary consolidation (CVPC). This study aimed to investigate the putative association between the humoral immune response against Mycoplasma hyopneumoniae (M. hyopneumoniae) and prevalence and extension of CVPC in 1) experimentally infected pigs, 2) slaughtered pigs and 3) sequentially necropsied pigs in a longitudinal study. CVPC was scored by means of the European Pharmacopoeia recommended methodology. Specific IgG, IgG1 and IgG2 antibodies were assessed in serum. In addition, mucosal IgG and IgA antibodies were analyzed in broncho-alveolar lavage fluid (BALF) from experimentally challenged pigs. The systemic humoral immune response in experimentally infected pigs was delayed in onset whereas humoral respiratory mucosal immune response appeared more rapidly but declined earlier. Although low, BALF IgG antibodies showed the highest correlation with CVPC scores (r = 0.49, phyopneumoniae seropositive farms compared to the seronegative ones (phyopneumoniae.

  12. Assessment of source of information for polio supplementary immunization activities in 2014 and 2015, Somali, Ethiopia.

    Science.gov (United States)

    Bedada, Selamawit Yilma; Gallagher, Kathleen; Aregay, Aron Kassahun; Mohammed, Bashir; Maalin, Mohammed Adem; Hassen, Hassen Abdisemed; Ali, Yusuf Mohammed; Braka, Fiona; Kilebou, Pierre M'pele

    2017-01-01

    Communication is key for the successful implementation of polio vaccination campaigns. The purpose of this study is to review and analyse the sources of information utilized by caregivers during polio supplementary immunization activities (SIAs) in Somali, Ethiopia in 2014 and 2015. Data on sources of information about the polio campaign were collected post campaign from caregivers by trained data collectors as part of house to house independent monitoring. The sources of information analysed in this paper include town criers (via megaphones), health workers, religious leaders, kebele leaders (Kebele is the lowest administrative structure in Ethiopia), radio, television, text message and others. The repetition of these sources of information was analysed across years and zones for trends. Polio vaccination campaign coverage was also reviewed by year and zones within the Somali region in parallel with the major sources of information used in the respective year and zones. 57,745 responses were used for this analysis but the responses were received from polio SIAs. Zonal trends in using town criers as a major source of information in both study years remained consistent except in two zones. 87.5% of zones that reported at least 90% coverage during both study years had utilized town criers as a major source of information while the rest (12.5%) used health workers. We found that town criers were consistently the major source of information about the polio campaigns for Somali region parents and caregivers during polio immunization days held in 2014 and 2015. Health workers and kebele leaders were also important sources of information about the polio campaign for parents.

  13. Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

    Science.gov (United States)

    Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

  14. Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder.

    Directory of Open Access Journals (Sweden)

    David N Ruskin

    Full Text Available Prenatal factors influence autism spectrum disorder (ASD incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD.

  15. Spatio-temporal regulation of Hsp90-ligand complex leads to immune activation.

    Directory of Open Access Journals (Sweden)

    Yasuaki eTamura

    2016-05-01

    Full Text Available Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We found that an Hsp90-cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived dendritic cells and induced peptide-specific cytotoxic T lymphocytes. Furthermore, we observed that the internalized Hsp90-peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through a endosome-recycling pathway. We also found that extracellular Hsp90 complexed with CpG-A or self-DNA stimulates production of a large amount of IFN-α from pDCs via static early endosome targeting. Thus, extracellular Hsp90 can target the antigen or nucleic acid to a static early endosome by spatio-temporal regulation. Moreover, we showed that Hsp90 associates with and delivers TLR7/9 from the ER to early endosomes for ligand recognition. Hsp90 inhibitor, geldanamycin derivative inhibited the Hsp90 association with TLR7/9, resulting in inhibition IFN-α production, leading to improvement of SLE symptoms. Interstingly, we observed that serum Hsp90 is clearly increased in patients with active SLE compared with that in patients with inactive disease. Serum Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading to stimulation of pDCs to produce IFN-α. Thus, Hsp90 plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will therefore provide a new therapeutic approach to SLE and other nucleic acid-related autoimmune diseases. We will discuss how spatio-temporal regulation of Hsp90-ligand complexes within antigen-presenting cells affects the innate immunity and adaptive immunity.

  16. Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage.

    Science.gov (United States)

    Rajasuriar, Reena; Wright, Edwina; Lewin, Sharon R

    2015-01-01

    The purpose of this review was to summarize recent studies on the effect of early antiretroviral therapy (ART) in HIV-infected patients on markers of immune activation/inflammation, viral persistence and serious non-AIDS events. Early ART, initiated within days to months of HIV infection, was associated with marked reduction in T-cell activation often reaching levels observed in HIV-uninfected individuals. However, the impact of early ART on markers of innate immune activation, microbial translocation and inflammation/coagulation was less clear. Early ART has also been associated with a significant reduction in the frequency of latently infected cells, which was greater if ART was initiated within days to weeks rather than months following infection. However, few studies have evaluated the relationship between immune activation and viral reservoirs, specifically following early ART. Early ART may potentially reduce serious non-AIDS events and associated mortality, but most of these studies have extrapolated from changes in surrogate markers, such as CD4 : CD8 ratio. Early ART was associated with beneficial effects on multiple markers of immune activation, inflammation and viral persistence. Longer term prospective studies are still needed to determine whether early ART translates to a significant reduction in serious non-AIDS events and mortality.

  17. The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity.

    Science.gov (United States)

    Bowen, David G; Zen, Monica; Holz, Lauren; Davis, Thomas; McCaughan, Geoffrey W; Bertolino, Patrick

    2004-09-01

    Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for primary activation of CD8+ T cells between the liver and secondary lymphoid tissues, with the immune outcome determined by the initial site of activation. Using a transgenic mouse model in which antigen is expressed within both liver and lymph nodes, we show that while naive CD8+ T cells activated within the lymph nodes were capable of mediating hepatitis, cells undergoing primary activation within the liver exhibited defective cytotoxic function and shortened half-life and did not mediate hepatocellular injury. The implications of these novel findings may pertain not only to the normal maintenance of peripheral tolerance, but also to hepatic allograft tolerance and the immunopathogenesis of chronic viral hepatitis.

  18. FACTORES FINANCIEROS LOCALES INFLUYEN LAS ACTIVIDADES DE LOS BANCOS COOPERATIVOS GRIEGOS / LOCAL FINANCIAL FACTORS INFLUENCING ACTIVITIES OF GREEK COOPERATIVE BANKS

    Directory of Open Access Journals (Sweden)

    GEORGE KONTEOS

    2010-09-01

    Full Text Available Este artículo examina la influencia de las condiciones locales en las actividades bancarias centrandose en el caso de los 14 bancos cooperativos en Grecia durante el período 1999-2007. Estos bancos han sido seleccionados por su carácter local y en consecuencia, están más influenciadas por las condiciones locales, en comparación con los bancos con red nacional e incluso internacional. Las condiciones locales pueden ser endógenas y exógenas al banco. Las endógenas al banco es la red bancaria que se desarrolla a nivel local o regional asi como a los miembros de los bancos que son la parte principal de la clientela de estas. Una macroeconómica y exógena condición del banco es la cantidad de ahorros en la localidad donde opera. Las actividades bancarias que han sido examinadas incluyen los depósitos y los préstamos que constituyen la parte principal de las actividades bancarias de los bancos cooperativos en Grecia. El crecimiento de la red bancaria es el principal factor de aumento de las actividades del banco; el crecimiento de los miembros de las cooperativas y el aumento de las economías locales tienen una influencia positiva, pero menos importante en las actividades de los bancos cooperativos./This paper examines the influence of local conditions on banking activities focusing on the case of 14 cooperative banks in Greece for the period 1999-2007. These banks have been chosen because of their local character and consequently they are more influenced by local conditions in comparison to banks having a national and even international network. Local conditions could be endogenous and exogenous to the bank. The endogenous to the bank are the banking network developed locally or regionally, and the members of the banks who are the main part of the banks’ clientele. A macroeconomic and exogenous to the bank condition is the amount of savings in the prefecture in which the cooperative bank operates. The banking activities which have

  19. Earthquake precursory events around epicenters and local active faults

    Science.gov (United States)

    Valizadeh Alvan, H.; Mansor, S. B.; Haydari Azad, F.

    2013-05-01

    shakes, mapping foreshocks and aftershocks, and following changes in the above-mentioned precursors prior to past earthquake instances all over the globe. Our analyses also encompass the geographical location and extents of local and regional faults which are considered as important factors during earthquakes. The co-analysis of direct and indirect observation for precursory events is considered as a promising method for possible future successful earthquake predictions. With proper and thorough knowledge about the geological setting, atmospheric factors and geodynamics of the earthquake-prone regions we will be able to identify anomalies due to seismic activity in the earth's crust.

  20. Enhancement of Immune Activation Activities of Spirulina maxima Grown in Deep-Sea Water

    Science.gov (United States)

    Choi, Woon Yong; Kang, Do Hyung; Lee, Hyeon Yong

    2013-01-01

    In this study, the immuno-modulatory and anticancer activities of marine algae, Spirulina maxima grown in deep-sea water (DSW), were investigated. It was found that the extract of S. maxima, cultured in DSW, effectively suppressed the expression of Bcl2 in A549 cells as well as inhibiting various human cancer cells with concentration dependency, which possibly implies that the extracts may play more important roles in controlling cancer cell growth. The secretion of cytokines IL-6 and TNF-α from human B cells was also greatly increased, compared to those of the extract grown in conventional sea-water. The growth of Human Natural Killer (NK) cells in the presence of the extracts from DSW was significantly higher (12.2 × 104 viable cells/mL) when compared to the control (1.1 × 104 viable cells/mL). Based on HPLC analysis, the increase in the biological activities of the extracts from DSW was caused by considerably high amounts of β-carotene and ascorbic acid because the DSW contained high concentrations and good ratios of several key minerals for biosynthesizing β-carotene and ascorbic acid, as well as maintaining high cell growth. PMID:23743830

  1. Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

    Science.gov (United States)

    Martins, M A; Silva, M L; Marciano, A P V; Peruhype-Magalhães, V; Eloi-Santos, S M; Ribeiro, j G L; Correa-Oliveira, R; Homma, A; Kroon, E G; Teixeira-Carvalho, A; Martins-Filho, O A

    2007-04-01

    Over past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broad-based immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19+interleukin(IL)10R+/CD19+CD32+) at day 15. Increased frequency of CD4+human leucocyte antigen D-related(HLA-DR+) at day 7 and CD8+HLA-DR+ at day 30 suggest distinct kinetics of T cell activation, with CD4+ T cells being activated early and CD8+ T cells representing a later event following 17DD vaccination. Up-regulation of modulatory features on CD4+ and CD8+ cells at day 15 seems to be the key event leading to lower frequency of CD38+ T cells at day 30. Taken together, our findings demonstrate the co-existence of phenotypic features associated with activation events and modulatory pathways. Positive correlations between CD4+HLA-DR+ cells and CD4+CD25high regulatory T cells and the association between the type 0 chemokine receptor CCR2 and the activation status of CD4+ and CD8+ cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature.

  2. Titanium dioxide nanoparticles stimulate sea urchin immune cell phagocytic activity involving TLR/p38 MAPK-mediated signalling pathway

    Science.gov (United States)

    Pinsino, Annalisa; Russo, Roberta; Bonaventura, Rosa; Brunelli, Andrea; Marcomini, Antonio; Matranga, Valeria

    2015-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are one of the most widespread-engineered particles in use for drug delivery, cosmetics, and electronics. However, TiO2NP safety is still an open issue, even for ethical reasons. In this work, we investigated the sea urchin Paracentrotus lividus immune cell model as a proxy to humans, to elucidate a potential pathway that can be involved in the persistent TiO2NP-immune cell interaction in vivo. Morphology, phagocytic ability, changes in activation/inactivation of a few mitogen-activated protein kinases (p38 MAPK, ERK), variations of other key proteins triggering immune response (Toll-like receptor 4-like, Heat shock protein 70, Interleukin-6) and modifications in the expression of related immune response genes were investigated. Our findings indicate that TiO2NPs influence the signal transduction downstream targets of p38 MAPK without eliciting an inflammatory response or other harmful effects on biological functions. We strongly recommend sea urchin immune cells as a new powerful model for nano-safety/nano-toxicity investigations without the ethical normative issue. PMID:26412401

  3. Active immunizations with peptide-DC vaccines and passive transfer with antibodies protect neutropenic mice against disseminated candidiasis.

    Science.gov (United States)

    Xin, Hong

    2016-01-04

    We previously report that peptide-pulsed dendritic cell (DC) vaccination, which targeting two peptides (Fba and Met6) expressed on the cell surface of Candida albicans, can induce high degree of protection against disseminated candidiasis in immunocompetent mice. Passive transfer of immune sera from the peptide immunized mice or peptide-related monoclonal antibodies demonstrated that protection was medicated by peptide-specific antibodies. In this study the efficacy of active and passive immunization against disseminated candidiasis was tested in mice with cyclophosphamide-induced neutropenia. Peptide-DC vaccines were given to mice prior to induction of neutropenia. We show active immunization with either Fba or Met6 peptide-DC vaccine significantly improved the survival and reduced the fungal burden of disseminated candidiasis in those immunocompromised mice. Importantly, we show that administration of two protective monoclonal antibodies also protect neutropenic mice against the disease, implying possibility of developing a successful passive immunotherapy strategy to treat the disease and protect against disseminated candidiasis. The results of this study are crucial as they address the fundamental questions as to whether the synthetic peptide vaccine induced immunity protects the host during a neutropenic episode. We anticipate that this peptide-vaccine study will serve as the foundation of future investigations into new peptide vaccines comprised of cell surface peptides from other medically important Candida species, as well as other fungi. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Active Immunizations with Peptide-DC Vaccines and Passive Transfer with Antibodies Protect Neutropenic Mice against Disseminated Candidiasis

    Science.gov (United States)

    Xin, Hong

    2015-01-01

    We previously report that peptide-pulsed dendritic cell (DC) vaccination, which targeting two peptides (Fba and Met6) expressed on the cell surface of Candida albicans, can induce high degree of protection against disseminated candidiasis in immunocompetent mice. Passive transfer of immune sera from the peptide immunized mice or peptide-related monoclonal antibodies demonstrated that protection was medicated by peptide-specific antibodies. In this study the efficacy of active and passive immunization against disseminated candidiasis was tested in mice with cyclophosphamide-induced neutropenia. Peptide-DC vaccines were given to mice prior to induction of neutropenia. We show active immunization with either Fba or Met6 peptide-DC vaccine significantly improved the survival and reduced the fungal burden of disseminated candidiasis in those immunocompromised mice. Importantly, we show that administration of two protective monoclonal antibodies also protect neutropenic mice against the disease, implying possibility of developing a successful passive immunotherapy strategy to treat the disease and protect against disseminated candidiasis. The results of this study are crucial as they address the fundamental questions as to whether the synthetic peptide vaccine induced immunity protects the host during a neutropenic episode. We anticipate that this peptide-vaccine study will serve as the foundation of future investigations into new peptide vaccines comprised of cell surface peptides from other medically important Candida species, as well as other fungi. PMID:26620842

  5. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  6. The Amide Local Anesthetic Lidocaine in Cancer Surgery—Potential Antimetastatic Effects and Preservation of Immune Cell Function? A Narrative Review

    Directory of Open Access Journals (Sweden)

    Thiên-Nga Chamaraux-Tran

    2017-12-01

    Full Text Available Surgical removal of the primary tumor in solid cancer is an essential component of the treatment. However, the perioperative period can paradoxically lead to an increased risk of cancer recurrence. A bimodal dynamics for early-stage breast cancer recurrence suggests a tumor dormancy-based model with a mastectomy-driven acceleration of the metastatic process and a crucial role of the immunosuppressive state during the perioperative period. Recent evidence suggests that anesthesia could also influence the progress of the disease. Local anesthetics (LAs have long been used for their properties to block nociceptive input. They also exert anti-inflammatory capacities by modulating the liberation or signal propagation of inflammatory mediators. Interestingly, LAs can reduce viability and proliferation of many cancer cells in vitro as well. Additionally, retrospective clinical trials have suggested that regional anesthesia for cancer surgery (either with or without general anesthesia might reduce the risk of recurrence. Lidocaine, a LA, which can be administered intravenously, is widely used in clinical practice for multimodal analgesia. It is associated with a morphine-sparing effect, reduced pain scores, and in major surgery probably also with a reduced incidence of postoperative ileus and length of hospital stay. Systemic delivery might therefore be efficient to target residual disease or reach cells able to form micrometastasis. Moreover, an in vitro study has shown that lidocaine could enhance the activity of natural killer (NK cells. Due to their ability to recognize and kill tumor cells without the requirement of prior antigen exposure, NKs are the main actor of the innate immune system. However, several perioperative factors can reduce NK activity, such as stress, pain, opioids, or general anesthetics. Intravenous lidocaine as part of the perioperative anesthesia regimen would be of major interest for clinicians, as it might bear the potential

  7. Effects of Polysaccharides from Platycodon grandiflorum on Immunity-Enhancing Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Xiaona Zhao

    2017-11-01

    Full Text Available The study is aimed at investigating the immunoenhancement activity of polysaccharides from Platycodon grandiflorum polysaccharides (PGPSs in vitro. In this study, some research on lymphocyte proliferation, cell cycle, and the levels of CD4+ and CD8+ T cells were performed. Four different concentrations of PGPSs (PGPStc, PGPS60c, PGPS80c, and PGPStp were harvested and added to peripheral blood T lymphocytes. We observed significant increases in T lymphocyte proliferation at PGPStc groups individually or synergistically with phytohemagglutinin (PHA at most concentrations, and their lymphocyte proliferation rates were the highest. The active sites of PGPStc and PGPS60c were subsequently chosen. Then, we utilized flow cytometry to determine lymphocyte cell cycle distribution and levels of CD4+ and CD8+ T cells. At most time points, PGPStc could facilitate lymphocyte cell cycle progression from the G0/G1 phase to the S and G2/M phases and, simultaneously, increase the levels of CD4+ and CD8+ T cells. These results indicate that PGPStc enhances the immune functions, suggesting that PGPStc could be a potential immunopotentiator for further in vivo and clinical trial experiments.

  8. Inflammasome Activation Is Critical to the Protective Immune Response during Chemically Induced Squamous Cell Carcinoma

    Science.gov (United States)

    Gasparoto, Thais Helena; de Oliveira, Carine Ervolino; de Freitas, Luisa Thomazini; Pinheiro, Claudia Ramos; Hori, Juliana Issa; Garlet, Gustavo Pompermaier; Cavassani, Karen Angélica; Schillaci, Roxana; da Silva, João Santana; Zamboni, Dario Simões; Campanelli, Ana Paula

    2014-01-01

    Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase (CASP)-1 in the antitumor immune response using a multistage model of squamous cell carcinoma (SCC) development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer (NK), dendritic (DC), CD4+, CD8+ and CD45RB+ T cells in the tumor lesions as well as in lymph nodes (LN) compared with WT mice. Increased percentage of CD4+CD25+Foxp3+ T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase (MPO), but not elastase (ELA), activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1β, IL-18, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development. PMID:25268644

  9. Inflammasome activation is critical to the protective immune response during chemically induced squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Thais Helena Gasparoto

    Full Text Available Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC and caspase (CASP-1 in the antitumor immune response using a multistage model of squamous cell carcinoma (SCC development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer (NK, dendritic (DC, CD4(+, CD8(+ and CD45RB(+ T cells in the tumor lesions as well as in lymph nodes (LN compared with WT mice. Increased percentage of CD4(+CD25(+Foxp3(+ T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase (MPO, but not elastase (ELA, activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1β, IL-18, Tumor Necrosis Factor (TNF-α and Interferon (IFN-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development.

  10. Dietary Immunogen® modulated digestive enzyme activity and immune gene expression in Litopenaeus vannamei post larvae.

    Science.gov (United States)

    Miandare, Hamed Kolangi; Mirghaed, Ali Taheri; Hosseini, Marjan; Mazloumi, Nastaran; Zargar, Ashkan; Nazari, Sajad

    2017-11-01

    Pacific white shrimp Litopenaeus vannamei (Boone, 1931) is an important economical shrimp species worldwide, especially in the Middle East region, and farming activities of this species have been largely affected by diseases, mostly viral and bacterial diseases. Scientists have started to use prebiotics for bolstering the immune status of the animal. This study aimed to investigate the influence of Immunogen ® on growth, digestive enzyme activity and immune related gene expression of Litopenaeus vannamei post-larvae. All post-larvae were acclimated to the laboratory condition for 14 days. Upon acclimation, shrimps were fed on different levels of Immunogen ® (0, 0.5, 1 and 1.5 g kg -1 ) for 60 days. No significant differences were detected in weight gain, specific growth rate (SGR) and food conversion ratio (FCR) in shrimp post-larvae in which fed with different levels of Immunogen ® and control diet. The results showed that digestive enzymes activity including protease and lipase increased with different amounts of Immunogen ® in the shrimp diet. Protease activity increased with 1.5 g kg -1 Immunogen ® after 60 days and lipase activity increased with 1 and 1.5 g kg -1 Immunogen ® after 30 and 60 days of the trial respectively (P  0.05). The expression of immune related genes including, prophenoloxidase, crustin and g-type lysozyme increased with diet 1.5 g kg -1 Immunogen ® (P < 0.05) while expression of penaeidin gene increased only with experimental diet 1 g kg -1 of Immunogen ® . These results indicated that increase in digestive enzymes activity and expression of immune related genes could modulate the Immunogen ® in the innate immune system in L. vannamei in this study. Copyright © 2017. Published by Elsevier Ltd.

  11. Female Choice Reveals Terminal Investment in Male Mealworm Beetles, Tenebrio molitor, after a Repeated Activation of the Immune System

    Science.gov (United States)

    Krams, I; Daukšte, J; Kivleniece, I; Krama, T; Rantala, MJ; Ramey, G; Šauša, L

    2011-01-01

    Increasing evidence suggests that secondary sexual traits reflect immunocompetence of males in many animal species. This study experimentally investigated whether a parasite-like immunological challenge via a nylon implant affects sexual attractiveness of males in Tenebrio molitor L. (Coleoptera: Tenebrionidae) Although a single immunological challenge significantly reduced sexual attractiveness and locomotor activity of males, it had no adverse effect on their survival. A second immune challenge of the same males increased their attractiveness. However, it was found that the repeated challenge significantly reduced locomotor activity of males and caused higher mortality. This result indicates terminal investment on sexual signaling, which is supposedly based on a trade-off between pheromone production and energy expenditures needed for such activities as recovery of immune system and locomotor activity. When the third implantation was carried out in the same group of males, melanization of nylon implants was found to be lower in more attractive than in less attractive males. This suggests that males that became sexually attractive after the second immune challenge did not invest in recovery of their immune system. PMID:21864151

  12. Markers of immune activation and apoptosis in endomyocardial biopsies of individuals with recent-onset dilated cardiomyopathy

    Czech Academy of Sciences Publication Activity Database

    Kubánek, M.; Sramko, M.; Malušková, J.; Chudíčková, Milada; Holáň, Vladimír; Kautzner, J.

    2013-01-01

    Roč. 34, č. 1 (2013), s. 211-211 ISSN 0195-668X. [Congress of the European-Society-of- Cardiology (ESC). 31.08.2013-,04.09.2013, Amsterdam] Institutional support: RVO:68378041 Keywords : dilated cardiomyopathy * immune activation and apoptosis Subject RIV: EC - Immunology

  13. The influence of concentration/meditation on autonomic nervous system activity and the innate immune response: a case study.

    NARCIS (Netherlands)

    Kox, M.; Stoffels, M.; Smeekens, S.P.; Alfen, N. van; Gomes, M.E.R.; Eijsvogels, T.M.H.; Hopman, M.T.E.; Hoeven, J.G. van der; Netea, M.G.; Pickkers, P.

    2012-01-01

    OBJECTIVE: In this case study, we describe the effects of a particular individual's concentration/meditation technique on autonomic nervous system activity and the innate immune response. The study participant holds several world records with regard to tolerating extreme cold and claims that he can

  14. Constitutive Activity of the Arabidopsis MAP Kinase 3 Confers Resistance to Pseudomonas syringae and Drives Robust Immune Responses

    KAUST Repository

    Lang, Julien; Genot, Baptiste; Hirt, Heribert; Colcombet, Jean

    2017-01-01

    of a constitutively active (CA) form of the protein led to auto-immune phenotypes. CA-MPK3 plants are dwarf and display defense responses that are characterized by the accumulation of salicylic acid and phytoalexins as well as by the upregulation

  15. Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment

    NARCIS (Netherlands)

    Mattei, D.; Ivanov, A.; Ferrai, C.; Jordan, P.; Guneykaya, D.; Buonfiglioli, A.; Schaafsma, W.; Przanowski, P.; Deuther-Conrad, W.; Brust, P.; Hesse, S.; Patt, M.; Sabri, O.; Ross, T. L.; Eggen, B. J. L.; Boddeke, E. W. G. M.; Kaminska, B.; Beule, D.; Pombo, A.; Kettenmann, H.; Wolf, S. A.

    2017-01-01

    Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of

  16. Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

    Directory of Open Access Journals (Sweden)

    Arun Kapoor

    Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

  17. Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

    International Nuclear Information System (INIS)

    Battaglia, Alessandra; Buzzonetti, Alexia; Martinelli, Enrica; Fanelli, Mara; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Fattorossi, Andrea

    2010-01-01

    Purpose: To assess how neoadjuvant chemoradiation regimens modulate the immune system state in tumor-draining lymph nodes (TDLN), in the setting of advanced cervical cancer. Methods and Materials: Tumor-draining lymph nodes of patients undergoing chemotherapy only (nonirradiated, NI-TDLN) and chemoradiation with lower-dose (39.6 Gy, LD-TDLN) and higher-dose radiation (50 Gy, HD-TDLN) were analyzed by multicolor flow cytometry. Results: Enlarging our previous data, LD-TDLN showed features overall indicative of an enhanced antitumor response as compared with NI-TDLN, namely a significant Th1 and Tc1 polarization and a lower amount of the potent CD4 + Foxp3 + CD25 high regulatory T cell (Treg) subset identified by neuropilin-1 expression. Conversely, compared with NI-TDLN, HD-TDLN showed features overall indicative of an impaired antitumor response, namely a significantly inverted CD4/CD8 cell ratio, a higher Nrp1 + Treg frequency, and a higher frequency of CCR4 + Treg, a Treg subset facilitated in migrating out from TDLN to suppress the immune response against distant cancer cells. Moreover, the Th1 and Tc1 polarization induced by LD radiation was lost, and there was an unfavorable tolerogenic/immunogenic dendritic cell ratio compared with LD-TDLN. Conclusions: Even minor differences in radiation dose in neoadjuvant regimens for locally advanced cervical cancer are crucial for determining the balance between a tolerogenic and an efficacious antitumor immune response in TDLN. Because most of the anticancer immune response takes place in TDLN, the present findings also emphasize the importance of chemoradiation protocols in the context of immunotherapeutic trials.

  18. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  19. Antimicrobial activity of innate immune molecules against Streptococcus pneumoniae, Moraxella catarrhalis and nontypeable Haemophilus influenzae

    Directory of Open Access Journals (Sweden)

    Teufert Karen

    2004-05-01

    Full Text Available Abstract Background Despite its direct connection to the nasopharynx which harbors otitis media pathogens as part of its normal flora, the middle ear cavity is kept free of these bacteria by as yet unknown mechanisms. Respiratory mucosal epithelia, including those of the middle ear and eustachian tube, secrete antimicrobial effectors including lysozyme, lactoferrin and β defensins-1 and -2. To elucidate the role of these innate immune molecules in the normal defense and maintenance of sterility of respiratory mucosa such as that of the middle ear, we assessed their effect on the respiratory pathogens nontypeable Haemophilus influenzae (NTHi 12, Moraxella catarrhalis 035E, and Streptococcus pneumoniae 3, and 6B. Methods Two assay methods, the radial assay and the liquid broth assay, were employed for testing the antimicrobial activity of the molecules. This was done in order to minimize the possibility that the observed effects were artifacts of any single assay system employed. Also, transmission electron microscopy (TEM was employed to evaluate the effect of antimicrobial innate immune molecules on OM pathogens. For the statistical analysis of the data, Student's t-test was performed. Results Results of the radial diffusion assay showed that β defensin-2 was active against all four OM pathogens tested, while treatment with β defensin-1 appeared to only affect M. catarrhalis. The radial assay results also showed that lysozyme was quite effective against S. pneumoniae 3 and 6B and was partially bacteriostatic/bactericidal against M. catarrhalis. Lysozyme however, appeared not to affect the growth of NTHi. Thus, lysozyme seems to have a more pronounced impact on the growth of the Gram-positive S. pneumoniae as compared to that of Gram-negative pathogens. Lactoferrin on the other hand, enhanced the growth of the bacteria tested. The results of the radial assays were confirmed using liquid broth assays for antimicrobial activity, and showed that

  20. Baltic salmon activates immune relevant genes in fin tissue when responding to Gyrodactylus salaris infection

    DEFF Research Database (Denmark)

    Kania, Per Walther; Larsen, Thomas Bjerre; Ingerslev, Hans C.

    2007-01-01

    A series of immune relevant genes are expressed when the Baltic salmon responds on infections with the ectoparasite Gyrodactylus salaris which leads to a decrease of the parasite infection......A series of immune relevant genes are expressed when the Baltic salmon responds on infections with the ectoparasite Gyrodactylus salaris which leads to a decrease of the parasite infection...

  1. Effect of nalbuphine preemptive analgesia combined with ropivacaine local infiltration on postoperative incision pain, stress response and immune function in children

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    Yu Yang

    2017-10-01

    Full Text Available Objective: To study the effect of nalbuphine preemptive analgesia combined with ropivacaine local infiltration on postoperative incision pain, stress response and immune function in children. Methods: Children who received selective laparotomy in Mianyang Central Hospital between August 2015 and August 2017 were selected and randomly divided into control group, nalbuphine group (N group, ropivacaine group (R group and nalbuphine + ropivacaine group (N+R group. The levels of pain and stress-related mediators in serum and the levels of immune cells in peripheral blood were detected before operation and 24 h after operation. Results: 24 h after operation, serum Cor, NE, MDA, SP, PGE2, BK, NPY, TNF-α, IL-6 and IL-10 levels of four groups of children were significantly higher than those before operation while serum SOD and CAT levels as well as peripheral blood CD3+, CD4+ and CD8+T cell levels were significantly lower than those before operation; serum Cor, NE, MDA, SP, PGE2, BK, NPY, TNF-α, IL-6 and IL-10 levels of N group, R group and N+R group were significantly lower than those of control group while serum SOD and CAT levels as well as peripheral blood CD3+, CD4+ and CD8+T cell levels were significantly higher than those of control group; serum Cor, NE, MDA, SP, PGE2, BK, NPY, TNF-α, IL-6 and IL-10 levels of N+R group were significantly lower than those of N group and R group while serum SOD and CAT levels as well as peripheral blood CD3+, CD4+ and CD8+T cell levels were significantly higher than those of N group and R group. Conclusion: Nalbuphine preemptive analgesia combined with ropivacaine local infiltration can reduce the postoperative incision pain and stress response and improve the immune function in children.

  2. Short Communication: Immunohistochemical localization of the immune cell marker CD68 in bovine adipose tissue: impact of tissue alterations and excessive fat accumulation in dairy cows.

    Science.gov (United States)

    Häussler, S; Germeroth, D; Laubenthal, L; Ruda, L F; Rehage, J; Dänicke, S; Sauerwein, H

    2017-01-01

    With the onset of lactation energy from feed intake is mostly insufficient to meet the requirements of dairy cows. Lipid mobilization from adipose tissue (AT) could lead to a compromised inflammatory response enhancing the incidence for diseases. In addition, tissue alterations can occur, displaying areas of necrosis and inflammation. Furthermore, over-conditioned cows mobilizing more lipids from AT than thin cows are prone to develop metabolic disorders. This might lead to an increased infiltration of phagocytic immune cells into AT. In the present study, CD68 positive cells were localized in AT from 10 early lactating Holstein cows displaying different grades of AT alterations. Biopsies were sampled from visceral and subcutaneous AT and the number of CD68 positive cells was immunohistochemically determined. In addition, AT biopsies from over-conditioned, non-pregnant, non-lactating cows (n=8) were immunohistochemically analyzed for CD68 positive cells. The percentage of CD68 positive cells was less than 2% in AT biopsies with tissue alterations and in AT from over-conditioned cows. Therefore, immune cell infiltration demonstrated via the localization of CD68 positive cells seems to play only a minor role in AT from over-conditioned cows as well as in different bovine AT depots with tissue alterations. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. LOCAL LUMINOUS INFRARED GALAXIES. II. ACTIVE GALACTIC NUCLEUS ACTIVITY FROM SPITZER/INFRARED SPECTROGRAPH SPECTRA

    Energy Technology Data Exchange (ETDEWEB)

    Alonso-Herrero, Almudena; Pereira-Santaella, Miguel [Centro de Astrobiologia, INTA-CSIC, E-28850 Torrejon de Ardoz, Madrid (Spain); Rieke, George H. [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Rigopoulou, Dimitra [Astrophysics Department, University of Oxford, Oxford OX1 3RH (United Kingdom)

    2012-01-01

    We quantify the active galactic nucleus (AGN) contribution to the mid-infrared (mid-IR) and the total infrared (IR, 8-1000 {mu}m) emission in a complete volume-limited sample of 53 local luminous infrared galaxies (LIRGs, L{sub IR} = 10{sup 11}-10{sup 12} L{sub Sun }). We decompose the Spitzer Infrared Spectrograph low-resolution 5-38 {mu}m spectra of the LIRGs into AGN and starburst components using clumpy torus models and star-forming galaxy templates, respectively. We find that 50% (25/50) of local LIRGs have an AGN component detected with this method. There is good agreement between these AGN detections through mid-IR spectral decomposition and other AGN indicators, such as the optical spectral class, mid-IR spectral features, and X-ray properties. Taking all the AGN indicators together, the AGN detection rate in the individual nuclei of LIRGs is {approx}62%. The derived AGN bolometric luminosities are in the range L{sub bol}(AGN) = (0.4-50) Multiplication-Sign 10{sup 43} erg s{sup -1}. The AGN bolometric contribution to the IR luminosities of the galaxies is generally small, with 70% of LIRGs having L{sub bol}[AGN]/L{sub IR} {<=} 0.05. Only {approx_equal} 8% of local LIRGs have a significant AGN bolometric contribution L{sub bol}[AGN]/L{sub IR} > 0.25. From the comparison of our results with literature results of ultraluminous infrared galaxies (L{sub IR} = 10{sup 12}-10{sup 13} L{sub Sun }), we confirm that in the local universe the AGN bolometric contribution to the IR luminosity increases with the IR luminosity of the galaxy/system. If we add up the AGN bolometric luminosities we find that AGNs only account for 5%{sub -3%}{sup +8%} of the total IR luminosity produced by local LIRGs (with and without AGN detections). This proves that the bulk of the IR luminosity of local LIRGs is due to star formation activity. Taking the newly determined IR luminosity density of LIRGs in the local universe, we then estimate an AGN IR luminosity density of {Omega}{sup AGN

  4. Altering the balance between immune activation versus regulation in the skin to promote CD8+ T-cell activity within epithelial cancers

    DEFF Research Database (Denmark)

    Bridge, Jennifer A.; Overgaard, Nana Haahr; Steptoe, Raymond

    . The expression, in a mouse model (“E7”), of the HPV16 E7 gene in keratinocytes under the control of the K14 promoter, leads to a local immune suppressive environment, as evidenced by the lack of graft rejection when E7 skin grafts are placed on WT recipient mice. Furthermore, well healed (>30 days) E7 skin...... did not reject. As in the WT mice however, rejection could be induced through the coadministration of an anti-CD4 antibody. The data suggest that the removal of a CD4+, non T-reg cell, leads to CD8+ T-cell activity in the skin as evidenced by E7 skin graft destruction....... grafts are not rejected when mice are immunised with E7 peptide in combination with Quil A- or CASAC-based adjuvants. This is despite a substantial increase in E7 peptide/H-2Db pentamer staining in the blood, and marked killing of E7-peptide expressing TC-1 cells when injected i.v., confirming that CD8 T...

  5. Dysregulation of TGFβ1 Activity in Cancer and Its Influence on the Quality of Anti-Tumor Immunity

    Directory of Open Access Journals (Sweden)

    Kristian M. Hargadon

    2016-08-01

    Full Text Available TGFβ1 is a pleiotropic cytokine that exhibits a variety of physiologic and immune regulatory functions. Although its influence on multiple cell types is critical for the regulation of numerous biologic processes in the host, dysregulation of both TGFβ1 expression and activity is frequently observed in cancer and contributes to various aspects of cancer progression. This review focuses on TGFβ1’s contribution to tumor immune suppression and escape, with emphasis on the influence of this regulatory cytokine on the differentiation and function of dendritic cells and T cells. Clinical trials targeting TGFβ1 in cancer patients are also reviewed, and strategies for future therapeutic interventions that build on our current understanding of immune regulation by TGFβ1 are discussed.

  6. Activation of specific cellular immunity toward murine leukemia in mice rejecting syngeneic somatic hybrid cells

    International Nuclear Information System (INIS)

    Liang, W.; Cohen, E.P.

    1977-01-01

    ASL-1 x LM(TK) - somatic hybrid cells form both H-2/sup a/ and H-2/sup k/ antigen complexes. After forming a localized tumor in syngeneic (A/J x C 3 H/HeJ)F 1 mice, they are rejected. Such mice are resistant to otherwise invariably lethal injections of ASL-1 cells, surviving for prolonged and, in some instances, indefinite periods. To examine the basis of immunity, the capacity of spleen cells from mice rejecting hybrid cells to stimulate the release of 51 Cr from labeled ASL-1 cells was investigated. Cells from the spleens of mice rejecting ASL-1 x LM(TK) - cells stimulated the release of 51 Cr from labeled ASL-1 cells, but not from Ehrlich ascites or P815 cells. Cells from mice injected with mitomycin-C-treated ASL-1 cells led to the release of 51 Cr from labeled ASL-1 cells as well, but the extent of 51 Cr release was approximately one-third as occurred in the presence of cells from hybrid cell-injected mice. Cells from noninjected mice or from mice injected with LM(TK) - cells failed to lead to the specific release of 51 Cr from ASL-1 cells. The presence of unlabeled ASL-1 cells, but not Ehrlich ascites cells, competitively inhibited the spleen cell-stimulated release of 51 Cr from labeled ASL-1 cells. Sera from A/J mice injected with mitomycin-C-treated ASL-1 cells contained antibodies specific for the tumor-associated antigen of ASL-1 cells

  7. Reevaluation of immune activation in the era of cART and an aging HIV-infected population.

    Science.gov (United States)

    de Armas, Lesley R; Pallikkuth, Suresh; George, Varghese; Rinaldi, Stefano; Pahwa, Rajendra; Arheart, Kristopher L; Pahwa, Savita

    2017-10-19

    Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets. Our results show that markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on CD4+ T cells, exhibit strong associations with HIV infection but not with biological age. Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection. Interestingly, the variable of biological age was not identified in a predictive model as significantly impacting vaccine responses in either group, while distinct IA and inflammatory variables were closely associated with vaccine response in HIV-infected and -uninfected populations. These findings shed light on the most relevant and persistent immune defects during virological suppression with antiretroviral therapy.

  8. Serum levels of innate immunity cytokines are elevated in dogs with metaphyseal osteopathy (hypertrophic osteodytrophy) during active disease and remission.

    Science.gov (United States)

    Safra, Noa; Hitchens, Peta L; Maverakis, Emanual; Mitra, Anupam; Korff, Courtney; Johnson, Eric; Kol, Amir; Bannasch, Michael J; Pedersen, Niels C; Bannasch, Danika L

    2016-10-15

    Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as chronic recurrent multifocal osteomyelitis (CRMO), and deficiency of interleukin-1 receptor antagonist (DIRA), involve impaired innate immunity pathways and aberrant cytokine production. Given the similarities between these diseases, we hypothesize that MO is an autoinflammatory disease mediated by cytokines involved in innate immunity. To characterize immune dysregulation in MO dogs we measured serum levels of inflammatory markers in 26 MO and 102 control dogs. MO dogs had significantly higher levels (pg/ml) of serum Interleukin-1beta (IL-1β), IL-18, IL-6, Granulocyte-macrophage colony stimulating factor (GM-CSF), C-X-C motif chemokine 10 (CXCL10), tumor necrosis factor (TNF), and IL-10. Notably, recovered MO dogs were not different from dogs during active MO disease, providing a suggestive mechanism for disease predisposition. This is the first documentation of elevated immune markers in MO dogs, uncovering an immune profile similar to comparable autoinflammatory disorders in children. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Directory of Open Access Journals (Sweden)

    Simon Heidegger

    Full Text Available Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  10. Design of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization.

    Science.gov (United States)

    Oresic Bender, Kristina; Ofori, Leslie; van der Linden, Wouter A; Mock, Elliot D; Datta, Gopal K; Chowdhury, Somenath; Li, Hao; Segal, Ehud; Sanchez Lopez, Mateo; Ellman, Jonathan A; Figdor, Carl G; Bogyo, Matthew; Verdoes, Martijn

    2015-04-15

    The cysteine cathepsins are a group of 11 proteases whose function was originally believed to be the degradation of endocytosed material with a high degree of redundancy. However, it has become clear that these enzymes are also important regulators of both health and disease. Thus, selective tools that can discriminate between members of this highly related class of enzymes will be critical to further delineate the unique biological functions of individual cathepsins. Here we present the design and synthesis of a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S which is highly expressed in immune cells. Importantly, this high degree of selectivity is retained both in vitro and in vivo. In combination with a new green-fluorescent pan-reactive cysteine cathepsin qABP we performed dual color labeling studies in bone marrow-derived immune cells and identified vesicles containing exclusively cathepsin S activity. This observation demonstrates the value of our complementary cathepsin probes and provides evidence for the existence of specific localization of cathepsin S activity in dendritic cells.

  11. Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4

    NARCIS (Netherlands)

    Olthof, E.D.; Gulich, A.F.; Renne, M.F.; Landman, S.; Joosten, L.A.B.; Roelofs, H.M.; Wanten, G.J.A.

    2015-01-01

    BACKGROUND: Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor

  12. 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.

  13. Kinetics of rabies antibodies as a strategy for canine active immunization

    Science.gov (United States)

    2014-01-01

    Background Rabies, a zoonosis found throughout the globe, is caused by a virus of the Lyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil. Findings During 12 months we evaluated the active immunity of dogs first vaccinated (booster shot at 30 days after first vaccination) against rabies using the Fuenzalida-Palácios modified vaccine in the urban area of Botucatu city, São Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (≥0.5 IU/mL) for 360 days after the first vaccination whereas 51.5% during all the study period. Conclusions The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30 days after the first and the third dose at 180 days after the first for the maintenance of protective titers during 12 months. PMID:26413082

  14. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  15. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Libregts, Sten F.W.M.; Nolte, Martijn A.

    2014-01-01

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

  16. Cytotoxic activity and apoptotic induction of some edible Thai local ...

    African Journals Online (AJOL)

    Purpose: To evaluate eight edible Thai local plant extracts (Camellia sinensis, Careya sphaerica, Cratoxylum formosum, Eleutherococcus trifoliatus, Ficus auriculata, Persicaria odorata, Schima wallichii, and Vaccinium sprengelii) against colon and liver cancer cell lines. Methods: The 80 % ethanol plant extracts were ...

  17. Women fishing activities in rural communities of Epe Local ...

    African Journals Online (AJOL)

    Women are not aware of fishery extension activities in the area and the fisherwomen faced different types of problems in their fishery activities. However, to improve fishery activities by women in the area, extension agents should organize training workshops for the women on how to construct and mend fishing nets and ...

  18. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection.

    Science.gov (United States)

    Hagberg, Lars; Cinque, Paola; Gisslen, Magnus; Brew, Bruce J; Spudich, Serena; Bestetti, Arabella; Price, Richard W; Fuchs, Dietmar

    2010-06-03

    HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients.In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays (<50 copies HIV RNA/mL), CSF neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued CNS infection and whether it causes continued indolent CNS injury.Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.

  19. Constitutive Activity of the Arabidopsis MAP Kinase 3 Confers Resistance to Pseudomonas syringae and Drives Robust Immune Responses

    KAUST Repository

    Lang, Julien

    2017-08-02

    Mitogen Activated Protein Kinases (MAPKs) are known to be important mediators of plant responses to biotic and abiotic stresses. In a recent report, we enlarged the understanding of the Arabidopsis thaliana MPK3 functions showing that the expression of a constitutively active (CA) form of the protein led to auto-immune phenotypes. CA-MPK3 plants are dwarf and display defense responses that are characterized by the accumulation of salicylic acid and phytoalexins as well as by the upregulation of several defense genes. Consistently with these data, we present here results demonstrating that, compared to wild type controls, CA-MPK3 plants are more resistant to the hemibiotrophic pathogen Pseudomonas syringae DC3000. Based on our previous work, we also discuss the mechanisms of robust plant immunity controlled by sustained MPK3 activity, focusing especially on the roles of disease resistance proteins.

  20. Activity modulation of microbial enzymes by llama (Lama glama) heavy-chain polyclonal antibodies during in vivo immune responses.

    Science.gov (United States)

    Ferrari, A; Weill, F S; Paz, M L; Cela, E M; González Maglio, D H; Leoni, J

    2012-03-01

    Since they were first described in 1993, it was found that recombinant variable fragments (rVHHs) of heavy-chain antibodies (HCAbs) from Camelidae have unusual biophysical properties, as well as a special ability to interact with epitopes that are cryptic for conventional Abs. It has been assumed that in vivo raised polyclonal HCAbs (pHCAbs) should behave in a similar manner than rVHHs; however, this assumption has not been tested sufficiently. Furthermore, our own preliminary work on a single serum sample from a llama immunized with a β-lactamase, has suggested that pHCAbs have no special ability to down-modulate catalytic activity. In this work, we further explored the interaction of pHCAbs from four llamas raised against two microbial enzymes and analyzed it within a short and a long immunization plan. The relative contribution of pHCAbs to serum titer was found to be low compared with that of the most abundant conventional subisotype (IgG(1)), during the whole immunization schedule. Furthermore, pHCAbs not only failed to inhibit the enzymes, but also activated one of them. Altogether, these results suggest that raising high titer inhibitory HCAbs is not a straightforward strategy - neither as a biotechnological strategy nor in the biological context of an immune response against infection - as raising inhibitory rVHHs.

  1. Anti-viral drug treatment along with immune activator IL-2: a control-based mathematical approach for HIV infection

    Science.gov (United States)

    Nath Chatterjee, Amar; Roy, Priti Kumar

    2012-02-01

    Recent development in antiretroviral treatment against HIV can help AIDS patients to fight against HIV. But the question that whether the disease is to be partially or totally eradicated from HIV infected individuals still remains unsolved. Usually, the most effective treatment for the disease is HAART which can only control the disease progression. But as the immune system becomes weak, the patients can not fight against other diseases. Immune cells are activated and proliferated by IL-2 after the identification of antigen. IL-2 production is impaired in HIV positive patients and intermitted administration of immune activator IL-2 together with HAART which is a more effective treatment to fight against the disease. Thus, its expediency is essential and is yet to be explored. In this article we anticipated a mathematical model of the effect of IL-2 together with RTIs therapy in HIV positive patients. Our analytical as well as numerical study shows that the optimal schedule of treatment for best result is to be obtained by systematic drug therapy. But at the last stage of treatment, the infection level raises again due to minimisation of drug dosage. Thus we study the perfect adherence of the drugs and found out if RTIs are taken with sufficient interval then for fixed interval of IL-2 therapy, certain amount of drug dosages may be able to sustain the immune system at pre-infection stage and the infected CD4+T cells are going towards extinction.

  2. Neuroendocrine immune interaction in fish: differential regulation of phagocyte activity by neuroendocrine factors

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Ribeiro, C.M.S.; Chadzinska, M.K.

    2011-01-01

    Coping with physical, chemical and biological disturbances depends on an extensive repertoire of physiological, endocrinological and immunological responses. Fish provide intriguing models to study bi-directional interaction between the neuroendocrine and the immune systems. Macrophages and

  3. Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response

    NARCIS (Netherlands)

    Zariri, Afshin; Beskers, Joep; van de Waterbeemd, Bas; Hamstra, Hendrik Jan; Bindels, Tim H E; van Riet, Elly; van Putten, Jos P M; van der Ley, Peter

    2016-01-01

    Meningococcal outer membrane vesicles (OMVs) have been extensively investigated and successfully implemented as vaccines. They contain pathogen associated molecular patterns including lipopolysaccharide (LPS), capable of triggering innate immunity. However, Neisseria meningitidis contains an

  4. Nitric oxide mediates insect cellular immunity via phospholipase A2 activation

    Science.gov (United States)

    After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, eicosanoids and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Se...

  5. Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers.

    Science.gov (United States)

    Shukla, Sourabh; Myers, Jay T; Woods, Sarah E; Gong, Xingjian; Czapar, Anna E; Commandeur, Ulrich; Huang, Alex Y; Levine, Alan D; Steinmetz, Nicole F

    2017-03-01

    Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers. The applicability of VNP platform technologies is governed by stringent structure-function relationships. We compare two distinct VNP platforms: icosahedral cowpea mosaic virus (CPMV) and filamentous potato virus X (PVX). Specifically, we evaluate in vivo capabilities of engineered VNPs delivering human epidermal growth factor receptor 2 (HER2) epitopes for therapy and prophylaxis of HER2 + malignancies. Our results corroborate the structure-function relationship where icosahedral CPMV particles showed significantly enhanced lymph node transport and retention, and greater uptake by/activation of APCs compared to filamentous PVX particles. These enhanced immune cell interactions and transport properties resulted in elevated HER2-specific antibody titers raised by CPMV- vs. PVX-based peptide vaccine. The 'synthetic virology' field is rapidly expanding with numerous platforms undergoing development and preclinical testing; our studies highlight the need for systematic studies to define rules guiding the design and rational choice of platform, in the context of peptide-vaccine display technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Activation of Anti-tumor Immune Response by Ablation of HCC with Nanosecond Pulsed Electric Field.

    Science.gov (United States)

    Xu, Xiaobo; Chen, Yiling; Zhang, Ruiqing; Miao, Xudong; Chen, Xinhua

    2018-03-28

    Locoregional therapy is playing an increasingly important role in the non-surgical management of hepatocellular carcinoma (HCC). The novel technique of non-thermal electric ablation by nanosecond pulsed electric field has been recognized as a potential locoregional methodology for indicated HCC. This manuscript explores the most recent studies to indicate its unique anti-tumor immune response. The possible immune mechanism, termed as nano-pulse stimulation, was also analyzed.

  7. Local jurisdictions and active shooters : building networks, building capacities

    OpenAIRE

    Frazzano, Tracy L.

    2010-01-01

    CHDS State/Local Approved for public release; distribution is unlimited States incidents (Columbine High School shooting (April 20, 1999) and North Hollywood Bank shoot out (February 28, 1997) were studied. Individuals from the U.S. cases were interviewed to explore information not necessarily documented. Data from the case studies and interviews were collated and reviewed for common themes. These themes were analyzed to draw conclusions on how smaller jurisdictions should proceed in bu...

  8. Toll-like receptor agonist augments virus-like particle-mediated protection from Ebola virus with transient immune activation.

    Directory of Open Access Journals (Sweden)

    Karen A O Martins

    Full Text Available Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNFα, IL6, MCP1, MIP1α, KC, and MIP1β levels in the periphery and with the activation of dendritic cells (DCs, NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels.

  9. Effect of potential probiotic Rhodotorula benthica D30 on the growth performance, digestive enzyme activity and immunity in juvenile sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Wang, Ji-hui; Zhao, Liu-qun; Liu, Jin-feng; Wang, Han; Xiao, Shan

    2015-04-01

    The effects of dietary addition of yeast Rhodotorula benthica (R. benthica) D30 which isolated from local sea mud at levels of 0 (control), 10(5), 10(6) and 10(7) CFU/g feed on the growth performance, digestive enzyme activity, immunity and disease resistance of juvenile sea cucumber Apostichopus japonicus were investigated. It was shown that dietary addition of R. benthica D30 significantly increased the growth rates of sea cucumbers (p  0.05). It was observed that adding R. benthica D30 could significantly decrease the cumulative mortality of sea cucumbers. The present study demonstrated that dietary addition of R. benthica D30 could increase growth performance and some digestive enzyme activities, improve immunity and disease resistance of A. japonicus. And the medium (10(6) CFU) and high (10(7) CFU) additional levels showed better effects. It suggests that yeast R. benthica D30 could be a good probiotic for aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.

    Science.gov (United States)

    Daley, Donnele; Mani, Vishnu R; Mohan, Navyatha; Akkad, Neha; Ochi, Atsuo; Heindel, Daniel W; Lee, Ki Buom; Zambirinis, Constantinos P; Pandian, Gautam Sd Balasubramania; Savadkar, Shivraj; Torres-Hernandez, Alejandro; Nayak, Shruti; Wang, Ding; Hundeyin, Mautin; Diskin, Brian; Aykut, Berk; Werba, Gregor; Barilla, Rocky M; Rodriguez, Robert; Chang, Steven; Gardner, Lawrence; Mahal, Lara K; Ueberheide, Beatrix; Miller, George

    2017-05-01

    The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA). Dectin 1 ligation accelerated the progression of PDA in mice, whereas deletion of Clec7a-the gene encoding dectin 1-or blockade of dectin 1 downstream signaling was protective. We found that dectin 1 can ligate the lectin galectin 9 in mouse and human PDA, which results in tolerogenic macrophage programming and adaptive immune suppression. Upon disruption of the dectin 1-galectin 9 axis, CD4 + and CD8 + T cells, which are dispensable for PDA progression in hosts with an intact signaling axis, become reprogrammed into indispensable mediators of anti-tumor immunity. These data suggest that targeting dectin 1 signaling is an attractive strategy for developing an immunotherapy for PDA.

  11. Dectin-1 Activation on Macrophages by Galectin-9 Promotes Pancreatic Carcinoma and Peritumoral Immune-Tolerance

    Science.gov (United States)

    Daley, Donnele; Mani, Vishnu R.; Mohan, Navyatha; Akkad, Neha; Ochi, Atsuo; Heindel, Daniel W.; Lee, Ki Buom; Zambirinis, Constantinos P.; Pandian, Gautam S.D. Balasubramania; Savadkar, Shivraj; Torres-Hernandez, Alejandro; Nayak, Shruti; Wang, Ding; Hundeyin, Mautin; Diskin, Brian; Aykut, Berk; Werba, Gregor; Barilla, Rocky M.; Rodriguez, Robert; Chang, Steven; Gardner, Lawrence; Mahal, Lara K.; Ueberheide, Beatrix; Miller, George

    2017-01-01

    The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intra-tumoral immune tolerance are uncertain. Dectin-1 is an innate immune receptor critical in anti-fungal immunity, but its role in sterile inflammation and oncogenesis is not well-defined. Further, non-pathogen-derived ligands for Dectin-1 have not been characterized. We found that Dectin-1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA). Dectin-1 ligation accelerated PDA, whereas Dectin-1 deletion or blockade of its downstream signaling was protective. We found that Dectin-1 ligates the lectin Galectin-9 in the PDA tumor microenvironment resulting in tolerogenic macrophage programming and adaptive immune suppression. Upon interruption of the Dectin-1–Galectin-9 axis, CD4+ and CD8+ T cells – which are dispensable to PDA progression in hosts with an intact signaling axis – become reprogrammed into indispensable mediators of anti-tumor immunity. These data suggest that targeting Dectin-1 signaling is an attractive strategy for the immunotherapy of PDA. PMID:28394331

  12. Innate Immune Activation Can Trigger Experimental Spondyloarthritis in HLA-B27/Huβ2m Transgenic Rats

    Directory of Open Access Journals (Sweden)

    Melissa N. van Tok

    2017-08-01

    Full Text Available Spondyloarthritis (SpA does not display the typical features of auto-immune disease. Despite the strong association with MHC class I, CD8+ T cells are not required for disease induction in the HLA-B27/Huβ2m transgenic rats. We used Lewis HLA-B27/Huβ2m transgenic rats [21-3 × 283-2]F1, HLA-B7/Huβ2m transgenic rats [120-4 × 283-2]F1, and wild-type rats to test our hypothesis that SpA may be primarily driven by the innate immune response. In vitro, splenocytes were stimulated with heat-inactivated Mycobacterium tuberculosis and cytokine expression and production was measured. In vivo, male and female rats were immunized with 30, 60, or 90 µg of heat-inactivated M. tuberculosis and clinically monitored for spondylitis and arthritis development. After validation of the model, we tested whether prophylactic and therapeutic TNF targeting affected spondylitis and arthritis. In vitro stimulation with heat-inactivated M. tuberculosis strongly induced gene expression of pro-inflammatory cytokines such as TNF, IL-6, IL-1α, and IL-1β, in the HLA-B27 transgenic rats compared with controls. In vivo immunization induced an increased spondylitis and arthritis incidence and an accelerated and synchronized onset of spondylitis and arthritis in HLA-B27 transgenic males and females. Moreover, immunization overcame the protective effect of orchiectomy. Prophylactic TNF targeting resulted in delayed spondylitis and arthritis development and reduced arthritis severity, whereas therapeutic TNF blockade did not affect spondylitis and arthritis severity. Collectively, these data indicate that innate immune activation plays a role in the initiation of HLA-B27-associated disease and allowed to establish a useful in vivo model to study the cellular and molecular mechanisms of disease initiation and progression.

  13. Capacity-building activities for local leadership in Egypt from the local to the national and regional levels.

    Science.gov (United States)

    El Sioufi, M

    1996-03-01

    In order to make the Sustainable Ismailia Project institutionally sustainable, the National Project Manager identified the need to build the capacity of local leadership. The Training Section, in UNCHS, proposed a capacity-building program designed to respond to this demand focusing on the skill-training and attitude formation needed for effective local leadership. The proposed program is adapted from the "Training for Elected Leadership" series widely tested and used in many regions. It combines direct training for local officials from villages in Ismailia, and indirect training for trainers from the Ministry of Local Administration (MLA). After the course, the MLA trainers would design a training program which they will implement nationally. The Minister for Local Administration decided to finance the translation and production of the manuals, while the Governor of Ismailia offered to cover the trainees' expenses. The UNCHS Training and Capacity-Building Section would provide technical guidance and coordinate and implement the program. Once the Arabic version of the training materials would be available, UNCHS would use it regionally to reach out to other Arab States. This example illustrates how concerned stakeholders cooperate to address capacity-building needs. The UNCHS Training Section assumes the role of facilitator and acts as a catalyst for the formulation of such activities. The feeling of ownership of the locally produced/adapted training materials enhances the propensity of their effective and extensive use. This approach has succeeded across regions, cultures, and languages with out-reaching multiplier effects. full text

  14. Innovations in communication technologies for measles supplemental immunization activities: lessons from Kenya measles vaccination campaign, November 2012

    Science.gov (United States)

    Mbabazi, William B; Tabu, Collins W; Chemirmir, Caleb; Kisia, James; Ali, Nasra; Corkum, Melissa G; Bartley, Gene L

    2015-01-01

    Background To achieve a measles free world, effective communication must be part of all elimination plans. The choice of communication approaches must be evidence based, locally appropriate, interactive and community owned. In this article, we document the innovative approach of using house visits supported by a web-enabled mobile phone application to create a real-time platform for adaptive management of supplemental measles immunization days in Kenya. Methods One thousand nine hundred and fifty-two Red Cross volunteers were recruited, trained and deployed to conduct house-to-house canvassing in 11 urban districts of Kenya. Three days before the campaigns, volunteers conducted house visits with a uniform approach and package of messages. All house visits were documented using a web-enabled mobile phone application (episurveyor®) that in real-time relayed information collected to all campaign management levels. During the campaigns, volunteers reported daily immunizations to their co-ordinators. Post-campaign house visits were also conducted within 4 days, to verify immunization of eligible children, assess information sources and detect adverse events following immunization. Results Fifty-six per cent of the 164 643 households visited said that they had heard about the planned 2012 measles vaccination campaign 1–3 days before start dates. Twenty-five per cent of households were likely to miss the measles supplemental dose if they had not been reassured by the house visit. Pre- and post-campaign reasons for refusal showed that targeted communication reduced misconceptions, fear of injections and trust in herbal remedies. Daily reporting of immunizations using mobile phones informed changes in service delivery plans for better immunization coverage. House visits were more remembered (70%) as sources of information compared with traditional mass awareness channels like megaphones (41%) and radio (37%). Conclusions In high-density settlements, house-to-house visits

  15. Implicit Active Contours Driven by Local and Global Image Fitting Energy for Image Segmentation and Target Localization

    Directory of Open Access Journals (Sweden)

    Xiaosheng Yu

    2013-01-01

    Full Text Available We propose a novel active contour model in a variational level set formulation for image segmentation and target localization. We combine a local image fitting term and a global image fitting term to drive the contour evolution. Our model can efficiently segment the images with intensity inhomogeneity with the contour starting anywhere in the image. In its numerical implementation, an efficient numerical schema is used to ensure sufficient numerical accuracy. We validated its effectiveness in numerous synthetic images and real images, and the promising experimental results show its advantages in terms of accuracy, efficiency, and robustness.

  16. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge.

    Science.gov (United States)

    Norden, Diana M; Trojanowski, Paige J; Villanueva, Emmanuel; Navarro, Elisa; Godbout, Jonathan P

    2016-02-01

    Activation of the peripheral immune system elicits a coordinated response from the central nervous system. Key to this immune to brain communication is that glia, microglia, and astrocytes, interpret and propagate inflammatory signals in the brain that influence physiological and behavioral responses. One issue in glial biology is that morphological analysis alone is used to report on glial activation state. Therefore, our objective was to compare behavioral responses after in vivo immune (lipopolysaccharide, LPS) challenge to glial specific mRNA and morphological profiles. Here, LPS challenge induced an immediate but transient sickness response with decreased locomotion and social interaction. Corresponding with active sickness behavior (2-12 h), inflammatory cytokine mRNA expression was elevated in enriched microglia and astrocytes. Although proinflammatory cytokine expression in microglia peaked 2-4 h after LPS, astrocyte cytokine, and chemokine induction was delayed and peaked at 12 h. Morphological alterations in microglia (Iba-1(+)) and astrocytes (GFAP(+)), however, were undetected during this 2-12 h timeframe. Increased Iba-1 immunoreactivity and de-ramified microglia were evident 24 and 48 h after LPS but corresponded to the resolution phase of activation. Morphological alterations in astrocytes were undetected after LPS. Additionally, glial cytokine expression did not correlate with morphology after four repeated LPS injections. In fact, repeated LPS challenge was associated with immune and behavioral tolerance and a less inflammatory microglial profile compared with acute LPS challenge. Overall, induction of glial cytokine expression was sequential, aligned with active sickness behavior, and preceded increased Iba-1 or GFAP immunoreactivity after LPS challenge. © 2015 Wiley Periodicals, Inc.

  17. In Situ complement activation and T-cell immunity in leprosy spectrum: An immunohistological study on leprosy lesional skin.

    Directory of Open Access Journals (Sweden)

    Nawal Bahia El Idrissi

    Full Text Available Mycobacterium leprae (M. leprae infection causes nerve damage and the condition worsens often during and long after treatment. Clearance of bacterial antigens including lipoarabinomannan (LAM during and after treatment in leprosy patients is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves by in situ generation of the membrane attack complex (MAC. Investigating the role of complement activation in skin lesions of leprosy patients might provide insight into the dynamics of in situ immune reactivity and the destructive pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy patients, whether M. leprae antigen LAM deposition correlates with the deposition of complement activation products MAC and C3d on nerves and cells in the surrounding tissue. Skin biopsies of paucibacillary (n = 7, multibacillary leprosy patients (n = 7, and patients with erythema nodosum leprosum (ENL (n = 6 or reversal reaction (RR (n = 4 and controls (n = 5 were analyzed. The percentage of C3d, MAC and LAM deposition was significantly higher in the skin biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p = <0.001 and p = <0.001 respectively, with a significant association between LAM and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001 and r = 0.8585, p<0.0001 respectively. In skin lesions of multibacillary patients, MAC deposition was found on axons and co-localizing with LAM. In skin lesions of paucibacillary patients, we found C3d positive T-cells in and surrounding granulomas, but hardly any MAC deposition. In addition, MAC immunoreactivity was increased in both ENL and RR skin lesions compared to non-reactional leprosy patients (p = <0.01 and p = <0.01 respectively. The present findings demonstrate that complement is deposited in skin lesions of leprosy patients, suggesting that inflammation driven by complement activation might contribute to nerve damage in the lesions

  18. Lithocholic acid controls adaptive immune responses by inhibition of Th1 activation through the Vitamin D receptor.

    Science.gov (United States)

    Pols, Thijs W H; Puchner, Teresa; Korkmaz, H Inci; Vos, Mariska; Soeters, Maarten R; de Vries, Carlie J M

    2017-01-01

    Bile acids are established signaling molecules next to their role in the intestinal emulsification and uptake of lipids. We here aimed to identify a potential interaction between bile acids and CD4+ Th cells, which are central in adaptive immune responses. We screened distinct bile acid species for their potency to affect T cell function. Primary human and mouse CD4+ Th cells as well as Jurkat T cells were used to gain insight into the mechanism underlying these effects. We found that unconjugated lithocholic acid (LCA) impedes Th1 activation as measured by i) decreased production of the Th1 cytokines IFNγ and TNFαα, ii) decreased expression of the Th1 genes T-box protein expressed in T cells (T-bet), Stat-1 and Stat4, and iii) decreased STAT1α/β phosphorylation. Importantly, we observed that LCA impairs Th1 activation at physiological relevant concentrations. Profiling of MAPK signaling pathways in Jurkat T cells uncovered an inhibition of ERK-1/2 phosphorylation upon LCA exposure, which could provide an explanation for the impaired Th1 activation. LCA induces these effects via Vitamin D receptor (VDR) signaling since VDR RNA silencing abrogated these effects. These data reveal for the first time that LCA controls adaptive immunity via inhibition of Th1 activation. Many factors influence LCA levels, including bile acid-based drugs and gut microbiota. Our data may suggest that these factors also impact on adaptive immunity via a yet unrecognized LCA-Th cell axis.

  19. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice

    Science.gov (United States)

    Gelderblom, Mathias; Leypoldt, Frank; Lewerenz, Jan; Birkenmayer, Gabriel; Orozco, Denise; Ludewig, Peter; Thundyil, John; Arumugam, Thiruma V; Gerloff, Christian; Tolosa, Eva; Maher, Pamela; Magnus, Tim

    2012-01-01

    The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor α (TNFα) production. Fisetin also inhibited LPS-induced TNFα production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor κB activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia. PMID:22234339

  20. The effect of local irradiation on the immune response in mice. I. Effect of sham-irradiation

    International Nuclear Information System (INIS)

    Gauci, C.L.; Gerber, M.; Dubois, J.-B.; Serrou, B.

    1979-01-01

    In C57BL/6 mice exposed to 1600 rads to the left foot pad, an important decrease of non-specific inflammatory responsiveness initiated by the injection of oyster glycogen into the peritoneal cavity was observed on the one hand and a diminution of the delayed hypersensitivity response following tuberculin injection, on the other hand. Nevertheless, the same immunosuppression was noted both in sham irradiated mice and in those receiving hydrocortisone. In irradiated mice this transient immunosuppression was related to a normal adrenal function. Bi-laterally adrenalectomised mice did not exhibit this reaction which reappeared after hydrocortisone administration. The reduction of delayed hypersensitivity is irrespective of the irradiated zone, but the duration of immune depression is longer in irradiated than in unirradiated tissue. During the depression of delayed hypersensitivity response an increase in the number of splenic B-lymphocytes and macrophages and a decrease of the number of splenic T-lymphocytes was observed these observations suggest that immunosuppression following irradiation is related to acute stress

  1. In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

    Science.gov (United States)

    Copin, Richard; Vitry, Marie-Alice; Hanot Mambres, Delphine; Machelart, Arnaud; De Trez, Carl; Vanderwinden, Jean-Marie; Magez, Stefan; Akira, Shizuo; Ryffel, Bernhard; Carlier, Yves; Letesson, Jean-Jacques; Muraille, Eric

    2012-01-01

    Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis. PMID:22479178

  2. Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.

    Directory of Open Access Journals (Sweden)

    Clarissa Santos Rocha

    Full Text Available Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD, showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327, also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.

  3. Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.

    Science.gov (United States)

    Santos Rocha, Clarissa; Gomes-Santos, Ana Cristina; Garcias Moreira, Thais; de Azevedo, Marcela; Diniz Luerce, Tessalia; Mariadassou, Mahendra; Longaray Delamare, Ana Paula; Langella, Philippe; Maguin, Emmanuelle; Azevedo, Vasco; Caetano de Faria, Ana Maria; Miyoshi, Anderson; van de Guchte, Maarten

    2014-01-01

    Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD), showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327), also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS) colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.

  4. Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

    Science.gov (United States)

    Canetta, S; Bolkan, S; Padilla-Coreano, N; Song, L J; Sahn, R; Harrison, N L; Gordon, J A; Brown, A; Kellendonk, C

    2016-07-01

    Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

  5. Dietary medicinal plant extracts improve growth, immune activity and survival of tilapia Oreochromis mossambicus.

    Science.gov (United States)

    Immanuel, G; Uma, R P; Iyapparaj, P; Citarasu, T; Peter, S M Punitha; Babu, M Michael; Palavesam, A

    2009-05-01

    The effects of supplementing diets with acetone extract (1% w/w) from four medicinal plants (Bermuda grass Cynodon dactylon, H(1), beal Aegle marmelos, H(2), winter cherry Withania somnifera, H(3) and ginger Zingiber officinale, H(4)) on growth, the non-specific immune response and ability to resist pathogen infection in tilapia Oreochromis mossambicus were assessed. In addition, the antimicrobial properties of the extract were assessed against Vibrio alginolyticus, Vibrioparahaemolyticus, Vibrio mimicus, Vibrio campbelli, Vibrio vulnificus, Vibrio harveyi and Photobacterium damselae. Oreochromis mossambicus were fed 5% of their body mass per day for 45 days, and those fed the experimental diets showed a greater increase in mass (111-139%) over the 45 days compared to those that received the control diet (98%). The specific growth rate of O. mossambicus fed the four diets was also significantly greater (1.66-1.93%) than control (1.52%) diet-fed fish. The blood plasma chemistry analysis revealed that protein, albumin, globulin, cholesterol, glucose and triglyceride levels of experimental fish were significantly higher than that of control fish. Packed cell volume of the blood samples of experimental diet-fed fish was also significantly higher (34.16-37.95%) than control fish (33.0%). Leucocrit value, phagocytic index and lysozyme activity were enhanced in fish fed the plant extract-supplemented diets. The acetone extract of the plants inhibited growth of Vibrio spp. and P. damselae with extracts from W. somnifera showing maximum growth inhibition. A challenge test with V. vulnificus showed 100% mortality in O. mossambicus fed the control diet by day 15, whereas the fish fed the experimental diets registered only 63-80% mortality at the end of challenge experiment (30 days). The cumulative mortality index for the control group was 12,000, which was equated to 1.0% mortality, and accordingly, the lowest mortality of 0.35% was registered in H(4)-diet-fed group.

  6. Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor

    Science.gov (United States)

    Walterscheid, Jeffrey P.; Nghiem, Dat X.; Kazimi, Nasser; Nutt, Leta K.; McConkey, David J.; Norval, Mary; Ullrich, Stephen E.

    2006-01-01

    Exposure to UV radiation induces skin cancer and suppresses the immune response. To induce immune suppression, the electromagnetic energy of UV radiation must be absorbed by an epidermal photoreceptor and converted into a biologically recognizable signal. Two photoreceptors have been recognized: DNA and trans-urocanic acid (UCA). Trans-UCA is normally found in the outermost layer of skin and isomerizes to the cis isomer upon exposure to UV radiation. Although UCA was identified as a UV photoreceptor years ago, and many have documented its ability to induce immune suppression, its exact mode of action remains elusive. Particularly vexing has been the identity of the molecular pathway by which cis-UCA mediates immune suppression. Here we provide evidence that cis-UCA binds to the serotonin [5-hydroxytryptamine (5-HT)] receptor with relatively high affinity (Kd = 4.6 nM). Anti-cis-UCA antibody precipitates radiolabeled 5-HT, and the binding is inhibited by excess 5-HT and/or excess cis-UCA. Similarly, anti-5-HT antibody precipitates radiolabeled cis-UCA, and the binding is inhibited by excess 5-HT or excess cis-UCA. Calcium mobilization was activated when a mouse fibroblast line, stably transfected with the human 5-HT2A receptor, was treated with cis-UCA. Cis-UCA-induced calcium mobilization was blocked with a selective 5-HT2A receptor antagonist. UV- and cis-UCA-induced immune suppression was blocked by antiserotonin antibodies or by treating the mice with 5-HT2A receptor antagonists. Our findings identify cis-UCA as a serotonin receptor ligand and indicate that the immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT2A receptor. PMID:17085585

  7. 78 FR 19632 - Special Local Regulations; St. Thomas Carnival Watersport Activities, Charlotte Amalie Harbor; St...

    Science.gov (United States)

    2013-04-02

    ...-AA08 Special Local Regulations; St. Thomas Carnival Watersport Activities, Charlotte Amalie Harbor; St... proposes to establish a special local regulation on the waters of Charlotte Amalie Harbor in St Thomas, USVI during the St. Thomas Carnival Watersport Activities, a high speed boat race. The event is...

  8. Localization-Aware Active Learning for Object Detection

    OpenAIRE

    Kao, Chieh-Chi; Lee, Teng-Yok; Sen, Pradeep; Liu, Ming-Yu

    2018-01-01

    Active learning - a class of algorithms that iteratively searches for the most informative samples to include in a training dataset - has been shown to be effective at annotating data for image classification. However, the use of active learning for object detection is still largely unexplored as determining informativeness of an object-location hypothesis is more difficult. In this paper, we address this issue and present two metrics for measuring the informativeness of an object hypothesis,...

  9. Novel active contour model based on multi-variate local Gaussian distribution for local segmentation of MR brain images

    Science.gov (United States)

    Zheng, Qiang; Li, Honglun; Fan, Baode; Wu, Shuanhu; Xu, Jindong

    2017-12-01

    Active contour model (ACM) has been one of the most widely utilized methods in magnetic resonance (MR) brain image segmentation because of its ability of capturing topology changes. However, most of the existing ACMs only consider single-slice information in MR brain image data, i.e., the information used in ACMs based segmentation method is extracted only from one slice of MR brain image, which cannot take full advantage of the adjacent slice images' information, and cannot satisfy the local segmentation of MR brain images. In this paper, a novel ACM is proposed to solve the problem discussed above, which is based on multi-variate local Gaussian distribution and combines the adjacent slice images' information in MR brain image data to satisfy segmentation. The segmentation is finally achieved through maximizing the likelihood estimation. Experiments demonstrate the advantages of the proposed ACM over the single-slice ACM in local segmentation of MR brain image series.

  10. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Directory of Open Access Journals (Sweden)

    Anna L Goodman

    Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

  11. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

    Science.gov (United States)

    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    Objective The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. Methods In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Results Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. Conclusion The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls

  12. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2017-08-01

    Full Text Available Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™ cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors.Results: Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response.Conclusion: The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that

  13. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro.

    Science.gov (United States)

    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3 + CD56 - T lymphocytes, CD3 + CD56 + NKT cells, CD3 - CD56 + NK cells, and also some cells within the CD3 - CD56 - non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls from live B. coagulans GBI-30, 6086

  14. Differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses to single epicutaneous immunization.

    Science.gov (United States)

    Lee, Chih-Hung; Chen, Jau-Shiuh; Chiu, Hsien-Ching; Hong, Chien-Hui; Liu, Ching-Yi; Ta, Yng-Cun; Wang, Li-Fang

    2016-12-01

    Epicutaneous immunization with allergens is an important sensitization route for atopic dermatitis. We recently showed in addition to the Th2 response following single epicutaneous immunization, a remarkable Th1 response is induced in B6 mice, but not in BALB/c mice, mimicking the immune response to allergens in human non-atopics and atopics. We investigated the underlying mechanisms driving this differential Th1 response between BALB/c and B6 mice. We characterized dermal dendritic cells by flow cytometric analysis. We measured the induced Th1/Th2 responses by measuring the IFN-γ/IL-13 contents of supernatants of antigen reactivation cultures of lymph node cells. We demonstrate that more dermal dendritic cells with higher activation status migrate into draining lymph nodes of B6 mice compared to BALB/c mice. Dermal dendritic cells of B6 mice have a greater ability to capture protein antigen than those of BALB/c mice. Moreover, increasing the activation status or amount of captured antigen in dermal dendritic cells induced a Th1 response in BALB/c mice. Further, differential activation behavior, but not antigen-capturing ability of dermal dendritic cells between BALB/c and B6 mice is dendritic cell-intrinsic. These results show that the differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses following single epicutaneous immunization. Furthermore, our findings highlight the potential differences between human atopics and non-atopics and provide useful information for the prediction and prevention of atopic diseases. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. The intracellular immune receptor Rx1 regulates the DNA-binding activity of a Golden2-like transcription factor.

    Science.gov (United States)

    Townsend, Philip D; Dixon, Christopher H; Slootweg, Erik J; Sukarta, Octavina C A; Yang, Ally W H; Hughes, Timothy R; Sharples, Gary J; Pålsson, Lars-Olof; Takken, Frank L W; Goverse, Aska; Cann, Martin J

    2018-03-02

    Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable the immune system to recognize and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming, and some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato is further able to bind and distort double-stranded DNA. However, Rx1 host targets that support a role for Rx1 in transcriptional reprogramming at DNA are unknown. Here, we report a functional interaction between Rx1 and Nb Glk1, a Golden2-like transcription factor. Rx1 binds to Nb Glk1 in vitro and in planta. Nb Glk1 binds to known Golden2-like consensus DNA sequences. Rx1 reduces the binding affinity of Nb Glk1 for DNA in vitro. Nb Glk1 activates cellular responses to potato virus X, whereas Rx1 associates with Nb Glk1 and prevents its assembly on DNA in planta unless activated by PVX. This study provides new mechanistic insight into how an NLR can coordinate an immune signaling response at DNA following pathogen perceptions. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis.

    Science.gov (United States)

    Sorbara, Matthew T; Philpott, Dana J

    2011-09-01

    Peptidoglycan is a conserved structural component of the bacterial cell wall with molecular motifs unique to bacteria. The mammalian immune system takes advantage of these properties and has evolved to recognize this microbial associated molecular pattern. Mammals have four secreted peptidoglycan recognition proteins, PGLYRP-1-4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2. Recognition of peptidoglycan is important in initiating and shaping the immune response under both homeostatic and infection conditions. During infection, peptidoglycan recognition drives both cell-autonomous and whole-organism defense responses. Here, we examine recent advances in the understanding of how peptidoglycan recognition shapes mammalian immune responses in these diverse contexts. © 2011 John Wiley & Sons A/S.

  17. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood.

    Science.gov (United States)

    Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W G M; Eggen, Bart J L

    2017-10-01

    Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia, the innate immune cells of the central nervous system (CNS). In mice, a challenge with LPS during late gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal microglia. Adult whole brain microglia of mice that were exposed to LPS during embryonic development displayed a persistent reduction in pro-inflammatory activation in response to a re-challenge with LPS. In contrast, hippocampal microglia of these mice displayed an increased inflammatory response to an LPS re-challenge. In addition, a reduced expression of brain-derived neurotrophic factor (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived BDNF has been shown to be important for learning and memory processes. In line with these observations, behavioral- and learning tasks with mice that were exposed to maternal inflammation revealed reduced home cage activity, reduced anxiety and reduced learning performance in a T-maze. These data show that exposure to maternal inflammation during late gestation results in long term changes in microglia responsiveness during adulthood, which is different in nature in hippocampus compared to total brain microglia. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Cytotoxic activity and apoptotic induction of some edible Thai local ...

    African Journals Online (AJOL)

    inverted microscopy and DNA fragmentation using agarose gel electrophoresis. Results: P. ... However, further studies are needed to isolate the active compounds responsible for the cytotoxic ..... D-E: TL at 500 and 4,000 μg/mL. Arrows ...

  19. Globalization of rheumatology: activities of ILAR. Think global - act local

    NARCIS (Netherlands)

    Dequeker, Jan; Rasker, Johannes J.; El-Hadidi, Tahsin

    2001-01-01

    In 1997 a distinguished EULAR rheumatologist involved in the development of biologics asked somewhat ironically, “What is ILAR [International League of Associations for Rheumatology] doing?” Now, 3 years later, we are in a position to review ILAR’s activities in recent years and its plans for the

  20. Platelets and the innate immune system: Mechanisms of bacterial-induced platelet activation.

    OpenAIRE

    Cox, Dermot; Kerrigan, Steven W; Watson, Steve

    2011-01-01

    It has become clear that platelets are not simply cell fragments that can plug the leak in a damaged blood vessel, they are in fact key components in the innate immune system which is supported by the presence of Toll-like receptors (TLRs) on platelets. As the first responding cell to a site of injury they are well placed to direct the immune response to deal with any resulting exposure to pathogens. The response is triggered by bacteria binding to platelets which usually triggers platelet ac...

  1. Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study

    International Nuclear Information System (INIS)

    Lee, Don Haeng; Kang, Sung-Gwon; Jeong, Seok; Yoon, Chang Jin; Choi, Jung-Ah; Byun, Ju Nam; Park, Jae Hyung; Lee, Kyu Back

    2006-01-01

    The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model

  2. Interferon-inducible p200-family protein IFI16, an innate immune sensor for cytosolic and nuclear double-stranded DNA: regulation of subcellular localization.

    Science.gov (United States)

    Veeranki, Sudhakar; Choubey, Divaker

    2012-01-01

    The interferon (IFN)-inducible p200-protein family includes structurally related murine (for example, p202a, p202b, p204, and Aim2) and human (for example, AIM2 and IFI16) proteins. All proteins in the family share a partially conserved repeat of 200-amino acid residues (also called HIN-200 domain) in the C-terminus. Additionally, most proteins (except the p202a and p202b proteins) also share a protein-protein interaction pyrin domain (PYD) in the N-terminus. The HIN-200 domain contains two consecutive oligosaccharide/oligonucleotide binding folds (OB-folds) to bind double stranded DNA (dsDNA). The PYD domain in proteins allows interactions with the family members and an adaptor protein ASC. Upon sensing cytosolic dsDNA, Aim2, p204, and AIM2 proteins recruit ASC protein to form an inflammasome, resulting in increased production of proinflammatory cytokines. However, IFI16 protein can sense cytosolic as well as nuclear dsDNA. Interestingly, the IFI16 protein contains a nuclear localization signal (NLS). Accordingly, the initial studies had indicated that the endogenous IFI16 protein is detected in the nucleus and within the nucleus in the nucleolus. However, several recent reports suggest that subcellular localization of IFI16 protein in nuclear versus cytoplasmic (or both) compartment depends on cell type. Given that the IFI16 protein can sense cytosolic as well as nuclear dsDNA and can initiate different innate immune responses (production of IFN-β versus proinflammatory cytokines), here we evaluate the experimental evidence for the regulation of subcellular localization of IFI16 protein in various cell types. We conclude that further studies are needed to understand the molecular mechanisms that regulate the subcellular localization of IFI16 protein. Published by Elsevier Ltd.

  3. Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Benoit T. Roux

    2017-08-01

    Full Text Available Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs are novel regulators of immu