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Sample records for disturbed immune response

  1. Human disturbance alters endocrine and immune responses in the Galapagos marine iguana (Amblyrhynchus cristatus).

    PubMed

    French, Susannah S; DeNardo, Dale F; Greives, Timothy J; Strand, Christine R; Demas, Gregory E

    2010-11-01

    Anthropogenic disturbance is a relevant and widespread facilitator of environmental change and there is clear evidence that it impacts natural populations. While population-level responses to major anthropogenic changes have been well studied, individual physiological responses to mild disturbance can be equally critical to the long-term survival of a species, yet they remain largely unexamined. The current study investigated the impact of seemingly low-level anthropogenic disturbance (ecotourism) on stress responsiveness and specific fitness-related immune measures in different breeding stages of the marine iguana (Amblyrhynchus cristatus). Specifically, we found stress-induced elevations in plasma corticosterone among tourist-exposed populations relative to undisturbed populations. We also found changes in multiple immunological responses associated with stress-related effects of human disturbance, including bacterial killing ability, cutaneous wound healing, and hemolytic complement activity, and the responses varied according to reproductive state. By identifying health-related consequences of human disturbance, this study provides critical insight into the conservation of a well-known species that has a very distinct ecology. The study also broadens the foundation of knowledge needed to understand the global significance of various levels of human disturbance.

  2. Human disturbance alters endocrine and immune responses in the Galapagos marine iguana (Amblyrhynchus cristatus)

    PubMed Central

    French, Susannah S; DeNardo, Dale F.; Greives, Timothy J.; Strand, Christine R.; Demas, Gregory E.

    2010-01-01

    Anthropogenic disturbance is a relevant and widespread facilitator of environmental change and there is clear evidence that it impacts natural populations. While population-level responses to major anthropogenic changes have been well studied, individual physiological responses to mild disturbance can be equally critical to the long-term survival of a species, yet they remain largely unexamined. The current study investigated the impact of seemingly low-level anthropogenic disturbance (ecotourism) on stress responsiveness and specific fitness-related immune measures in different breeding stages of the marine iguana (Amblyrhynchus cristatus). Specifically, we found stress-induced elevations in plasma corticosterone among tourist-exposed populations relative to undisturbed populations. We also found changes in multiple immunological responses associated with stress-related effects of human disturbance, including bacterial killing ability, cutaneous wound healing, and hemolytic complement activity, and the responses varied according to reproductive state. By identifying health-related consequences of human disturbance, this study provides critical insight into the conservation of a well-known species that has a very distinct ecology. The study also broadens the foundation of knowledge needed to understand the global significance of various levels of human disturbance. PMID:20708010

  3. Mice Chronically Fed High-Fat Diet Have Increased Mortality and Disturbed Immune Response in Sepsis

    PubMed Central

    Strandberg, Louise; Verdrengh, Margareta; Enge, Maria; Andersson, Niklas; Amu, Sylvie; Önnheim, Karin; Benrick, Anna; Brisslert, Mikael; Bylund, Johan; Bokarewa, Maria; Nilsson, Staffan; Jansson, John-Olov

    2009-01-01

    Background Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. Methodology/Principal Findings The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5–7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1β. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. Conclusions Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis. PMID:19865485

  4. Disturbance of the intestinal mucosal immune system of farmed Atlantic salmon (Salmo salar), in response to long-term hypoxic conditions.

    PubMed

    Niklasson, L; Sundh, H; Fridell, F; Taranger, G L; Sundell, K

    2011-12-01

    The gastrointestinal (GI) tract has many important biological functions. One is to serve as a barrier between the fish and the external environment. A decreased physical barrier function of the intestine may lead to increased inflow of luminal content and subsequent activation of the intestinal mucosal immune system. This activation is governed by the ability of various compounds to induce cytokine release and immune cell activity, leading to an immune response. In mammals, the impact of stress on the intestinal barrier is well documented and results in increased intestinal permeability and thus increased stimulation of the mucosal immune system. Fish reared in sea cages may at times be exposed to unfavourable environmental conditions leading to chronic stress and disturbed intestinal integrity. This change in permeability may increase the exposure of the mucosal immune system to activating compounds. In the present study, the effect of a prolonged stress on the intestinal mucosal immune system of fish is therefore addressed. Atlantic salmon were exposed to low levels (50%) of dissolved oxygen (DO) for 6-7 weeks in consecutive experiments performed at 8 and 16 °C. Immune parameters were assessed in terms of mRNA expression of the key cytokines, interleukin-1β (IL-1β), IL-8, IL-10, interferon-γ (IFNγ) and transforming growth factor-β (TGFβ) as well as the immune regulatory inhibitor of nuclear factor κB (IκB). In the experiment at 8 °C also mucosal neutrophil infiltration was monitored. Subjecting the fish to low DO levels at 8 °C resulted in an increased mucosal neutrophil infiltration together with a down-regulation of IκB. At the higher temperature, 16 °C, low DO levels created decreased expression of the pro-inflammatory cytokine IL-1β in both intestinal regions as well as an increased expression of IL-10 in the proximal intestine. These results suggest that husbandry conditions in sea cages with DO levels as low as 50% clearly affects the

  5. [THE CHANGES OF THE INTERRELATIONS OF THE PINEAL GLAND AND THE ORGANS OF THE IMMUNE SYSTEM IN RATS IN RESPONSE TO MELATONIN ADMINISTRATION IN LIGHT REGIME DISTURBANCES].

    PubMed

    Litvinenko, G I; Gritzyk, O B; Mel'nikova, Ye V; Avrorov, P A; Tenditnik, M V; Shurlygina, A V; Trufakin, V A

    2015-01-01

    In this work the correlation analysis was applied to detect the integrated response of the pineal gland (PG) and immunocompetent organs of male Wistar rats in response to administration of melatonin (MT) in light regime disturbances. Animals were kept for 14 days under natural or continuous light (CL). Then for 7 days they received the injections of either 0.9% solution of sodium chloride or MT, after which the rats were decapitated and the mass of their body, PG, thymus and spleen was determined. The lymphocyte subpopulations of the thymus and spleen were studied by flow cytometry. The amount of lipofuscin in PG was assessed by the intensity of autofluorescence in organ frozen sections in 560-600 nm wavelength range. It was found that under the influence of MT, the number of intraorgan correlations in the immune system increased, regardless of the light regime. In animals on CL treated with MT, the number of interorgan connections was reduced, while negative correlations appeared between PG lipofuscin content and cellular composition of the spleen. The synchronizing and adaptogenic effects of MT were most pronounced under conditions of CL.

  6. The impact of immune disturbances on the failure of antituberculosis treatment

    PubMed Central

    LESNIC, EVELINA; GHINDA, SERGHEI; POP, CARMEN MONICA

    2016-01-01

    Background and aim Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex, with an evolution and treatment outcome determined by the interaction between the mycobacterial and human genotypes. Various deficiencies of innate immune response starting from the first encounter of M. tuberculosis with lung cells endanger host infection control due to decreased triggering of cellular immune resistance and disturbed humoral immunity. Disturbed cell mediated immunity, known as the basic immune response in tuberculous infection, contributes to the deficient generation of central necrosis granuloma, consequently being responsible for severe clinical aspects and low final outcome. The tuberculosis patient’s immune assessment is important before treatment initiation, for establishing the risk reduction measures and increasing success rate. Material and methods The immune study was conducted on 54 new pulmonary tuberculosis cases with treatment failure, 34 new pulmonary tuberculosis cases that successfully ended the treatment and 50 healthy group individuals. Immune assays performed were: blastic transformation of lymphocytes induced by different antigens, quantitatitve assessment of cellular immunity through CD4+ T cell and CD8+ T cell phenotyping, humoral immunity - through immunoglobulin isotyping, innate resistance – through phagocyte activity of neutrophils, the titter of anti-tuberculosis antibodies and the serum level of circulating immune complexes. Investigations were performed at the onset the treatment and at the end of intensive phase of the standard anti-tuberculosis treatment. Results Immune disturbances evidenced in patients with treatment failure were: important deficiencies of cellular immunity, hyperactivity of humoral immunity and deficiencies of innate immunity. High predictive value for treatment failure showed the indices: deficiency of T lymphocytes count (OR=62.5) and T helper count (OR=12.5), high level of circulating

  7. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  8. Immune responses to metastases

    SciTech Connect

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors.

  9. Monitoring response to disturbance in dynamic rangelands

    USDA-ARS?s Scientific Manuscript database

    Arid and semi-arid rangelands worldwide provide important ecosystem services and see a diversity of land uses. To maintain the health of these lands, it is necessary to monitor rangeland conditions in response to management and disturbance. Spatial patterns from disturbance are superimposed on patte...

  10. Exercise boosts immune response.

    PubMed

    Sander, Ruth

    2012-06-29

    Ageing is associated with a decline in normal functioning of the immune system described as 'immunosenescence'. This contributes to poorer vaccine response and increased incidence of infection and malignancy seen in older people. Regular exercise can enhance vaccination response, increase T-cells and boost the function of the natural killer cells in the immune system. Exercise also lowers levels of the inflammatory cytokines that cause the 'inflamm-ageing' that is thought to play a role in conditions including cardiovascular disease; type 2 diabetes; Alzheimer's disease; osteoporosis and some cancers.

  11. Never deem lightly the "less harmful" low-molecular-weight PAH, NPAH, and OPAH - Disturbance of the immune response at real environmental levels.

    PubMed

    Wang, Cui; Yang, Jinhuan; Zhu, Linwensi; Yan, Lu; Lu, Dezhao; Zhang, Quan; Zhao, Meirong; Li, Zhuoyu

    2017-02-01

    The upcoming energy structure optimization and the implementation of strict emissions control will effectively alleviated the pollution of high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs) in the atmosphere. Compared to HMW PAHs, the immune response to low-molecular-weight (LMW) PAHs is recognized as "less harmful", despite the high proportions of these substances. The present study intends to investigate the effects of several of the most abundant LMW PAHs on macrophages RAW264.7 at environmentally relevant doses. The data assembled herein showed that Fluoranthene (Fluo, PAH) formed a π-π interaction with the Phe12 residue of AhR while inhibiting the transcription of CYP1A1 and CYP1B1, and ultimately induced the inflammatory cytokines in RAW264.7. The 1-Nitropyrene (1-Nitro, NPAH) formed both a π-π interaction and a hydrogen bond with AhR, stimulated CYP1A1transcription, while suppressed the cytokine levels. Additionally, the inflammation potency caused by TPAHs was highly correlated with the cytotoxic potency rather than the oxidative stress potency. When stimulated by LPS, the transcription of IL-6 was inhibited by Fluo, and 1-Nitro suppressed both IL-6 and TNFα transcription. Furthermore, only 1-Nitro gave a significant inhibition on phagocytosis. The effects of 9-Fluorenone (9-Fluo, OPAH) on macrophages remained insignificant throughout the study since the low affinity for AhR, which resulted in low cytotoxicity. Collectively, this study suggested that LMW PAHs tended to cause mild inflammation when they bind without activating AhR. During infection, AhR ligands caused immunosuppression and this potency for TPAHs may be higher in AhR activator than that in AhR inactivator. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Aberrant methylation of PSD disturbs Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis in ulcerative colitis-associated carcinogenesis.

    PubMed

    Kato, Takaharu; Suzuki, Koichi; Okada, Shinichiro; Kamiyama, Hidenori; Maeda, Takafumi; Saito, Masaaki; Koizumi, Kei; Miyaki, Yuichiro; Konishi, Fumio

    2012-04-01

    We previously reported that the Pleckstrin and Sec7 domain-containing (PSD) gene is preferentially methylated in patients with ulcerative colitis (UC) who developed colorectal cancer (CRC), and is implicated in UC-associated carcinogenesis through its inhibition of apoptosis. This study aimed to determine the potential effect of PSD methylation on its downstream molecule, Ras-related C3 botulinum toxin substrate 1 (Rac1), which governs neutrophil chemotaxis and apoptosis signaling. PSD was knocked down in a normal human fibroblast cell line (HNDF) and a neutrophil-like cell line (HL-60). Both NHDF and HL-60 cells exhibited numerous filamentous-actin (F-actin) rich membrane extensions, resulting in the activation of Rac1; this activation was hampered by PSD silencing. Lipopolysaccharide, a reactive oxygen species (ROS) inducer, stimulated NHDF cells to release ROS and activated caspase‑3/7 in the presence of neutrophils, which was inhibited by PSD knockdown. Migration assays demonstrated that chemotaxis of HL-60 cells was affected by PSD silencing in NHDF cells. Tissue sections from 6 UC patients with CRC and 15 UC patients without CRC were examined. To verify Rac1-mediated chemotaxis in tissue sections, we evaluated the grade of neutrophil infiltration by histological assessment and assessed F-actin and PSD expression by immunohistochemistry. Neutrophil infiltration, F-actin and PSD expression were significantly decreased in specimens from UC patients with PSD methylation compared with those without. Decreased levels of F-actin expression were observed in colorectal mucosa, as well as in infiltrating cells with PSD methylation. PSD expression was preferentially inhibited in colorectal mucosa by PSD methylation, whereas PSD expression was rarely observed in infiltrating cells, regardless of PSD methylation status. These data indicate that aberrant methylation of PSD occurs in UC-associated colorectal mucosa, enabling circumvention of Rac1-mediated immune responses

  13. Glycobiology of immune responses

    PubMed Central

    Rabinovich, Gabriel A.; van Kooyk, Yvette; Cobb, Brian A.

    2013-01-01

    Unlike their protein “roommates” and their nucleic acid “cousins,” carbohydrates remain an enigmatic arm of biology. The central reason for the difficulty in fully understanding how carbohydrate structure and biological function are tied is the nontemplate nature of their synthesis and the resulting heterogeneity. The goal of this collection of expert reviews is to highlight what is known about how carbohydrates and their binding partners—the microbial (non-self), tumor (altered-self), and host (self)—cooperate within the immune system, while also identifying areas of opportunity to those willing to take up the challenge of understanding more about how carbohydrates influence immune responses. In the end, these reviews will serve as specific examples of how carbohydrates are as integral to biology as are proteins, nucleic acids, and lipids. Here, we attempt to summarize general concepts on glycans and glycan-binding proteins (mainly C-type lectins, siglecs, and galectins) and their contributions to the biology of immune responses in physiologic and pathologic settings. PMID:22524422

  14. Selenium and immune responses

    SciTech Connect

    Kiremidjian-Schumacher, L.; Stotzky, G.

    1987-04-01

    Selenium (Se) affects all components of the immune system, i.e., the development and expression of nonspecific, humoral, and cell-mediated responses. In general, a deficiency in Se appears to result in immunosuppression, whereas supplementation with low doses of Se appears to result in augmentation and/or restoration of immunologic functions. A deficiency of Se has been shown to inhibit (1) resistance to microbial and viral infections, (2) neutrophil function, (3) antibody production, (4) proliferation of T and B lymphocytes in response to mitogens, and (5) cytodestruction by T lymphocytes and NK cells. Supplementation with Se has been shown to stimulate (1) the function of neutrophils, (2) production of antibodies, (3) proliferation of T and B lymphocytes in response to mitogens, (4) production of lymphokines, (5) NK cell-mediated cytodestruction, (6) delayed-type hypersensitivity reactions and allograft rejection, and (7) the ability of a host to reject transplanted malignant tumors. The mechanism(s) whereby Se affects the immune system is speculative. The effects of Se on the function of glutathione peroxidase and on the cellular levels of reduced glutathione and H/sub 2/Se, as well as the ability of Se to interact with cell membranes, probably represent only a few of many regulatory mechanisms. The manipulation of cellular levels of Se may be significant for the maintenance of general health and for the control of immunodeficiency disorders and the chemoprevention of cancer.

  15. Human immune responses in cryptosporidiosis

    PubMed Central

    Borad, Anoli; Ward, Honorine

    2010-01-01

    Immune responses play a critical role in protection from, and resolution of, cryptosporidiosis. However, the nature of these responses, particularly in humans, is not completely understood. Both innate and adaptive immune responses are important. Innate immune responses may be mediated by Toll-like receptor pathways, antimicrobial peptides, prostaglandins, mannose-binding lectin, cytokines and chemokines. Cell-mediated responses, particularly those involving CD4+ T cells and IFN-γ play a dominant role. Mucosal antibody responses may also be involved. Proteins mediating attachment and invasion may serve as putative protective antigens. Further knowledge of human immune responses in cryptosporidiosis is essential in order to develop targeted prophylactic and therapeutic interventions. This review focuses on recent advances and future prospects in the understanding of human immune responses to Cryptosporidium infection. PMID:20210556

  16. Remune. Immune Response.

    PubMed

    Lai, Derhsing; Jones, Taff

    2002-03-01

    The Immune Response Corp (IRC) is developing Remune, a potential HIV therapeutic vaccine. Remune is based on the Salk Immunogen, which is derived from an HIV isolate which has been inactivated by chemical depletion of glycoprotein 120 (gp120). Preliminary data suggested that Remune, in combination with antiviral drug therapy, results in undetectable levels of HIV. Phase III trials commenced in May 1997 and it was initially expected that registration filings would be made in 1999. However, following interim analysis of the 2500-patient, multicenter, double-blind, pivotal phase III study (study 806) in May 1999, an independent panel recommended concluding the clinical endpoint trial and IRC and licensee, Agouron, decided to pursue alternative regulatory strategies, including initiating two additional phase III surrogate marker trials. Despite this, Agouron gave IRC notice of termination of its continued development in July 2001. In August 2001, IRC informed Agouron that, due to the total number of endpoints to date falling short of that previously assumed by Agouron, it did not intend to continue Agouron's Study 202 of Remune. In July 2001, licensee Trinity Medical Group filed an NDA with the governing health authorities in Thailand for Remune. The Thai FDA certified Immune Response's Remune manufacturing facility as being in compliance with GMP standards, following an on site inspection by Thai officials in November 2001 that was performed as a requirement of Trinity's Thai NDA. As a result of this certification, Trinity expected that a "timely determination" could be made by the Thai FDA. Rhĵne-Poulenc Rorer discontinued its part in the development of Remune, with all manufacturing, marketing and distribution rights reverting to IRC. After Agouron returned rights to Remune in July 2001, IRC heldfull rights in the US, Europe and Japan, while collaborating with its partners Trinity Medical Group and Roemmers Laboratory in the Southeast Asian and Latin American

  17. Response of Ionosphere to the Tropospheric disturbances

    NASA Astrophysics Data System (ADS)

    Maurya, A. K.; Dube, A.; Singh, R.; Cohen, M.

    2015-12-01

    The aim of the present work is to find out response of the ionosphere to the various cases of tropical cyclones. The main process involved is suggested through Atmospheric Gravity waves (AGWs) originating from strong convective systems, propagating upward upto the ionospheric heights and perturbing ionospheric parameters (Bishop et al., 2006). We have used ground and satellite data to extract cyclone induced perturbations at different ionospheric heights along with the various parameters of AGWs during cyclones and associated thunderstorm. The initial results suggest that there is increase in total electron content of the ionosphere with wave like signatures in ionosphere. The satellite observation in optical band shows presence of concentric gravity wave pattern associated with troposphere disturbances with horizontal wavelength of ~50-200km and periods ranging from hours to days. The ground based Very Low Frequency (VLF) measurement shows fluctuations in VLF navigational transmitter signal passing over the region of disturbance. The lightning data from GLD360 lightning network shows intense activity associated with cyclones and increase in lightning peak current and energy during main phase of cyclones which seems to be sufficient enough to derive ionospheric disturbances in the ionosphere. This multi-instrument analysis provide detail information of the three dimensional structure of cyclone and their effect at different altitudes of the ionosphere in the Indian subcontinent.

  18. Ubiquitin signaling in immune responses

    PubMed Central

    Hu, Hongbo; Sun, Shao-Cong

    2016-01-01

    Ubiquitination has emerged as a crucial mechanism that regulates signal transduction in diverse biological processes, including different aspects of immune functions. Ubiquitination regulates pattern-recognition receptor signaling that mediates both innate immune responses and dendritic cell maturation required for initiation of adaptive immune responses. Ubiquitination also regulates the development, activation, and differentiation of T cells, thereby maintaining efficient adaptive immune responses to pathogens and immunological tolerance to self-tissues. Like phosphorylation, ubiquitination is a reversible reaction tightly controlled by the opposing actions of ubiquitin ligases and deubiquitinases. Deregulated ubiquitination events are associated with immunological disorders, including autoimmune and inflammatory diseases. PMID:27012466

  19. Variability in geomorphic response to anthropogenic disturbance

    NASA Astrophysics Data System (ADS)

    Verstraeten, Gert; Notebaert, Bastiaan; D'Haen, Koen; Broothaerts, Nils; De Brue, Hanne

    2013-04-01

    Humans have greatly impacted the processes and intensities of erosion, sediment transport and storage since the introduction of agriculture. However, the relation between the intensity of anthropogenic disturbance and the magnitude of change in sediment dynamics is highly non-linear due to the importance of intrinsic controls on sediment propagation. Especially the buffering capacity of slopes and floodplains can be held responsible for this non-linearity, as both sinks store the produced sediment temporarily, obscuring the relation between sediment production and sediment output. Slope-stream connectivity, but also the duration and typology of anthropogenic disturbance controls the existence of thresholds that need to be crossed before significant changes in downstream sediment dynamics are recorded following human impact. Many internal feedback mechanisms, such as those between erosion and soil thickness, further complicate the story. Several concepts have been developed over the last few decades to explain the complex behavior of sediment transfers in the combined hillslope-fluvial system, including the 'sediment cascade' model and the 'fast-in, slow-out' model. However, none of these concepts seems to hold universally when reconstructing historical sediment dynamics for contrasting environments, as is illustrated with case-studies from a range of environments in Belgium, Turkey and the USA. Detailed field-based sediment budgets from these contrasting settings combined with spatial modeling of sediment fluxes covering time periods ranging from 200 to over 5000 years, as well as the use of pollen and sediment provenancing techniques, shows that no overarching concept of sediment source-to-sink following anthropogenic disturbance can be established. Rather, depending on the duration and typology of anthropogenic disturbances, in combination with local environmental conditions, unique patterns of geomorphic process response emerge. As a result, unraveling the human

  20. Arbuscular mycorrhizal fungus responses to disturbance are context-dependent.

    PubMed

    van der Heyde, Mieke; Ohsowski, Brian; Abbott, Lynette K; Hart, Miranda

    2017-01-24

    Anthropogenic disturbance is one of the most important forces shaping soil ecosystems. While organisms that live in the soil, such as arbuscular mycorrhizal (AM) fungi, are sensitive to disturbance, their response is not always predictable. Given the range of disturbance types and differences among AM fungi in their growth strategies, the unpredictability of the responses of AM fungi to disturbance is not surprising. We investigated the role of disturbance type (i.e., soil disruption, agriculture, host perturbation, and chemical disturbance) and fungus identity on disturbance response in the AM symbiosis. Using meta-analysis, we found evidence for differential disturbance response among AM fungal species, as well as evidence that particular fungal species are especially susceptible to certain disturbance types, perhaps because of their life history strategies.

  1. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  2. Immune Responses in Parasitic Diseases

    DTIC Science & Technology

    1982-09-01

    RESPONSES IN PARASITIC DISEASES Final Scientific Report Daniel J. Stechschulte, M.D. Herbert B. Lindsley, M.D. September 1982 (July 1974 - December 1979...REPORT & PERIOD COVERED IMMUNE RESPONSES IN PARASITIC DISEASES Final Report July 1977 - Dec. 1979 6. PERFORMING ORG. REPORT NUMBER S 4 7. AUTNIOR(a) 6...DAMD 17-74-C-4136 AD_______________ IMMUNE RESPONSES IN PARASITIC DISEASES Final Scientific Report Daniel J. Stechschulte, M.D. Herbert B. Lindsley

  3. Forest response and recovery following disturbance (Invited)

    NASA Astrophysics Data System (ADS)

    Schafer, K. V.; Clark, K. L.; Renninger, H. J.; Carlo, N.; Medvigy, D.

    2013-12-01

    Forest management and global climate change may modulate forest responses to disturbances such as drought, insect infestation or windthrow. Forest responses to drought and gypsy moth defoliation measured from 2005 to present in an oak/pine ecosystem in the Atlantic Coastal Plain (New Jersey Pinelands) show a relative conservatism of water use but longer lasting effects on carbon balance. While post-defoliation transpiration and evapotranspiration were similar to pre-defoliation levels, post-defoliation carbon fluxes have not returned to pre-disturbance levels even after five years of recovery due to a 25% reduction in basal area following tree mortality. Defoliation frequency also affects recovery with modeled carbon fluxes under various defoliation scenarios, showing pronounced reduction in productivity under frequent defoliation, but no effect if defoliation occurs at a rate of less than 15 years. Despite a relatively consistent seasonal water use through various disturbances, defoliation and drought affect water use differently. For example, canopy transpiration (EC) after defoliation and subsequent re-sprouting, was reduced by 25% compared to pre-defoliation levels, even though only half of the leaf area was replaced. However under severe drought conditions in 2006 and 2010, EC was only reduced by 8% and 18% respectively. Therefore, prolonged drought had a lesser effect on EC than reduced foliage or episodic defoliation, suggesting these trees have access to deeper soil moisture. These data also suggest that defoliation may make trees more sensitive to drought as evidenced by the higher reduction of Ec in 2010 compared to 2006 (pre-defoliation). Differential physiological responses of the various oak species as well as pitch pine may also create a species shift in an ecosystem that is also prone to fire. In this ecosystem, Quercus prinus showed consistently lower stomatal conductance, photosynthesis and maximum carboxylation rate compared to Quercus velutina

  4. Leptin Regulation of Immune Responses.

    PubMed

    Naylor, Caitlin; Petri, William A

    2016-02-01

    Leptin is a regulatory hormone with multiple roles in the immune system. We favor the concept that leptin signaling 'licenses' various immune cells to engage in immune responses and/or to differentiate. Leptin is an inflammatory molecule that is capable of activating both adaptive and innate immunity. It can also 'enhance' immune functions, including inflammatory cytokine production in macrophages, granulocyte chemotaxis, and increased Th17 proliferation. Leptin can also 'inhibit' cells; CD4(+) T cells are inhibited from differentiating into regulatory T cells in the presence of elevated leptin, while NK cells can exhibit impaired cytotoxicity under the same circumstances. Consequently, understanding the effect of leptin signaling is important to appreciate various aspects of immune dysregulation observed in malnutrition, obesity, and autoimmunity.

  5. The response of avian feeding guilds to tropical forest disturbance.

    PubMed

    Gray, Michael A; Baldauf, Sandra L; Mayhew, Peter J; Hill, Jane K

    2007-02-01

    Anthropogenic habitat disturbance is a major threat to tropical forests and understanding the ecological consequences of this disturbance is crucial for the conservation of biodiversity. There have been many attempts to determine the ecological traits associated with bird species' vulnerability to disturbance, but no attempt has been made to synthesize these studies to show consensus. We analyzed data from 57 published studies (covering 1214 bird species) that investigated the response of tropical bird assemblages to moderate forest disturbance (e.g., selective logging). Our results show that the mean abundance of species from six commonly reported feeding guilds responded differently to disturbance and that species' ecological traits (body size, local population size, and geographic range size) and evolutionary relationships may influence responses in some guilds. Granivore abundance increased significantly and insectivore and frugivore abundance decreased significantly following disturbance. These general conclusions were robust to the effects of ecological traits and phylogeny. Responses of carnivores, nectarivores, and omnivores were less clear, but analyses that accounted for phylogeny indicated that these guilds declined following disturbance. In contrast to the other guilds, the reported responses of carnivores and nectarivores differed among regions (Asia vs. Neotropics) and were influenced by the sampling protocols used in different studies (e.g., time since disturbance), which may explain the difficulty in detecting general responses to disturbance in these guilds. Overall, general patterns governed the responses of species to habitat disturbance, and the differential responses of guilds suggested that disturbance affects trophic organization and thus ecosystem functioning.

  6. Sleep Disturbance and Older Adults' Inflammatory Responses to Acute Stress

    PubMed Central

    Heffner, Kathi L.; Ng, H. Mei; Suhr, Julie A.; France, Christopher R.; Marshall, Gailen D.; Pigeon, Wilfred R.; Moynihan, Jan A.

    2013-01-01

    Objectives Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Design Observational study of community-dwelling, healthy older adults. Setting Participants completed the study in a clinical research laboratory of a mid-sized university. Participants Generally healthy, community-dwelling men and women 50 years of age and older. Measurements IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Results Participants categorized as poor sleepers based on Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors compared to good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Conclusions Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation. PMID:22327621

  7. Sleep disturbance and older adults' inflammatory responses to acute stress.

    PubMed

    Heffner, Kathi L; Ng, H Mei; Suhr, Julie A; France, Christopher R; Marshall, Gailen D; Pigeon, Wilfred R; Moynihan, Jan A

    2012-09-01

    Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Observational study of community-dwelling, healthy older adults. Participants completed the study in a clinical research laboratory of a mid-sized university. Generally healthy, community-dwelling men and women age 50 and older. IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Participants categorized as poor sleepers on the basis of Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors than good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation.

  8. Wild salmon response to natural disturbance processes

    Treesearch

    Russ Thurow; John M. Buffington

    2016-01-01

    Dynamic landscapes are shaped by a variety of natural processes and disturbances operating across multiple temporal and spatial scales. Persistence of species in these dynamic environments is also a matter of scale: how do species dispersal and reproductive rates merge with the scales of disturbance?

  9. Correlations of sleep disturbance with the immune system in type 2 diabetes mellitus.

    PubMed

    Tsujimura, Takahiro; Matsuo, Yoshinobu; Keyaki, Takahiro; Sakurada, Kumi; Imanishi, Jiro

    2009-09-01

    The circadian rhythm and immune system are thought to be associated with the pathological state of diabetes. The aim of this study was to examine the correlation of circadian rhythm disturbance including sleep disturbance with the immune state in patients with type 2 diabetes compared to healthy controls. Nineteen patients with type 2 diabetes (11 males and 8 females; aged 46-85 years) and 19 healthy controls (7 males and 12 males; aged 45-85 years) were recruited, and the presence of circadian rhythm disturbance including sleep disturbance was examined using an actigraph. Immunological parameters were also measured. Sleep and circadian rhythm disturbances were more frequently noted in diabetic patients than in healthy controls. Higher fasting plasma glucose and hemoglobin A1c levels were correlated with stronger sleep and circadian rhythm disturbances. The levels of B lymphocytes, helper T lymphocytes, natural killer cells, natural killer activity, and several cytokines were increased in diabetic patients compared to healthy controls. Correlations were shown among sleep disturbance (circadian rhythm disturbance), immunological measures, and diabetic indices. The exacerbation of diabetes was related to the level of sleep disturbance, circadian rhythm disturbance, and activation of the immune system.

  10. The geocoronal responses to the geomagnetic disturbances

    NASA Astrophysics Data System (ADS)

    Kuwabara, M.; Yoshioka, K.; Murakami, G.; Tsuchiya, F.; Kimura, T.; Yamazaki, A.; Yoshikawa, I.

    2017-01-01

    Atomic hydrogen atoms in the terrestrial exosphere resonantly scatter solar Lyman alpha (121.6 nm) radiation, observed as the hydrogen geocorona. Measurements of scattered solar photons allow us to probe time-varying distributions of exospheric hydrogen atoms. The Hisaki satellite with the extreme ultraviolet spectrometer (EXtreme ultraviolet spectrosCope for ExosphEric Dynamics: EXCEED) was launched in September 2013. EXCEED acquires spectral images (52-148 nm) of the atmospheres/magnetospheres of planets from Earth orbit. Due to its low orbital altitude ( 1000 km), the images taken by the instrument also contain the geocoronal emissions. In this context, EXCEED has provided quasi-continuous remote sensing observations of the geocorona with high temporal resolution ( 1 min) since 2013. These observations provide a unique database to determine the long-term behavior of the exospheric density structure. In this paper, we report exospheric structural responses observed by EXCEED to geomagnetic disturbances. Several geomagnetic storms with decreases of Dst index occurred in February 2014 and the Lyman alpha column brightness on the night side of the Earth increased abruptly and temporarily by approximately 10%. Hisaki reveal that the time lag between the peaks of the magnetic activity and the changes in the Lyman alpha column brightness is found to be about 2 to 6 h during storms. In order to interpret the observational results, we evaluate quantitatively the factors causing the increase. On the basis of these results, a coupling effect via charge exchange between the exosphere and plasmasphere causes variations of the exospheric density structure.

  11. Immune responses in space flight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.

    1998-01-01

    Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological

  12. Immune responses in space flight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.

    1998-01-01

    Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological

  13. Immune Response to Giardia duodenalis

    PubMed Central

    Faubert, Gaétan

    2000-01-01

    The intestinal protozoan Giardia duodenalis is a widespread opportunistic parasite of humans and animals. This parasite inhabits the upper part of the small intestine and has a direct life cycle. After ingestion of cysts, which are the infective stage, the trophozoites emerge from the cysts in the duodenum and attach to the small intestinal mucosa of the host. Since the migration of trophozoites from the lumen of the intestine into surrounding tissues is an unusual occurrence, the immune response to Giardia remains localized. The identification of antigens that play a role in acquired immunity has been difficult because of the occurrence of antigenic variation and because, Giardia being an ubiquituous organism, it is possible that the antigenic profiles of isolates from different geographic areas will vary. Innate-immunity mechanisms play a role in the control and/or severity of the infection. Both humoral and cell-mediated immune responses play a role in acquired immunity, but the mechanisms involved are unknown. A variety of serological assays have been used to detect circulating antibodies in serum. Because of the biological characteristics of the parasite and the lack of suitable antigens, the sensitivity of serological assays remains poor. On the other hand, detection of antigens in feces of infected patients has met with success. Commercial kits are available, and they are reported to be more sensitive than microscopic examination for the detection of giardiasis on a single specimen. PMID:10627490

  14. Immune responses to improving welfare

    PubMed Central

    Berghman, L. R.

    2016-01-01

    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that “increased vigilance of the immune system is by definition better” because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as “sickness behavior,” includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  15. Geomagnetic response to solar and interplanetary disturbances

    NASA Astrophysics Data System (ADS)

    Saiz, Elena; Cerrato, Yolanda; Cid, Consuelo; Dobrica, Venera; Hejda, Pavel; Nenovski, Petko; Stauning, Peter; Bochnicek, Josef; Danov, Dimitar; Demetrescu, Crisan; Gonzalez, Walter D.; Maris, Georgeta; Teodosiev, Dimitar; Valach, Fridich

    2013-07-01

    The space weather discipline involves different physical scenarios, which are characterised by very different physical conditions, ranging from the Sun to the terrestrial magnetosphere and ionosphere. Thanks to the great modelling effort made during the last years, a few Sun-to-ionosphere/thermosphere physics-based numerical codes have been developed. However, the success of the prediction is still far from achieving the desirable results and much more progress is needed. Some aspects involved in this progress concern both the technical progress (developing and validating tools to forecast, selecting the optimal parameters as inputs for the tools, improving accuracy in prediction with short lead time, etc.) and the scientific development, i.e., deeper understanding of the energy transfer process from the solar wind to the coupled magnetosphere-ionosphere-thermosphere system. The purpose of this paper is to collect the most relevant results related to these topics obtained during the COST Action ES0803. In an end-to-end forecasting scheme that uses an artificial neural network, we show that the forecasting results improve when gathering certain parameters, such as X-ray solar flares, Type II and/or Type IV radio emission and solar energetic particles enhancements as inputs for the algorithm. Regarding the solar wind-magnetosphere-ionosphere interaction topic, the geomagnetic responses at high and low latitudes are considered separately. At low latitudes, we present new insights into temporal evolution of the ring current, as seen by Burton's equation, in both main and recovery phases of the storm. At high latitudes, the PCC index appears as an achievement in modelling the coupling between the upper atmosphere and the solar wind, with a great potential for forecasting purposes. We also address the important role of small-scale field-aligned currents in Joule heating of the ionosphere even under non-disturbed conditions. Our scientific results in the framework of the

  16. Sex differences in immune responses.

    PubMed

    Klein, Sabra L; Flanagan, Katie L

    2016-10-01

    Males and females differ in their immunological responses to foreign and self-antigens and show distinctions in innate and adaptive immune responses. Certain immunological sex differences are present throughout life, whereas others are only apparent after puberty and before reproductive senescence, suggesting that both genes and hormones are involved. Furthermore, early environmental exposures influence the microbiome and have sex-dependent effects on immune function. Importantly, these sex-based immunological differences contribute to variations in the incidence of autoimmune diseases and malignancies, susceptibility to infectious diseases and responses to vaccines in males and females. Here, we discuss these differences and emphasize that sex is a biological variable that should be considered in immunological studies.

  17. Fetal immune response to chorioamnionitis.

    PubMed

    Kallapur, Suhas G; Presicce, Pietro; Rueda, Cesar M; Jobe, Alan H; Chougnet, Claire A

    2014-01-01

    Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, gastrointestinal tract, brain, and other fetal organs. Chorioamnionitis is a polymicrobial nontraditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection-related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis-induced injury in different fetal compartments. As chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Fetal immune response to chorioamnionitis

    PubMed Central

    Kallapur, Suhas G.; Presicce, Pietro; Rueda, Cesar M.; Jobe, Alan H.; Chougnet, Claire A.

    2014-01-01

    Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, GI tract, brain and other fetal organs. Chorioamnionitis is a polymicrobial non-traditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis induced injury in different fetal compartments. Since chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses. PMID:24390922

  19. [Immune response to influenza vaccination].

    PubMed

    Alvarez, I; Corral, J; Arranz, A; Foruria, A; Landa, V; Lejarza, J R; Marijuán, L; Martínez, J M

    1989-01-01

    The present study investigated the level of immunity of the population against three strains of the influenza virus (A Chile/1/83 -A Philippines/2/82 and B URSS/100/83) before and three months after vaccination, and the immune response to whole virus vaccine as compared with fragmented virus vaccine. A high percentage of the population had titers greater than or equal to 1/10 before vaccination for the Chile (54%) and Philippines (65.7%) strains, while titers against the URSS strain were lower (25.4%). There was a definitive increase in antibody titer in the vaccinated population, although it was lower than expected. The overall response to both vaccines, with protecting titers greater than or equal to 1/40 after vaccination was 65.2% for the Chile strain, 74.6% for the Philippines strain, and 15% for the URSS strain. No differences in the overall immune response were found between the groups vaccinated with whole and fragmented virus.

  20. Conditioning of the immune response.

    PubMed

    Ader, R; Cohen, N

    1991-10-01

    Experimental studies in humans and experimental animals document the acquisition and extinction of classically conditioned alterations of different parameters of humoral- and cell-mediated immune responses. Although the aversive effects of cyclophosphamide in a taste aversion learning paradigm has been the most frequently used model, conditioned immunomodulatory effects are not confined to this conditioning procedure, and they are not limited to cyclophosphamide or, for that matter, the use of immunomodulating drugs as unconditioned stimuli. Conditioned changes in immunologic reactivity have also been found to modulate the progression of spontaneously-developing or experimentally-induced pathophysiological processes in experimental animals. The available data on the immunoregulatory effects of conditioning indicate that the immune system, like other systems operating in the interests of homeostasis, is integrated with other physiological processes and is therefore influenced by and capable of influencing the brain.

  1. Immune responses to resistance exercise.

    PubMed

    Freidenreich, Daniel J; Volek, Jeff S

    2012-01-01

    Resistance exercise induces changes in leukocyte redistribution, phenotypical surface expression and leukocyte functionality. Several factors have been shown to alter the temporal pattern and/or magnitude of response including manipulation of acute program variables, the aging process, and nutritional supplementation. Rest period length and load can modify the temporal pattern and/or magnitude of leukocytosis post exercise. Aging diminishes both the duration and magnitude of the post exercise leukocytosis and reduces leukocyte functionality. The few studies that assessed the effects of nutritional supplements (e.g., carbohydrate, whey protein, caffeine) peri-resistance exercise showed minimal effects on leukocyte responses. Sex differences exist in the timing and magnitude of leukocyte infiltration into skeletal muscle. The immune response to resistance exercise is only a small part of the recovery paradigm. A better understanding of how acute program variables and other factors such as aging, sex and nutritional supplementation affect the immune response to resistance exercise is important in the context of improving recovery, performance and health.

  2. Eosinophils in mucosal immune responses

    PubMed Central

    Travers, J; Rothenberg, M E

    2015-01-01

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

  3. Immune responses to bioengineered organs

    PubMed Central

    Ochando, Jordi; Charron, Dominique; Baptista, Pedro M.; Uygun, Basak E.

    2017-01-01

    Purpose of review Organ donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation. Recent findings Development of bioengineered organs represents a promising approach to increase the pool of organs for transplantation. The technology involves obtaining complex three-dimensional scaffolds that support cellular activity and functional remodeling though tissue recellularization protocols using progenitor cells. This innovative approach integrates cross-thematic approaches from specific areas of transplant immunology, tissue engineering and stem cell biology, to potentially manufacture an unlimited source of donor organs for transplantation. Summary Although bioengineered organs are thought to escape immune recognition, the potential immune reactivity toward each of its components has not been studied in detail. Here, we summarize the host immune response toward different progenitor cells and discuss the potential implications of using nonself biological scaffolds to develop bioengineered organs. PMID:27926545

  4. EVOLUTION OF THE IMMUNE RESPONSE

    PubMed Central

    Papermaster, Ben W.; Condie, Richard M.; Finstad, Joanne; Good, Robert A.

    1964-01-01

    1. The California hagfish, Eptatretus stoutii, seems to be completely lacking in adaptive immunity: it forms no detectable circulating antibody despite intensive stimulation with a range of antigens; it does not show reactivity to old tuberculin following sensitization with BCG; and gives no evidence of homograft immunity. 2. Studies on the sea lamprey, Petromyzon marinus, have been limited to the response to bacteriophage T2 and hemocyanin in small groups of spawning animals. They suggest that the lamprey may have a low degree of immunologic reactivity. 3. One holostean, the bowfin (Amia calva) and the guitarfish (Rhinobatos productus), an elasmobranch, showed a low level of primary response to phage and hemocyanin. The response is slow and antibody levels low. Both the bowfin and the guitarfish showed a vigorous secondary response to phage, but neither showed much enhancement of reactivity to hemocyanin in the secondary response. The bowfin formed precipitating antibody to hemocyanin, but the guitarfish did not. Both hemagglutinating and precipitating antibody to hemocyanin were also observed in the primary response of the black bass. 4. The bowfin was successfully sensitized to Ascaris antigen, and lesions of the delayed type developed after challenge at varying intervals following sensitization. 5. The horned shark (Heterodontus franciscii) regularly cleared hemocyanin from the circulation after both primary and secondary antigenic stimulation, and regularly formed hemagglutinating antibody, but not precipitating antibody, after both primary and secondary stimulation with this antigen. These animals regularly cleared bacteriophage from the circulation after both the primary and secondary stimulation with bacteriophage T2. Significant but small amounts of antibody were produced in a few animals in the primary response, and larger amounts in the responding animals after secondary antigenic stimulation. 6. Studies by starch gel and immunoelectrophoresis show that

  5. Tilapia show immunization response against Ich

    USDA-ARS?s Scientific Manuscript database

    This study compares the immune response of Nile tilapia and red tilapia against parasite Ichthyophthirius multifiliis (Ich) using a cohabitation challenge model. Both Nile and red tilapia showed strong immune response post immunization with live Ich theronts by IP injection or immersion. Blood serum...

  6. A genetic inference on cancer immune responsiveness

    PubMed Central

    Wang, Ena; Uccellini, Lorenzo; Marincola, Francesco M.

    2012-01-01

    A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness. PMID:22754772

  7. Medium term ecohydrological response of peatland bryophytes to canopy disturbance

    NASA Astrophysics Data System (ADS)

    Leonard, Rhoswen; Kettridge, Nick; Krause, Stefan; Devito, Kevin; Granath, Gustaf; Petrone, Richard; Mandoza, Carl; Waddington, James Micheal

    2016-04-01

    Canopy disturbance in northern forested peatlands is widespread. Canopy changes impact the ecohydrological function of moss and peat, which provide the principal carbon store within these carbon rich ecosystems. Different mosses have contrasting contributions to carbon and water fluxes (e.g. Sphagnum fuscum and Pleurozium schreberi) and are strongly influenced by canopy cover. As a result, changes in canopy cover lead to long-term shifts in species composition and associated ecohydrological function. Despite this, the medium-term response to such disturbance, the associated lag in this transition to a new ecohydrological and biogeochemical regime, is not understood. Here we investigate this medium term ecohydrological response to canopy removal using a randomised plot design within a north Albertan peatland. We show no significant ecohydrological change in treatment plots four years after canopy removal. Notably, Pleurozium schreberi and Sphagnum fuscum remained within respective plots post treatment and there was no significant difference in plot resistance to evapotranspiration or carbon exchange. Our results show that canopy removal alone has little impact on bryophyte ecohydrology in the short/medium term. This resistance to disturbance contrasts strongly with dramatic short-term changes observed within mineral soils suggesting that concurrent shifts in the large scale hydrology induced within such disturbances are necessary to cause rapid ecohydrological transitions. Understanding this lagged response is critical to determine the decadal response of carbon and water fluxes in response to disturbance and the rate at which important medium term ecohydrological feedbacks are invoked.

  8. Soil respiration response to experimental disturbances over 3 years

    Treesearch

    Amy Concilio; Siyan Ma; Soung-Ryoul Ryu; Malcolm North; Jiquan Chen

    2006-01-01

    Soil respiration is a major pathway for carbon cycling in terrestrial ecosystems yet little is known about its response to natural and anthropogenic disturbances. This study examined soil respiration response to prescribed burning and thinning treatments in an old-growth, mixed-conifer forest on the western slope of the Sierra Nevada Mountains. Experimental treatments...

  9. Response of geese to aircraft disturbances

    USGS Publications Warehouse

    Ward, David; Stehn, Robert A.; Derksen, Dirk V.

    2000-01-01

    Low-flying aircraft can affect behavior, physiology, and distribution of wildlife (Manci et al., 1988), and over time, may impact a population by reducing survival and reproductive performance. Thus, it is important to identify the particular aspects of overflights that affect animals so that management strategies can be developed to minimize adverse effects.Waterfowl are particularly sensitive to low-flying aircraft (Manci et al., 1988) and respond at all stages of their annual cycle, including breeding (Gollop et al., 1974a; Laing, 1991), molting (Derksen et al., 1979; Mosbech and Glahder, 1991), migration (Jones and Jones, 1966; Belanger and Bedard, 1989), and wintering (Owens, 1977; Kramer et al., 1979; Henry, 1980). Waterfowl response can be quite variable both within and among species (Fleming et al., 1996). For example, response can vary with age, sex, and body condition of individual, habitat type and quality, and previous exposure to aircraft (Dahlgren and Korshgen, 1992). However, the most important factors influencing a response are aircraft type (Davis and Wiseley, 1974; Jensen, 1990), noise (Mosbech and Glahder, 1991; Temple, 1993), and proximity to the birds, as measured in altitude and lateral distance (Derksen et al., 1979; Belanger and Bedard, 1989; Ward et al., 1994). Wildlife managers can reduce impacts on a population by controlling or modifying these factors.In an experimental study conducted at Izembek Lagoon in southwestern Alaska in 1985-1988 (Ward and Stehn, 1989), we conducted planned aircraft overflights with control of aircraft type, noise, altitude, and lateral distance to flocks (hereafter called lateral distance) to measure behavioral response of fall-staging Pacific brant (Branta bernicla nigricans) and Canada geese (B. canadensis taverneri) to fixed- and rotary-wing aircraft. These data were then used to develop predictive models of the relationship between aircraft type, noise, altitude, and lateral distance and the response of

  10. Immune responses and vaccination against periodontal infections.

    PubMed

    Persson, G Rutger

    2005-01-01

    The infectious aetiology of periodontitis is complex and no curative treatment modality exists. Palliative therapy is available. To review the evidence that active or passive immunization against periodontitis provides immune protection. PubMed (Medline), the National Institutes of Health, the Food and Drug Administration, and the Center for Disease Control electronic databases were searched to extrapolate information on immune responses to immunization against periodontitis. Studies in non-human primate models using ligature-induced experimental periodontitis suggest that antibody responses by active immunization against Porphyromonas gingivalis can safely be induced, enhanced, and obtained over time. Immune responses to whole bacterial cell and purified protein preparations considered as vaccine candidates have been evaluated in different animal models demonstrating that there are several valid vaccine candidates. Data suggest that immunization reduces the rate and severity of bone loss. It is also, temporarily, possible to alter the composition of the subgingival microflora. Natural active immunization by therapeutic interventions results in antibody titre enhancement and potentially improves treatment outcomes. Passive immunization of humans using P. gingivalis monoclonal antibodies temporarily prevents colonization of P. gingivalis. Probiotic therapy may be an alternative approach. Regulatory and safety issues for human periodontal vaccine trials must be considered. Shared infectious aetiology between periodontitis and systemic diseases may enhance vaccine effort developments. Proof of principle that active and passive immunization can induce protective antibody responses is given. The impact of natural immunization and passive immunization in humans should be explored and may, presently, be more feasible than active immunization studies.

  11. The immune response to surgery and infection

    PubMed Central

    Słotwiński, Robert

    2014-01-01

    Surgical trauma affects both the innate and acquired immunity. The severity of immune disorders is proportional to the extent of surgical trauma and depends on a number of factors, including primarily the basic disease requiring surgical treatment (e.g. cancer), often coexisting infections and impaired nutritional status. Disorder of the immune response following surgical trauma may predispose to septic complications burdened with the highest mortality rate. Extensive surgery in cancer patients is associated with simultaneous activation of pro- and anti-inflammatory processes defined as SIRS (systemic inflammatory immune response) and CARS (compensatory anti-inflammatory immune response). However, it is generally believed that major surgical trauma is accompanied by sustained postoperative immunosuppression, which is particularly important in patients operated on for cancer, since the suppression of the immune system promotes not only septic complications, but also proliferation and tumor metastasis. This paper reviews the main features of immune response to surgical trauma and possibilities of its regulation. PMID:26155175

  12. Lichen Persistence and Recovery in Response to Varied Volcanic Disturbances

    NASA Astrophysics Data System (ADS)

    Nelson, P.; Wheeler, T. B.

    2015-12-01

    Volcanic eruptions produce many ecological disturbances that structure vegetation. While lichens are sensitive to disturbances, little is known about their responses to volcanic disturbances, except for colonization of lava. We examined lichen community responses through time to different disturbances produced by the May 1, 2008 eruption of Volcan Chaiten in south-central Chile. Pre-eruption vegetation near the volcano was old-growth Valdivian temperate rainforest dominated by closed-canopy Nothofagus sp... In 2012, we installed thirteen 1-acre plots across volcanic disturbance zones on which a time-constrained search was done for all macrolichen species, each of which was assigned an approximate log10 categorical abundance. We also installed a 0.2 m2 quadrat on two representative trees per plot for repeat photography of lichen cover. We remeasured at least one plot per disturbance zone in 2014 and re-photographed tree quadrats in 2013 and 2014. We then analyzed species composition and abundance differences among disturbance zones. In 2012, the blast (pyroclastic density flow), scorch (standing scorched forest at the edge of the blast) and deep tephra (>10 cm) zones had the lowest lichen species richness (5-13 species), followed by reference (unimpacted) and shallow (<10 cm) tephra (17-20 species). Gravel rain (preexisting rock ejected by eruption initiation), gravel rain + pumice and flooded forests (fluvially reworked volcanic material entrained by heavy rains) were species-rich (25-42 species). In 2014, the blast and deep tephra had regained 2-3 times the number of lichen species since 2012 while the light tephra and reference were essentially unchanged. Gravel rain, gravel rain + pumice and flooded forest plots all had about the same number of species in 2014 as 2012. Lichen colonization and growth in tree quadrats varied widely, from very little colonization in the blast to prolific colonization in the gravel rain + pumice zone. Lichen's varied responses to

  13. Frequency response of slot coating flow to gap disturbances

    NASA Astrophysics Data System (ADS)

    Lee, Semi; Nam, Jaewook

    2016-03-01

    Slot coating is a common method of manufacturing films such as optical films, adhesive tapes, etc. It is a pre-metered method: the final wet film thickness is set by the flow rate and the web speed, and independent of other operating parameters and coating liquid properties. Therefore, it is ideal for precise film thickness control. To produce uniform film, the coating flow needs to be steady-state, two-dimensional, and stable. In the slot coating process, however, there are always some small-scale disturbances generated by rotating process units, such as pumps, rolls, etc., and they usually have periodicity. These disturbances cause a non-uniformity of the moving web direction and could spoil the film quality. Therefore, the sensitivity analysis of coating flow under the periodic disturbances is important. Among all disturbances, a change of coating gap, i.e. the distance between the die lip and the moving substrate, is known to the most dangerous disturbance. This type of disturbance is usually called the gap oscillation, and caused by the substrate thickness variations, mechanical vibration of the coating die or roll, and roll run outs. Here, we analyze the effect of fluid properties, operating conditions and die configurations on response of slot coating flow to gap disturbances. In this study, we use Galerkin/finite element method to solve transient Navier-Stokes equation under periodic disturbance. We define the amplification factor as an indicator of film non-uniformity and analyze the effect of different parameters by comparing the factor. In particular, we use Carreau-Yasuda model to describe shear-thinning property of xanthan gum solution and compare with Newtonian fluid.

  14. Spaceflight and immune responses of Rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies indicates that alterations in immunological parameters occur after space flight. The objective of this project is to determine the effects of space flight on immune responses of Rhesus monkeys. The expected significance of the work is a determination of the range of immunological functions of the Rhesus monkey, a primate similar in many ways to man, affected by space flight. Changes in immune responses that could yield alterations in resistance to infection may be determined as well as the duration of alterations in immune responses. Additional information on the nature of cellular interactions for the generation of immune responses may also be obtained.

  15. Short-term response of estuarine sandflat trophodynamics to pulse anthropogenic physical disturbance: Support for the Intermediate Disturbance Hypothesis

    NASA Astrophysics Data System (ADS)

    Lee, Ka-Man; Lee, S. Y.; Connolly, Rod M.

    2011-05-01

    Many anthropogenic activities physically disturb urbanised coastal habitats. The functional response of ecosystems to physical disturbances remains largely unknown due to the lack of suitable quantitative tools for assessing impacts. We conducted a manipulative field experiment to investigate the short-term (i.e. temporally sensitive) response of estuarine sandflat trophodynamics to pulse anthropogenic physical disturbance, using combined chemical tracer ( 13C), compartmental modelling and network analysis techniques. Pulse physical disturbance, as sediment pumping for an infaunal bait species, was applied at two disturbance intensities at the commencement of the experiment, in 0.09 m 2 quadrats. Six compartments and three trophic levels in the estuarine sandflat food web were sampled, including the microphytobenthos, four meiofaunal groups, and soldier crabs ( Mictyris longicarpus). Compared with undisturbed controls, in the low disturbance intensity treatment: 1) carbon flow rates between compartments increased, 2) carbon cycling increased, 3) more carbon was retained in the food web, and 4) system indices reflecting ecosystem functioning and resilience were higher. Low disturbance intensity facilitated carbon transfer between organisms and apparently increased resilience. Conversely, high disturbance intensity reduced carbon flow among compartments and carbon cycling, thus lowering resilience. This is the first study with field data quantifying structural and functional changes of sandflat food webs in response to physical disturbance and showed that both ecosystem structure and processes may support the Intermediate Disturbance Hypothesis. This alternative approach to assessing the immediate functional response of estuarine trophic interactions to physical disturbances allows impact detection not possible using conventional approaches.

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

    PubMed

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

    2015-06-23

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

  17. Noninvasive imaging of immune responses

    PubMed Central

    Rashidian, Mohammad; Keliher, Edmund J.; Bilate, Angelina M.; Duarte, Joao N.; Wojtkiewicz, Gregory R.; Jacobsen, Johanne Tracey; Cragnolini, Juanjo; Swee, Lee Kim; Victora, Gabriel D.; Weissleder, Ralph; Ploegh, Hidde L.

    2015-01-01

    At their margins, tumors often contain neutrophils, dendritic cells, and activated macrophages, which express class II MHC and CD11b products. The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. We developed alpaca-derived antibody fragments specific for mouse class II MHC and CD11b products, expressed on the surface of a variety of myeloid cells. We validated these reagents by flow cytometry and two-photon microscopy to obtain images at cellular resolution. To enable noninvasive imaging of the targeted cell populations, we developed a method to site-specifically label VHHs [the variable domain (VH) of a camelid heavy-chain only antibody] with 18F or 64Cu. Radiolabeled VHHs rapidly cleared the circulation (t1/2 ≈ 20 min) and clearly visualized lymphoid organs. We used VHHs to explore the possibility of imaging inflammation in both xenogeneic and syngeneic tumor models, which resulted in detection of tumors with remarkable specificity. We also imaged the infiltration of myeloid cells upon injection of complete Freund’s adjuvant. Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity. Given the ease of manufacture and labeling of VHHs, we believe that this method could transform the manner in which antitumor responses and/or infectious events may be tracked. PMID:25902531

  18. Brainstem Auditory Evoked Response in Children with Central Language Disturbance.

    ERIC Educational Resources Information Center

    Piggott, Leonard R.; Anderson, Theodora

    1983-01-01

    Two groups of 10 children between the ages of 94 and 165 months were paired for age (wthin 6 months) and sex and were compared for Brainstem Auditory Evoked Response patterns. One child in each pair showed evidence of central language disturbance as determined by neuropsychological testing. The other did not. All had normal hearing and IQs of 80…

  19. Hypothalamic neurohormones and immune responses

    PubMed Central

    Quintanar, J. Luis; Guzmán-Soto, Irene

    2013-01-01

    The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH). In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed. PMID:23964208

  20. Hypothalamic neurohormones and immune responses.

    PubMed

    Quintanar, J Luis; Guzmán-Soto, Irene

    2013-01-01

    The aim of this review is to provide a comprehensive examination of the current literature describing the neural-immune interactions, with emphasis on the most recent findings of the effects of neurohormones on immune system. Particularly, the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH), Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH). In the past few years, interest has been raised in extrapituitary actions of these neurohormones due to their receptors have been found in many non-pituitary tissues. Also, the receptors are present in immune cells, suggesting an autocrine or paracrine role within the immune system. In general, these neurohormones have been reported to exert immunomodulatory effects on cell proliferation, immune mediators release and cell function. The implications of these findings in understanding the network of hypothalamic neuropeptides and immune system are discussed.

  1. Cellular immunity in ASFV responses.

    PubMed

    Takamatsu, Haru-Hisa; Denyer, Michael S; Lacasta, Anna; Stirling, Catrina M A; Argilaguet, Jordi M; Netherton, Christopher L; Oura, Chris A L; Martins, Carlos; Rodríguez, Fernando

    2013-04-01

    African swine fever virus (ASFV) infection usually results in an acute haemorrhagic disease with a mortality rate approaching 100% in domestic pigs. However, pigs can survive infection with less-virulent isolates of ASFV and may become chronically infected. Surviving animals are resistant to challenge with homologous or, in some cases, closely related isolates of the virus indicating that pigs can develop protective immunity against ASFV. During asymptomatic, non-virulent ASFV infections natural killer cell activity increases in pigs, suggesting this cell type plays a role in ASFV immunity. Furthermore, depletion of CD8(+) lymphocytes from ASFV immune pigs demolishes protective immunity against related virulent viruses. This suggests that ASFV specific antibody alone is not sufficient for protection against ASFV infection and that there is an important role for the CD8(+) lymphocyte subset in ASFV protective immunity. These results were supported by DNA immunization studies, demonstrating a correlation between the protection afforded against lethal challenge and the detection of a large number of vaccine-induced antigen-specific CD8(+) T-cells. Peripheral blood mononuclear cells (PBMCs) from ASF immune pigs protected from clinical disease show higher proportions of ASFV specific CD4(+)CD8(high+) double positive cytotoxic T cells than PBMCs from ASF immune but clinically diseased pig. The frequency of ASFV specific IFNγ producing T cells induced by immunization correlates to the degree of protection from ASFV challenge, and this may prove to be a useful indicator of any potential cross-protection against heterologous ASFV isolates.

  2. Hyperferritinaemia in Dengue Virus Infected Patients Is Associated with Immune Activation and Coagulation Disturbances

    PubMed Central

    Pannuti, Cláudio S.; Brouns, Rosalba M.; van den Berg, Riemsdijk W. A.; van den Ham, Henk-Jan; Martina, Byron E. E.; Osterhaus, Albert D. M. E.; Netea, Mihai G.; Meijers, Joost C. M.; van Gorp, Eric C. M.; Kallas, Esper G.

    2014-01-01

    Background During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Methodology/Principal Findings Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile. Conclusions/Significance Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully. PMID:25299654

  3. The Immune Response to Astrovirus Infection

    PubMed Central

    Marvin, Shauna A.

    2016-01-01

    Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of astrovirus infection and pathogenesis, little is known about the immune response to astrovirus infection. Studies from humans and animals suggest that adaptive immunity is important in restricting classic and novel astrovirus infections, while studies from animal models and cell culture systems suggest that an innate immune system plays a role in limiting astrovirus replication. The relative contribution of each arm of the immune system in restricting astrovirus infection remains unknown. This review summarizes our current understanding of the immune response to astrovirus infection and highlights some of the key questions that stem from these studies. A full understanding of the immune response to astrovirus infection is required to be able to treat and control astrovirus-induced gastroenteritis. PMID:28042824

  4. Cytokines and the immune response.

    PubMed

    Van der Meide, P H; Schellekens, H

    1996-01-01

    Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. These effector molecules are produced transiently and locally controlling the amplitude and duration of the response. A variety of experiments has shown that excessive or insufficient production may significantly contribute to the pathophysiology of a range of diseases. Particularly cytokines released by CD4+ T cells at the onset of an immune response are thought to be decisive for pathological or physiological consequences. The meeting in Budapest was focussed on cytokines known to contribute to the pathophysiology of autoimmune diseases, infectious diseases and allograft rejection (e.g., IL-1, IL-4, IL-6, IL-10, IL-12, TNF-alpha and IFN-alpha, -beta, -gamma). A central role for IFN-gamma in autoimmunity was suggested by blocking experiments in vivo using monoclonal antibodies and soluble forms of the IFN-gamma receptor (IFN-gamma SR). These agents ameliorated disease development in a variety of experimental autoimmune diseases in rodents. In a mouse model for the human disease Myasthenia gravis, IFN-alpha was found to reduce both the incidence and progression of the disease. Treatment of R. aurantiacus-infected mice with anti-IL-4 monoclonal antibodies (mAbs) was reported to interfere with the regression of granulomas in spleen and liver, most likely through inadequate IL-4-mediated suppression of IFN-gamma production. In addition, it was shown that mice with disrupted IFN-gamma R genes died rapidly after infection with the BCG strain of M. bovis, whereas normal mice survived the infection. IL-12 was found to be the main inductor of IFN-gamma during the lethal Shwartzman reaction. TNF-alpha was identified as the principal cause of mortality after the second injection with LPS. In a variety of studies examining the role of cytokines in the pathogenesis of AIDS, much attention was given to the in vitro effects of HIV-1 and/or the HIV-1 viral membrane

  5. Idiosyncratic responses of Amazonian birds to primary forest disturbance.

    PubMed

    Moura, Nárgila G; Lees, Alexander C; Aleixo, Alexandre; Barlow, Jos; Berenguer, Erika; Ferreira, Joice; Mac Nally, Ralph; Thomson, James R; Gardner, Toby A

    2016-03-01

    As humans continue to alter tropical landscapes across the world, it is important to understand what environmental factors help determine the persistence of biodiversity in modified ecosystems. Studies on well-known taxonomic groups can offer critical insights as to the fate of biodiversity in these modified systems. Here we investigated species-specific responses of 44 forest-associated bird species with different behavioural traits to forest disturbance in 171 transects distributed across 31 landscapes in two regions of the eastern Brazilian Amazon. We investigated patterns of species occurrence in primary forests varyingly disturbed by selective-logging and fire and examined the relative importance of local, landscape and historical environmental variables in determining species occurrences. Within undisturbed and disturbed primary forest transects, we found that distance to forest edge and the biomass of large trees were the most important predictors driving the occurrence of individual species. However, we also found considerable variation in species responses to different environmental variables as well as inter-regional variation in the responses of the same species to the same environmental variables. We advocate the utility of using species-level analyses to complement community-wide responses in order to uncover highly variable and species-specific responses to environmental change that remain so poorly understood.

  6. Lambs prevented from suckling their mothers display behavioral, immune and endocrine disturbances.

    PubMed

    Napolitano, Fabio; Annicchiarico, Giovanni; Caroprese, Mariangela; De Rosa, Giuseppe; Taibi, Luigi; Sevi, Agostino

    2003-01-01

    The aim of the experiment was to assess the effects of either maternal deprivation or prevented suckling on lambs. Thirty Comisana lambs were assigned to a control dam-suckled group (DS) and two test groups of 10 each. Test lambs were maintained with their mothers 24 to 30 h after parturition and subsequently offered ewe milk from buckets: EM lambs were separated from their mothers, while EM+D animals were reared with their dams but suckling was denied by covering ewe udders with juta bags. Behavioral, immune and cortisol responses of lambs were assessed throughout the experiment. EM+D lambs spent less time (P<.001) on investigative behavior compared to the two other groups. When isolated in a novel environment, EM+D lambs exhibited a shorter duration of movement (P<.01) and a longer latency time compared to DS and EM lambs (P<.001 and P<.05, respectively) as well as a higher number of bleats (P<.01) than EM lambs. EM+D lambs also displayed higher (P<.001) plasma cortisol levels than the other two groups when isolated at 4 days of age. When subjected to discrimination tests, EM+D lambs spent less time near their companions (P<.01) than EM lambs and took a longer time to reach their pen mates (P<.01) than DS and EM lambs. EM+D lambs displayed reduced growth (P<.001) compared to DS animals during the 0-7 and 8-14-day periods. We conclude that frustration arising from maternal feeding deprivation results in altered endocrine and behavioral responses and reduced growth suggesting emotional disturbances of lambs.

  7. Protective host immune responses to Salmonella infection.

    PubMed

    Pham, Oanh H; McSorley, Stephen J

    2015-01-01

    Salmonella enterica serovars Typhi and Paratyphi are the causative agents of human typhoid fever. Current typhoid vaccines are ineffective and are not widely used in endemic areas. Greater understanding of host-pathogen interactions during Salmonella infection should facilitate the development of improved vaccines to combat typhoid and nontyphoidal Salmonellosis. This review will focus on our current understanding of Salmonella pathogenesis and the major host immune components that participate in immunity to Salmonella infection. In addition, recent findings regarding host immune mechanisms in response to Salmonella infection will be also discussed, providing a new perspective on the utility of improved tools to study the immune response to Salmonella infections.

  8. Protective host immune responses to Salmonella infection

    PubMed Central

    Pham, Oanh H; McSorley, Stephen J.

    2015-01-01

    Salmonella enterica serovars Typhi and Paratyphi are the causative agents of human typhoid fever. Current typhoid vaccines are ineffective and are not widely used in endemic areas. Greater understanding of host–pathogen interactions during Salmonella infection should facilitate the development of improved vaccines to combat typhoid and nontyphoidal Salmonellosis. This review will focus on our current understanding of Salmonella pathogenesis and the major host immune components that participate in immunity to Salmonella infection. In addition, recent findings regarding host immune mechanisms in response to Salmonella infection will be also discussed, providing a new perspective on the utility of improved tools to study the immune response to Salmonella infections. PMID:25598340

  9. Human Immune Responses to Dengue Viruses.

    DTIC Science & Technology

    1983-09-01

    A-Al?l 362 HUMAN IMMUNE RESPONSES TO DENGUE YXRUSES(U) MASSACHUSETTS UNIV MEDICAL SCHOOL NORCESTER F A ENNIS SE 83" I ?-2C23 UNCLASSI FIED SE 3IRD?8...SHEET PREVIOUS EDITION MAY BE USED UNTILDTIC FORM 70A OUMNPRESIGSETSTOCK IS EXHAUSTED.DEC 83 AD IHuman Immune Responses to Dengue Viruses Annual Report...edilon may be ued Y01dxffnUICFMCASIAZIlow f~ rolit SUMMARY The purpose of this contract is to analyse the immune responses to dengue virus infections

  10. Human Immune Response to Dengue Infections.

    DTIC Science & Technology

    1987-07-30

    W5l "I± H"MN IMMUNE RESPONSE TO DENGUE INFECTIONS(U) i/il MASSACHUSETTS UNIV MEDICAL CENTER NORCESTER MR1 F R ENIS 36 JUL 87 DAMD7-86-C-6200...1 U . AD HUMAN IMMUNE RESPONSE TO DENGUE INFECTIONS ANNUAL REPORT In 00 FRANCIS A. ENNIS JULY 30, 1987 Supported by U.S. ARMY MEDICAL RESEARCH...Human Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Ennis, Francis A. 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year

  11. [Correlation between chemical carcinogenesis and immune response].

    PubMed

    Brai, M; Bonasera, L; Tolone, G

    1975-01-01

    Methylcholanthrene, in amount sufficient to induce tumors in 100% of treated animals failed to influence primary and secondary phases of antibody synthesis in mice immunized with sheep erythrocytes and human serum albumin. The early immune response in tumor bearing mice was also indistinguischable from that of normal animals, despite the presence of marked splenomegaly in the former group.

  12. Innate immune responses to Pseudomonas aeruginosa infection

    PubMed Central

    Lavoie, Elise G.; Wangdi, Tamding; Kazmierczak, Barbara I.

    2011-01-01

    Innate immune responses play a critical role in controlling acute infections due to Pseudomonas aeruginosa in both mice and in humans. In this review we focus on innate immune recognition and clearance mechanisms that are important for controlling P. aeruginosa in the mammalian lung, with particular attention to those that influence the outcome of in vivo infection in murine models. PMID:21839853

  13. Epigenetics and the Adaptive Immune Response

    PubMed Central

    Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.

    2012-01-01

    Cells of the adaptive immune response undergo dynamic epigenetic changes as they develop and respond to immune challenge. Plasticity is a necessary prerequisite for the chromosomal dynamics of lineage specification, development, and the immune effector function of the mature cell types. The alterations in DNA methylation and histone modification that characterize activation may be integral to the generation of immunologic memory, thereby providing an advantage on secondary exposure to pathogens. While the immune system benefits from the dynamic nature of the epigenome, such benefit comes at a cost – increased likelihood of disease-causing mutation. PMID:22789989

  14. Single-walled carbon nanotubes disturbed the immune and metabolic regulation function 13-weeks after a single intratracheal instillation.

    PubMed

    Park, Eun-Jung; Hong, Young-Shick; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

    2016-07-01

    Due to their unique physicochemical properties, the potential health effects of single-walled carbon nanotubes (SWCNTs) have attracted continuous attention together with their extensive application. In this study, we aimed to identify local and systemic health effects following pulmonary persistence of SWCNTs. As expected, SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation (50, 100, and 200μg/kg). In the lung, the total number of cells and the percentages of lymphocytes and neutrophils significantly increased at 200μg/kg compared to the control, and the Th1-polarized immune response was induced accompanying enhanced expression of tissue damage-related genes and increased release of chemokines. Additionally, SWCNTs enhanced the expression of antigen presentation-related proteins on the surface of antigen-presenting cells, however, maturation of dendritic cells was inhibited by their persistence. As compared to the control, a significant increase in the percentage of neutrophils and a remarkable decrease of BUN and potassium level were observed in the blood of mice treated with the highest dose. This was accompanied by the down-regulation of the expression of antigen presentation-related proteins on splenocytes. Moreover, protein and glucose metabolism were disturbed with an up-regulation of fatty acid β-oxidation. Taken together, we conclude that SWCNTs may induce adverse health effects by disturbing immune and metabolic regulation functions in the body. Therefore, careful application of SWCNTs is necessary for the enforcement of safety in nano-industries.

  15. Functional response of ungulate browsers in disturbed eastern hemlock forests

    USGS Publications Warehouse

    Destefano, Stephen

    2015-01-01

    Ungulate browsing in predator depleted North American landscapes is believed to be causing widespread tree recruitment failures. However, canopy disturbances and variations in ungulate densities are sources of heterogeneity that can buffer ecosystems against herbivory. Relatively little is known about the functional response (the rate of consumption in relation to food availability) of ungulates in eastern temperate forests, and therefore how “top down” control of vegetation may vary with disturbance type, intensity, and timing. This knowledge gap is relevant in the Northeastern United States today with the recent arrival of hemlock woolly adelgid (HWA; Adelges tsugae) that is killing eastern hemlocks (Tsuga canadensis) and initiating salvage logging as a management response. We used an existing experiment in central New England begun in 2005, which simulated severe adelgid infestation and intensive logging of intact hemlock forest, to examine the functional response of combined moose (Alces americanus) and white-tailed deer (Odocoileus virginianus) foraging in two different time periods after disturbance (3 and 7 years). We predicted that browsing impacts would be linear or accelerating (Type I or Type III response) in year 3 when regenerating stem densities were relatively low and decelerating (Type II response) in year 7 when stem densities increased. We sampled and compared woody regeneration and browsing among logged and simulated insect attack treatments and two intact controls (hemlock and hardwood forest) in 2008 and again in 2012. We then used AIC model selection to compare the three major functional response models (Types I, II, and III) of ungulate browsing in relation to forage density. We also examined relative use of the different stand types by comparing pellet group density and remote camera images. In 2008, total and proportional browse consumption increased with stem density, and peaked in logged plots, revealing a Type I response. In 2012

  16. Cellular immune response in intraventricular experimental neurocysticercosis.

    PubMed

    Moura, Vania B L; Lima, Sarah B; Matos-Silva, Hidelberto; Vinaud, Marina C; Loyola, Patricia R A N; Lino, Ruy S

    2016-03-01

    Neurocysticercosis (NCC) is considered a neglected parasitic infection of the human central nervous system. Its pathogenesis is due to the host immune response, stage of evolution and location of the parasite. The aim of this study was to evaluate the in situ and systemic immune response through cytokines dosage (IL-4, IL-10, IL-17 and IFN-γ) as well as the local inflammatory response of the experimental NCC with Taenia crassiceps. The in situ and systemic cellular and inflammatory immune response were evaluated through the cytokines quantification at 7, 30, 60 and 90 days after inoculation and histopathological analysis. All cysticerci were found within the cerebral ventricles. There was a discrete intensity of inflammatory cells of mixed immune profile, polymorphonuclear and mononuclear cells, at the beginning of the infection and predominance of mononuclear cells at the end. The systemic immune response showed a significant increase in all the analysed cytokines and predominance of the Th2 immune profile cytokines at the end of the infection. These results indicate that the location of the cysticerci may lead to ventriculomegaly. The acute phase of the infection showed a mixed Th1/Th17 profile accompanied by high levels of IL-10 while the late phase showed a Th2 immune profile.

  17. Adaptive immune responses to Acanthamoeba cysts.

    PubMed

    McClellan, Kathy; Howard, Kevin; Mayhew, Elizabeth; Niederkorn, Jerry; Alizadeh, Hassan

    2002-09-01

    Acanthamoeba cysts are not eliminated from the corneas of human subjects or experimentally infected animals. The persistence of Acanthamoeba cysts in the cornea indicates that either the cysts escape immunological elimination or are not recognized by the host's immunological elements. The aim of this study was to determine the immunogenicity and antigenicity of the Acanthamoeba cyst. Mice were immunized intraperitoneally and serum anti-Acanthamoeba IgG was measured by ELISA. Lymphoproliferative assay and delayed type hypersensitivity (DTH) responses to Acanthamoeba castellanii cyst and trophozoite antigens were used to determine the cell mediated immune responses against Acanthamoeba cysts. A. castellanii cysts were both immunogenic and antigenic, producing anti-Acanthamoeba serum IgG, T lymphocyte proliferation, and delayed type hypersensitivity responses. These results indicate that Acanthamoeba cysts are recognized by the immune system. The persistence of the organism in the human cornea means that these adaptive immune responses fail to kill Acanthamoeba cysts.

  18. Immune Response in Hepatitis B Virus Infection

    PubMed Central

    Tan, Anthony; Koh, Sarene; Bertoletti, Antonio

    2015-01-01

    Hepatitis B virus (HBV) can replicate within hepatocytes without causing direct cell damage. The host immune response is, therefore, not only essential to control the spread of virus infection, but it is also responsible for the inflammatory events causing liver pathologies. In this review, we discuss how HBV deals with host immunity and how we can harness it to achieve virus control and suppress liver damage. PMID:26134480

  19. Cellular immune response experiment MA-031

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.

    1976-01-01

    Significant changes in phytohemagglutinin (PHA) lymphocytic responsiveness occurred in the cellular immune response of three astronauts during the 9 day flight of the Apollo Soyuz Test Project. Parameters studied were white blood cell concentrations, lymphocyte numbers, B- and T-lymphocyte distributions in peripheral blood, and lymphocyte responsiveness to PHA, pokeweed mitogen, Concanavalin A, and influenza virus antigen.

  20. Natural immunity has significant impact on immune responses against cancer.

    PubMed

    Rubin, B

    2009-03-01

    The immune system defends the host against pathogenic attacks by micro-organisms and their products. It does not react against self-components due to the relatively efficient negative selection of developing T lymphocytes in the thymus. This process does permit T cells with low avidity against self to be present in the T cell repertoire. Such cells play an important physiological role as the host needs so-called autoimmune reactions in order to eliminate dying cells or transformed tumour cells. One of the mysteries in immunology is how the host maintains beneficial autoimmune reactions and avoids pathogenic autoimmune reactions. Activation of the adaptive T lymphocytes is mediated by the low avidity interaction between T-cell antigen receptors and antigenic peptides associated with major histocompatibility complex class I or class II molecules. This interaction is strengthened by T-cell co-receptors such as CD2, CD4, CD8, CD28 and CD154, which react with ligands expressed by cells of the innate immune system. In recent years, the importance of pre-activation of the innate immune system for initiation of adaptive T-cell immune responses has been appreciated. In the present review, I will summarize our work on how natural immunity plays an important role in determining the level of beneficial autoimmune reactions against cancer.

  1. Immune response to lipoproteins in atherosclerosis.

    PubMed

    Samson, Sonia; Mundkur, Lakshmi; Kakkar, Vijay V

    2012-01-01

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

  2. Initiation of adaptive immune responses by transcutaneous immunization.

    PubMed

    Warger, Tobias; Schild, Hansjörg; Rechtsteiner, Gerd

    2007-03-15

    The development of new, effective, easy-to-use and lower-cost vaccination approaches for the combat against malignant and infectious diseases is a pre-eminent need: cancer is a leading cause of morbidity in the Western World; there are numerous pathogenic diseases for which we still have no protective or therapeutic cure; and the financial limitations of developing countries to fight these diseases. In this mini-review we focus on transcutaneous immunization (TCI), a relatively new route for antigen delivery. TCI protocols appear to be particularly promising by gaining access to skin resident APC, which are highly efficient for the initiation of humoral and/or cellular immune responses. Consisting of an adjuvant as a stimulus in combination with an antigen which defines the target, TCI offers a most attractive immunization strategy to mount highly specific full-blown adaptive immune responses. As a topically applicable cell-free adjuvant/antigen mixture, TCI might be suitable to improve patient compliance, as well as feasible economically for the use in Third World countries. In addition, this non-invasive procedure might increase the safety of vaccinations by eliminating the risk of infections related to the recycling and improper disposal of needles. The dissection of antigen and adjuvant is important because it allows "free" combinations in contrast to classical immunizations which are based on application of the pathogen of interest. The most relevant ways and means to find new, effective pathogenic target antigens are "reverse vaccinology" and the direct peptide-epitope identification from MHC molecules with mass-spectrometry. Due to these efficient approaches the variety of antigenic epitopes for potential protective/therapeutic use is perpetually expanding. The most studied adjuvants in TCI approaches are cholera toxin (CT) and its less toxic relative, the heat-labile enterotoxin (LT). Both CT and LT can serve as antigen as well. In contrast to these large

  3. Humoral immune response to the antigen administered as an immune complex.

    PubMed

    Marusić, M; Marusić-Galesić, S; Pokrić, B

    1992-12-01

    Antigen (HSA) bound in immune complexes at equivalence with syngeneic anti-HSA antibodies elicit much stronger humoral immune response then soluble HSA. On the other hand, administration of immune complexes formed with xenogeneic (rabbit) anti-HSA antibodies suppressed humoral immune response against HSA, but not against rabbit IgG in mice. We suggest that immunization with antigen bound in immune complex might represent a powerful tool in enhancing humoral immune responses.

  4. Modulating immune responses with probiotic bacteria.

    PubMed

    Matsuzaki, T; Chin, J

    2000-02-01

    For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria.

  5. Immune response to biologic scaffold materials.

    PubMed

    Badylak, Stephen F; Gilbert, Thomas W

    2008-04-01

    Biologic scaffold materials composed of mammalian extracellular matrix are commonly used in regenerative medicine and in surgical procedures for the reconstruction of numerous tissue and organs. These biologic materials are typically allogeneic or xenogeneic in origin and are derived from tissues such as small intestine, urinary bladder, dermis, and pericardium. The innate and acquired host immune response to these biologic materials and the effect of the immune response upon downstream remodeling events has been largely unexplored. Variables that affect the host response include manufacturing processes, the rate of scaffold degradation, and the presence of cross species antigens. This manuscript provides an overview of studies that have evaluated the immune response to biologic scaffold materials and variables that affect this response.

  6. Coastal Bacterioplankton Community Dynamics in Response to a Natural Disturbance

    PubMed Central

    Rappé, Michael S.

    2013-01-01

    In order to characterize how disturbances to microbial communities are propagated over temporal and spatial scales in aquatic environments, the dynamics of bacterial assemblages throughout a subtropical coastal embayment were investigated via SSU rRNA gene analyses over an 8-month period, which encompassed a large storm event. During non-perturbed conditions, sampling sites clustered into three groups based on their microbial community composition: an offshore oceanic group, a freshwater group, and a distinct and persistent coastal group. Significant differences in measured environmental parameters or in the bacterial community due to the storm event were found only within the coastal cluster of sampling sites, and only at 5 of 12 locations; three of these sites showed a significant response in both environmental and bacterial community characteristics. These responses were most pronounced at sites close to the shoreline. During the storm event, otherwise common bacterioplankton community members such as marine Synechococcus sp. and members of the SAR11 clade of Alphaproteobacteria decreased in relative abundance in the affected coastal zone, whereas several lineages of Gammaproteobacteria, Betaproteobacteria, and members of the Roseobacter clade of Alphaproteobacteria increased. The complex spatial patterns in both environmental conditions and microbial community structure related to freshwater runoff and wind convection during the perturbation event leads us to conclude that spatial heterogeneity was an important factor influencing both the dynamics and the resistance of the bacterioplankton communities to disturbances throughout this complex subtropical coastal system. This heterogeneity may play a role in facilitating a rapid rebound of regions harboring distinctly coastal bacterioplankton communities to their pre-disturbed taxonomic composition. PMID:23409156

  7. Effect of cellular mobility on immune response

    NASA Astrophysics Data System (ADS)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  8. Immune responses and Lassa virus infection.

    PubMed

    Russier, Marion; Pannetier, Delphine; Baize, Sylvain

    2012-11-05

    Lassa fever is a hemorrhagic fever endemic to West Africa and caused by Lassa virus, an Old World arenavirus. It may be fatal, but most patients recover from acute disease and some experience asymptomatic infection. The immune mechanisms associated with these different outcomes have not yet been fully elucidated, but considerable progress has recently been made, through the use of in vitro human models and nonhuman primates, the only relevant animal model that mimics the pathophysiology and immune responses induced in patients. We discuss here the roles of the various components of the innate and adaptive immune systems in Lassa virus infection and in the control of viral replication and pathogenesis.

  9. Human Immune Responses to Dengue Viruses.

    DTIC Science & Technology

    1984-08-01

    ND-R171 381 HUR IMMUNE RESPONSES TO DENGUE VIRUSES(U) 1/1 MASSRCHUSETTS UNIY M9DICAL SCHOOL WORCESTER F R~ ENNIS RUG 94 DRMt17-2-C-2233 UNCLASSIFIED...Responses to Dengue Viruses Annual Report 0(August 1983-July 1984) Francis A. Ennis, M.D. August 1984 Supported by U.S. Army Medical Research and...3M1- NO. SON No. Frederick, Maryland 21701-5012 61102A 61102BSI0 AA 104 11. TITLE Oxkf* Samqy Oao" Human Immune Responses to Dengue Viruses 12. PERSON

  10. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1989-07-31

    lhuman Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Francis A. Ennis 13a. TYPE OF REPORT 13b. TIME COVERED T14. DATE OF REPORT (Year, Month...Stimulation with live dengue virus of peripheral blood mononuclear cells from a dengue 4-immune donor generated virus-specific serotype cross-reactive CD4- CD8...class I-restricted cytotoxic T lymphocytes (CL) capable of lysing dengue virus-infected autologous fibroblasts and cells pulsed with dengue I

  11. Coral community response to bleaching on a highly disturbed reef.

    PubMed

    Guest, J R; Low, J; Tun, K; Wilson, B; Ng, C; Raingeard, D; Ulstrup, K E; Tanzil, J T I; Todd, P A; Toh, T C; McDougald, D; Chou, L M; Steinberg, P D

    2016-02-15

    While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress.

  12. Coral community response to bleaching on a highly disturbed reef

    PubMed Central

    Guest, J. R.; Low, J.; Tun, K.; Wilson, B.; Ng, C.; Raingeard, D.; Ulstrup, K. E.; Tanzil, J. T. I.; Todd, P. A.; Toh, T. C.; McDougald, D.; Chou, L. M.; Steinberg, P. D.

    2016-01-01

    While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress. PMID:26876092

  13. Coral community response to bleaching on a highly disturbed reef

    NASA Astrophysics Data System (ADS)

    Guest, J. R.; Low, J.; Tun, K.; Wilson, B.; Ng, C.; Raingeard, D.; Ulstrup, K. E.; Tanzil, J. T. I.; Todd, P. A.; Toh, T. C.; McDougald, D.; Chou, L. M.; Steinberg, P. D.

    2016-02-01

    While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress.

  14. Cytomegalovirus infection improves immune responses to influenza

    PubMed Central

    Furman, David; Jojic, Vladimir; Sharma, Shalini; Shen-Orr, Shai; Angel, Cesar J Lopez; Onengut-Gumuscu, Suna; Kidd, Brian; Maecker, Holden T; Concannon, Patrick; Dekker, Cornelia L; Thomas, Paul G; Davis, Mark M

    2015-01-01

    Cytomegalovirus (CMV) is a beta-herpes virus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV serostatus. In contrast, CMV-infected young adults exhibited an overall up-regulation of immune components including enhanced antibody responses to influenza vaccination, increased CD8+ T cell sensitivity, and elevated levels of circulating IFN-γ compared to uninfected individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the continued coexistence of CMV and mammals throughout their evolution. PMID:25834109

  15. Innate Immune Responses to AAV Vectors.

    PubMed

    Rogers, Geoffrey L; Martino, Ashley T; Aslanidi, George V; Jayandharan, Giridhara R; Srivastava, Arun; Herzog, Roland W

    2011-01-01

    Gene replacement therapy by in vivo delivery of adeno-associated virus (AAV) is attractive as a potential treatment for a variety of genetic disorders. However, while AAV has been used successfully in many models, other experiments in clinical trials and in animal models have been hampered by undesired responses from the immune system. Recent studies of AAV immunology have focused on the elimination of transgene-expressing cells by the adaptive immune system, yet the innate immune system also has a critical role, both in the initial response to the vector and in prompting a deleterious adaptive immune response. Responses to AAV vectors are primarily mediated by the TLR9-MyD88 pathway, which induces the production of pro-inflammatory cytokines by activating the NF-κB pathways and inducing type I IFN production; self-complementary AAV vectors enhance these inflammatory processes. Additionally, the alternative NF-κB pathway influences transgene expression in cells transduced by AAV. This review highlights these recent discoveries regarding innate immune responses to AAV and discusses strategies to ablate these potentially detrimental signaling pathways.

  16. Vaccination strategies for mucosal immune responses.

    PubMed

    Ogra, P L; Faden, H; Welliver, R C

    2001-04-01

    Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans.

  17. Vaccination Strategies for Mucosal Immune Responses

    PubMed Central

    Ogra, Pearay L.; Faden, Howard; Welliver, Robert C.

    2001-01-01

    Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans. PMID:11292646

  18. Variability in fluvial geomorphic response to anthropogenic disturbance

    NASA Astrophysics Data System (ADS)

    Verstraeten, Gert; Broothaerts, Nils; Van Loo, Maarten; Notebaert, Bastiaan; D'Haen, Koen; Dusar, Bert; De Brue, Hanne

    2017-10-01

    Humans have greatly impacted the processes and intensities of erosion, sediment transport and storage since the introduction of agriculture. In many regions around the world, accelerated floodplain sedimentation can be related to increases in human pressure on the environment. However, the relation between the intensity of anthropogenic disturbance and the magnitude of change in fluvial sediment dynamics is not straightforward and often non-linear. Here, we review a number of case studies from contrasting environmental settings in the European loess belt, the Eastern Mediterranean mountain ranges and the eastern USA. Detailed field-based sediment archive studies and sediment budgets covering time periods ranging from 200 to over 5000 year, as well as the use of pollen and sediment provenance techniques, show that no overarching concept of changes in floodplain sedimentation following anthropogenic disturbance can be established. Slope-channel (dis)connectivity controls the existence of thresholds or tipping points that need to be crossed before significant changes in downstream sediment dynamics are recorded following human impact. This coupling can be related to characteristics of human pressure such as its duration, intensity and spatial patterns, but also to the geomorphic and tectonic setting. Furthermore, internal feedback mechanisms, such as those between erosion and soil thickness, further complicate the story. All these factors controlling the propagation of sediment from eroding hillslopes to river channels vary between regions. Hence, only unique patterns of fluvial geomorphic response can be identified. As a result, unravelling the human impact from current-day sediment archives and predicting the impact of future human disturbances on fluvial sediment dynamics remain a major challenge. This has important implications for interpreting contemporary sediment yields as well as downstream sediment records in large floodplains, deltas and the marine

  19. Bacterial vaginosis and the cervicovaginal immune response

    PubMed Central

    Mitchell, Caroline; Marrazzo, Jeanne

    2014-01-01

    Bacterial vaginosis (BV) is a common cause of vaginal discharge in reproductive age women around the world, and is associated with several poor reproductive health outcomes, including HIV-1 acquisition. One possible mechanism for this association is the inflammatory immune response induced by BV in the cervical and vaginal mucosae. There is significant heterogeneity in reports of markers of cervicovaginal inflammation in women with bacterial vaginosis, likely due to microbial and host diversity, as well as differences in study design. In this article we review the characteristics of the mucosal immune response in BV, the potential role of lactobacilli in modulating that response, and the impact of individual BV-associated bacterial species on mucosal immunity. We focus on inflammatory markers that are proposed to increase the risk of HIV-1 acquisition. PMID:24832618

  20. Immune responses after live attenuated influenza vaccination.

    PubMed

    Mohn, Kristin G-I; Smith, Ingrid; Sjursen, Haakon; Cox, Rebecca

    2017-09-21

    Since 2003 (US) and 2012 (Europe) the live attenuated influenza vaccine (LAIV) has been used as an alternative to the traditional inactivated influenza vaccines (IIV). The immune responses elicted by LAIV mimic natural infection and have been found to provide broader clinical protection in children compared to the IIVs. However, our knowledge of the detailed immunological mechanisims induced by LAIV remain to be fully elucidated, and despite 14 years on the global market, there exists no correlate of protection. Recently, matters are further complicated by differing efficacy data from the US and Europe which are not understood. Better understanding of the immune responses after LAIV may aid in achieving the ultimate goal of a future "universal influenza vaccine". In this review we aim to cover the current understanding of the immune responses induced after LAIV.

  1. Radiation triggering immune response and inflammation.

    PubMed

    Hekim, Nezih; Cetin, Zafer; Nikitaki, Zacharenia; Cort, Aysegul; Saygili, Eyup Ilker

    2015-11-28

    Radiation therapy (RT) is a well-established but still under optimization branch of Cancer Therapy (CT). RT uses electromagnetic waves or charged particles in order to kill malignant cells, by accumulating the energy onto these cells. The issue at stake for RT, as well as for any other Cancer Therapy technique, is always to kill only cancer cells, without affecting the surrounding healthy ones. This perspective of CT is usually described under the terms "specificity" and "selectivity". Specificity and selectivity are the ideal goal, but the ideal is never entirely achieved. Thus, in addition to killing healthy cells, changes and effects are observed in the immune system after irradiation. In this review, we mainly focus on the effects of ionizing radiation on the immune system and its components like bone marrow. Additionally, we are interested in the effects and benefits of low-dose ionizing radiation on the hematopoiesis and immune response. Low dose radiation has been shown to induce biological responses like inflammatory responses, innate immune system activation and DNA repair (adaptive response). This review reveals the fact that there are many unanswered questions regarding the role of radiation as either an immune-activating (low dose) or immunosuppressive (high dose) agent.

  2. Trichinella spiralis: shaping the immune response.

    PubMed

    Ilic, Natasa; Gruden-Movsesijan, Alisa; Sofronic-Milosavljevic, Ljiljana

    2012-04-01

    The co-evolution of a wide range of helminth parasites and vertebrates represented a constant pressure on the host's immune system and a selective force for shaping the immune response. Modulation of the immune system by parasites is accomplished partly by dendritic cells. When exposed to helminth parasites or their products, dendritic cells do not become classically mature and are potent inducers of Th2 and regulatory responses. Treating animals with helminths (eggs, larvae, extracts) causes dampening or in some cases prevention of allergic or autoimmune diseases. Trichinella spiralis (T. spiralis) possess a capacity to retune the immune cell repertoire, acting as a moderator of the host response not only to itself but also to third party antigens. In this review, we will focus on the ability of T. spiralis-stimulated dendritic cells to polarize the immune response toward Th2 and regulatory mode in vitro and in vivo and also on the capacity of this parasite to modulate autoimmune disease--such as experimental autoimmune encephalomyelitis.

  3. Variation in responses of late-seral herbs to disturbance and environmental stress.

    Treesearch

    Cara R. Nelson; Charles B. Halpern; Joseph A. Antos

    2007-01-01

    Clonal herbs that attain maximum development in late-seral forest are often assumed to have similar responses to disturbance and to be functionally equivalent. However, little is known about the demographic or physiological responses of these plants to disturbance or to the altered conditions of the post-disturbance environment. Following harvest of a mature coniferous...

  4. Injury-induced immune responses in Hydra.

    PubMed

    Wenger, Yvan; Buzgariu, Wanda; Reiter, Silke; Galliot, Brigitte

    2014-08-01

    The impact of injury-induced immune responses on animal regenerative processes is highly variable, positive or negative depending on the context. This likely reflects the complexity of the innate immune system that behaves as a sentinel in the transition from injury to regeneration. Early-branching invertebrates with high regenerative potential as Hydra provide a unique framework to dissect how injury-induced immune responses impact regeneration. A series of early cellular events likely require an efficient immune response after amputation, as antimicrobial defence, epithelial cell stretching for wound closure, migration of interstitial progenitors toward the wound, cell death, phagocytosis of cell debris, or reconstruction of the extracellular matrix. The analysis of the injury-induced transcriptomic modulations of 2636 genes annotated as immune genes in Hydra identified 43 genes showing an immediate/early pulse regulation in all regenerative contexts examined. These regulations point to an enhanced cytoprotection via ROS signaling (Nrf, C/EBP, p62/SQSMT1-l2), TNFR and TLR signaling (TNFR16-like, TRAF2l, TRAF5l, jun, fos-related, SIK2, ATF1/CREB, LRRC28, LRRC40, LRRK2), proteasomal activity (p62/SQSMT1-l1, Ced6/Gulf, NEDD8-conjugating enzyme Ubc12), stress proteins (CRYAB1, CRYAB2, HSP16.2, DnaJB9, HSP90a1), all potentially regulating NF-κB activity. Other genes encoding immune-annotated proteins such as NPYR4, GTPases, Swap70, the antiproliferative BTG1, enzymes involved in lipid metabolism (5-lipoxygenase, ACSF4), secreted clotting factors, secreted peptidases are also pulse regulated upon bisection. By contrast, metalloproteinases and antimicrobial peptide genes largely follow a context-dependent regulation, whereas the protease inhibitor α2macroglobulin gene exhibits a sustained up-regulation. Hence a complex immune response to injury is linked to wound healing and regeneration in Hydra. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights

  5. Damage signals in the insect immune response

    PubMed Central

    Krautz, Robert; Arefin, Badrul; Theopold, Ulrich

    2014-01-01

    Insects and mammals share an ancient innate immune system comprising both humoral and cellular responses. The insect immune system consists of the fat body, which secretes effector molecules into the hemolymph and several classes of hemocytes, which reside in the hemolymph and of protective border epithelia. Key features of wound- and immune responses are shared between insect and mammalian immune systems including the mode of activation by commonly shared microbial (non-self) patterns and the recognition of these patterns by dedicated receptors. It is unclear how metazoan parasites in insects, which lack these shared motifs, are recognized. Research in recent years has demonstrated that during entry into the insect host, many eukaryotic pathogens leave traces that alert potential hosts of the damage they have afflicted. In accordance with terminology used in the mammalian immune systems, these signals have been dubbed danger- or damage-associated signals. Damage signals are necessary byproducts generated during entering hosts either by mechanical or proteolytic damage. Here, we briefly review the current stage of knowledge on how wound closure and wound healing during mechanical damage is regulated and how damage-related signals contribute to these processes. We also discuss how sensors of proteolytic activity induce insect innate immune responses. Strikingly damage-associated signals are also released from cells that have aberrant growth, including tumor cells. These signals may induce apoptosis in the damaged cells, the recruitment of immune cells to the aberrant tissue and even activate humoral responses. Thus, this ensures the removal of aberrant cells and compensatory proliferation to replace lost tissue. Several of these pathways may have been co-opted from wound healing and developmental processes. PMID:25071815

  6. Immune Response in Human Cerebral Cavernous Malformations

    PubMed Central

    Shi, Changbin; Shenkar, Robert; Du, Hongyan; Duckworth, Edward; Raja, Harish; Batjer, H. Hunt; Awad, Issam A.

    2009-01-01

    Background and Purpose Preliminary observations suggesting the presence of B and plasma cells and oligoclonality of immunoglobulin (Ig) G in cerebral cavernous malformations (CCMs) have motivated a systematic study correlating the infiltration of the immune cells with clinical activity and antigen-triggered immune response in surgically excised lesions. Methods Infiltration of plasma, B, T and HLA-DR expressing cells and macrophages within 23 excised CCMs was related to clinical activity. Relative amounts of Ig isotypes were determined. IgG clonality of mRNA from CCMs was assessed by spectratyping, cloning and sequencing. Results Infiltration of the immune cells ranged widely within CCM lesions and cells were generally co-expressed with each other. Immune cell infiltration did not associate with recent bleeding and lesion growth. Significantly more B lymphocytes in CCM lesions were associated with venous anomaly. More T cells were present in solitary lesions. More T cells and less macrophages were present in CCMs from younger subjects. IgG isotype was present in all CCM lesions. Most lesions also expressed IgM and IgA, with IgM predominance over IgA correlating with recent CCM growth. Oligoclonality was shown in IgG mRNA from CCMs, but not from peripheral blood lymphocytes, with only eight CDR3 sequences observed among 134 clones from two CCM lesions. Conclusions An antigen-directed oligoclonal IgG immune response is present within CCM lesions regardless of recent clinical activity. Apparent differences in immune response in younger patients and in lesions with recent growth will need confirmation in other series. The pathogenicity of oligoclonal immune response will require systematic hypothesis testing in recently available CCM murine models. PMID:19286587

  7. Immune Responses in Parasitic Diseases.

    DTIC Science & Technology

    1982-09-01

    prepared in pure form so that quantitative radial immunodiffusion studies are feasible. The IgGl response to T. rhodesiense infection in the rat has been...sera of infected animals and definitely-separate and quantitate the 19S from 8S species by combining radial immunodiffusion techniques and sucrose

  8. Immune response inhibits associative learning in insects.

    PubMed Central

    Mallon, Eamonn B; Brockmann, Axel; Schmid-Hempel, Paul

    2003-01-01

    In vertebrates, it is well established that there are many intricate interactions between the immune system and the nervous system, and vice versa. Regarding insects, until now little has been known about the link between these two systems. Here, we present behavioural evidence indicating a link between the immune system and the nervous system in insects. We show that otherwise non-infected honeybees whose immune systems are challenged by a non-pathogenic immunogenic elicitor lipopolysaccharide (LPS) have reduced abilities to associate an odour with sugar reward in a classical conditioning paradigm. The cost of an immune response therefore not only affects survival of the host, as previously shown, but also everyday behaviour and memory formation. PMID:14667337

  9. A nonequilibrium phase transition in immune response

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Qi, An-Shen

    2004-07-01

    The dynamics of immune response correlated to signal transduction in immune thymic cells (T cells) is studied. In particular, the problem of the phosphorylation of the immune-receptor tyrosine-based activation motifs (ITAM) is explored. A nonlinear model is established on the basis of experimental observations. The behaviours of the model can be well analysed using the concepts of nonequilibrium phase transitions. In addition, the Riemann-Hugoniot cusp catastrophe is demonstrated by the model. Due to the application of the theory of nonequilibrium phase transitions, the biological phenomena can be clarified more precisely. The results can also be used to further explain the signal transduction and signal discrimination of an important type of immune T cell.

  10. Human Immune Responses to Dengue Viruses.

    DTIC Science & Technology

    1986-08-01

    D-Ai8i 71S UMAN IMMUNE RESPONSES TO DENGUE VIRUSES(U) MASSACHUSETTS UNIV M DICAL CENTER WORCESTER MA F A ENNIS 81 AUG 86 DAD17-82-C-2233 UNCLSE...Classification) (U) Human Immune Responses to Dengue Viruses 12. PERSONAL AUTHOR(S) Ennis. Francis A. 13a. TYPE OF REPORT 13b. TIME COVERED 414. DATE OF...Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP06 13 Virus; Dengue ; Arbovirus; Immunology 06 03 I9% ABSTRACT

  11. Human Immune Responses to Dengue Viruses.

    DTIC Science & Technology

    1985-08-01

    t-Ril 630 HuMAN IMMUNE RESPONSES TO DENGUE VIRUSES(U) 1 - MASSACHUSETTS UNIV MEDICAL SCHOOL WORCESTER F A ENNIS 01 AUGO 95 DAMDI-2-C-2233 UNCASSIFIED...Classification) (U) Human Immune Responses to Dengue Viruses 12. PERSONAL AUTHOR(S) Ennis, Francis A. 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF...on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP06 13 Virus; Dengue ; Arbovirus; Immunology 06 13 19. ABSTRACT (Continue on

  12. Human Immune Response to Dengue Infections.

    DTIC Science & Technology

    1991-06-30

    DTIC AD-A240 717 AD ____ HUMAN IMMUNE RESPONSE TO DENGUE INFECTIONS ANNUAL REPORT FRANCIS A. ENNIS JUNE 30, 1991 Supported by U.S. ARMY MEDICAL...Immune Response to Dengue Infections DAMDI7-86-C-6208 6. AUTHOR(S) 61102A 1 3M161102BS13 AA Francis A. Ennis WUDA3 12059 7. PERFORMING ORGANIZATION...of NS3, respectively. We also established 16 dengue virus-specific CD8+ CD4_ T cell clones. The clone #/2.8 recognize dengue virus types 2 and 4, and

  13. Clinical iron deficiency disturbs normal human responses to hypoxia.

    PubMed

    Frise, Matthew C; Cheng, Hung-Yuan; Nickol, Annabel H; Curtis, M Kate; Pollard, Karen A; Roberts, David J; Ratcliffe, Peter J; Dorrington, Keith L; Robbins, Peter A

    2016-06-01

    Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography. Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7-9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, -8.3 to -0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups. Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health. ClinicalTrials.gov (NCT01847352). M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was supported by R&D funding from National Health Service (NHS) Blood and Transplant and

  14. Clinical iron deficiency disturbs normal human responses to hypoxia

    PubMed Central

    Frise, Matthew C.; Cheng, Hung-Yuan; Nickol, Annabel H.; Curtis, M. Kate; Pollard, Karen A.; Roberts, David J.; Ratcliffe, Peter J.; Dorrington, Keith L.; Robbins, Peter A.

    2016-01-01

    BACKGROUND. Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. METHODS. We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography. RESULTS. Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7–9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, –8.3 to –0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups. CONCLUSION. Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01847352). FUNDING. M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was

  15. Immune response from a resource allocation perspective

    PubMed Central

    Rauw, Wendy M.

    2012-01-01

    The immune system is a life history trait that can be expected to trade off against other life history traits. Whether or not a trait is considered to be a life history trait has consequences for the expectation on how it responds to natural selection and evolution; in addition, it may have consequences for the outcome of artificial selection when it is included in the breeding objective. The immune system involved in pathogen resistance comprises multiple mechanisms that define a host's defensive capacity. Immune resistance involves employing mechanisms that either prevent pathogens from invading or eliminate the pathogens when they do invade. On the other hand, tolerance involves limiting the damage that is caused by the infection. Both tolerance and resistance traits require (re)allocation of resources and carry physiological costs. Examples of trade-offs between immune function and growth, reproduction and stress response are provided in this review, in addition to consequences of selection for increased production on immune function and vice versa. Reaction norms are used to deal with questions of immune resistance vs. tolerance to pathogens that relate host health to infection intensity. In essence, selection for immune tolerance in livestock is a particular case of selection for animal robustness. Since breeding goals that include robustness traits are required in the implementation of more sustainable agricultural production systems, it is of interest to investigate whether immune tolerance is a robustness trait that is positively correlated with overall animal robustness. Considerably more research is needed to estimate the shapes of the cost functions of different immune strategies, and investigate trade-offs and cross-over benefits of selection for disease resistance and/or disease tolerance in livestock production. PMID:23413205

  16. The Innate Immune Response Against Staphylococcus aureus.

    PubMed

    Bekeredjian-Ding, Isabelle; Stein, Christoph; Uebele, Julia

    2015-12-15

    The innate immune system harbors a multitude of different receptor systems and cells that are constantly prepared to sense and eliminate invading microbial pathogens. Staphylococcus aureus enters the body on its exposed epithelial surfaces, e.g., on skin and mucosa. The initial interaction with epithelial cells is governed by Toll-like receptor (TLR)-2-mediated local production of soluble mediators, including cytokines, chemokines, and antimicrobial peptides. The overall goal is to achieve a steady state of immune mediators and colonizing bacteria. Following cell and tissue invasion clearance of bacteria depends on intracellular microbial sensors and subsequent activation of the inflammasomes. Tissue-resident mast cells and macrophages recruit neutrophils, macrophages, and NK cells. This inflammatory response supports the generation of IL-17 producing NKT, γδ T cells, and T helper cells. Local dendritic cells migrate to the lymph nodes and fine-tune the adaptive immune response. The scope of this chapter is to provide an overview on the major cell types and receptors involved in innate immune defense against S. aureus. By segregating the different stages of infection from epithelial barrier to intracellular and systemic infection, this chapter highlights the different qualities of the innate immune response to S. aureus at different stages of invasiveness.

  17. Peroxiredoxin 5 modulates immune response in Drosophila

    PubMed Central

    Radyuk, Svetlana N.; Michalak, Katarzyna; Klichko, Vladimir I.; Benes, Judith; Orr, William C.

    2010-01-01

    Background Peroxiredoxins are redox-sensing enzymes with multiple cellular functions. Previously, we reported on the potent antioxidant function of Drosophila peroxiredoxin 5 (dPrx5). Studies with mammalian and human cells suggest that peroxiredoxins can modulate immune-related signaling. Methods Survivorship studies and bacteriological analysis were used to determine resistance of flies to fungal and bacterial infections. RT-PCR and immunoblot analyses determined expression of dPrx5 and immunity factors in response to bacterial challenge. Double mutants for dprx5 gene and genes comprising the Imd/Relish and dTak1/Basket branches of the immune signaling pathways were used in epistatic analysis. Results The dprx5 mutant flies were more resistant to bacterial infection than controls, while flies overexpressing dPrx5 were more susceptible. The enhanced resistance to bacteria was accompanied by rapid induction of the Imd-dependent antimicrobial peptides, phosphorylation of the JNK kinase Basket and altered transcriptional profiling of the transient response genes, puckered, ets21C and relish, while the opposite effects were observed in flies over-expressing dPrx5. Epistatic analysis of double mutants, using attacin D and Puckered as read outs of activation of the Imd and JNK pathways, implicated dPrx5 function in the control of the dTak1-JNK arm of immune signaling. Conclusions Differential effects on fly survivorship suggested a trade-off between the antioxidant and immune functions of dPrx5. Molecular and epistatic analyses identified dPrx5 as a negative regulator in the dTak1-JNK arm of immune signaling. General significance Our findings suggest that peroxiredoxins play an important modulatory role in the Drosophila immune response. PMID:20600624

  18. Response of the lower equatorial ionosphere to strong tropospheric disturbances

    NASA Astrophysics Data System (ADS)

    Vanina-Dart, L. B.; Pokrovskaya, I. V.; Sharkov, E. A.

    2008-04-01

    A morphological analysis of the results of sounding the lower equatorial ionosphere (the D region) in the region of action of strong tropospheric vortex disturbances (tropical cyclones, TC) is presented in this work. Based on the rocket sounding of the lower ionosphere at Thumba rocket site (8° N, 77° E) in May-June 1985 and on the satellite monitoring of TC in the northern Indian Ocean, it is demonstrated that a sharp depletion (by a factor of 2-4) of the electron concentration at altitudes of 60-80 km could be a response of the ionosphere during the TC active phase. In this case the lower boundary of the D region rose by several kilometers (not more than 5 km), and the temperature in the region of the stratopause slightly (by 2°-3°) increases. It is assumed that internal gravity waves (IGWs) generated by TC cause the effect on the lower ion-osphere.

  19. Responses of boundary layers to strong external disturbances

    NASA Astrophysics Data System (ADS)

    Asai, Masahito

    1990-10-01

    The transition from laminar flow to turbulent flow of the boundary layer is an important phenomenon for various problems in astronautical engineering. When the turbulence in the flow is weak, the boundary layer transition starts from the spatial amplification of a viscous T-S (Tollmien Schlichting) wave. The initial wave starts as a two dimensional wave and grows rapidly to a three dimensional wave with amplification. Finally, it corrupts to small scale hairpin eddies. The transitions starting from these wave amplifications are studied, and instability mechanisms are analyzed. In order to analyze the mechanism, the strength of turbulence (eddies) in the air flow that develops a transitional structure in the boundary layer and leads to a turbulent flow transition is analyzed. The responses of the boundary layers to the strong external disturbances are studied experimentally by introducing sonic wave which simulates hairpin eddies in the lower part of the front edge of a flat plate.

  20. Adaptive immune responses to Candida albicans infection

    PubMed Central

    Richardson, Jonathan P; Moyes, David L

    2015-01-01

    Fungal infections are becoming increasingly prevalent in the human population and contribute to morbidity and mortality in healthy and immunocompromised individuals respectively. Candida albicans is the most commonly encountered fungal pathogen of humans, and is frequently found on the mucosal surfaces of the body. Host defense against C. albicans is dependent upon a finely tuned implementation of innate and adaptive immune responses, enabling the host to neutralise the invading fungus. Central to this protection are the adaptive Th1 and Th17 cellular responses, which are considered paramount to successful immune defense against C. albicans infections, and enable tissue homeostasis to be maintained in the presence of colonising fungi. This review will highlight the recent advances in our understanding of adaptive immunity to Candida albicans infections. PMID:25607781

  1. Response of intertidal macrofauna to multiple disturbance types and intensities - an experimental approach.

    PubMed

    Whomersley, P; Huxham, M; Bolam, S; Schratzberger, M; Augley, J; Ridland, D

    2010-06-01

    Two of the best-supported theories which describe the effects of disturbance within marine benthic habitats are the organic enrichment 'Successional Model' and the 'Intermediate Disturbance Hypothesis'. Underlying these models, biological mechanisms thought to drive community change include competition, facilitation, inhibition, tolerance and random colonisation. To further examine the effects of disturbance an experimental test of the effects of different types (burial, raking and organic enrichment) and intensities of disturbance on infaunal intertidal communities at two different sites with similar suites of species was carried out. The same type and frequency of disturbance, applied to the two different sites, produced different responses at the species, community and trophic group level. In models that assume a linear relationship between disturbance intensity and effect, knowledge of the intensity of any novel disturbance, combined with the original disturbance regime experienced by a community (i.e. its 'starting point'), should be sufficient to predict final community characteristics. The current results do not conform to such a linear interpretation, as at both sites the intensity of treatments did not always predict the degree of disturbance. Therefore the response to disturbance may depend on site-specific factors such as the history of prior disturbance and the inherent ecological plasticity exhibited by many benthic species. Whilst current models perform well in predicting benthic responses to gross disturbance, detecting subtler effects requires a recognition that community response may depend on the site, the species and the sources of disturbance.

  2. Immune Response in Mussels To Environmental Pollution.

    ERIC Educational Resources Information Center

    Pryor, Stephen C.; Facher, Evan

    1997-01-01

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

  3. [Modulation of immune response by bacterial lipopolysaccharides].

    PubMed

    Aldapa-Vega, Gustavo; Pastelín-Palacios, Rodolfo; Isibasi, Armando; Moreno-Eutimio, Mario A; López-Macías, Constantino

    2016-01-01

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

  4. Adaptive immune cells temper initial innate responses.

    PubMed

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2007-10-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

  5. Adaptive immune cells temper initial innate responses

    PubMed Central

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2008-01-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25−Foxp3− or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. PMID:17891146

  6. Immune Response in Mussels To Environmental Pollution.

    ERIC Educational Resources Information Center

    Pryor, Stephen C.; Facher, Evan

    1997-01-01

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

  7. [Immune response genes products in human physiology].

    PubMed

    Khaitov, R M; Alekseev, L P

    2012-09-01

    Current data on physiological role of human immune response genes' proteomic products (antigens) are discussed. The antigens are specified by a very high level of diversity that mediates a wide specter ofphysiological functions. They actually provide integrity and biological stability of human as species. These data reveal new ideas on many pathological processes as well as drafts new approaches for prophylaxis and treatment.

  8. Innate immune responses to hepatitis C virus.

    PubMed

    Schoggins, John W; Rice, Charles M

    2013-01-01

    The innate immune response provides the first line of defense against invading viral pathogens. Incoming viruses are sensed by dedicated host factors that, when triggered, initiate multiple signal transduction pathways. Activation of these pathways leads to the induction of highly orchestrated transcriptional programs designed to limit virus replication and spread. In recent years, our understanding of innate immune responses targeting hepatitis C virus (HCV) has increased substantially, largely due to the development of new systems and methodologies to study HCV-host interactions in vitro and in vivo. However, significant gaps still remain. Here, we aim to provide a comprehensive view of the innate immune response to HCV, focusing primarily on knowledge gained from cell culture models of HCV infection, as well as data from human patients infected with HCV. While some paradigms of the host response to HCV revealed in cell culture translate to human infection in vivo, others are less clear. Further insight into the similarities and differences in these systems will not only reveal directions for future studies on HCV immunity, but may also guide the development of novel strategies to control HCV and other viral infections.

  9. Innate Immune Sensing and Response to Influenza

    PubMed Central

    Pulendran, Bali; Maddur, Mohan S.

    2015-01-01

    Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocom-promised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza. PMID:25078919

  10. Humoral Immune Response to AAV.

    PubMed

    Calcedo, Roberto; Wilson, James M

    2013-10-18

    Adeno-associated virus (AAV) is a member of the family Parvoviridae that has been widely used as a vector for gene therapy because of its safety profile, its ability to transduce both dividing and non-dividing cells, and its low immunogenicity. AAV has been detected in many different tissues of several animal species but has not been associated with any disease. As a result of natural infections, antibodies to AAV can be found in many animals including humans. It has been shown that pre-existing AAV antibodies can modulate the safety and efficacy of AAV vector-mediated gene therapy by blocking vector transduction or by redirecting distribution of AAV vectors to tissues other than the target organ. This review will summarize antibody responses against natural AAV infections, as well as AAV gene therapy vectors and their impact in the clinical development of AAV vectors for gene therapy. We will also review and discuss the various methods used for AAV antibody detection and strategies to overcome neutralizing antibodies in AAV-mediated gene therapy.

  11. Pulmonary contusion primes systemic innate immunity responses.

    PubMed

    Hoth, J Jason; Martin, R S; Yoza, Barbara K; Wells, Jonathan D; Meredith, J W; McCall, Charles E

    2009-07-01

    Traumatic injury may result in an exaggerated response to subsequent immune stimuli such as nosocomial infection. This "second hit" phenomenon and molecular mechanism(s) of immune priming by traumatic lung injury, specifically, pulmonary contusion, remain unknown. We used an animal model of pulmonary contusion to determine whether the injury resulted in priming of the innate immune response and to test the hypothesis that resuscitation fluids could attenuate the primed response to a second hit. Male, 8 to 9 weeks, C57/BL6 mice with a pulmonary contusion were challenged by a second hit of intratracheal administration of the Toll-like receptor 4 agonist, lipopolysaccharide (LPS, 50 microg) 24 hours after injury (injury + LPS). Other experimental groups were injury + vehicle or LPS alone. A separate group was injured and resuscitated by 4 cc/kg of hypertonic saline (HTS) or Lactated Ringer's (LR) resuscitation before LPS challenge. Mice were killed 4 hours after LPS challenge and blood, bronchoalveolar lavage, and tissue were isolated and analyzed. Data were analyzed using one-way analysis of variance with Bonferroni multiple comparison posttest for significant differences (*p < or = 0.05). Injury + LPS showed immune priming observed by lung injury histology and increased bronchoalveolar lavage neutrophilia, lung myeloperoxidase and serum IL-6, CXCL1, and MIP-2 levels when compared with injury + vehicle or LPS alone. After injury, resuscitation with HTS, but not Lactated Ringer's was more effective in attenuating the primed response to a second hit. Pulmonary contusion primes innate immunity for an exaggerated response to a second hit with the Toll-like receptor 4 agonist, LPS. We observed synergistic increases in inflammatory mediator expression in the blood and a more severe lung injury in injured animals challenged with LPS. This priming effect was reduced when HTS was used to resuscitate the animal after lung contusion.

  12. Pulmonary contusion primes systemic innate immunity responses

    PubMed Central

    Hoth, JJ; Martin, RS; Yoza, BK; Wells, JD; Meredith, JW; McCall, CE

    2010-01-01

    Introduction Traumatic injury may result in an exaggerated response to subsequent immune stimuli such as nosocomial infection. This “second hit” phenomenon, and molecular mechanism(s) of immune priming by traumatic lung injury, specifically pulmonary contusion, remains unknown. We used an animal model of pulmonary contusion to determine if the injury resulted in priming of the innate immune response and to test the hypothesis that resuscitation fluids could attenuate the primed response to a second hit. Methods Male, 8-9 wk, C57/BL6 mice with a pulmonary contusion were challenged by a second hit of intratracheal administration of the Toll like receptor (TLR) 4 agonist, lipopolysaccharide (LPS, 50mcg) 24hrs after injury (injury+LPS). Other experimental groups were injury+vehicle or LPS alone. A separate group were injured and resuscitated by 4cc/kg of hypertonic saline (HTS) or Lactated Ringer's (LR) resuscitation prior to LPS challenge. Mice were euthanized 4hrs after LPS challenge and blood, bronchoalveolar lavage (BAL), and tissue were isolated and analyzed. Data were analyzed using one way ANOVA with Bonferroni multiple comparison post-test for significant differences (*, p≤0.05). Results Injury+LPS showed immune priming observed by lung injury histology and increased BAL neutrophilia, lung myeloperoxidase, and serum IL-6, CXCL1 and MIP-2 levels when compared to injury+vehicle or LPS alone. After injury, resuscitation with HTS, but not LR was more effective in attenuating the primed response to a second hit. Conclusion Pulmonary contusion primes innate immunity for an exaggerated response to a second hit with the TLR4 agonist, LPS. We observed synergistic increases in inflammatory mediator expression in the blood and a more severe lung injury in injured animals challenged with LPS. This priming effect was reduced when HTS was used to resuscitate the animal after lung contusion. PMID:19590302

  13. Humoral immune responses in foetal sheep.

    PubMed Central

    Fahey, K J; Morris, B

    1978-01-01

    A total of fifty-two foetal sheep between 49 and 126 days gestation were injected with polymeric and monomeric flagellin, dinitrophenylated monomeric flagellin, chicken red blood cells, ovalbumin, ferritin, chicken gamma-globulin and the somatic antigens of Salmonella typhimurium in a variety of combinations. Immune responses were followed in these animals by taking serial blood samples from them through indwelling vascular cannulae and measuring the circulating titres of antibody. Of the antigens tested, ferritin induced immune responses in the youngest foetuses. A short time later in gestation, the majority of foetuses responded to chicken red blood cells, polymeric flagellin, monomeric flagellin and dinitrophenylated monomeric flagellin. Only older foetuses responded regularly to chicken gamma-globulin and ovalbumin. However, antibodies to all these antigens were first detected over the relatively short period of development between 64 and 82 days gestation and this made it difficult to define any precise order in the development of immune responsiveness. Of the antigens tested only the somatic antigens of S. typhimurium failed to induce a primary antibody response during foetal life. The character and magnitude of the antibody responses in foetuses changed throughout in utero development. Both the total amount of antibody produced and the duration of the response increased with foetal age. Foetuses younger than 87 days gestation did not synthesize 2-mercaptoethanol resistant antibodies or IgG1 immunoglobulin to any of the antigens tested, whereas most foetuses older than this regularly did so. PMID:711249

  14. A meta-analysis of soil microbial biomass responses to forest disturbances

    PubMed Central

    Holden, Sandra R.; Treseder, Kathleen K.

    2013-01-01

    Climate warming is likely to increase the frequency and severity of forest disturbances, with uncertain consequences for soil microbial communities and their contribution to ecosystem C dynamics. To address this uncertainty, we conducted a meta-analysis of 139 published soil microbial responses to forest disturbances. These disturbances included abiotic (fire, harvesting, storm) and biotic (insect, pathogen) disturbances. We hypothesized that soil microbial biomass would decline following forest disturbances, but that abiotic disturbances would elicit greater reductions in microbial biomass than biotic disturbances. In support of this hypothesis, across all published studies, disturbances reduced soil microbial biomass by an average of 29.4%. However, microbial responses differed between abiotic and biotic disturbances. Microbial responses were significantly negative following fires, harvest, and storms (48.7, 19.1, and 41.7% reductions in microbial biomass, respectively). In contrast, changes in soil microbial biomass following insect infestation and pathogen-induced tree mortality were non-significant, although biotic disturbances were poorly represented in the literature. When measured separately, fungal and bacterial responses to disturbances mirrored the response of the microbial community as a whole. Changes in microbial abundance following disturbance were significantly positively correlated with changes in microbial respiration. We propose that the differential effect of abiotic and biotic disturbances on microbial biomass may be attributable to differences in soil disruption and organic C removal from forests among disturbance types. Altogether, these results suggest that abiotic forest disturbances may significantly decrease soil microbial abundance, with corresponding consequences for microbial respiration. Further studies are needed on the effect of biotic disturbances on forest soil microbial communities and soil C dynamics. PMID:23801985

  15. Ovine model for studying pulmonary immune responses

    SciTech Connect

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

    1984-11-25

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

  16. Space flight, microgravity, stress, and immune responses

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, G.

    1999-01-01

    Exposure of animals and humans to space flight conditions has resulted in numerous alterations in immunological parameters. Decreases in lymphocyte blastogenesis, cytokine production, and natural killer cell activity have all been reported after space flight. Alterations in leukocyte subset distribution have also been reported after flight of humans and animals in space. The relative contribution of microgravity conditions and stress to the observed results has not been established. Antiorthostatic, hypokinetic, hypodynamic, suspension of rodents and chronic head-down tilt bed-rest of humans have been used to model effects of microgravity on immune responses. After use of these models, some effects of space flight on immune responses, such as decreases in cytokine function, were observed, but others, such as alterations in leukocyte subset distribution, were not observed. These results suggest that stresses that occur during space flight could combine with microgravity conditions in inducing the changes seen in immune responses after space flight. The biological/biomedical significance of space flight induced changes in immune parameters remains to be established.

  17. Differential temperature operation of plant immune responses

    PubMed Central

    Cheng, Cheng; Gao, Xiquan; Feng, Baomin; Sheen, Jen; Shan, Libo; He, Ping

    2014-01-01

    Temperature fluctuation is a key determinant for microbial invasion and host evasion. In contrast to mammalians that maintain constant body temperature, plant temperature oscillates on a daily basis. It remains elusive how plants operate inducible defenses in response to temperature fluctuation. Here we report that ambient temperature changes lead to pronounced shifts of two distinct plant immune responses: pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). Plants preferentially activate ETI signaling at relatively low temperatures (10~23°C), whereas they switch to PTI signaling at moderately elevated temperatures (23~32°C). The Arabidopsis arp6 and hta9hta11 mutants, phenocopying plants grown at the elevated temperatures, exhibit enhanced PTI and yet reduced ETI responses. As the secretion of bacterial effectors favors low temperatures whereas bacteria multiply vigorously at elevated temperatures accompanied with increased microbe-associated molecular pattern production, our findings suggest that temperature oscillation might have driven dynamic co-evolution of distinct plant immune signaling responding to pathogen physiological changes. PMID:24067909

  18. Immune responses to infectious diseases in bivalves.

    PubMed

    Allam, Bassem; Raftos, David

    2015-10-01

    Many species of bivalve mollusks (phylum Mollusca, class Bivalvia) are important in fisheries and aquaculture, whilst others are critical to ecosystem structure and function. These crucial roles mean that considerable attention has been paid to the immune responses of bivalves such as oysters, clams and mussels against infectious diseases that can threaten the viability of entire populations. As with many invertebrates, bivalves have a comprehensive repertoire of immune cells, genes and proteins. Hemocytes represent the backbone of the bivalve immune system. However, it is clear that mucosal tissues at the interface with the environment also play a critical role in host defense. Bivalve immune cells express a range of pattern recognition receptors and are highly responsive to the recognition of microbe-associated molecular patterns. Their responses to infection include chemotaxis, phagolysosomal activity, encapsulation, complex intracellular signaling and transcriptional activity, apoptosis, and the induction of anti-viral states. Bivalves also express a range of inducible extracellular recognition and effector proteins, such as lectins, peptidoglycan-recognition proteins, thioester bearing proteins, lipopolysaccharide and β1,3-glucan-binding proteins, fibrinogen-related proteins (FREPs) and antimicrobial proteins. The identification of FREPs and other highly diversified gene families in bivalves leaves open the possibility that some of their responses to infection may involve a high degree of pathogen specificity and immune priming. The current review article provides a comprehensive, but not exhaustive, description of these factors and how they are regulated by infectious agents. It concludes that one of the remaining challenges is to use new "omics" technologies to understand how this diverse array of factors is integrated and controlled during infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Microbes and mucosal immune responses in asthma.

    PubMed

    Hansel, Trevor T; Johnston, Sebastian L; Openshaw, Peter J

    2013-03-09

    The substantial increase in the worldwide prevalence of asthma and atopy has been attributed to lifestyle changes that reduce exposure to bacteria. A recent insight is that the largely bacterial microbiome maintains a state of basal immune homoeostasis, which modulates immune responses to microbial pathogens. However, some respiratory viral infections cause bronchiolitis of infancy and childhood wheeze, and can exacerbate established asthma; whereas allergens can partly mimic infectious agents. New insights into the host’s innate sensing systems, combined with recently developed methods that characterise commensal and pathogenic microbial exposure, now allow a unified theory for how microbes cause mucosal inflammation in asthma. The respiratory mucosa provides a key microbial interface where epithelial and dendritic cells interact with a range of functionally distinct lymphocytes. Lymphoid cells then control a range of pathways, both innate and specific, which organise the host mucosal immune response. Fundamental to innate immune responses to microbes are the interactions between pathogen-associated molecular patterns and pattern recognition receptors, which are associated with production of type I interferons, proinflammatory cytokines, and the T-helper-2 cell pathway in predisposed people. These coordinated, dynamic immune responses underlie the differing asthma phenotypes, which we delineate in terms of Seven Ages of Asthma. An understanding of the role of microbes in the atopic march towards asthma, and in causing exacerbations of established asthma, provides the rationale for new specific treatments that can be assessed in clinical trials. On the basis of these new ideas, specific host biomarkers might then allow personalised treatment to become a reality for patients with asthma.

  20. Cytokines and Immune Responses in Murine Atherosclerosis.

    PubMed

    Kusters, Pascal J H; Lutgens, Esther

    2015-01-01

    Atherosclerosis is an inflammatory disease of the vessel wall characterized by activation of the innate immune system, with macrophages as the main players, as well as the adaptive immune system, characterized by a Th1-dominant immune response. Cytokines play a major role in the initiation and regulation of inflammation. In recent years, many studies have investigated the role of these molecules in experimental models of atherosclerosis. While some cytokines such as TNF or IFNγ clearly had atherogenic effects, others such as IL-10 were found to be atheroprotective. However, studies investigating the different cytokines in experimental atherosclerosis revealed that the cytokine system is complex with both disease stage-dependent and site-specific effects. In this review, we strive to provide an overview of the main cytokines involved in atherosclerosis and to shed light on their individual role during atherogenesis.

  1. The adaptive immune response in celiac disease.

    PubMed

    Qiao, Shuo-Wang; Iversen, Rasmus; Ráki, Melinda; Sollid, Ludvig M

    2012-07-01

    Compared to other human leukocyte antigen (HLA)-associated diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, fundamental aspects of the pathogenesis in celiac disease are relatively well understood. This is mostly because the causative antigen in celiac disease-cereal gluten proteins-is known and the culprit HLA molecules are well defined. This has facilitated the dissection of the disease-relevant CD4+ T cells interacting with the disease-associated HLA molecules. In addition, celiac disease has distinct antibody responses to gluten and the autoantigen transglutaminase 2, which give strong handles to understand all sides of the adaptive immune response leading to disease. Here we review recent developments in the understanding of the role of T cells, B cells, and antigen-presenting cells in the pathogenic immune response of this instructive disorder.

  2. Regeneration, tissue injury and the immune response

    PubMed Central

    Godwin, James W; Brockes, Jeremy P

    2006-01-01

    The involvement of the immune system in the response to tissue injury has raised the possibility that it might influence tissue, organ or appendage regeneration following injury. One hypothesis that has been discussed is that inflammatory aspects may preclude the occurrence of regeneration, but there is also evidence for more positive roles of immune components. The vertebrate eye is an immunoprivileged site where inflammatory aspects are inhibited by several immunomodulatory mechanisms. In various newt species the ocular tissues such as the lens are regenerative and it has recently been shown that the response to local injury of the lens involves activation of antigen-presenting cells which traffic to the spleen and return to displace and engulf the lens, thereby inducing regeneration from the dorsal iris. The activation of thrombin from prothrombin in the dorsal iris is one aspect of the injury response that is important in the initiation of regeneration. The possible relationships between the immune response and the regenerative response are considered with respect to phylogenetic variation of regeneration in general, and lens regeneration in particular. PMID:17005015

  3. Disturbance-response analysis: a method for rapid assessment of the threat to species in disturbed areas.

    PubMed

    Martorell, Carlos; Peters, Edward M

    2009-04-01

    We developed a method with which to analyze a specie's response to chronic anthropogenic disturbance (CAD). We regressed density of individuals on the intensity of 3 disturbance agents (human activities, raising livestock, and land degradation) along CAD gradients to determine how much CAD is experienced by a species; whether species are ruderal (achieving maximum densities in disturbed sites); whether density declines as a result of CAD; which disturbance agents are responsible for this reduction; and the number of populations that decline as a result of CAD. We tested the method on 9 threatened Mammillaria species (Cactaceae). Seven species were ruderal. In 4 species, actual disturbance surpassed the CAD intensity in which plants achieved their maximum densities; thus, the density of those 4 species appeared to be declining. For 7 species, some populations were threatened by human activities or livestock, whereas others were favored by them. Land degradation negatively affected all species. Our results allowed us to distinguish 4 groups of species that had similar responses and thus may require different forms of management. Our method provided an estimation of the growth rate (lambda) of the studied populations that was significantly correlated with lambdas obtained from demographic studies. The size structures of populations were consistent with the predictions of the analysis, which suggests our results are consistent and reliable. Disturbance-response analysis provides a basis for management in heavily populated areas, where conservation must be achieved along with development activities that cause CAD. The method provides readily interpretable information, which facilitates participative decision making; the data are rapidly generated, which makes it appropriate when results are required promptly or for assessment of large numbers of species; and it provides a comprehensive perception of how threatened species behave in the real world.

  4. Changing the energy of an immune response

    PubMed Central

    Delmastro-Greenwood, Meghan M; Piganelli, Jon D

    2013-01-01

    The breakdown of nutrients into the critical energy source ATP is the general purpose of cellular metabolism and is essential for sustaining life. Similarly, the immune system is composed of different cell subsets that are indispensable for defending the host against pathogens and disease. The interplay between metabolic pathways and immune cells leads to a plethora of different signaling pathways as well as cellular activities. The activation of T cells via glycolysis-mediated upregulation of surface markers, for example, is necessary for an appropriate effector response against an infection. However, tight regulation of immune cell metabolism is required for protecting the host and resuming homeostasis. An imbalance of immunological metabolic function and/or metabolic byproducts (reactive oxygen species) can oftentimes lead to diseases. In the case of cancer, overactive glucose metabolism can lead to hyperproliferation of cells and subsequent decreases in cytotoxic T cell activity, which attack and destroy the tumor. For this reason and many more, targeting metabolism in immune cells may be a novel therapeutic strategy for treatment of disease. The metabolic pathways of immune cells and the possibilities of immunometabolic therapies will be discussed. PMID:23885324

  5. Multiscale modeling of mucosal immune responses

    PubMed Central

    2015-01-01

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

  6. Multiscale modeling of mucosal immune responses.

    PubMed

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

    2015-01-01

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

  7. Mesenchymal stem cells and adaptive immune responses.

    PubMed

    Cao, Wei; Cao, Kai; Cao, Jianchang; Wang, Ying; Shi, Yufang

    2015-12-01

    Over the past decade, our understanding of the regulatory role of mesenchymal stem cells (MSCs) in adaptive immune responses through both preclinical and clinical studies has dramatically expanded, providing great promise for treating various inflammatory diseases. Most studies are focused on the modulatory effects of these cells on the properties of T cell-mediated immune responses, including activation, proliferation, survival, and subset differentiation. Interestingly, the immunosuppressive function of MSCs was found to be licensed by IFN-γ and TNF-α produced by T cells and that can be further amplified by cytokines such as IL-17. However, the immunosuppressive function of MSCs can be reversed in certain situation, such as suboptimal levels of inflammatory cytokines, or in the presence of immunosuppressive molecules. Here we review the influence of MSCs on adaptive immune system, especially their bidirectional interaction in tuning the immune microenvironment and subsequently repairing damaged tissue. Understanding MSC-mediated regulation of T cells is expected to provide fundamental information for guiding appropriate applications of MSCs in clinical settings. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. The Memory Immune Response to Tuberculosis.

    PubMed

    Kirman, Joanna R; Henao-Tamayo, Marcela I; Agger, Else Marie

    2016-12-01

    Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to Mycobacterium tuberculosis will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity. More recently, we have learned that the memory response required for effective control of M. tuberculosis is much more complex, probably involving several phenotypically different CD4 T cell subsets as well as other cell types that are yet to be defined. Herein, we describe recent insights into memory immunity to TB in the context of both animal models and the human infection. With the increasing amount of data generated from clinical testing of novel TB vaccines, we also summarize recent knowledge of vaccine-induced memory immunity.

  9. THE EVOLUTION OF THE IMMUNE RESPONSE

    PubMed Central

    Finstad, Joanne; Good, Robert A.

    1964-01-01

    1. Studies of the immune response have been carried out in more than 1700 lampreys representing three stages in the life cycle of these animals. 2. Lampreys used in this study were unable to clear certain soluble protein antigens and bacteriophage and were unable to make antibodies to these antigens. Hemocyanin was cleared from the circulation. 3. The immune responses demonstrated in lampreys include the production of specific antibody to killed Brucella cells, the rejection of skin homografts, and the development of a delayed allergic response to old tuberculin. 4. A responsive proliferation of lymphoid cells occurred in the protovertebral arch following antigen-adjuvant stimulation. 5. Electrophoretic and immunoelectrophoretic analysis of lamprey serum revealed gamma globulin. Ultracentrifugal analysis of serum revealed proteins with sedimentation coefficients of 17S, 8S, 7S, and 3S. 6. The antibodies thus far observed in the lamprey are of relatively high molecular weight and destroyed by 2-mercaptoethanol. 7. In the lamprey it would appear that there is reflected the coordinate evolution of a primitive thymus, primitive spleen containing lymphoid foci, a family of lymphocytes in the peripheral blood and capacity for gamma globulin synthesis and expression of adaptive immunity. PMID:14238932

  10. The innate and adaptive immune response to avian influenza virus

    USDA-ARS?s Scientific Manuscript database

    Protective immunity against viruses is mediated by the early innate immune responses and later on by the adaptive immune responses. The early innate immunity is designed to contain and limit virus replication in the host, primarily through cytokine and interferon production. Most all cells are cap...

  11. MYC and HIF in shaping immune response and immune metabolism.

    PubMed

    Gnanaprakasam, J N Rashida; Sherman, John William; Wang, Ruoning

    2017-06-01

    Upon antigen stimulation, quiescent naive T cells undergo a phase of cell mass accumulation followed by cell cycle entry, clonal expansion, differentiation into functional subsets and back again to a quiescent state as they develop into memory cells. The transitions between these distinct cellular states place unique metabolic demands on energy, redox and biosynthesis. To fulfill these demands, T cells switch back and forth between their primary catabolic pathways. While quiescent naive and memory T cells largely rely on the oxidation of fatty acids and glucose, active T cells rely on glycolysis and glutaminolysis to sustain cell growth, proliferation and differentiation. Beyond several key signaling kinase cascades, the hypoxia inducible factor 1 (HIF-1) and the proto-oncogene MYC, act alone or in concert, to coordinate T cell metabolic reprogramming, cell proliferation, functional differentiation and apoptosis, enabling a robust T cell-mediated adaptive immune response. Copyright © 2017. Published by Elsevier Ltd.

  12. Depleted uranium disturbs immune parameters in zebrafish, Danio rerio: an ex vivo/in vivo experiment.

    PubMed

    Gagnaire, Béatrice; Bado-Nilles, Anne; Sanchez, Wilfried

    2014-10-01

    In this study, we investigated the effects of depleted uranium (DU), the byproduct of nuclear enrichment of uranium, on several parameters related to defence system in the zebrafish, Danio rerio, using flow cytometry. Several immune cellular parameters were followed on kidney leucocytes: cell proportion, cell mortality, phagocytosis activity and associated oxidative burst and lysosomal membrane integrity (LMI). Effects of DU were tested ex vivo after 17 h of contact between DU and freshly isolated leucocytes from 0 to 500 µg DU/L. Moreover, adult zebrafish were exposed in vivo during 3 days at 20 and 250 µg DU/L. Oxidative burst results showed that DU increased reactive oxygen species (ROS) basal level and therefore reduced ROS stimulation index in both ex vivo and in vivo experiments. ROS PMA-stimulated level was also increased at 250 µg DU/L in vivo only. Furthermore, a decrease of LMI was detected after in vivo experiments. Cell mortality was also decreased at 20 µg DU/L in ex vivo experiment. However, phagocytosis activity was not modified in both ex vivo and in vivo experiments. A reduction of immune-related parameters was demonstrated in zebrafish exposed to DU. DU could therefore decrease the ability of fish to stimulate its own immune system which could, in turn, enhance the susceptibility of fish to infection. These results encourage the development and the use of innate immune analysis by flow cytometry in order to understand the effects of DU and more generally radionuclides on fish immune system and response to infectious diseases.

  13. Humoral innate immune response and disease

    PubMed Central

    Shishido, Stephanie N.; Varahan, Sriram; Yuan, Kai; Li, Xiangdong; Fleming, Sherry D.

    2012-01-01

    The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathogy. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies. PMID:22771788

  14. Evolutionary responses of innate Immunity to adaptive immunity

    USDA-ARS?s Scientific Manuscript database

    Innate immunity is present in all metazoans, whereas the evolutionarily more novel adaptive immunity is limited to jawed fishes and their descendants (gnathostomes). We observe that the organisms that possess adaptive immunity lack diversity in their innate pattern recognition receptors (PRRs), rais...

  15. Hydrological and geochemical response and recovery in disturbed Arctic ecosystems

    SciTech Connect

    Not Available

    1992-01-01

    This progress report is a funding, extension request to continue the database work for the Hydrological and Geochemical Response and Recovery in Disturbed Arctic Ecosystems Program. Throughout the period from 1985 to 1992 the Department of Energy supported research on the hydrology and geochemistry of the headwater basin of Imnavait Creek has focused on the quantification of the input from atmospheric sources of biologically significant and other related chemical variables; the transport of these variables in surface and subsurface flow and their efflux from the basin; and the development of geochemical budgets. The acquisition of multi-year data sets (the longest and most detailed sets in the Arctic) have made it possible to define seasonal ranges and amplitudes; determine spatial and temporal relationships within the different flow compartments; to begin to model the pathways and rates of movement through and across different landscape units. The length of record has also made it possible to examine the quantity and influence of local and extra-regional additions.

  16. Response to natural disturbance and attack in a trade model

    NASA Astrophysics Data System (ADS)

    Su, Bei-Bei; Xu, Tian; He, Da-Ren

    2005-03-01

    We suggest a trade model, which may describe the trade activities between the open ports along Yangzi River. The cumulative distribution of the quantities of port export and import, generalized by the model, shows a good agreement with our statistical results over 229 open ports. Randomly select a port and let its production decrease greatly by a fixed ratio (a disturbance), we find that the averaged quantities of port export and import increase obviously. This means that, in a healthy trade network, a lot of elements can make benefits when one of them is hit by a natural calamity. When select the port that has most trade relationship with others and let its production decrease greatly by a fixed ratio (an attack), we find that the averaged quantities of port export and import soon recovers and reach the original value. This healthy response will significantly change if the trade rules in the model are only slightly revised. This result may suggest a feature, which can distinguish healthy complex systems from others.

  17. Response of High Subsonic Jet to Nonaxisymmetric Disturbances

    NASA Technical Reports Server (NTRS)

    Bayliss, A.; Maestrello, L.

    1997-01-01

    A model of sound generated in a high subsonic (Mach 0.9) circular jet is solved numerically in cylindrical coordinates for nonaxisymmetric disturbances. The jet is excited by transient mass injection by a finite duration pulse via a modulated ring source. The nonaxisymmetric solution is computed for long times after the initial disturbance has exited the computational domain. The long time behavior of the jet is dominated by vorticity and pressure disturbances generated at the nozzle lip and growing as they convect down-stream in the jet. These disturbances generate sound as they propagate. The primary non-axisymmetric effect that we simulate is that of a flapping mode where regions of high and low pressure alternate on opposite sides of the jet. The predominant feature of this mode is the appearance of relatively large deviations of the pressure from the ambient pressure on opposite sides of the jet and the convection of these regions downstream. We illustrate flow field, near field and far field data. Important nonaxisymmetric characteristics of the near and flow field disturbances include roughly periodic pressure elevations and depressions at opposite values of the azimuthal angle psi. These correspond to pressure disturbances propagating in the axial direction. The azimuthal velocity exhibits a sinusoidal dependence on psi with similar roughly periodic disturbances. For every azimuthal angle psi, the jet radiation peaks about 30 deg. from the jet axis, however there is now a pronounced dependence of the far field radiation pattern on psi.

  18. Immune responses to pertussis vaccines and disease.

    PubMed

    Edwards, Kathryn M; Berbers, Guy A M

    2014-04-01

    In this article we discuss the following: (1) acellular vaccines are immunogenic, but responses vary by vaccine; (2) pertussis antibody levels rapidly wane but promptly increase after vaccination; (3) whole-cell vaccines vary in immunogenicity and efficacy; (4) whole-cell vaccines and naturally occurring pertussis generate predominantly T-helper 1 (Th1) responses, whereas acellular vaccines generate mixed Th1/Th2 responses; (5) active transplacental transport of pertussis antibody is documented; (6) neonatal immunization with diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine has been associated with some suppression of pertussis antibody, but suppression has been seen less often with acellular vaccines; (7) memory B cells persist in both acellular vaccine- and whole cell vaccine-primed children; and (8) in acellular vaccine-primed children, T-cell responses remain elevated and do not increase with vaccine boosters, whereas in whole-cell vaccine-primed children, these responses can be increased by vaccine boosting and natural exposure. Despite these findings, challenges remain in understanding the immune response to pertussis vaccines.

  19. Correction of age-associated deficiency in germinal center response by immunization with immune complexes.

    PubMed

    Zheng, Biao; Switzer, Kirsten; Marinova, Ekaterina; Wansley, Daniel; Han, Shuhua

    2007-08-01

    In aging, both primary and secondary antibody responses are impaired. One of the most notable changes in age-associated immune deficiency is the diminished germinal center (GC) reaction. This impaired GC response reduces antibody affinity maturation, decreases memory B cell development, and prevents the establishment of long-term antibody-forming cells in the bone marrow. It is of great importance to explore novel strategy in improving GC response in the elderly. In this study, the efficacy of immunization with immune complexes in overcoming age-associated deficiency in GC response was investigated. We show that the depressed GC response in aged mice can be significantly elevated by immunization with immune complexes. Importantly, there is a significant improvement of B cell memory response and long-lived plasma cells. Our results demonstrate that immune complex immunization may represent a novel strategy to elicit functional GC response in aging, and possibly, to overcome age-related immune deficiency in general.

  20. Cellular immune responses towards regulatory cells.

    PubMed

    Larsen, Stine Kiær

    2016-01-01

    This thesis describes the results from two published papers identifying spontaneous cellular immune responses against the transcription factors Foxp3 and Foxo3. The tumor microenvironment is infiltrated by cells that hinder effective tumor immunity from developing. Two of these cell types, which have been linked to a bad prognosis for patients, are regulatory T cells (Treg) and tolerogenic dendritic cells (DC). Tregs inhibit effector T cells from attacking the tumor through various mechanisms, including secreted factors and cell-to-cell contact. Tregs express the transcription factor Foxp3, which is necessary for their development and suppressive activities. Tolerogenic DCs participate in creating an environment in the tumor where effector T cells become tolerant towards the tumor instead of attacking it. The transcription factor Foxo3 was recently described to be highly expressed by tolerogenic DCs and to programme their tolerogenic influence. This thesis describes for the first time the existence of spontaneous cellular immune responses against peptides derived from Foxp3 and Foxo3. We have detected the presence of cytotoxic T cells that recognise these peptides in an HLA-A2 restricted manner in cancer patients and for Foxp3 in healthy donors as well. In addition, we have demonstrated that the Foxp3- and Foxo3-specific CTLs recognize Foxp3- and Foxo3-expressing cancer cell lines and importantly, suppressive immune cells, namely Tregs and in vitro generated DCs. Cancer immunotherapy is recently emerging as an important treatment modality improving the survival of selected patients. The current progress is largely owing to targeting of the immune suppressive milieu that is dominating the tumor microenvironment. This is being done through immune checkpoint blockade with CTLA-4 and PD-1/PD-L1 antibodies and through lymphodepleting conditioning of patients and ex vivo activation of TILs in adoptive cell transfer. Several strategies are being explored for depletion of

  1. Immune response and immunopathology during toxoplasmosis1

    PubMed Central

    Dupont, Christopher D.; Christian, David A.; Hunter, Christopher A.

    2012-01-01

    Toxoplasma gondii is a protozoan parasite of medical and veterinary significance that is able to infect any warm-blooded vertebrate host. In addition to its importance to public health, several inherent features of the biology of T. gondii have made it an important model organism to study host-pathogen interactions. One factor is the genetic tractability of the parasite, which allows studies on the microbial factors that affect virulence and allows the development of tools that facilitate immune studies. Additionally, mice are natural hosts for T. gondii, and the availability of numerous reagents to study the murine immune system makes this an ideal experimental system to understand the functions of cytokines and effector mechanisms involved in immunity to intracellular microorganisms. In this article, we will review current knowledge of the innate and adaptive immune responses required for resistance to toxoplasmosis, the events that lead to the development of immunopathology, and the natural regulatory mechanisms that limit excessive inflammation during this infection. PMID:22955326

  2. Staphylococcal manipulation of host immune responses

    PubMed Central

    Thammavongsa, Vilasack; Kim, Hwan Keun; Missiakas, Dominique; Schneewind, Olaf

    2015-01-01

    Staphylococcus aureus, a bacterial commensal of the human nares and skin, is a frequent cause of soft tissue and bloodstream infections. A hallmark of staphylococcal infections is their frequent recurrence, even when treated with antibiotics and surgical intervention, which demonstrates the bacterium’s ability to manipulate innate and adaptive immune responses. In this Review, we highlight how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B and T cell responses, and we discuss how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S. aureus. PMID:26272408

  3. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1988-07-31

    Security Classification) (U) Human Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Francis A. Ennis 13a. TYPE OF’REPORTn 13b. TIME COVERED 14...8217SUBJECT TERMS (Continue on reverse if necessary and identify by Nock rumber) FIELD GROUP SUB-GROUP RA .1, Dengue virus, T lymphopytes. 06 03 InB-GROP1.In...responses to dengue antigens in vitro to elucidate the possible role of T lymphocytes in the pathogeneeis of dengue hemorrhagic fever and dengue

  4. Antiviral immune responses of bats: a review.

    PubMed

    Baker, M L; Schountz, T; Wang, L-F

    2013-02-01

    Despite being the second most species-rich and abundant group of mammals, bats are also among the least studied, with a particular paucity of information in the area of bat immunology. Although bats have a long history of association with rabies, the emergence and re-emergence of a number of viruses from bats that impact human and animal health has resulted in a resurgence of interest in bat immunology. Understanding how bats coexist with viruses in the absence of disease is essential if we are to begin to develop therapeutics to target viruses in humans and susceptible livestock and companion animals. Here, we review the current status of knowledge in the field of bat antiviral immunology including both adaptive and innate mechanisms of immune defence and highlight the need for further investigations in this area. Because data in this field are so limited, our discussion is based on both scientific discoveries and theoretical predictions. It is hoped that by provoking original, speculative or even controversial ideas or theories, this review may stimulate further research in this important field. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Although bats appear to share most features of the immune system with other mammals, several studies have reported qualitative and quantitative differences in the immune responses of bats. These observations warrant further investigation to determine whether such differences are associated with the asymptomatic nature of viral infections in bats.

  5. Assessing anthropogenic and natural disturbances: forest response to similarly aged clearcut and tornado disturbances in an east Tennessee oak-hickory forest

    Treesearch

    Jonathan C. McGrath; Wayne K. Clatterbuck

    2013-01-01

    In February of 1993, an F3 tornado caused a large-scale disturbance in an east Tennessee oak-hickory (Quercus spp.-Carya spp.) forest. Vegetation response to anthropogenic and natural disturbances was compared by examining two tornado-disturbed areas and five adjacent 1-acre silvicultural clearcut areas unaffected by the tornado...

  6. Erosion response of a disturbed sagebrush steppe hillslope

    USGS Publications Warehouse

    Goff, B.F.; Bent, G.C.; Hart, G.E.

    1993-01-01

    Land management activities that disrupt surface vegetation cover pose a serious threat to the long-term stability of buried-waste sites located within the semiarid sagebrush (Artemisia tridentata Nutt.) steppe region of the northwestern USA. In this study, we evaluated the erosion response of a sagebrush hillslope subjected to three vegetation cover treatments: natural (undisturbed), bare (plant canopy and litter cover removed), and clipped (canopy removed). A rotating boom rainfall simulator was used to apply rain at 60 or 120 mm/h intensities to runoff plots (3.0 m by 10.7 m) with dry, wet, and very wet antecedent moisture conditions, and during two late and one early summer seasons. Supplemental overland flow was added at the upper end of each plot to simulate increased slope length during very wet runs. Maximum soil loss rates on the natural, clipped, and bare treatments were, respectively, 1, 5, and 216 mg/m2 per s during the 60 mm/h rainfall intensity, and 13, 79, and 1473 mg/m2 per s during the 120 mm/h rainfall intensity. Cumulative soil loss was typically 100 to 1000 times greater on the bare treatment than on the natural or clipped treatments. Increases in simulated slope length produced a near linear increase in soil loss from the bare treatment plots (about 0.02 g/m2 per s soil loss per m of slope length) until 30 m, after which the effect of slope length declined. Surface crust development and mound-intermound microtopography played important roles in governing soil detachment and transport on the hillslope. Despite high rainfall intensity and surface runoff rates, rill erosion was negligible on both the undisturbed and disturbed portions of the hillslope.

  7. Immune Response among Patients Exposed to Molds

    PubMed Central

    Edmondson, David A.; Barrios, Christy S.; Brasel, Trevor L.; Straus, David C.; Kurup, Viswanath P.; Fink, Jordan N.

    2009-01-01

    Macrocyclic trichothecenes, mycotoxins produced by Stachybotrys chartarum, have been implicated in adverse reactions in individuals exposed to mold-contaminated environments. Cellular and humoral immune responses and the presence of trichothecenes were evaluated in patients with mold-related health complaints. Patients underwent history, physical examination, skin prick/puncture tests with mold extracts, immunological evaluations and their sera were analyzed for trichothecenes. T-cell proliferation, macrocyclic trichothecenes, and mold specific IgG and IgA levels were not significantly different than controls; however 70% of the patients had positive skin tests to molds. Thus, IgE mediated or other non-immune mechanisms could be the cause of their symptoms. PMID:20054481

  8. IL-1 and T Helper Immune Responses

    PubMed Central

    Santarlasci, Veronica; Cosmi, Lorenzo; Maggi, Laura; Liotta, Francesco; Annunziato, Francesco

    2013-01-01

    CD4 T cells play a critical role in mediating adaptive immunity to a variety of pathogens as well as in tumor immunity. If not adequately regulated, CD4 T cells can be also involved in autoimmunity, asthma, and allergic responses. During TCR activation in a particular cytokine milieu, naïve CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, and Th17, as defined by their pattern of cytokine production and function. IL-1, the prototypic proinflammatory cytokine, has been shown to influence growth and differentiation of immunocompetent lymphocytes. The differential expression of IL-1RI on human CD4 T cell subsets confers distinct capacities to acquire specific effector functions. In this review, we summarize the role of IL-1 on CD4 T cells, in terms of differentiation, activation, and maintenance or survival. PMID:23874332

  9. Managing forest disturbances and community responses: lessons from the Kenai Peninsula, Alaska.

    Treesearch

    Courtney G. Flint; Richard. Haynes

    2006-01-01

    Managing forest disturbances can be complicated by diverse human community responses. Interview and quantitative analysis of mail surveys were used to assess risk perceptions and community actions in response to forest disturbance by spruce bark beetles. Despite high risk perception of immediate threats to personal safety and property, risk perceptions of broader...

  10. Spaceflight and Development of Immune Responses

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1996-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The objective of the studies contained in this project was to determine the effects of space flight on immune responses of pregnant rats and their offspring. The hypothesis was that space flight and the attendant period of microgravity will result in alteration of immunological parameters of both the pregnant rats as well as their offspring carried in utero during the flight. The parameters tested included: production of cytokines, composition of leukocyte sub- populations, response of bone marrow/liver cells to granulocyte/monocyte colony stimulating factor, and leukocyte blastogenesis. Changes in immune responses that could yield alterations in resistance to infection were determined. This yielded useful information for planning studies that could contribute to crew health. Additional information that could eventually prove useful to determine the potential for establishment of a permanent colony in space was obtained.

  11. [Types of immune response in advanced suppurative peritonitis].

    PubMed

    Borisov, A G; Savchenko, A A; Cherdantsev, D V; Zdzitovetsky, D E; Pervova, O V; Kudryavtsev, I V; Belenyuk, V D; Shapkina, V A

    to assess types of immune response in patients with advanced suppurative peritonitis and course of disease. We examined 79 patients with acute surgical abdominal diseases and injuries complicated by advanced suppurative peritonitis. Blood immunological parameters were estimated using flowing cytometry and enzyme immunoassay. It was concluded that functional parameters of immune system are very various in patients with advanced suppurative peritonitis. Cluster analysis defined 4 immune types which are determined by different state of congenital and acquired immunity. Immunodeficient and unreactive immune types are unfavorable. Immune types with activation of congenital and acquired immunity are the most favourable. This stratification personifies diagnosis and treatment of immune disorders in patients with advanced suppurative peritonitis.

  12. Convergent structural responses of tropical forests to diverse disturbance regimes.

    PubMed

    Kellner, James R; Asner, Gregory P

    2009-09-01

    Size frequency distributions of canopy gaps are a hallmark of forest dynamics. But it remains unknown whether legacies of forest disturbance are influencing vertical size structure of landscapes, or space-filling in the canopy volume. We used data from LiDAR remote sensing to quantify distributions of canopy height and sizes of 434,501 canopy gaps in five tropical rain forest landscapes in Costa Rica and Hawaii. The sites represented a wide range of variation in structure and natural disturbance history, from canopy gap dynamics in lowland Costa Rica and Hawaii, to stages and types of stand-level dieback on upland Mauna Kea and Kohala volcanoes. Large differences in vertical canopy structure characterized these five tropical rain forest landscapes, some of which were related to known disturbance events. Although there were quantitative differences in the values of scaling exponents within and among sites, size frequency distributions of canopy gaps followed power laws at all sites and in all canopy height classes. Scaling relationships in gap size at different heights in the canopy were qualitatively similar at all sites, revealing a remarkable similarity despite clearly defined differences in species composition and modes of prevailing disturbance. These findings indicate that power-law gap-size frequency distributions are ubiquitous features of these five tropical rain forest landscapes, and suggest that mechanisms of forest disturbance may be secondary to other processes in determining vertical and horizontal size structure in canopies.

  13. Realtime Prediction in Disturbed Landscapes: Identifying Highest Priority Disturbance Characteristics Impacting Streamflow Response in a CONUS-Scale Operational Model

    NASA Astrophysics Data System (ADS)

    Dugger, A. L.; Gochis, D. J.; Yu, W.; McCreight, J. L.; Barlage, M. J.

    2014-12-01

    The "next generation" of hydrologic prediction systems - targeting unified, process-based, real-time prediction of the total water cycle - bring with them an increased need for real-time land surface characterization. Climatologically-derived estimates may perform well under stationary conditions, however disturbance can significantly alter hydrologic behavior and may be poorly represented by mean historical conditions. Fortunately, remote sensing and on-the-ground observation networks are collecting snapshots of these land characteristics over an increasing fraction of the globe. Given the computing constraints of operating a large-domain, real-time prediction system, to take advantage of these data streams we need a way to prioritize which landscape characteristics are most important to hydrologic prediction post-disturbance. To address this need, we setup a model experiment over the contiguous US using the community WRF-Hydro system with the NoahMP land surface model to assess the value of incorporating various aspects of disturbed landscapes into a real-time streamflow prediction model. WRF-Hydro will serve as the initial operational model for the US National Weather Service's new national water prediction effort, so use of WRF-Hydro allows us to leverage both an existing CONUS-scale model implementation and a short research-to-operations path. We first identify USGS GAGES-II basins that experienced more than 25% forest loss between 2000 and 2013. Based on basin disturbance type, geophysical setting, and climate regime, we formulate a conceptual model of which "disturbed" landscape characteristics we expect to dominate streamflow response. We test our conceptual model using WRF-Hydro by modeling a baseline (no disturbance) case, and then bringing in empirically-derived model state shifts representing key disturbance characteristics (e.g., leaf area index, rooting depth, overland roughness, surface detention). For each state update and each basin, we quantify

  14. Realtime Prediction in Disturbed Landscapes: Identifying Highest Priority Disturbance Characteristics Impacting Streamflow Response in a CONUS-Scale Operational Model

    NASA Astrophysics Data System (ADS)

    Dugger, A. L.; Gochis, D. J.; Yu, W.; McCreight, J. L.; Barlage, M. J.

    2015-12-01

    The "next generation" of hydrologic prediction systems - targeting unified, process-based, real-time prediction of the total water cycle - bring with them an increased need for real-time land surface characterization. Climatologically-derived estimates may perform well under stationary conditions, however disturbance can significantly alter hydrologic behavior and may be poorly represented by mean historical conditions. Fortunately, remote sensing and on-the-ground observation networks are collecting snapshots of these land characteristics over an increasing fraction of the globe. Given the computing constraints of operating a large-domain, real-time prediction system, to take advantage of these data streams we need a way to prioritize which landscape characteristics are most important to hydrologic prediction post-disturbance. To address this need, we setup a model experiment over the contiguous US using the community WRF-Hydro system with the NoahMP land surface model to assess the value of incorporating various aspects of disturbed landscapes into a real-time streamflow prediction model. WRF-Hydro will serve as the initial operational model for the US National Weather Service's new national water prediction effort, so use of WRF-Hydro allows us to leverage both an existing CONUS-scale model implementation and a short research-to-operations path. We first identify USGS GAGES-II basins that experienced more than 25% forest loss between 2000 and 2013. Based on basin disturbance type, geophysical setting, and climate regime, we formulate a conceptual model of which "disturbed" landscape characteristics we expect to dominate streamflow response. We test our conceptual model using WRF-Hydro by modeling a baseline (no disturbance) case, and then bringing in empirically-derived model state shifts representing key disturbance characteristics (e.g., leaf area index, rooting depth, overland roughness, surface detention). For each state update and each basin, we quantify

  15. Roles of Toll-like receptors in innate immune responses.

    PubMed

    Takeda, K; Akira, S

    2001-09-01

    Innate immunity recognizes invading micro-organisms and triggers a host defence response. However, the molecular mechanism for innate immune recognition was unclear. Recently, a family of Toll-like receptors (TLRs) was identified, and crucial roles for these receptors in the recognition of microbial components have been elucidated. The TLR family consists of 10 members and will be expanding. Each TLR distinguishes between specific patterns of microbial components to provoke innate immune responses. The activation of innate immunity then leads to the development of antigen-specific adaptive immunity. Thus, TLRs control both innate and adaptive immune responses.

  16. Human Immune Responses to Dengue Viruses.

    DTIC Science & Technology

    1986-07-01

    AD-AISI 652 NUMAN IMMUNE RESPONSES TO DENGUE YIRUSES(U) / MASSACHUSETTS UNJY MEDICAL CENTER WORCESTER "A F A ENNIS 61 JUL 86 DRMDI?-82-C-2233...A S. PAGE COUNT Ie ..U rO l-9SJulyl (vw = T 21 Virus; Dengue ; Arbovirus; Immunology -- 4b he,. SAaaY~d the Interaction between the peripheral blood...lymphocytes (PBL) of non- 10m.0 deors ad dengue virus-Infected cells, which results in Interferon (113) production. AutelepMu mecyts@ or the Zpstein

  17. Monitoring Regulatory Immune Responses in Tumor Immunotherapy Clinical Trials

    PubMed Central

    Olson, Brian M.; McNeel, Douglas G.

    2013-01-01

    While immune monitoring of tumor immunotherapy often focuses on the generation of productive Th1-type inflammatory immune responses, the importance of regulatory immune responses is often overlooked, despite the well-documented effects of regulatory immune responses in suppressing anti-tumor immunity. In a variety of malignancies, the frequency of regulatory cell populations has been shown to correlate with disease progression and a poor prognosis, further emphasizing the importance of characterizing the effects of immunotherapy on these populations. This review focuses on the role of suppressive immune populations (regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages) in inhibiting anti-tumor immunity, how these populations have been used in the immune monitoring of clinical trials, the prognostic value of these responses, and how the monitoring of these regulatory responses can be improved in the future. PMID:23653893

  18. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica

    PubMed Central

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  19. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica.

    PubMed

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis.

  20. Inter-specific variation in avian responses to human disturbance

    Treesearch

    Daniel T. Blumstein; Esteban Fernandez-Juricic; Patrick A. Zollner; Susan C. Garity

    2005-01-01

    1. Increasing urbanization and recreational activities around and within biodiversity hotspots require an understanding of how to reduce the impacts of human disturbance on more than a single species; however, we lack a general framework to study multiple species. One approach is to expand on knowledge about the theory of anti-predator behaviour to understand and...

  1. Biomarker responses of mussels exposed to earthquake disturbances

    NASA Astrophysics Data System (ADS)

    Chandurvelan, Rathishri; Marsden, Islay D.; Glover, Chris N.; Gaw, Sally

    2016-12-01

    The green-lipped mussel, Perna canaliculus is recognised as a bioindicator of coastal contamination in New Zealand (NZ). Mussels (shell length 60-80 mm) were collected from three intertidal areas of Canterbury in the South Island of NZ prior to extreme earthquake disturbances on 22nd February 2011, and 9 months later in October 2011. Trace elements, including arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn), were measured in the gills, digestive gland, foot and mantle. Metal levels in tissues were site specific, and mostly unaffected by earthquake disturbances. Physiological biomarkers were negatively affected by earthquake disturbances and mussels from the Port of Lyttelton had higher negative scope for growth post-earthquake. Metallothionein-like protein in the digestive gland correlated with metal content of tissues, as did catalase activity in the gill and lipid peroxidation values for the digestive gland. This research demonstrates that physiological and other biomarkers are effective at detecting the effects of multiple stressors following seismic disturbances.

  2. A meta-analysis of bees' responses to anthropogenic disturbance.

    PubMed

    Winfree, Rachael; Aguilar, Ramiro; Vázquez, Diego P; LeBuhn, Gretchen; Aizen, Marcelo A

    2009-08-01

    Pollinators may be declining globally, a matter of concern because animal pollination is required by most of the world's plant species, including many crop plants. Human land use and the loss of native habitats is thought to be an important driver of decline for wild, native pollinators, yet the findings of published studies on this topic have never been quantitatively synthesized. Here we use meta-analysis to synthesize the literature on how bees, the most important group of pollinators, are affected by human disturbances such as habitat loss, grazing, logging, and agriculture. We obtained 130 effect sizes from 54 published studies recording bee abundance and/or species richness as a function of human disturbance. Both bee abundance and species richness were significantly, negatively affected by disturbance. However, the magnitude of the effects was not large. Furthermore, the only disturbance type showing a significant negative effect, habitat loss and fragmentation, was statistically significant only in systems where very little natural habitat remains. Therefore, it would be premature to draw conclusions about habitat loss having caused global pollinator decline without first assessing the extent to which the existing studies represent the status of global ecosystems. Future pollinator declines seem likely given forecasts of increasing land-use change.

  3. Herbaceous response to type and severity of disturbance

    Treesearch

    Katherine J. Elliott; Craig A. Harper; Beverly Collins

    2011-01-01

    The herbaceous layer varies with topographic heterogeneity and harbors the great majority of plant diversity in eastern deciduous forests. We described the interplay between disturbances, both natural and human-caused, and composition, dynamics, and diversity of herbaceous vegetation, especially those in early successional habitats. Management actions that create low...

  4. Long-term effects of early life microbiota disturbance on adaptive immunity in laying hens.

    PubMed

    Simon, K; Verwoolde, M B; Zhang, J; Smidt, H; de Vries Reilingh, G; Kemp, B; Lammers, A

    2016-07-01

    Due to an interplay between intestinal microbiota and immune system, disruption of intestinal microbiota composition during immune development may have consequences for immune responses later in life. The present study investigated the effects of antibiotic treatment in the first weeks of life on the specific antibody response later in life in chickens. Layer chicks received an antibiotic cocktail consisting of vancomycin, neomycin, metronidazole, and amphotericin-B by oral gavage every 12 h, and ampicillin and colistin in drinking water for the first week of life. After the first week of life, chicks received ampicillin and colistin in drinking water for two more weeks. Control birds received no antibiotic cocktail and plain drinking water. Fecal microbiota composition was determined during antibiotic treatment (d 8 and 22), two weeks after cessation of antibiotic treatment (d 36), and at the end of the experimental period at d 175 using a 16S ribosomal RNA gene targeted microarray, the Chicken Intestinal Tract Chip (ChickChip). During antibiotic treatment fecal microbiota composition differed strongly between treatment groups. Fecal microbiota of antibiotic treated birds consisted mainly of Proteobacteria, and in particular E.coli, whereas fecal microbiota of control birds consisted mainly of Firmicutes, such as lactobacilli and clostridia. Two weeks after cessation of antibiotic treatment fecal microbiota composition of antibiotic treated birds had recovered and was similar to that of control birds. On d 105, 12 weeks after cessation of antibiotic treatment, chicks of both treatment groups received an intra-tracheal lipopolysaccharide (LPS)/human serum albumin (HuSA) challenge. Antibody titers against LPS and HuSA were measured 10 days after administration of the challenge. While T cell independent antibody titers (LPS) were not affected by antibiotic treatment, antibiotic treated birds showed lower T cell dependent antibody titers (HuSA) compared with control

  5. Immune responses to coiled coil supramolecular biomaterials.

    PubMed

    Rudra, Jai S; Tripathi, Pulak K; Hildeman, David A; Jung, Jangwook P; Collier, Joel H

    2010-11-01

    Self-assembly has been increasingly utilized in recent years to create peptide-based biomaterials for 3D cell culture, tissue engineering, and regenerative medicine, but the molecular determinants of these materials' immunogenicity have remained largely unexplored. In this study, a set of molecules that self-assembled through coiled coil oligomerization was designed and synthesized, and immune responses against them were investigated in mice. Experimental groups spanned a range of oligomerization behaviors and included a peptide from the coiled coil region of mouse fibrin that did not form supramolecular structures, an engineered version of this peptide that formed coiled coil bundles, and a peptide-PEG-peptide triblock bioconjugate that formed coiled coil multimers and supramolecular aggregates. In mice, the native peptide and engineered peptide did not produce any detectable antibody response, and none of the materials elicited detectable peptide-specific T cell responses, as evidenced by the absence of IL-2 and interferon-gamma in cultures of peptide-challenged splenocytes or draining lymph node cells. However, specific antibody responses were elevated in mice injected with the multimerizing peptide-PEG-peptide. Minimal changes in secondary structure were observed between the engineered peptide and the triblock peptide-PEG-peptide, making it possible that the triblock's multimerization was responsible for this antibody response.

  6. Precision Immunization: NASA Studies Immune Response to Flu Vaccine

    NASA Image and Video Library

    NASA Human Research Program Twins Study investigator Emmanuel Mignot, M.D., Ph.D, known for discovering the cause of narcolepsy is related to the immune system, is studying twin astronauts Scott an...

  7. Neuroendocrine and Immune System Responses with Spaceflights

    NASA Technical Reports Server (NTRS)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  8. Neuroendocrine and Immune System Responses with Spaceflights

    NASA Technical Reports Server (NTRS)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  9. Impact of nutrition on immune function and the inflammatory response

    USDA-ARS?s Scientific Manuscript database

    The review utilizes data on three micronutrients (vitamin A, zinc and iron), anthropometrically defined undernutrition (stunting, wasting and underweight) and obesity to evaluate the effect on immune function, recovery of immune function in response to nutritional interventions, related health outco...

  10. Responses of temperate forest productivity to insect and pathogen disturbances

    NASA Astrophysics Data System (ADS)

    Flower, C. E.; Gonzalez-Meler, M. A.

    2014-12-01

    Climate forcing factors have been documented to directly (e.g. CO2 fertilization) or indirectly (e.g. temperature and vapor pressure deficit) affect net primary productivity (NPP) of forests. Climate variations can also affect the vulnerability of forests to pests and pathogens, causing diffuse or widespread mortality. The introduction of novel pests is causing rapid mortality of targeted species with undetermined effects on forest productivity: NPP could decrease or increase depending on the severity (proportion of basal area impacted) and species diversity. We attempted to document the impact of diffuse mortality caused by insect outbreaks on North American temperate forests through synthesis of literature. Despite the large number of studies (>500) only a few (12) documented NPP in a systematic manner. The magnitude of insect and pathogen disturbance was larger in western than eastern forests due to the redundancy and functional diversity of temperate deciduous and mixed deciduous forests. Recovery from disturbance was more rapid from diffuse short duration defoliation events relative to the long lasting impacts of wood boring insects. Forest resilience may decrease as insect disturbance increases, particularly with generalist invasive pests that target a variety of species. We conclude that these biotic interactions, particularly when caused by invasive pests, impose biological forcing to forest NPP at similar magnitude and time scales than climate forcing.

  11. Responses of temperate forest productivity to insect and pathogen disturbances.

    PubMed

    Flower, Charles E; Gonzalez-Meler, Miquel A

    2015-01-01

    Pest and pathogen disturbances are ubiquitous across forest ecosystems, impacting their species composition, structure, and function. Whereas severe abiotic disturbances (e.g., clear-cutting and fire) largely reset successional trajectories, pest and pathogen disturbances cause diffuse mortality, driving forests into nonanalogous system states. Biotic perturbations that disrupt forest carbon dynamics either reduce or enhance net primary production (NPP) and carbon storage, depending on pathogen type. Relative to defoliators, wood borers and invasive pests have the largest negative impact on NPP and the longest recovery time. Forest diversity is an important contributing factor to productivity: NPP is neutral, marginally enhanced, or reduced in high-diversity stands in which a small portion of the canopy is affected (temperate deciduous or mixed forests) but very negative in low-diversity stands in which a large portion of the canopy is affected (western US forests). Pests and pathogens reduce forest structural and functional redundancy, affecting their resilience to future climate change or new outbreaks. Therefore, pests and pathogens can be considered biotic forcing agents capable of causing consequences of similar magnitude to climate forcing factors.

  12. Response of a Hypersonic Boundary Layer to Freestream Pulse Acoustic Disturbance

    PubMed Central

    Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing

    2014-01-01

    The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter. PMID:24737993

  13. Response of a hypersonic boundary layer to freestream pulse acoustic disturbance.

    PubMed

    Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing

    2014-01-01

    The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter.

  14. Identifying functional groups for response to disturbance in an abandoned pasture

    NASA Astrophysics Data System (ADS)

    Lavorel, Sandra; Touzard, Blaise; Lebreton, Jean-Dominique; Clément, Bernard

    1998-06-01

    In an abandoned pasture in Brittany, we compared artificial small-scale disturbances to natural disturbances by wild boar and undisturbed vegetation. We developed a multivariate statistical approach which analyses how species biological attributes explain the response of community composition to disturbances. This technique, which reconciles the inductive and deductive approaches for functional classifications, identifies groups of species with similar responses to disturbance and characterizes their biological profiles. After 5 months of recolonization, artificial disturbances had a greater species richness than undisturbed vegetation as a result of recruitment of new species without the exclusion of pre-existing matrix species. Species morphology, described by canopy structure, canopy height and lateral spread, explained a large part (16 %) of community response to disturbance. Regeneration strategies, described by life history, seed mass, dispersal agent, dormancy and the existence of vegetative multiplication, explained a smaller part of community response to disturbance (8 %). Artificial disturbances were characterized by therophyte and compact rosettes with moderately dormant seeds, including a number of Asteraceae and other early successional species. Natural disturbances were colonized by leafy guerrilla species without seed dormancy. Few species were tightly related to undisturbed vegetation and were essentially grasses with a phalanx rosette morphology. The functional classification obtained is consistent with the classification of the community into fugitives, regenerators and persistors. These groups are structured according to Grubb's model for temperate grasslands, with regenerators and persistors in the matrix and fugitives taking advantage of gaps open by small-scale disturbances. The conjunction of functional diversity and species diversity within functional groups is the key to resilience to disturbance, an important ecosystem function.

  15. Virus-like particle (VLP) lymphatic trafficking and immune response generation after immunization by different routes.

    PubMed

    Cubas, Rafael; Zhang, Sheng; Kwon, Sunkuk; Sevick-Muraca, Eva M; Li, Min; Chen, Changyi; Yao, Qizhi

    2009-01-01

    Virus-like particles (VLPs) have gained increasing interest for their use as vaccines due to their repetitive antigenic structure that is capable of efficiently activating the immune system. The efficacy of VLP immunization may lie in its ability to traffic into draining lymph nodes while activating antigen-presenting cells to initiate the orchestration of signals required for the development of a robust immune response. Currently, there is no comprehensive study showing the correlation of different VLP vaccination routes to immune outcome. In this study, we took an optical imaging approach to directly visualize the trafficking of simian-human immunodeficiency (SHIV) VLPs after immunization by commonly used routes and analyzed the corresponding humoral and cellular immune responses generated. We found that VLPs can easily enter the subcapsular sinus of draining lymph nodes with quantitative differences in the number of lymph node involvement depending on the immunization route used. Intradermal immunization led to the largest level of lymph node involvement for the longest period of time, which correlated with the strongest humoral and cellular immune responses. Flow cytometry analysis from extracted splenocytes showed that intradermal immunization led to the largest population of germinal center and activated B cells, which translated into higher antibody levels and antigen-specific cytotoxic T lymphocyte responses. Our results indicate that VLPs traffic into lymph nodes upon immunization and can be directly visualized by optical imaging techniques. Intradermal immunization showed improved responses and might be a preferable delivery route to use for viral and cancer immunotherapeutic studies involving VLPs.

  16. Disturbance-specific social responses in long-finned pilot whales, Globicephala melas

    NASA Astrophysics Data System (ADS)

    Visser, Fleur; Curé, Charlotte; Kvadsheim, Petter H.; Lam, Frans-Peter A.; Tyack, Peter L.; Miller, Patrick J. O.

    2016-06-01

    Social interactions among animals can influence their response to disturbance. We investigated responses of long-finned pilot whales to killer whale sound playbacks and two anthropogenic sources of disturbance: tagging effort and naval sonar exposure. The acoustic scene and diving behaviour of tagged individuals were recorded along with the social behaviour of their groups. All three disturbance types resulted in larger group sizes, increasing social cohesion during disturbance. However, the nature and magnitude of other responses differed between disturbance types. Tagging effort resulted in a clear increase in synchrony and a tendency to reduce surface logging and to become silent (21% of cases), whereas pilot whales increased surface resting during sonar exposure. Killer whale sounds elicited increased calling rates and the aggregation of multiple groups, which approached the sound source together. This behaviour appears to represent a mobbing response, a likely adaptive social defence against predators or competitors. All observed response-tactics would reduce risk of loss of group coordination, suggesting that, in social pilot whales, this could drive behavioural responses to disturbance. However, the behavioural means used to achieve social coordination depends upon other considerations, which are disturbance-specific.

  17. Disturbance-specific social responses in long-finned pilot whales, Globicephala melas.

    PubMed

    Visser, Fleur; Curé, Charlotte; Kvadsheim, Petter H; Lam, Frans-Peter A; Tyack, Peter L; Miller, Patrick J O

    2016-06-29

    Social interactions among animals can influence their response to disturbance. We investigated responses of long-finned pilot whales to killer whale sound playbacks and two anthropogenic sources of disturbance: tagging effort and naval sonar exposure. The acoustic scene and diving behaviour of tagged individuals were recorded along with the social behaviour of their groups. All three disturbance types resulted in larger group sizes, increasing social cohesion during disturbance. However, the nature and magnitude of other responses differed between disturbance types. Tagging effort resulted in a clear increase in synchrony and a tendency to reduce surface logging and to become silent (21% of cases), whereas pilot whales increased surface resting during sonar exposure. Killer whale sounds elicited increased calling rates and the aggregation of multiple groups, which approached the sound source together. This behaviour appears to represent a mobbing response, a likely adaptive social defence against predators or competitors. All observed response-tactics would reduce risk of loss of group coordination, suggesting that, in social pilot whales, this could drive behavioural responses to disturbance. However, the behavioural means used to achieve social coordination depends upon other considerations, which are disturbance-specific.

  18. Disturbance-specific social responses in long-finned pilot whales, Globicephala melas

    PubMed Central

    Visser, Fleur; Curé, Charlotte; Kvadsheim, Petter H.; Lam, Frans-Peter A.; Tyack, Peter L.; Miller, Patrick J. O.

    2016-01-01

    Social interactions among animals can influence their response to disturbance. We investigated responses of long-finned pilot whales to killer whale sound playbacks and two anthropogenic sources of disturbance: tagging effort and naval sonar exposure. The acoustic scene and diving behaviour of tagged individuals were recorded along with the social behaviour of their groups. All three disturbance types resulted in larger group sizes, increasing social cohesion during disturbance. However, the nature and magnitude of other responses differed between disturbance types. Tagging effort resulted in a clear increase in synchrony and a tendency to reduce surface logging and to become silent (21% of cases), whereas pilot whales increased surface resting during sonar exposure. Killer whale sounds elicited increased calling rates and the aggregation of multiple groups, which approached the sound source together. This behaviour appears to represent a mobbing response, a likely adaptive social defence against predators or competitors. All observed response-tactics would reduce risk of loss of group coordination, suggesting that, in social pilot whales, this could drive behavioural responses to disturbance. However, the behavioural means used to achieve social coordination depends upon other considerations, which are disturbance-specific. PMID:27353529

  19. Testing genotypic variation of an invasive plant species in response to soil disturbance and herbivory.

    PubMed

    Bayliss, Shannon L J; terHorst, Casey P; Lau, Jennifer A

    2017-01-28

    Herbivores, competitors, and predators can inhibit biological invasions ("biotic resistance" sensu Elton 1959), while disturbance typically promotes biological invasions. Although biotic resistance and disturbance are often considered separately in the invasion literature, these two forces may be linked. One mechanism by which disturbance may facilitate biological invasions is by decreasing the effectiveness of biotic resistance. The effects of both disturbance and biotic resistance may vary across invading genotypes, and genetic variation in the invasive propagule pool may increase the likelihood that some genotypes can overcome biotic resistance or take greater advantage of disturbance. We conducted an experimental field trial in which we manipulated soil disturbance (thatch removal and loosening soil) and the presence of insect herbivores and examined their effects on the invasion success of 44 Medicago polymorpha genotypes. As expected, insecticide reduced leaf damage and increased Medicago fecundity, suggesting that insect herbivores in this system provide some biotic resistance. Soil disturbance increased Medicago fecundity, but did not alter the effectiveness of biotic resistance by insect herbivores. We found significant genetic variation in Medicago in response to disturbance, but not in response to insect herbivores. These results suggest that the ability of Medicago to invade particular habitats depends on the amount of insect herbivory, the history of disturbance in the habitat, and how the specific genotypes in the invader pool respond to these factors.

  20. Ontogeny of the Bovine Immune Response 1

    PubMed Central

    Schultz, R. D.; Dunne, H. W.; Heist, C. E.

    1973-01-01

    The ontogenesis of the bovine immune response was studied in three embryos (<40 days) and 106 fetuses of various ages. In the absence of overt antigenic stimulation, fetuses had lymphoid development of the thymus at 42 days of gestation, the spleen was structurally present at 55 days, and certain peripheral lymph nodes were present at 60 days. Mesenteric lymph nodes were structurally present by 100 days of gestation, and lymphoid tissue of the gastrointestinal tract, particularly the lower ileum, was observed in histologic sections of a 175-day fetus with a bacterial infection. Pyroninophilic cells, plasma cells, and germinal centers were present in lymph node sections of antigenically stimulated fetuses. Lymphoid tissue developed more rapidly in fetuses with bacteria, viral antigens, or apparent maternal red-blood-cell antigens than in the normal fetus. Thymic and splenic indices reached maximal values in the 205- to 220-day fetal age group. Immunoglobulin M (IgM)-containing cells were first observed, by immunofluorescence, in a single fetus at 59 days of gestation. Immunoglobulin G (IgG)-containing cells were observed at 145 days of gestation in one fetus with a bacterial and viral infection. IgM-containing cells were observed in 36 fetuses and IgM and IgG cells were present in seven fetuses. Spleen, lymph nodes, thymus, bone marrow, and liver of one fetus from a dam with lymphosarcoma had immunoglobulin-containing cells. Hemal lymph nodes, blood (buffy coat), Peyer patches, and heart and lung sections from fetuses with immunoglobulin-containing cells in spleen or lymph node did not have immunoglobulin-containing cells. Antigens of the virus of bovine virus diarrhea-mucosal disease (BVD) were detected in one fetus, and antigens of infectious bovine rhinotracheitis (IBR) virus were detected in three fetuses; however, viruses were not isolated in primary bovine embryonic kidney cells. Two of the three fetuses with IBR virus antigens had neutralizing serum antibody

  1. Local Immune Response in Helicobacter pylori Infection

    PubMed Central

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-01-01

    Abstract There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori–infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC). In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines—interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32—in H pylori–infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients. We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori–infected NGM group. This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  2. Immune response in the turtle (Chrysemys picta)

    PubMed Central

    Coe, J. E.

    1972-01-01

    The immune response of painted turtles (Chrysemys picta) to four purified protein antigens was evaluated by radioimmunoelectrophoresis. Specific antibody production was consistently detected and antigen binding was related to four immunoglobulin (Ig) precipitin lines (called Ig1, 2, 3, 4) in turtle serum. Antibody activity was detected first in the Ig1 or Ig2 and then later in the course of immunization in Ig3 and Ig4. Ig1 was about 19S in size, was not detectable after reduction and alkylation, and was the only Ig absent from turtle lymph. Ig3 and Ig4 were about 7S in size and Ig2 appeared slightly heavier by sucrose density gradient and Sephadex G-200 analysis. Haemagglutinins produced after primary inoculation were routinely sensitive to mild reduction and alkylation although antigen-binding capacity was still detectable. However, mercaptoethanol-resistant haemagglutinins were found in sera from turtles after booster injections of antigen. The electrophoretically slowest gamma globulin in turtle serum did not develop specific antigen-binding capacity, but did bind Fe59 and presumably represents a transferrin-like protein. ImagesFIG. 1FIG. 2FIG. 4 PMID:4114647

  3. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    PubMed Central

    Bajgar, Adam; Kucerova, Katerina; Jonatova, Lucie; Tomcala, Ales; Schneedorferova, Ivana; Okrouhlik, Jan; Dolezal, Tomas

    2015-01-01

    Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues. PMID:25915062

  4. The immune response and its therapeutic modulation in bronchiectasis.

    PubMed

    Daheshia, Massoud; Prahl, James D; Carmichael, Jacob J; Parrish, John S; Seda, Gilbert

    2012-01-01

    Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interestingly, a defect in the immune system or suppression of immune response during conditions such as immunodeficiency may well predispose one to the devastating effects of BC. Thus, the outcome of an active immune response as detrimental or protective in the pathogenesis of BC may be dependent on the state of the patient's immunity, the severity of infection, and the magnitude of immune response. Here we reassess the function of the innate and acquired immunity in BC, the major sites of immune response, and the nature of the bioactive mediators. Furthermore, the potential link(s) between an ongoing immune response and structural alterations accompanying the disease and the success of therapies that can modulate the nature and extent of immune response in BC are elaborated upon.

  5. Evidence of bacterioplankton community adaptation in response to long-term mariculture disturbance.

    PubMed

    Xiong, Jinbo; Chen, Heping; Hu, Changju; Ye, Xiansen; Kong, Dingjiang; Zhang, Demin

    2015-10-16

    Understanding the underlying mechanisms that shape the temporal dynamics of a microbial community has important implications for predicting the trajectory of an ecosystem's response to anthropogenic disturbances. Here, we evaluated the seasonal dynamics of bacterioplankton community composition (BCC) following more than three decades of mariculture disturbance in Xiangshan Bay. Clear seasonal succession and site (fish farm and control site) separation of the BCC were observed, which were primarily shaped by temperature, dissolved oxygen and sampling time. However, the sensitive bacterial families consistently changed in relative abundance in response to mariculture disturbance, regardless of the season. Temporal changes in the BCC followed the time-decay for similarity relationship at both sites. Notably, mariculture disturbance significantly (P < 0.001) flattened the temporal turnover but intensified bacterial species-to-species interactions. The decrease in bacterial temporal turnover under long-term mariculture disturbance was coupled with a consistent increase in the percentage of deterministic processes that constrained bacterial assembly based on a null model analysis. The results demonstrate that the BCC is sensitive to mariculture disturbance; however, a bacterioplankton community could adapt to a long-term disturbance via attenuating temporal turnover and intensifying species-species interactions. These findings expand our current understanding of microbial assembly in response to long-term anthropogenic disturbances.

  6. Evidence of bacterioplankton community adaptation in response to long-term mariculture disturbance

    PubMed Central

    Xiong, Jinbo; Chen, Heping; Hu, Changju; Ye, Xiansen; Kong, Dingjiang; Zhang, Demin

    2015-01-01

    Understanding the underlying mechanisms that shape the temporal dynamics of a microbial community has important implications for predicting the trajectory of an ecosystem’s response to anthropogenic disturbances. Here, we evaluated the seasonal dynamics of bacterioplankton community composition (BCC) following more than three decades of mariculture disturbance in Xiangshan Bay. Clear seasonal succession and site (fish farm and control site) separation of the BCC were observed, which were primarily shaped by temperature, dissolved oxygen and sampling time. However, the sensitive bacterial families consistently changed in relative abundance in response to mariculture disturbance, regardless of the season. Temporal changes in the BCC followed the time-decay for similarity relationship at both sites. Notably, mariculture disturbance significantly (P < 0.001) flattened the temporal turnover but intensified bacterial species-to-species interactions. The decrease in bacterial temporal turnover under long-term mariculture disturbance was coupled with a consistent increase in the percentage of deterministic processes that constrained bacterial assembly based on a null model analysis. The results demonstrate that the BCC is sensitive to mariculture disturbance; however, a bacterioplankton community could adapt to a long-term disturbance via attenuating temporal turnover and intensifying species-species interactions. These findings expand our current understanding of microbial assembly in response to long-term anthropogenic disturbances. PMID:26471739

  7. Cell-autonomous stress responses in innate immunity.

    PubMed

    Moretti, Julien; Blander, J Magarian

    2017-01-01

    The innate immune response of phagocytes to microbes has long been known to depend on the core signaling cascades downstream of pattern recognition receptors (PRRs), which lead to expression and production of inflammatory cytokines that counteract infection and induce adaptive immunity. Cell-autonomous responses have recently emerged as important mechanisms of innate immunity. Either IFN-inducible or constitutive, these processes aim to guarantee cell homeostasis but have also been shown to modulate innate immune response to microbes and production of inflammatory cytokines. Among these constitutive cell-autonomous responses, autophagy is prominent and its role in innate immunity has been well characterized. Other stress responses, such as metabolic stress, the ER stress/unfolded protein response, mitochondrial stress, or the DNA damage response, seem to also be involved in innate immunity, although the precise mechanisms by which they regulate the innate immune response are not yet defined. Of importance, these distinct constitutive cell-autonomous responses appear to be interconnected and can also be modulated by microbes and PRRs, which add further complexity to the interplay between innate immune signaling and cell-autonomous responses in the mediation of an efficient innate immune response.

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

    SciTech Connect

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

    2014-07-01

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

  9. Meeting report VLPNPV: Session 3: Immune responses.

    PubMed

    Morrison, Trudy G

    2014-01-01

    Virus-like particles (VLPs) and nano-particles (NP) are increasingly considered for both prophylactic and therapeutic vaccines for a wide variety of human and animal diseases. Indeed, 2 VLPs have already been licensed for use in humans, the human papilloma virus vaccine and the hepatitis B virus vaccine. (1) Reflecting this increased interest, a second international conference with a specific focus on VLPs and NP was held at the Salk Institute for Biological Studies in La Jolla, California, in June 2014. Approximately 100 attendees, hailing from many nations, came from academic institutions, research institutes, and biotech companies. A wide variety of topics were discussed, ranging from development and characterization of specific VLP and NP vaccine candidates to methods of production of these particles. Session three was focused on the general question of immune responses to VLPs.

  10. Natural selection on immune responsiveness in blue tits Parus caeruleus.

    PubMed

    Råberg, Lars; Stjernman, Martin

    2003-07-01

    What is the form of natural selection on immune responsiveness? For a population at evolutionary equilibrium, there are two different scenarios. First, it is generally assumed that immune defense has both benefits and costs. If variation in immune responsiveness is due to variation in how individuals trade off these costs and benefits, one would expect immune responsiveness to be subject to stabilizing selection. Second, it is well known that an individual's immune responsiveness is often dependent on its overall condition. If immune responsiveness is condition-dependent, one would expect immune responsiveness to be under positive directional selection. We would therefore expect that the form of natural selection on immune responsiveness depends on the relative magnitude of these two sources of variation: variation in how individuals trade off the costs and benefits of defense, and variation in condition. We measured primary and secondary antibody responsiveness to diphtheria-tetanus vaccine in blue tits during winter and investigated the relationship between responsiveness and survival to the following breeding season. We use responsiveness to these antigens as measures of an individual's ability or propensity to mount an antibody response in case of an infection. Interestingly, different measures of responsiveness were subject to different selective regimes: primary responsiveness to diphtheria was subject to stabilizing selection, whereas secondary responsiveness to tetanus was subject to positive directional selection. In contrast, there was no significant selection on primary responsiveness to tetanus or secondary responsiveness to diphtheria. The finding of stabilizing selection on a measure of responsiveness is evidence that immune defense can incur fitness costs; a central but little-tested assumption of theories of the ecology and evolution of immunological defense. The finding of directional selection on a measure of responsiveness is consistent with the

  11. Immune response of pregnant cows to bovine rotavirus immunization.

    PubMed

    Saif, L J; Smith, K L; Landmeier, B J; Bohl, E H; Theil, K W; Todhunter, D A

    1984-01-01

    Fifteen pregnant Holstein cows were freely assigned to 3 experimental groups (5 cows in each group). Cows in group I were inoculated IM and intramammarily (IMm) with Ohio Agricultural Research and Development Center (OARDC) tissue culture-propagated modified-live Nebraska calf diarrhea bovine rotavirus with added adjuvant (OARDC vaccine-immunized cows). Group II cows were given IM injections of a commercial modified-live rotavirus-coronavirus vaccine (commercial vaccine-immunized cows), and the remaining 5 cows were noninoculated controls (group III). Rotavirus antibody in colostrum and milk was mainly associated with immunoglobulin (Ig)G1, and less so with IgG2, IgA, and IgM, as analyzed by the enzyme-linked immunosorbent assay (ELISA), using monospecific anti-bovine IgG1, IgG2, IgM, and IgA sera. In serum, the rotavirus antibody was distributed almost equally between IgG1 and IgG2. The same relationships appeared in both immunized and nonvaccinated cows. All OARDC vaccine-injected cows had virus-neutralization (VN) and ELISA IgG1 rotavirus antibody titers in serum and mammary secretions at significantly increased levels (at least 100-fold; P less than 0.05) compared with the titers in groups II (commercial vaccine-immunized cows) and III (controls). Serum, colostrum, and milk antibody titers from these latter 2 groups did not differ statistically. The ELISA IgG2, IgA, and IgM rotavirus antibody titers also were significantly greater in mammary secretions from OARDC vaccine-immunized cows than in groups II and III cows. There was a high correlation between ELISA IgG1 and VN rotavirus antibody titers for all samples tested (r = 0.97, P less than 0.001), but ELISA IgG1 antibody titers were consistently higher than VN titers. The ELISA IgG1 and VN antibody titers of milk samples collected from cows 30 days after parturition were higher from the OARDC vaccine-immunized cows (ELISA IgG1, geometric mean titer (GMT) = 3,511; VN GMT = 1,689) than were titers from the

  12. Chemical agents and the immune response.

    PubMed Central

    Luster, M I; Rosenthal, G J

    1993-01-01

    Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals has increased, in part, due to the fact that chemical companies are moving to larger and/or different markets. It has been estimated that 35 million Americans suffer from allergic disease, of which 2-5% are from occupational exposure. Although there is not yet a clear understanding of dose-response relationships or disease predisposition, there are many well-defined examples (isocyanates, anhydrides) of chemical sensitizers in humans and experimental animals. Evidence that chemicals suppress immune responses in humans is considerably less well established, although there is a public perception that chemicals generally cause immunosuppression. This perception has been fueled by highly publicized legal cases and scientific controversies within the academic and industrial communities. As a consequence of these public and scientific concerns, many of the regulatory agencies are developing immunotoxicity testing guidelines. At the present, however, there are limitations on adequate human methodology and data that allow the extrapolation of animal data to assess human risk. The potential for human immunosuppression remains of concern, however, because of a large database generated from animal studies that demonstrates immunosuppression as well as reports of immunosuppression in humans inadvertently (e.g., halogenated aromatic hydrocarbons) or occupationally (asbestos, benzene) exposed to xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS) Images FIGURE 1. PMID:8354170

  13. Population-expression models of immune response

    NASA Astrophysics Data System (ADS)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  14. Fetal immune response following prematurely ruptured membranes.

    PubMed

    Cederqvist, L L; Francis, L C; Zervoudakis, I A; Becker, C G; Litwin, S D

    1976-10-01

    Concentrations of immunoglobulins (Ig)A1, and IgA2, IgD, IgE, IgG, and IgM have been determined in cord blood, amniotic fluid, and maternal serum in a group of patients with a history of prematurely ruptured membranes (PRM) prior to the onset of labor and in a control group of patients undergoing normal delivery and without a history of infection during pregnancy. IgA and IgD were determined by sensitive hemagglutination-inhibition tests; IgG and IgM, by radial immunodiffusion; IgE, by a radioimmunoassay. There was evidence for an immune response in 10 of 16 cases of PRM: five of 16 had increased IgA but normal IgM; three of 16 had increased IgA and IgM; two of 16 had high IgM and normal IgA in cord blood. In patients with significantly increased levels of either IgA or IgM or both, there was a decreased level of IgD. These changes are most likely the result of the immune response to ascending infection from the maternal genitals. The sensitive testing method employed could demonstrate the presence of IgD in 53 per cent of normal cord blood samples and 72 per cent of amniotic fluid samples obtained at term. IgE was found in all normal cord blood and amniotic fluid samples tested. By concentrating the amniotic fluid up to 180-fold, IgM was demonstrated in all normal samples tested. The potential importance of IgA determinations in cord blood in addition to IgM determination for detection of intrauterine infections is stressed.

  15. The innate immune response to adjuvants dictates the adaptive immune response to autoantigens.

    PubMed

    Staykova, Maria A; Liñares, David; Fordham, Susan A; Paridaen, Judith T; Willenborg, David O

    2008-06-01

    To elucidate the role of innate immunity in susceptibility to the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we induced EAE by immunization with spinal cord homogenate (SCH) plus complete Freund adjuvant or carbonyl iron in 3 inbred rat strains. Lewis are considered "susceptible," PVG/c-Rt7a (PVG) as "semisusceptible," and Brown Norway (BN) as "resistant" to EAE. Immunization with SCH-carbonyl iron resulted in clinical disease in all 3 strains, but the pathologic features of EAE in the resistant BN and the semisusceptible PVG rats differed from those in the Lewis and PVG model of EAE induced with SCH-complete Freund adjuvant. In BN and PVG rats, there were numerous inflammatory lesions with prominent involvement of microglia and, to a lesser extent, perivascular macrophages. These data suggest that different levels of activation of the innate immune system by different adjuvants determine whether EAE will or will not develop. Accordingly, the widely accepted scale of susceptibility to EAE development (Lewis > PVG > BN) should be revised because it does not take into account the important contribution of the composition of the adjuvant to the quality and quantity of the innate immune response and, consequently, to the generation and extent of the pathogenic T-cell-mediated, that is, adaptive, autoimmune disease.

  16. Immune Responses to HCV and Other Hepatitis Viruses

    PubMed Central

    Park, Su-Hyung; Rehermann, Barbara

    2014-01-01

    Summary Five human hepatitis viruses cause most acute and chronic liver disease worldwide. Over the past 25 years hepatitis C virus (HCV) in particular has received much interest because of its ability to persist in most immunocompetent adults and the lack of a protective vaccine. Here we examine innate and adaptive immune responses to HCV infection. Although HCV activates an innate immune response, it employs an elaborate set of mechanisms to evade interferon (IFN)-based antiviral immunity. By comparing innate and adaptive immune responses to HCV with those to hepatitis A and B viruses, we suggest that prolonged innate immune activation impairs the development of successful adaptive immune responses. Comparative immunology furthermore provides insights into the maintenance of immune protection. We conclude by discussing prospects for an HCV vaccine and future research needs for the hepatitis viruses. PMID:24439265

  17. Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

    PubMed

    Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

    2011-08-01

    The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity.

  18. Time of appearance and distribution of cells capable of secondary immune response following primary immunization

    PubMed Central

    Vischer, T. L.; Stastny, P.

    1967-01-01

    Immunological memory was studied by measurement of tritiated thymidine incorporation in tissue culture. After primary immunization with keyhole limpet haemocyanin (KLH) secondary responsiveness could be detected as early as the 2nd day after immunization with Freund's adjuvant into the footpads and on the 4th day after injection of KLH intravenously. In each case immunological memory developed first in the area of the injection, that is, the popliteal lymph nodes after footpad immunization and the spleen after intravenous injection. The secondary response could also be detected in the lymphoid cells of the blood. Cell suspensions enriched in small lymphocytes showed a similar reactivity. Cells from the thymus, however, did not develop immunological memory. Rabbits immunized with BSA showed a relatively weaker response which was clearly detectable only when Freund's adjuvant was used for immunization. The results suggest that a response essentially of a secondary type may play an important role in what is usually considered the primary immune response. PMID:6027423

  19. Staphylococcus aureus strategies to evade the host acquired immune response.

    PubMed

    Goldmann, Oliver; Medina, Eva

    2017-09-15

    Staphylococcus aureus poses a significant public-health problem. Infection caused by S. aureus can manifest as acute or long-lasting persistent diseases that are often refractory to antibiotic and are associated with significant morbidity and mortality. To develop more effective strategies for preventing or treating these infections, it is crucial to understand why the immune response is incapable to eradicate the bacterium. When S. aureus first infect the host, there is a robust activation of the host innate immune responses. Generally, S. aureus can survive this initial interaction due to the expression of a wide array of virulence factors that interfere with the host innate immune defenses. After this initial interaction the acquired immune response is the arm of the host defenses that will try to clear the pathogen. However, S. aureus is capable of maintaining infection in the host even in the presence of a robust antigen-specific immune response. Thus, understanding the mechanisms underlying the ability of S. aureus to escape immune surveillance by the acquired immune response will help uncover potentially important targets for the development of immune-based adjunctive therapies and more efficient vaccines. There are several lines of evidence that lead us to believe that S. aureus can directly or indirectly disable the acquired immune response. This review will discuss the different immune evasion strategies used by S. aureus to modulate the different components of the acquired immune defenses. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Individual-level behavioral responses of immature green turtles to snorkeler disturbance.

    PubMed

    Griffin, Lucas P; Brownscombe, Jacob W; Gagné, Tyler O; Wilson, Alexander D M; Cooke, Steven J; Danylchuk, Andy J

    2017-03-01

    Despite many positive benefits of ecotourism, increased human encounters with wildlife may have detrimental effects on wild animals. As charismatic megafauna, nesting and foraging sea turtles are increasingly the focus of ecotourism activities. The purpose of our study was to quantify the behavioral responses of immature green turtles (Chelonia mydas) to disturbance by snorkelers, and to investigate whether turtles have individual-level responses to snorkeler disturbance. Using a standardized disturbance stimulus in the field, we recorded turtle behaviors pre- and post-disturbance by snorkelers. Ninety percent of turtles disturbed by snorkeler (n = 192) initiated their flights at distances of ≤3 m. Using principal component analysis, we identified two distinct turtle personality types, 'bold' and 'timid', based upon 145 encounters of 19 individually identified turtles and five disturbance response variables. There was significant intra-individual repeatability in behavioral responses to disturbance, but bolder turtles had more behavioral plasticity and less consistent responses than more timid individuals. Bolder individuals with reduced evasion responses might be at a higher risk of shark predation, while more timid turtles might have greater energetic consequences due to non-lethal predator effects and repeated snorkeler disturbance. Over the longer term, a turtle population with a mix of bold and timid individuals may promote more resilient populations. We recommend that snorkelers maintain >3 m distance from immature green turtles when snorkeling, and that ecotourism activities be temporally and spatially stratified. Further, turtle watching guidelines need to be communicated to both tour operators and independent snorkelers to reduce the disturbance of turtles.

  1. Summertime Climate Response to Mountain Pine Beetle Disturbance

    NASA Astrophysics Data System (ADS)

    Maness, Holly; Kushner, Paul; Fung, Inez

    2013-04-01

    The current mountain pine beetle infestation in British Columbian forests ranks among the largest ecological disturbances recorded to date and may foreshadow similar scale outbreaks in North American forests over the coming decades. The associated dieback may result in substantial shifts in evapotranspiration and albedo, which alter the local surface energy balance, thereby affecting regional temperature and climate. Here we quantify the surface energy budget impact for summertime, by reporting changes to evapotranspiration, albedo, and surface temperature measured primarily via remotely-sensed observations. Over the 170,000 square-kilometers of affected forest, the typical decrease in summertime evapotranspiration is 19%; changes to the absorbed shortwave flux are comparatively negligible. The resulting increases in the outgoing sensible and radiative heat fluxes of 8% and 1%, respectively, correspond to a typical increase in surface temperature of 1 degree Celsius. These changes are comparable to those observed for other types of disturbance, such as wildfire, and may have secondary consequences for climate, including modifications to circulation, cloud cover, and precipitation.

  2. A framework to assess biogeochemical response to ecosystem disturbance using nutrient partitioning ratios

    USGS Publications Warehouse

    Kranabetter, J. Marty; McLauchlan, Kendra K.; Enders, Sara K.; Fraterrigo, Jennifer M.; Higuera, Philip E.; Morris, Jesse L.; Rastetter, Edward B.; Barnes, Rebecca; Buma, Brian; Gavin, Daniel G.; Gerhart, Laci M.; Gillson, Lindsey; Hietz, Peter; Mack, Michelle C.; McNeil, Brenden; Perakis, Steven

    2016-01-01

    Disturbances affect almost all terrestrial ecosystems, but it has been difficult to identify general principles regarding these influences. To improve our understanding of the long-term consequences of disturbance on terrestrial ecosystems, we present a conceptual framework that analyzes disturbances by their biogeochemical impacts. We posit that the ratio of soil and plant nutrient stocks in mature ecosystems represents a characteristic site property. Focusing on nitrogen (N), we hypothesize that this partitioning ratio (soil N: plant N) will undergo a predictable trajectory after disturbance. We investigate the nature of this partitioning ratio with three approaches: (1) nutrient stock data from forested ecosystems in North America, (2) a process-based ecosystem model, and (3) conceptual shifts in site nutrient availability with altered disturbance frequency. Partitioning ratios could be applied to a variety of ecosystems and successional states, allowing for improved temporal scaling of disturbance events. The generally short-term empirical evidence for recovery trajectories of nutrient stocks and partitioning ratios suggests two areas for future research. First, we need to recognize and quantify how disturbance effects can be accreting or depleting, depending on whether their net effect is to increase or decrease ecosystem nutrient stocks. Second, we need to test how altered disturbance frequencies from the present state may be constructive or destructive in their effects on biogeochemical cycling and nutrient availability. Long-term studies, with repeated sampling of soils and vegetation, will be essential in further developing this framework of biogeochemical response to disturbance.

  3. Simulation of the low latitude ionosphere response to disturbed winds and electric fields: Brazilian region

    NASA Astrophysics Data System (ADS)

    Batista, Inez S.; Souza, Jonas; Bailey, Graham; Bravo, Manuel

    2016-07-01

    Modeling the ionosphere during disturbed periods is one of the most challenging tasks due to the complexity of the phenomena that affect the electric fields and the thermosphere environment as whole. It is well known that depending on the direction of the interplanetary magnetic field disturbance electric fields (undershielding or overshielding) can penetrate from high to low latitudes causing significant disturbances in the electron density distribution and in the equatorial ionization anomaly (EIA) development. Besides that, the large amount of energy deposited in the polar region during disturbed periods will be responsible for the generation of disturbed winds that will flow towards the equator where they produce a disturbance dynamo which also affects the EIA density distribution. The TIDs and TADs are also sources of disturbances that propagate at high velocity reaching the equator 2-3 hours after the beginning of the magnetic storm. In this work we use the Sheffield University Plasmasphere-Ionosphere Model at INPE (SUPIM-INPE), to simulate the drastic effects that were observed at the low latitude ionosphere in the Brazilian region during a very intense magnetic storm event. A few models are tested for the disturbed electric field and wind. The simulation results showed that the observations are better explained when considering a traveling waveform disturbance propagating from north to south at a velocity equal to 200 m/s.

  4. Highly variable functional response of microbial communities to experimental temperature disturbances

    NASA Astrophysics Data System (ADS)

    Wanek, Wolfgang; Mooshammer, Maria; Hofhansl, Florian; Frank, Alexander H.; Leitner, Sonja; Schnecker, Jörg; Wild, Birgit; Watzka, Margarete; Keiblinger, Katharina M.; Zechmeister-Boltenstern, Sophie; Richter, Andreas

    2015-04-01

    Climate change is expected to alter the frequency and intensity of climate excursions, such as heat, drought and freeze-thaw events, requiring a thorough mechanistic understanding of the response of microbially-mediated nutrient cycling processes to such transient but severe disturbances. Here, we investigated the resistance and resilience of major gross processes of microbial carbon (C), nitrogen (N) and phosphorus (P) cycling, determined by isotope pool dilution assays, as well as potential enzyme activities in decomposing beech litter to two contrasting temperature disturbances (freeze-thaw and heat treatment for 9 days) in four different litter types. Microbial processes were substantially altered by the temperature disturbances but both the magnitude and direction of the disturbance effect varied among them. Phosphorus processes and hydrolytic enzyme activities showed lowest resistance as well as resilience, whereas N processes were more resistant and C processes intermediate. In general, responses of microbial processes were mainly consistent across disturbances but partially dependent on litter-specific microbial communities. The transient disturbances affected the relative availability of essential nutrients through a decoupling of microbial C, N and P cycling processes. Understanding the underlying mechanisms through which a decoupling of the supply of these elements as a result of microbial responses to environmental disturbances occurs will help to better predicting ecosystem responses to global change.

  5. Tumor escape from immune response: mechanisms and targets of activity.

    PubMed

    Gabrilovich, Dmitry; Pisarev, Vladimir

    2003-10-01

    Immune system plays an important role in control of tumor progression. Effective antitumor immune response depends on close interaction of several elements of immune system. They include antigen-presenting cells, different subsets of T cells, B cells and NK cells. However, tumor cells developed a number of mechanisms to escape recognition and elimination by immune system. In this review we will discuss these mechanisms and address possible approaches to correct them.

  6. Opioid peptides and innate immune response in mollusc.

    PubMed

    Liu, Dong-Wu

    2008-01-01

    The nervous and the immune systems can exchange information through opioid peptides. Furthermore, some opioid peptides can function as endogenous messengers of the immune system, and participate in an important part in the regulation of the various components of the immune response. Since the capacity of immunocytes to release and respond to opioid neuropeptide messengers is not restricted to mammalian organisms, recent studies have indicated that invertebrate models have been particularly useful to understand the mechanisms of the immune response. Moreover, the immunocytes of molluscs resemble cells of the vertebrate monocyte/macrophage lineage and are activated by similar substances, which control the main immune responses, i.e. phagocytosis, chemotaxis, and cytotoxicity. Recently, Mytilus edulis has been the subject of recent studies to determine whether the relationship between the immune and nervous systems seen in vertebrates also exists in invertebrates. The focus of this review is to describe how the opioid peptides participate in immune processes in molluscs.

  7. GENETIC CONTROL OF THE IMMUNE RESPONSE

    PubMed Central

    McDevitt, Hugh O.; Deak, Beverly D.; Shreffler, Donald C.; Klein, Jan; Stimpfling, Jack H.; Snell, George D.

    1972-01-01

    Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome. Both of these recombinants were derived from crossovers between the H-2K locus and the Ss-Slp locus near the center of the H-2 region. One of these recombinants, H-2y, was derived from a known single crossover event. These results indicate that Ir-1 lies near the center of the H-2 region between the H-2K locus and the Ss-Slp locus. The results of a four-point linkage test were consistent with these results. In 484 offspring of a cross designed to detect recombinants between H-2 and Ir-1, only two putative recombinants were detected. Both of these recombinants were confirmed by progeny testing. Extensive analysis of one of them has shown that the crossover event occurred within the H-2 region. (Testing of the second recombinant is currently under way.) Thus, in the linkage test, recombinants between H-2 and Ir-1 are in fact intra-H-2 crossovers. These results permit assignment of Ir-1 to a position between the H-2K locus and the Ss-Slp locus. PMID:4554451

  8. Spaceflight and immune responses of rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1995-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  9. Spaceflight and Immune Responses of Rhesus Monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1997-01-01

    In the grant period, we perfected techniques for determination of interleukin production and leukocyte subset analysis of rhesus monkeys. These results are outlined in detail in publication number 2, appended to this report. Additionally, we participated in the ARRT restraint test to determine if restraint conditions for flight in the Space Shuttle could contribute to any effects of space flight on immune responses. All immunological parameters listed in the methods section were tested. Evaluation of the data suggests that the restraint conditions had minimal effects on the results observed, but handling of the monkeys could have had some effect. These results are outlined in detail in manuscript number 3, appended to this report. Additionally, to help us develop our rhesus monkey immunology studies, we carried out preliminary studies in mice to determine the effects of stressors on immunological parameters. We were able to show that there were gender-based differences in the response of immunological parameters to a stressor. These results are outlined in detail in manuscript number 4, appended to this report.

  10. Maternal antibodies reduce costs of an immune response during development.

    PubMed

    Grindstaff, Jennifer L

    2008-03-01

    Young vertebrates are dependent primarily on innate immunity and maternally derived antibodies for immune defense. This reliance on innate immunity and the associated inflammatory response often leads to reduced growth rates after antigenic challenge. However, if offspring have maternal antibodies that recognize an antigen, these antibodies should block stimulation of the inflammatory response and reduce growth suppression. To determine whether maternal and/or offspring antigen exposure affect antibody transmission and offspring growth, female Japanese quail (Coturnix japonica) and their newly hatched chicks were immunized. Mothers were immunized with lipopolysaccharide (LPS), killed avian reovirus vaccine (AR), or were given a control, phosphate-buffered saline, injection. Within each family, one-third of offspring were immunized with LPS, one-third were immunized with AR, and one-third were given the control treatment. Maternal immunization significantly affected the specific types of antibodies that were transmitted. In general, immunization depressed offspring growth. However, offspring immunized with the same antigen as their mother exhibited elevated growth in comparison to siblings immunized with a different antigen. This suggests that the growth suppressive effects of antigen exposure during development can be partially ameliorated by the presence of maternal antibodies, but in the absence of specific maternal antibodies, offspring are dependent on more costly innate immune defenses. Together, the results suggest that the local disease environment of mothers prior to reproduction significantly affects maternal antibody transmission and these maternal antibodies may allow offspring to partially maintain growth during infection in addition to providing passive humoral immune defense.

  11. Immune function trade-offs in response to parasite threats.

    PubMed

    Kirschman, Lucas J; Quade, Adam H; Zera, Anthony J; Warne, Robin W

    2017-04-01

    Immune function is often involved in physiological trade-offs because of the energetic costs of maintaining constitutive immunity and mounting responses to infection. However, immune function is a collection of discrete immunity factors and animals should allocate towards factors that combat the parasite threat with the highest fitness cost. For example, animals on dispersal fronts of expanding population may be released from density-dependent diseases. The costs of immunity, however, and life history trade-offs in general, are often context dependent. Trade-offs are often most apparent under conditions of unusually limited resources or when animals are particularly stressed, because the stress response can shift priorities. In this study we tested how humoral and cellular immune factors vary between phenotypes of a wing dimorphic cricket and how physiological stress influences these immune factors. We measured constitutive lysozyme activity, a humoral immune factor, and encapsulation response, a cellular immune factor. We also stressed the crickets with a sham predator in a full factorial design. We found that immune strategy could be explained by the selective pressures encountered by each morph and that stress decreased encapsulation, but not lysozyme activity. These results suggest a possible trade-off between humoral and cellular immunity. Given limited resources and the expense of immune factors, parasite pressures could play a key factor in maintaining insect polyphenism via disruptive selection.

  12. The reciprocal link between sleep and immune responses.

    PubMed

    Del Gallo, F; Opp, M R; Imeri, L

    2014-01-01

    Good sleep is necessary for both physical and mental health; sleep and immune responses are reciprocally and closely linked. Sleep loss impairs the immune response, while, on the other hand, the immune response, activated for instance by an infection, alters sleep. Sleep alterations induced by immune activation are mediated by cytokines such as interleukin-1. In the past, it was thought that cytokines were produced only by the immune system, and active only there as signaling molecules. Today it is clear that IL-1 and other cytokines are present and active in the healthy brain, where they physiologically interact with the brain circuits and the neurotransmitter systems (for instance the serotonergic, GABAergic, and cholinergic systems) that control sleep. These interactions are altered by immune response, and, as a result, non-rapid eye movement (NREM) sleep is increased and fragmented, whereas rapid eye movements (REM) sleep is inhibited.

  13. B cell function in the immune response to helminths

    PubMed Central

    Harris, Nicola

    2010-01-01

    Similar T helper (Th)2-type immune responses are generated against different helminths parasites, but the mechanisms that initiate Th2 immunity, and the specific immune components that mediate protection against these parasites, can vary greatly. B cells are increasingly recognized as important during the Th2-type immune response to helminths, and B cell activation might be a target for effective vaccine development. Antibody production is a function of B cells during helminth infection and understanding how polyclonal and antigen-specific antibodies contribute should provide important insights into how protective immunity develops. In addition, B cells might also contribute to the host response against helminths through antibody-independent functions including, antigen-presentation, as well as regulatory and effector activity. In this review, we examine the role of B cells during Th2-type immune response to these multicellular parasites. PMID:21159556

  14. The unfolded protein response in immunity and inflammation

    PubMed Central

    Grootjans, Joep; Kaser, Arthur; Kaufman, Randal J.; Blumberg, Richard S.

    2017-01-01

    The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses. PMID:27346803

  15. Plant hydrodynamics help govern forest water cycling response to intermediate severity disturbance

    NASA Astrophysics Data System (ADS)

    Matheny, A. M.; Bohrer, G.; Mirfenderesgi, G.; Morin, T. H.; Rey Sanchez, C.; Vogel, C. S.; Gough, C. M.; Curtis, P.

    2016-12-01

    Intermediate severity disturbances alter forest structure and composition, which in turn affect water and carbon cycling. We studied a large-scale experiment in a forest where an intermediate severity disturbance was enacted by stem-girdling all early successional trees to simulate age-related senescence associated with natural succession. Using six years of eddy covariance and sap flux measurements in the disturbed area and an adjacent control plot, we analyzed disturbance induced changes to plot level and species-specific water fluxes. Ecosystem scale transpiration was 15% lower in disturbed plots than in control plots. Species-specific responses to changes in microclimate varied on the basis of plant hydraulic strategy and differential carbon allocation. These changes resulted in altered patterns and magnitudes of species' transpiration. We employed the Penman-Monteith model to demonstrate that such species-specific responses to disturbance are not well captured using current modeling strategies, and that accounting for changes to LAI and microclimate are insufficient to fully describe the effects of disturbance on transpiration. Specifically, the diurnal hysteresis of transpiration is not well resolved by models which lack the ability to represent individual plant hydrodynamic processes and water storage. The hysteresis of transpiration is controlled abiotically through the time lag between PAR and VPD and biotically through plant water status. Using the FETCH2 plant hydrodynamics model, we showed that the ability to mechanistically link stomatal conductance to soil moisture through the vegetation hydraulic pathway provides a means to capture the influence of stem water storage and plant hydraulic strategy on transpiration following disturbance. FETCH2 offers a platform with which hydraulic traits and structural differences can be incorporated into land-surface models to improve the simulation of forest biogeochemical responses to intermediate disturbance.

  16. Species-specific transpiration responses to intermediate disturbance in a northern hardwood forest

    NASA Astrophysics Data System (ADS)

    Matheny, Ashley M.; Bohrer, Gil; Vogel, Christoph S.; Morin, Timothy H.; He, Lingli; Frasson, Renato Prata de Moraes; Mirfenderesgi, Golnazalsadat; Schäfer, Karina V. R.; Gough, Christopher M.; Ivanov, Valeriy Y.; Curtis, Peter S.

    2014-12-01

    Intermediate disturbances shape forest structure and composition, which may in turn alter carbon, nitrogen, and water cycling. We used a large-scale experiment in a forest in northern lower Michigan where we prescribed an intermediate disturbance by stem girdling all canopy-dominant early successional trees to simulate an accelerated age-related senescence associated with natural succession. Using 3 years of eddy covariance and sap flux measurements in the disturbed area and an adjacent control plot, we analyzed disturbance-induced changes to plot level and species-specific transpiration and stomatal conductance. We found transpiration to be ~15% lower in disturbed plots than in unmanipulated control plots. However, species-specific responses to changes in microclimate varied. While red oak and white pine showed increases in stomatal conductance during postdisturbance (62.5 and 132.2%, respectively), red maple reduced stomatal conductance by 36.8%. We used the hysteresis between sap flux and vapor pressure deficit to quantify diurnal hydraulic stress incurred by each species in both plots. Red oak, a ring porous anisohydric species, demonstrated the largest mean relative hysteresis, while red maple, bigtooth aspen, and paper birch, all diffuse porous species, had the lowest relative hysteresis. We employed the Penman-Monteith model for LE to demonstrate that these species-specific responses to disturbance are not well captured using current modeling strategies and that accounting for changes to leaf area index and plot microclimate are insufficient to fully describe the effects of disturbance on transpiration.

  17. Innate immune response development in nestling tree swallows

    USGS Publications Warehouse

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

    2011-01-01

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

  18. Probiotics and the immune response to vaccines.

    PubMed

    MacDonald, Thomas T; Bell, Iona

    2010-08-01

    Probiotics are bacteria, but sometimes fungi, which when taken by the oral route may give some health benefits. The most compelling evidence for beneficial effects of probiotics is in the prevention and reduction in the duration of symptoms related to gut infectious disease. There is also evidence to show that some specific probiotics are beneficial in Clostridium difficile diarrhoea in the elderly. As further and better controlled clinical studies have appeared, some specific probiotics also appear to have beneficial effects in perhaps preventing and reducing the duration of symptoms due to acquired upper respiratory tract infections. In an attempt to explain these effects, attention has turned to the effects of some specific probiotics on the immune system. There is evidence that some specific probiotics can alter monocyte and natural killer cell function in the blood. Evidence is also accumulating that taking some specific probiotics can boost antibody responses to oral and systemically administered vaccines. The effect when shown is modest and is not always seen in different studies to all vaccines, but there is enough of a trend to make the area worthy of further investigation, particularly to tease out the mechanisms involved.

  19. Humoral immune response to Aggregatibacter actinomycetemcomitans leukotoxin.

    PubMed

    Brage, M; Holmlund, A; Johansson, A

    2011-04-01

    Periodontal disease is an inflammatory condition caused by bacterial infections that result in loss of the tooth supporting tissue. The periodontal pathogens produce virulence factors with capacity to affect the host immune response. Aggregatibacter actinomycetemcomitans is a periodontal pathogen that produces a leukotoxin that specifically affects human leukocytes. The aims of the present study were to examine the presence and function of systemic antibodies to the leukotoxin. One hundred and ninety-seven middle-aged (57 ± 5 years) Swedes with well-documented periodontal status and medical factors related to cardiovascular diseases were studied. These data have been published previously. The serum samples were examined for the presence of leukotoxin antibodies by western blot and the capacity to neutralize leukotoxicity in an activity assay with leukotoxin and cultured leukemic cells. The results showed a high prevalence (57%) of antibodies against A. actinomycetemcomitans leukotoxin in the analyzed population. These antibodies were correlated with leukotoxin neutralizing capacity as well as with the ELISA titers of A. actinomycetemcomitans-specific IgA and IgG. In addition, high levels of leukotoxin antibodies were correlated with increasing age, but not with periodontal disease parameters or cardiovascular risk factors. Systemic antibodies against A. actionmycetemcomitans leukotoxin were common in this adult Swedish population. These antibodies might contribute to limit the systemic effects of the infection. © 2010 John Wiley & Sons A/S.

  20. Importins and exportins regulating allergic immune responses.

    PubMed

    Aggarwal, Ankita; Agrawal, Devendra K

    2014-01-01

    Nucleocytoplasmic shuttling of macromolecules is a well-controlled process involving importins and exportins. These karyopherins recognize and bind to receptor-mediated intracellular signals through specific signal sequences that are present on cargo proteins and transport into and out of the nucleus through nuclear pore complexes. Nuclear localization signals (NLS) present on cargo molecules to be imported while nuclear export signals (NES) on the molecules to be exported are recognized by importins and exportins, respectively. The classical NLS are found on many transcription factors and molecules that are involved in the pathogenesis of allergic diseases. In addition, several immune modulators, including corticosteroids and vitamin D, elicit their cellular responses by regulating the expression and activity of importin molecules. In this review article, we provide a comprehensive list of importin and exportin molecules and their specific cargo that shuttled between cytoplasm and the nucleus. We also critically review the role and regulation of specific importin and exportin involved in the transport of activated transcription factors in allergic diseases, the underlying molecular mechanisms, and the potential target sites for developing better therapeutic approaches.

  1. Linear ubiquitination signals in adaptive immune responses.

    PubMed

    Ikeda, Fumiyo

    2015-07-01

    Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways.

  2. Suppression of immune response to Listeria monocytogenes: mechanism(s) of immune complex suppression.

    PubMed Central

    Virgin, H W; Wittenberg, G F; Bancroft, G J; Unanue, E R

    1985-01-01

    We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice adoptively transferred with specific antibody. Suppression was also found when nonimmune mice were injected with immune complexes preformed in vitro. We investigated the role of complement by decomplementing mice with cobra venom factor purified by high-pressure liquid chromatography. Complete depletion of serum C3 did not eliminate immune complex suppression of resistance to L. monocytogenes, suggesting that complement activation is not required for immune complex suppression. Infection-induced changes in the surface phenotype and functional properties of macrophages from normal and immune complex-suppressed mice were also investigated. Macrophage expression of both H-2K and Ia molecules increased during the response of normal mice to L. monocytogenes. However, these changes were not found in immune complex-suppressed mice. In contrast, membrane interleukin 1 expression was increased in macrophages from suppressed mice compared with macrophages from normal mice. Macrophages from L. monocytogenes-infected normal and immune complex-suppressed mice expressed cytotoxicity against tumor cells in vitro. We conclude that immune complexes do not inhibit resistance to L. monocytogenes by activation of complement or decreasing macrophage cytotoxic activity. Rather, defects in Ia expression by macrophages from suppressed mice might be one component responsible for immune complex suppression of resistance to L. monocytogenes. PMID:3932204

  3. Soil Response to Aeolian Disturbance in West Greenland

    NASA Astrophysics Data System (ADS)

    Heindel, R. C.; Culler, L. E.; Chipman, J. W.; Virginia, R. A.

    2015-12-01

    Arctic soils are a critical ecological resource, yet are increasingly vulnerable to global change. In the Kangerlussuaq region of West Greenland, aeolian disturbance is the greatest threat to soil stability, with strong katabatic winds eroding vegetation and soil down to the underlying glacial till or bedrock. Little is known about what controls the distribution and rate of the aeolian erosion, which initially results in a state change from tundra to a deflated and nearly unvegetated ground. It is unclear if vegetation can eventually reestablish after erosion occurs, potentially aided by the biological soil crust (BSC) that develops within the eroded areas, or if this soil loss is an irreversible change in vegetation and soil carbon (C) and nitrogen (N) cycling. Our analysis of high-resolution satellite imagery shows that across the entire study region, deflated ground covers 22% of the terrestrial landscape. Aeolian erosion occurs more frequently closer to the Greenland Ice Sheet and on S-facing slopes. Using lichenometry, we estimate that erosional fronts move across the landscape at rates of 2.5 cm yr-1, leaving unproductive ground in their wake. The onset of widespread aeolian erosion occurred roughly 700-1000 years ago, pointing toward regional cooling and aridity as the drivers behind erosion. Finally, we consider whether the BSCs can improve soil quality enough to allow for full vegetation regrowth. Preliminary results show that while the BSCs fix atmospheric N and increase C storage, the rate of soil quality recovery is extremely slow. Understanding the thresholds between vegetated tundra and eroded ground is critical for predicting how the Kangerlussuaq landscape will respond to anticipated changes in climate and ice sheet dynamics.

  4. Evaluating immune responses after sipuleucel-T therapy.

    PubMed

    Strauss, Julius; Madan, Ravi A; Figg, William D

    2015-01-01

    Following FDA approval of sipuleucel-T in 2010 for metastatic castration resistant prostate cancer (mCRPC), several studies have described the effect of sipuleucel-T on peripheral immune responses. Retrospective associations have also been made with immune responses and survival. A recently published study by Fong et al. was the first to characterize the immune response of sipuleucel-T in the tumor microenvironment. The findings of this study have been hypothesis generating, yet it remains unclear whether the peri-tumor immune response described is predictive of survival. Increasing evidence suggests that radiographic or PSA progression does not accurately reflect survival with sipuleucel-T and other immunotherapies. Finding an immune biomarker which can accurately reflect clinical benefit and validating it prospectively offers the potential for a predictive indicator of response in an area where none currently exists.

  5. [Immune response and digestive cancers: Prognostic and therapeutic implications].

    PubMed

    Bibeau, Frédéric; Bazille, Céline; Svrcek, Magali; Pierson, Rémi; Lagorce-Pagès, Christine; Cohen, Romain; André, Thierry

    2017-02-01

    The aim of this article is to emphasize the impact of the immune response in digestive cancers, especially from colorectal (CRC) origin. In this setting, an adaptive lymphocytic infiltrate underlines the prognostic impact of the immune response, because it is associated to a favorable outcome. The next challenge will be to validate, in a prospective therapeutic trial, the integration of the immune response as decisional parameter for adjuvant therapy. The immune response is also a predictive parameter in microsatellite instable metastatic CRC, characterized by an adaptive lymphocytic infiltrate, leading to a very high response rate to immune therapies. However, prognostic and predictive biomarkers still need to be optimized in order to better select patients. These data are also valuable for digestive non-colorectal cancers, which are briefly analyzed. The methodology for the assessment of these prognostic and predictive biomarkers, which represents an important issue in precision medicine, is also discussed.

  6. Continuous immunotypes describe human immune variation and predict diverse responses.

    PubMed

    Kaczorowski, Kevin J; Shekhar, Karthik; Nkulikiyimfura, Dieudonné; Dekker, Cornelia L; Maecker, Holden; Davis, Mark M; Chakraborty, Arup K; Brodin, Petter

    2017-07-25

    The immune system consists of many specialized cell populations that communicate with each other to achieve systemic immune responses. Our analyses of various measured immune cell population frequencies in healthy humans and their responses to diverse stimuli show that human immune variation is continuous in nature, rather than characterized by discrete groups of similar individuals. We show that the same three key combinations of immune cell population frequencies can define an individual's immunotype and predict a diverse set of functional responses to cytokine stimulation. We find that, even though interindividual variations in specific cell population frequencies can be large, unrelated individuals of younger age have more homogeneous immunotypes than older individuals. Across age groups, cytomegalovirus seropositive individuals displayed immunotypes characteristic of older individuals. The conceptual framework for defining immunotypes suggested by our results could guide the development of better therapies that appropriately modulate collective immunotypes, rather than individual immune components.

  7. Immune response, not immune maintenance, is energetically costly in wild white-footed mice (Peromyscus leucopus).

    PubMed

    Derting, Terry L; Compton, Stephen

    2003-01-01

    Understanding the cost of immune function is essential for more accurate characterization of energy budgets of animals and better understanding of the role of immunity in the evolution of life-history strategies. We examined the energetic cost of maintaining a normally functioning immune system and mounting a mild immune response in wild male white-footed mice (Peromyscus leucopus). To evaluate the cost of maintaining immunocompetence, we compared resting and daily metabolic rates (RMR; DMR) and masses of body organs of mice whose immune systems were suppressed by cyclophosphamide with those of control mice. To evaluate the cost of mounting an immune response, we measured RMR, DMR, and organ masses in mice whose humoral and cell-mediated immune responses had been stimulated by injections of sheep red blood cells and phytohemagglutinin, respectively. Immunosuppression resulted in a significant reduction in circulating leukocytes, by 225%, but no significant effect on metabolic rates or organ masses. Immunochallenged animals showed no significant differences in metabolic rates compared with control animals but did exhibit significantly smaller dry masses of the small intestine and testes, by 74% and 22%, respectively. We concluded that the cost of maintaining the immune system was minimal. In contrast, there was a significant energetic cost of mounting an immune response that, depending on its magnitude, can be met through reductions in energy allocation to other physiological systems.

  8. Biomimetic and synthetic interfaces to tune immune responses (Review)

    PubMed Central

    Garapaty, Anusha; Champion, Julie A.

    2015-01-01

    Organisms depend upon complex intercellular communication to initiate, maintain, or suppress immune responses during infection or disease. Communication occurs not only between different types of immune cells, but also between immune cells and nonimmune cells or pathogenic entities. It can occur directly at the cell–cell contact interface, or indirectly through secreted signals that bind cell surface molecules. Though secreted signals can be soluble, they can also be particulate in nature and direct communication at the cell–particle interface. Secreted extracellular vesicles are an example of native particulate communication, while viruses are examples of foreign particulates. Inspired by communication at natural immunological interfaces, biomimetic materials and designer molecules have been developed to mimic and direct the type of immune response. This review describes the ways in which native, biomimetic, and designer materials can mediate immune responses. Examples include extracellular vesicles, particles that mimic immune cells or pathogens, and hybrid designer molecules with multiple signaling functions, engineered to target and bind immune cell surface molecules. Interactions between these materials and immune cells are leading to increased understanding of natural immune communication and function, as well as development of immune therapeutics for the treatment of infection, cancer, and autoimmune disease. PMID:26178262

  9. Assessment of the immune response to duck plague vaccinations.

    PubMed

    Kulkarni, D D; James, P C; Sulochana, S

    1998-01-01

    An experiment was conducted to assess the immune responses of ducks to duck plague (DP) vaccinations employing one commercial and one laboratory-adapted (LA) DP vaccines. Virus neutralisation and leucocyte migration-inhibition tests were conducted at regular intervals before and after vaccinations. Similarly, ducks in vaccinated and control groups were subjected to challenge infection with virulent DP virus. The commercial vaccine yielded a poor immune response and partial protection on challenge whereas satisfactory responses were obtained in ducks receiving two doses of LA vaccine. The humoral as well as cellular factors were stimulated indicating possible involvement of both the immune responses in the protection from duck plague.

  10. Response of soil invertebrates to disturbance across three resource regions in North Carolina.

    PubMed

    Barbercheck, M E; Neher, D A; Anas, O; El-Allaf, S M; Weicht, T R

    2009-05-01

    We evaluated the potential of soil microarthropods and enchytraeid worms to be useful as bioindicators of soil condition in forest, wetland, and agricultural ecosystems over a range of ecoregions. Selected mesofauna and soil characteristics in soil and litter in relatively undisturbed and disturbed examples of each of three ecosystems within each of three land resource regions were monitored over two years. Optimal times of year to sample these organisms as indicators of disturbance were April, May, July and September. No single measure reflected disturbance across all three ecosystems. Among forest sites, Simpson's diversity index, evenness, abundance of ants, and proportion of enchytraeids in the mesofauna differed between soils of different disturbance levels. Among agricultural sites, richness, evenness, abundance of mites, and proportions of collembolans and of enchytraeids in the mesofauna differed between disturbance levels. Among wetland sites, Shannon's and Simpson's diversity indices, richness based on the total mesofauna, and abundances of mites, diplurans, ants, and isotomid and onychiurid collembolans differed between disturbance levels. Covariates most frequently associated with abundance and diversity of the measured mesofauna were soil electrical conductivity, available N, organic matter, and pH. Canonical correspondence analysis provided information somewhat different to bivariate analysis. Using both approaches to examine soil and litter taxa that have distinctive responses to disturbance may help to identify candidate groups applicable for use in large-scale environmental monitoring programs.

  11. Response latencies to postural disturbances in three species of teleostean fishes.

    PubMed

    Webb, Paul W

    2004-02-01

    Flow in aquatic systems is characterized by unsteadiness that creates destabilizing perturbations. Appropriate correction responses depend on response latency. The time between a disturbance induced by either removal of a flow refuge or striking various parts of the body with a narrow water jet was measured for three species, chosen as examples of modes in teleostean body/fin organization that are expected to affect stability. Creek chub Semotilus atromaculatus is representative of fusiform-bodied soft-rayed teleosts, smallmouth bass Micropterus dolomieu of fusiform-bodied spiny-rayed forms and bluegill Lepomis macrochirus of deep-bodied spiny-rayed forms. Observations were made at 23 degrees C. Loss of refuge resulted in a surge that fish corrected by starting to swim within 129+/-29 ms (mean +/- 2 S.E.M.) for chub, which was significantly shorter than minimal times of approximately 200 ms for bluegill and bass. Slips and heaves induced by water jets initially resulted in extension of the median and paired fins that would damp growth of the disturbance, but otherwise these disturbances were ignored. Yaws and pitches were more likely to cause fish to swim away from the stimulus, making corrections as they did so. There were no differences in latencies for slip, heave, yaw and pitch disturbances within each species, but latencies varied among species. For these disturbances, responses averaged 123+/-19 ms for chub, again significantly smaller than those of 201+/-24 ms for bass and 208+/-52 ms for bluegill. Values for the two centrarchids were not significantly different (P>0.08). The response latency for rolling disturbances did not differ among species but was significantly smaller than that for other disturbances, with an overall latency of 70+/-15 ms. The greater responsiveness to hydrostatic rolling instability is attributed to functions requiring an upright posture and differences among species in habitat preferences.

  12. Gingival wound healing: an essential response disturbed by aging?

    PubMed

    Smith, P C; Cáceres, M; Martínez, C; Oyarzún, A; Martínez, J

    2015-03-01

    Gingival wound healing comprises a series of sequential responses that allow the closure of breaches in the masticatory mucosa. This process is of critical importance to prevent the invasion of microbes or other agents into tissues, avoiding the establishment of a chronic infection. Wound healing may also play an important role during cell and tissue reaction to long-term injury, as it may occur during inflammatory responses and cancer. Recent experimental data have shown that gingival wound healing is severely affected by the aging process. These defects may alter distinct phases of the wound-healing process, including epithelial migration, granulation tissue formation, and tissue remodeling. The cellular and molecular defects that may explain these deficiencies include several biological responses such as an increased inflammatory response, altered integrin signaling, reduced growth factor activity, decreased cell proliferation, diminished angiogenesis, reduced collagen synthesis, augmented collagen remodeling, and deterioration of the proliferative and differentiation potential of stem cells. In this review, we explore the cellular and molecular basis of these defects and their possible clinical implications. © International & American Associations for Dental Research 2014.

  13. Statistical methods for analysing responses of wildlife to human disturbance.

    Treesearch

    Haiganoush K. Preisler; Alan A. Ager; Michael J. Wisdom

    2006-01-01

    1. Off-road recreation is increasing rapidly in many areas of the world, and effects on wildlife can be highly detrimental. Consequently, we have developed methods for studying wildlife responses to off-road recreation with the use of new technologies that allow frequent and accurate monitoring of human-wildlife interactions. To illustrate these methods, we studied the...

  14. Statistical methods for analysing responses of wildlife to human disturbance

    Treesearch

    Haiganoush K. Preisler; Alan A. Ager; Michael J. Wisdom

    2006-01-01

    Off-road recreation is increasing rapidly in many areas of the world, and effects on wildlife can be highly detrimental. Consequently, we have developed methods for studying wildlife responses to off-road recreation with the use of new technologies that allow frequent and accurate monitoring of human-wildlife interactions. To...

  15. Salicylic Acid Activates DNA Damage Responses to Potentiate Plant Immunity

    PubMed Central

    Yan, Shunping; Wang, Wei; Marqués, Jorge; Mohan, Rajinikanth; Saleh, Abdelaty; Durrant, Wendy E.; Song, Junqi; Dong, Xinnian

    2013-01-01

    SUMMARY DNA damage is normally detrimental to living organisms. Here we show that it can also serve as a signal to promote immune responses in plants. We found that the plant immune hormone salicylic acid (SA) can trigger DNA damage in the absence of a genotoxic agent. The DNA damage sensor proteins, RAD17 and ATR, are required for effective immune responses. These sensor proteins are negatively regulated by a key immune regulator SNI1 (suppressor of npr1-1, inducible 1), which we discovered as a missing subunit of the Structural Maintenance of Chromosome (SMC) 5/6 complex required for controlling DNA damage. Elevated DNA damage caused by the sni1 mutation or treatment with a DNA-damaging agent markedly enhances SA-mediated defense gene expression. Our study suggests that activation of DNA damage responses is an intrinsic component of the plant immune responses. PMID:24207055

  16. Immune responses and disease enhancement during respiratory syncytial virus infection.

    PubMed

    Openshaw, Peter J M; Tregoning, John S

    2005-07-01

    Respiratory syncytial virus (RSV) is one of the commonest and most troublesome viruses of infancy. It causes most cases of bronchiolitis, which is associated with wheezing in later childhood. In primary infection, the peak of disease typically coincides with the development of specific T- and B-cell responses, which seem, in large part, to be responsible for disease. Animal models clearly show that a range of immune responses can enhance disease severity, particularly after vaccination with formalin-inactivated RSV. Prior immune sensitization leads to exuberant chemokine production, an excessive cellular influx, and an overabundance of cytokines during RSV challenge. Under different circumstances, specific mediators and T-cell subsets and antibody-antigen immune complex deposition are incriminated as major factors in disease. Animal models of immune enhancement permit a deep understanding of the role of specific immune responses in RSV disease, assist in vaccine design, and indicate which immunomodulatory therapy might be beneficial to children with bronchiolitis.

  17. The innate immune response during urinary tract infection and pyelonephritis.

    PubMed

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

    2014-07-01

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

  18. The innate immune response during urinary tract infection and pyelonephritis

    PubMed Central

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

    2013-01-01

    Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides – a ubiquitous component of the innate immune response. PMID:23732397

  19. Serological response to immunization with tetanus toxoid.

    PubMed

    Setarunnahar; Hossain, A; Khatun, R; Parveen, S; Ahmad, Z; Haleem, A; Alam, S K

    2000-04-01

    A total of two hundred women were immunized with tetanus toxoid vaccine. Two batches of toxoid prepared at the Institute of Public Health (IPH), Dhaka and one batch of imported vaccines, were being used by the EPI in Bangladesh for immunization. Each hundred women were immunized by IPH and imported vaccine. Two human doses were given in one month interval. Blood samples from all the study subjects were collected on the day of 1st dose and one month after second dose. Both the preimmunized sera and the sera after vaccination were tested to determine the antibody titre against tetanus toxoid by the haemagglutination method. The preimmunized sera showed the presence of protective antibody in 50(25%) subjects who had the history of previous immunization. Including these initial antitoxin positive cases the seroconversions found among 95% and 96% of the study population respectively after immunization with IPH and imported toxoids, which were 93.05% and 94.87% when these 50 subjects were excluded. No significant difference (p = 1.0) was observed between the immunity of the subjects after receiving IPH and imported vaccine. Antibody titre of initial tetanus-antitoxin positive cases raised eight folds after getting more doses. The result gave fair indication of the antigenicity of all the toxoids used in the study.

  20. Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.

    PubMed

    Dubinsky, Marla C; Lin, Ying-Chao; Dutridge, Debra; Picornell, Yoana; Landers, Carol J; Farrior, Sharmayne; Wrobel, Iwona; Quiros, Antonio; Vasiliauskas, Eric A; Grill, Bruce; Israel, David; Bahar, Ron; Christie, Dennis; Wahbeh, Ghassan; Silber, Gary; Dallazadeh, Saied; Shah, Praful; Thomas, Danny; Kelts, Drew; Hershberg, Robert M; Elson, Charles O; Targan, Stephan R; Taylor, Kent D; Rotter, Jerome I; Yang, Huiying

    2006-02-01

    Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.

  1. Serum Immune Responses Predict Rapid Disease Progression among Children with Crohn’s Disease: Immune Responses Predict Disease Progression

    PubMed Central

    Dubinsky, Marla C.; Lin, Ying-Chao; Dutridge, Debra; Picornell, Yoana; Landers, Carol J.; Farrior, Sharmayne; Wrobel, Iwona; Quiros, Antonio; Vasiliauskas, Eric A.; Grill, Bruce; Israel, David; Bahar, Ron; Christie, Dennis; Wahbeh, Ghassan; Silber, Gary; Dallazadeh, Saied; Shah, Praful; Thomas, Danny; Kelts, Drew; Hershberg, Robert M.; Elson, Charles O.; Targan, Stephan R.; Taylor, Kent D.; Rotter, Jerome I.; Yang, Huiying

    2007-01-01

    BACKGROUND AND AIM Crohn’s disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. METHODS Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. RESULTS Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5–80.4); p = 0.03). Pediatric CD patients positive for ≥1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). CONCLUSIONS The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients. PMID:16454844

  2. Transcutaneous DNA immunization following waxing-based hair depilation elicits both humoral and cellular immune responses

    PubMed Central

    Xiao, Gang; Li, Xinran; Kumar, Amit; Cui, Zhengrong

    2012-01-01

    Previously, we showed that transcutaneous (TC) DNA immunization by applying plasmid DNA onto a mouse skin area wherein the hair follicles were induced into growth stage by plucking the hair using warm waxing induced strong and functional antigen-specific antibody responses. In the present study, using plasmids that encode β-galactosidase gene or ovalbumin (OVA) gene, we showed that this mode of TC DNA immunization not only induced specific antibody responses, but also induced antigen-specific cytotoxic T lymphocyte responses. In fact, TC DNA immunization using a plasmid that encodes OVA gene prevented the growth of OVA-expressing B16-OVA tumor cells in the immunized mice. Moreover, we provided additional evidence supporting that hair follicles are essential for this mode of TC DNA immunization. PMID:22771558

  3. Sexual dimorphism in immunity: improving our understanding of vaccine immune responses in men.

    PubMed

    Furman, David

    2015-03-01

    Weaker immune responses are often observed in males compared to females. Since female hormones have proinflammatory properties and androgens have potent immunomodulatory effects, this sexual dimorphism in the immune response seems to be hormone dependent. Despite our current knowledge about the effect of sex hormones on immune cells, definition of the factors driving the sex differences in immunoclinical outcomes, such as the diminished response to infection and vaccination observed in men or the higher rates of autoimmunity observed in females, remains elusive. Recently, systems approaches to immune function have started to suggest a way toward establishing this connection. Such studies promise to improve our understanding of the mechanisms underlying the sexual dimorphism observed in the human immune system.

  4. The X-files in immunity: sex-based differences predispose immune responses.

    PubMed

    Fish, Eleanor N

    2008-09-01

    Despite accumulating evidence in support of sex-based differences in innate and adaptive immune responses, in the susceptibility to infectious diseases and in the prevalence of autoimmune diseases, health research and clinical practice do not address these distinctions, and most research studies of immune responses do not stratify by sex. X-linked genes, hormones and societal context are among the many factors that contribute to disparate immune responses in males and females. It is crucial to address sex-based differences in disease pathogenesis and in the pharmacokinetics and pharmacodynamics of therapeutic medications to provide optimal disease management for both sexes.

  5. Innate and adaptive immune responses in neurodegeneration and repair.

    PubMed

    Amor, Sandra; Woodroofe, M Nicola

    2014-03-01

    Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders. The articles highlight the role of the traditional resident immune cell of the CNS - the microglia - as well as the role of other glia astrocytes and oligodendrocytes in immune responses and their interplay with other immune cells including, mast cells, T cells and B cells. Future research should lead to new discoveries which highlight targets for therapeutic interventions which may be applicable to a range of neurodegenerative diseases.

  6. Innate and adaptive immune responses in neurodegeneration and repair

    PubMed Central

    Amor, Sandra; Woodroofe, M Nicola

    2014-01-01

    Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders. The articles highlight the role of the traditional resident immune cell of the CNS - the microglia - as well as the role of other glia astrocytes and oligodendrocytes in immune responses and their interplay with other immune cells including, mast cells, T cells and B cells. Future research should lead to new discoveries which highlight targets for therapeutic interventions which may be applicable to a range of neurodegenerative diseases. PMID:23758741

  7. Clinical investigation of the lesions responsible for sensory disturbance in Minamata disease.

    PubMed

    Uchino, M; Mita, S; Satoh, H; Hirano, T; Arimura, K; Nakagawa, M; Nakamura, M; Uyama, E; Ando, Y; Wakamiya, J; Futatsuka, M

    2001-11-01

    To clarify the lesions responsible for sensory disturbance in Minamata disease (MD), we clinically investigated the characteristics of sensory disturbance. In all patients with the classical type MD, two-point discrimination was severely disturbed, but the involvement of superficial sensation was relatively mild. On short-latency somatosensory evoked potential study, the component corresponding to N20 was completely absent with normal N9, N11, and N13 components. Although 14 of 38 chronic MD patients demonstrated intact superficial sensation, 10 of these 14 showed mild to moderate disturbance in two-point discrimination. The two-point discrimination in chronic MD patients was significantly high irrespective of the disturbance of superficial sensation. These findings suggest that the sensory disturbance of MD patients may mainly be caused by a lesion in the sensory cortex rather than in the peripheral nerves. However, other foci could be also responsible for the sensory impairment, since 9 of 38 chronic MD patients showed intact two-point discrimination.

  8. Response diversity can increase ecological resilience to disturbance in coral reefs.

    PubMed

    Baskett, Marissa L; Fabina, Nicholas S; Gross, Kevin

    2014-08-01

    Community-level resilience depends on the interaction between multiple populations that vary in individual responses to disturbance. For example, in tropical reefs, some corals can survive higher stress (resistance) while others exhibit faster recovery (engineering resilience) following disturbances such as thermal stress. While each type will negatively affect the other through competition, each might also benefit the other by reducing the potential for an additional competitor such as macroalgae to invade after a disturbance. To determine how community composition affects ecological resilience, we modeled coral-macroalgae interactions given either a resistant coral, a resilient coral, or both together. Having both coral types (i.e., response diversity) can lead to observable enhanced ecological resilience if (1) the resilient coral is not a superior competitor and (2) disturbance levels are high enough such that the resilient coral would collapse when considered alone. This enhanced resilience occurs through competitor-enabled rescue where each coral increases the potential for the other to recover from disturbance through external recruitment, such that both corals benefit from the presence of each other in terms of total cover and resilience. Therefore, conservation management aimed at protecting resilience under global change requires consideration of both diversity and connectivity between sites experiencing differential disturbance.

  9. Immune adjuvants in early life: targeting the innate immune system to overcome impaired adaptive response.

    PubMed

    de Brito, Cyro Alves; Goldoni, Adriana Letícia; Sato, Maria Notomi

    2009-09-01

    The neonatal phase is a transitory period characterized by an absence of memory cells, favoring a slow adaptive response prone to tolerance effects and the development of Th2-type responses. However, when appropriately stimulated, neonates may achieve an immune response comparable with adult counterparts. One strategy to stimulate the immunological response of neonates or children in early infancy has been to explore natural or synthetic ligands of cell receptors to stimulate innate immunity. The use of adjuvants for activating different cell receptors may be the key to enhancing neonatal adaptive immunity. This review highlights recent advances in the emerging field of molecular adjuvants of innate immune response and their implications for the development of immunotherapies, with particular focus on the neonatal period.

  10. Plant response strategies to stress and disturbance: the case of aquatic plants.

    PubMed

    Trémolières, Michèle

    2004-12-01

    The environmental factors controlling the establishment and development of plants in different ecosystems are of two types, stress and disturbance. The effects of stress or disturbance on aquatic systems are discussed in relation to the following questions: Can we predict the state and rate of recolonization after a disturbance? What are the strategies of recolonization developed by plants? How high is the resilience of a disturbed system? Two theories, the intermediate disturbance hypothesis, and the patch dynamics concept proposed to predict the composition, structure and dynamics of plants due to physical-chemical factors, were tested on two scales, that of communities and that of species, within two alluvial floodplains (the Rhine and the Rhone systems in France). With regard to the change of community on a larger scale (i.e. the whole network of the cut-off channels in the floodplain), large gradients of connection and disturbance induce high diversities within communities. Moreover, the highest flood disturbance induces a higher species richness and the occurrence of a particular species. The change in species is analysed using biological traits (morphological, reproductive or physiological). In the floodplain of the river Rhone, the response of plants corresponds well to theory, i.e. that habitats with an intermediate disturbance are richer than more or less disturbed habitats. So we can predict, through the biological traits, the functioning of a habitat. The last remaining question is that of the resilience of the system, which can be discussed in terms of species competition and the risk of biological invasion after an opening of habitat.

  11. Forest response and recovery following disturbance in upland forests of the Atlantic Coastal Plain.

    PubMed

    Schäfer, Karina V R; Renninger, Heidi J; Carlo, Nicholas J; Vanderklein, Dirk W

    2014-01-01

    Carbon and water cycling of forests contribute significantly to the Earth's overall biogeochemical cycling and may be affected by disturbance and climate change. As a larger body of research becomes available about leaf-level, ecosystem and regional scale effects of disturbances on forest ecosystems, a more mechanistic understanding is developing which can improve modeling efforts. Here, we summarize some of the major effects of physical and biogenic disturbances, such as drought, prescribed fire, and insect defoliation, on leaf and ecosystem-scale physiological responses as well as impacts on carbon and water cycling in an Atlantic Coastal Plain upland oak/pine and upland pine forest. During drought, stomatal conductance and canopy stomatal conductance were reduced, however, defoliation increased conductance on both leaf-level and canopy scale. Furthermore, after prescribed fire, leaf-level stomatal conductance was unchanged for pines but decreased for oaks, while canopy stomatal conductance decreased temporarily, but then rebounded the following growing season, thus exhibiting transient responses. This study suggests that forest response to disturbance varies from the leaf to ecosystem level as well as species level and thus, these differential responses interplay to determine the fate of forest structure and functioning post disturbance.

  12. Forest response and recovery following disturbance in upland forests of the Atlantic Coastal Plain

    PubMed Central

    Schäfer, Karina V. R.; Renninger, Heidi J.; Carlo, Nicholas J.; Vanderklein, Dirk W.

    2014-01-01

    Carbon and water cycling of forests contribute significantly to the Earth's overall biogeochemical cycling and may be affected by disturbance and climate change. As a larger body of research becomes available about leaf-level, ecosystem and regional scale effects of disturbances on forest ecosystems, a more mechanistic understanding is developing which can improve modeling efforts. Here, we summarize some of the major effects of physical and biogenic disturbances, such as drought, prescribed fire, and insect defoliation, on leaf and ecosystem-scale physiological responses as well as impacts on carbon and water cycling in an Atlantic Coastal Plain upland oak/pine and upland pine forest. During drought, stomatal conductance and canopy stomatal conductance were reduced, however, defoliation increased conductance on both leaf-level and canopy scale. Furthermore, after prescribed fire, leaf-level stomatal conductance was unchanged for pines but decreased for oaks, while canopy stomatal conductance decreased temporarily, but then rebounded the following growing season, thus exhibiting transient responses. This study suggests that forest response to disturbance varies from the leaf to ecosystem level as well as species level and thus, these differential responses interplay to determine the fate of forest structure and functioning post disturbance. PMID:25018759

  13. Transcriptional analysis of the innate immune response using the avian innate immunity microarray

    USDA-ARS?s Scientific Manuscript database

    The avian innate immunity microarray (AIIM) is a genomics tool designed to study the transcriptional activity of the avian immune response (Cytogenet. Genome Res. 117:139-145, 2007). It is an avian cDNA microarray representing 4,959 avian genes spotted in triplicate. The AIIM contains 25 avian int...

  14. Interplay between behavioural thermoregulation and immune response in mealworms.

    PubMed

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

    2012-11-01

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

  15. Immune Response in Thyroid Cancer: Widening the Boundaries

    PubMed Central

    Ward, Laura Sterian

    2014-01-01

    The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. PMID:25328756

  16. Immunomodulator-based enhancement of anti smallpox immune responses.

    PubMed

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

    2015-01-01

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

  17. PDT-apoptotic tumor cells induce macrophage immune response

    NASA Astrophysics Data System (ADS)

    Zhou, Fei-fan; Xing, Da; Chen, Wei R.

    2008-02-01

    Photodynamic therapy (PDT) functions as a cancer therapy through two major cell death mechanisms: apoptosis and necrosis. Immunological responses induced by PDT has been mainly associated with necrosis while apoptosis associated immune responses have not fully investigated. Heat shock proteins (HSPs) play an important role in regulating immune responses. In present study, we studied whether apoptotic tumor cells could induce immune response and how the HSP70 regulates immune response. The endocytosis of tumor cells by the activated macrophages was observed at single cell level by LSM. The TNF-α release of macrophages induced by co-incubated with PDT-apoptotic tumor cells was detected by ELISA. We found that apoptotic tumor cells treated by PDT could activate the macrophages, and the immune effect decreased evidently when HSP70 was blocked. These findings not only show that apoptosis can induce immunological responses, but also show HSP70 may serves as a danger signal for immune cells and induce immune responses to regulate the efficacy of PDT.

  18. Innate immune responses in raccoons after raccoon rabies virus infection.

    PubMed

    Srithayakumar, Vythegi; Sribalachandran, Hariharan; Rosatte, Rick; Nadin-Davis, Susan A; Kyle, Christopher J

    2014-01-01

    Zoonotic wildlife diseases pose significant health risks not only to their primary vectors but also to humans and domestic animals. Rabies is a lethal encephalitis caused by rabies virus (RV). This RNA virus can infect a range of terrestrial mammals but each viral variant persists in a particular reservoir host. Active management of these host vectors is needed to minimize the negative impacts of this disease, and an understanding of the immune response to RV infection aids strategies for host vaccination. Current knowledge of immune responses to RV infection comes primarily from rodent models in which an innate immune response triggers activation of several genes and signalling pathways. It is unclear, however, how well rodent models represent the immune response of natural hosts. This study investigates the innate immune response of a primary host, the raccoon, to a peripheral challenge using the raccoon rabies virus (RRV). The extent and temporal course of this response during RRV infection was analysed using genes predicted to be upregulated during infection (IFNs; IFN regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV activated components of the innate immune system, with changes in levels of transcripts correlated with presence of viral RNA. Our results suggest that natural reservoirs of rabies may not mimic the immune response triggered in rodent models, highlighting the need for further studies of infection in primary hosts.

  19. Innate immune responses of Drosophila melanogaster are altered by spaceflight.

    PubMed

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

    2011-01-11

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

  20. Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

    PubMed Central

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

    2011-01-01

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

  1. [Immune response in the pathogenesis of hepatitis C virus infection].

    PubMed

    Chalupa, P; Holub, M; Davidová, A; Arientová, S; Beran, O

    2015-10-01

    The pathogenesis of hepatitis C virus (HCV) infection is regulated by the host immunity and several metabolic factors affecting liver metabolism, including oxidative stress, insulin resistance, and hepatic steatosis. Both innate and adaptive immunity play an important role in HCV infection. Cytotoxic lymphocytes have a crucial role in viral eradication or viral persistence. Major cause of viral persistence during HCV infection could be the development of a weak antiviral immune response to the viral antigens, with corresponding inability to eradicate infected cells.

  2. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    PubMed

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

  3. Global analysis of the immune response

    NASA Astrophysics Data System (ADS)

    Ribeiro, Leonardo C.; Dickman, Ronald; Bernardes, Américo T.

    2008-10-01

    The immune system may be seen as a complex system, characterized using tools developed in the study of such systems, for example, surface roughness and its associated Hurst exponent. We analyze densitometric (Panama blot) profiles of immune reactivity, to classify individuals into groups with similar roughness statistics. We focus on a population of individuals living in a region in which malaria endemic, as well as a control group from a disease-free region. Our analysis groups individuals according to the presence, or absence, of malaria symptoms and number of malaria manifestations. Applied to the Panama blot data, our method proves more effective at discriminating between groups than principal-components analysis or super-paramagnetic clustering. Our findings provide evidence that some phenomena observed in the immune system can be only understood from a global point of view. We observe similar tendencies between experimental immune profiles and those of artificial profiles, obtained from an immune network model. The statistical entropy of the experimental profiles is found to exhibit variations similar to those observed in the Hurst exponent.

  4. Interferon regulatory factor 3 in adaptive immune responses.

    PubMed

    Ysebrant de Lendonck, Laure; Martinet, Valerie; Goriely, Stanislas

    2014-10-01

    Interferon regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Indeed, activation of this transcription factor triggers the expression of type I interferons and downstream interferon-stimulated genes in infected cells. Recent evidences indicate that this pathway also modulates adaptive immune responses. This review focuses on the different mechanisms that are implicated in this process. We discuss the role of IRF3 within antigen-presenting cells and T lymphocytes in the polarization of the cellular immune response and its implication in the pathogenesis of immune disorders.

  5. Outsmarting the host: bacteria modulating the immune response.

    PubMed

    Woolard, Matthew D; Frelinger, Jeffrey A

    2008-01-01

    Pathogenic bacteria and their hosts have had a two-way conversation for millions of years. This interaction has led to many measure/counter-measure responses by the host and bacteria. The host immune response has developed many mechanisms to neutralize and remove pathogen bacteria. In turn pathogenic bacteria have developed mechanisms to alter and evade the host immune response. We will review some of the mechanisms utilized by bacteria to accomplish this goal. We will also examine the current state of understanding of Francisella tularensis mediated immune evasion.

  6. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness

    PubMed Central

    Furman, David; Jojic, Vladimir; Kidd, Brian; Shen-Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M

    2013-01-01

    Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20–30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health. PMID:23591775

  7. Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

    PubMed Central

    Mooij, Merel

    2017-01-01

    The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection. PMID:28280748

  8. Subversion of the Immune Response by Rabies Virus.

    PubMed

    Scott, Terence P; Nel, Louis H

    2016-08-19

    Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses-including age, sex, cerebral lateralization and temperature-are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host's response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment.

  9. Tissue engineering tools for modulation of the immune response

    PubMed Central

    Boehler, Ryan M.; Graham, John G.; Shea, Lonnie D.

    2012-01-01

    Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine. PMID:21988690

  10. Immune and stress responses in oysters with insights on adaptation.

    PubMed

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

    2015-09-01

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

  11. Context-dependence of long-term responses of terrestrial gastropod populations to large-scale disturbance.

    Treesearch

    Christopher P. Bloch; Michael R. Willi

    2006-01-01

    Large-scale natural disturbances, such as hurricanes, can have profound effects on animal populations. Nonetheless, generalizations about the effects of disturbance are elusive, and few studies consider long-term responses of a single population or community to multiple large-scale disturbance events. In the last 20 y, twomajor hurricanes (Hugo and Georges) have struck...

  12. Photodynamic therapy and immune response in tumor-bearing mice

    NASA Astrophysics Data System (ADS)

    Canti, Gianfranco L.; Cubeddu, Rinaldo; Taroni, Paola; Valentini, Gianluca

    1999-06-01

    Since immune response of the host is important in the control of tumor growth and spreading, and the Photodynamic therapy (PDT) is able to increase the antitumor immunity, in our laboratory we examine the effect of PDT on immune compartment of tumor bearing mice. Lymphocytes and macrophages collected from tumor bearing mice pretreated with PDT are cytotoxic in vitro and in vivo against the parental tumor lines, in contrast the same immune cells population collected from tumor bearing mice pretreated only with laser light are unable to lyse the parental tumor cells. In adoptive immunotherapy experiments, treatment of mice bearing MS-2 tumor with adoptive transfer of immune lymphocytes collected from mice pretreated with PDT is able to significantly increase the survival time; in contrast the lymphocytes collected from mice pretreated only with laser light were not able to modify the survival time suggesting that the laser treatment alone did not increase the immune response of the host. In conclusion these results demonstrate that the PDT induce a strong immune response on the host and the stimulated lymphocytes generated could be used for an adoptive immunotherapy approach; moreover laser treatment alone (thermal effect) is unable to modulate the immune response of the host.

  13. Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

    PubMed

    Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

    2014-01-30

    The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Forest response to increased disturbance in the central Amazon and comparison to western Amazonian forests

    NASA Astrophysics Data System (ADS)

    Holm, J. A.; Chambers, J. Q.; Collins, W. D.; Higuchi, N.

    2014-10-01

    Uncertainties surrounding vegetation response to increased disturbance rates associated with climate change remains a major global change issue for Amazonian forests. Additionally, turnover rates computed as the average of mortality and recruitment rates in the western Amazon basin are doubled when compared to the central Amazon, and notable gradients currently exist in specific wood density and aboveground biomass (AGB) between these two regions. This study investigates the extent to which the variation in disturbance regimes contributes to these regional gradients. To address this issue, we evaluated disturbance-recovery processes in a central Amazonian forest under two scenarios of increased disturbance rates using first ZELIG-TROP, a dynamic vegetation gap model which we calibrated using long-term inventory data, and second using the Community Land Model (CLM), a global land surface model that is part of the Community Earth System Model (CESM). Upon doubling the mortality rate in the central Amazon to mirror the natural disturbance regime in the western Amazon of ∼2% mortality, the two regions continued to differ in multiple forest processes. With the inclusion of elevated natural disturbances, at steady state, AGB significantly decreased by 41.9% with no significant difference between modeled AGB and empirical AGB from the western Amazon data sets (104 vs. 107 Mg C ha-1, respectively). However, different processes were responsible for the reductions in AGB between the models and empirical data set. The empirical data set suggests that a decrease in wood density is a driver leading to the reduction in AGB. While decreased stand basal area was the driver of AGB loss in ZELIG-TROP, a forest attribute that does not significantly vary across the Amazon Basin. Further comparisons found that stem density, specific wood density, and basal area growth rates differed between the two Amazonian regions. Last, to help quantify the impacts of increased disturbances on

  15. (Hydrological and geochemical response and recovery in disturbed arctic ecosystems)

    SciTech Connect

    Everett, K.R.

    1990-08-31

    Ionic concentration of snow prior to meltoff in 1990 as in previous years ranged widely from point to point within the basin. Overland flow began on May 12 and was monitored at closely-spaced time intervals for discharge volume and ionic concentrations to better define this relationship in non-channelized flow. Ionic concentration in both watertrack flow and in Imnavait Creek were closely monitored during meltoff. During the post melt period daily sampling was maintained in watertrack 7 and Imnavait Creek. Rainfall collection and analysis on an eight day schedule was maintained as in previous years. Soil solution composition was monitored on an event basis in conjunction with a similar schedule of precipitation sampling to determine relationships between precipitation and near surface and overland flow. Composition of deeper soil solution was also monitored and sampled for {sup 18}O analyses to determine the age structure of water contributed by the active layer to stream and watertracks. A pilot experiment employing salt tracers was conducted across landscape units to determine rates and pathways of soil solution movement in response to individual rain events. Nutrient addition in rime and fog were also recorded to add detail to the input side of the balance equation.

  16. Provider response to different formats of the adult immunization schedule.

    PubMed

    Davis, Matthew M; Halasyamani, Lakshmi K; Sneller, Vishnu-Priya; Bishop, Kathy R; Clark, Sarah J

    2005-07-01

    Providers' failure to administer vaccines in accordance with established recommendations is a well-recognized barrier to national immunization efforts. This study evaluated the ease of use of two different formats of the Centers for Disease Control and Prevention's (CDC) adult immunization schedule by physicians in private practice, where the majority of adult immunizations are administered. A series of focus groups was conducted with 94 physicians and other clinical staff in 11 private practices (family medicine and internal medicine) in six U.S. cities. Each session was based on a structured set of questions that explored barriers to adult immunizations, followed by three mock clinical scenarios to examine how each of two graphical depictions of the 2003-2004 adult immunization schedule (one from the CDC's Advisory Committee on Immunization Practices, and the other from the Immunization Action Coalition) might facilitate assessments of recommended immunizations. Group dialogue and individual participants' written responses to the scenarios and the alternate schedule formats were analyzed. Providers perceived multiple barriers to adult immunization independent of immunization schedule formats, chiefly patients' low interest in immunization and refusal of vaccines. Most participants were not familiar with either format of CDC's adult immunization schedule before the study, but quickly developed strong preferences for one versus the other (usually the second format that they encountered). About half of the providers changed their vaccine recommendations for clinical scenarios when they consulted either schedule format, although some of the changes were not clinically appropriate. Participants suggested several ways to enhance the availability of the information contained in the schedule formats, especially through electronic means. This qualitative study suggests ways in which graphic depictions of an adult immunization schedule may address adult immunization

  17. Receptivity and Forced Response to Acoustic Disturbances in High-Speed Boundary Layers

    NASA Technical Reports Server (NTRS)

    Balakumar, P.; King, Rudolph A.; Chou, Amanda; Owens, Lewis R.; Kegerise, Michael A.

    2016-01-01

    Supersonic boundary-layer receptivity to freestream acoustic disturbances is investigated by solving the Navier-Stokes equations for Mach 3.5 flow over a sharp flat plate and a 7-deg half-angle cone. The freestream disturbances are generated from a wavy wall placed at the nozzle wall. The freestream acoustic disturbances radiated by the wavy wall are obtained by solving the linearized Euler equations. The results for the flat plate show that instability modes are generated at all the incident angles ranging from zero to highly oblique. However, the receptivity coefficient decreases by about 20 times when the incident angle increases from zero to a highly oblique angle of 68 degrees. The results for the cone show that no instability modes are generated when the acoustic disturbances impinge the cone obliquely. The results show that the perturbations generated inside the boundary layer by the acoustic disturbances are the response of the boundary layer to the external forcing. The amplitude of the forced disturbances inside the boundary layer are about 2.5 times larger than the incoming field for zero azimuthal wavenumber and they are about 1.5 times for large azimuthal wavenumbers.

  18. Universal time variation of high-latitude thermospheric disturbance wind in response to a substorm

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Zhang, Ke Deng; Wan, Xin; Lühr, Hermann

    2017-04-01

    The temporal and spatial variation in thermospheric winds are studied at 400 km altitude in response to substorms that start at different universal time (UT), using a global ionosphere and thermosphere model. The substorm-induced disturbance winds at high latitudes are mainly in the poleward, westward, and upward directions in the dusk sector and in the equatorward, westward, and upward directions in the nighttime. The daytime perturbation is due to ion drag, driven by variations in interplanetary magnetic field Bz, whereas the nighttime perturbation is due to both the Bz and hemispheric power input. The nightside disturbed winds respond somewhat later than the dayside owing to low background ion density. Ion drag is the dominant driving force in the daytime for both meridional and zonal disturbed winds, whereas Joule heating is the dominant factor for the vertical winds. The nighttime meridional and zonal winds are driven by a combination of ion drag, Joule heating, and heating of the auroral belt, whereas the vertical winds are mainly caused by auroral belt heating. The viscous force acts to resist the ion drag, whereas the Coriolis force is negligible. The disturbed winds exhibit large variations with UT during equinox and local winter conditions. With more solar illumination, stronger disturbed winds can be generated. Weak or even opposite variations with UT in the disturbed winds are found in local summer, which is due to a smaller UT variation of the daytime ion density and a larger contribution from auroral heating than from ion drag.

  19. Radiation Induced Immune Response in Prostate Cancer

    DTIC Science & Technology

    2014-12-01

    immune effector cells. Glucose Regulated Protein-78 (GRP78), and Tax interacting protein-1 (TIP1) are overexpressed in cancer and participate in the...vivo. KEY WORDS: Glucose Regulated Protein-78 (GRP78) Tax interacting protein-1 (TIP1) IgG antibody dependent cell mediated cytotoxicity (ADCC

  20. Social Behavior, Prolactin and the Immune Response

    DTIC Science & Technology

    1989-04-01

    treated with neomycin for diarrhea during the last week of July. Some of the fluctuations in SI’s during late July and early August might be due to...Behavior, and immunity, 1987, 1, 7-20. Gross, W. B. Effect ot social stress on occurrence of Marek’s disease in chickens . Am. J. Vet. Res., 1972, 933, 2275

  1. DNA-mediated immunization and the energetic immune response to hepatitis B surface antigen.

    PubMed

    Whalen, R G; Davis, H L

    1995-04-01

    A new and unusual approach for evoking an immune response has recently been introduced--that of DNA-based immunization. Purified plasmid DNA, containing protein coding sequences and the necessary regulatory elements to express them, can be introduced into tissues of the organism by means of a parenteral injection or by particle bombardment. The number of cells transfected and the amount of protein produced is sufficient to produce a remarkably strong and broad-based immune response to a wide variety of foreign proteins. The absence of an exogenous infectious agent or immunogen results in the abrupt appearance of a foreign protein within the normal cells of an immunologically mature and healthy animal and provokes an energetic and efficient reaction to this form of antigen presentation. This review summarizes the results obtained with the various experimental models that have been described to date and considers in greater depth the immune response to the surface antigen of the human hepatitis B virus that has been achieved using DNA-based immunization. Several issues are addressed in a prospective manner in order to anticipate some future developments and to point out topics likely to be pertinent to this field. DNA-mediated induction of immune responses may soon be applied as a form of therapeutic treatment. Although this method may constitute a revolution for vaccination, many issues must first be dealt with, especially concerning the safety of using DNA as an immunizing molecule.

  2. Taenia solium: immune response against oral or systemic immunization with purified recombinant calreticulin in mice.

    PubMed

    Fonseca-Coronado, Salvador; Ruiz-Tovar, Karina; Pérez-Tapia, Mayra; Mendlovic, Fela; Flisser, Ana

    2011-01-01

    Recombinant functional Taenia solium calreticulin (rTsCRT) confers different degrees of protection in the experimental model of intestinal taeniosis in hamsters. The aim of this study was to evaluate the immune response induced after oral or systemic immunization with an electroeluted rTsCRT in BALB/c mice. Oral immunization elicited high fecal IgA and the production of IL-4 and IL-5 by mesenteric lymph node cells after in vitro stimulation with rTSCRT, indicating a Th2 response. Mice subcutaneously immunized produced high amounts of serum IgG, being IgG1 (Th2-related) the predominant isotype, while in vitro stimulated spleen cells synthesized IL-4, IL-5 and also IFN-γ, indicating a mixed Th1/Th2 cellular response after systemic immunization. Our data show that purified rTsCRT induces polarized Th2 responses after oral immunization of mice, a common characteristic of protective immunity against helminths and, consequently, a desirable hallmark in the search for a vaccine.

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

    PubMed Central

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

    2011-01-01

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses. PMID:24213131

  4. Subversion of the Immune Response by Rabies Virus

    PubMed Central

    Scott, Terence P.; Nel, Louis H.

    2016-01-01

    Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses—including age, sex, cerebral lateralization and temperature—are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host’s response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment. PMID:27548204

  5. Plant hydraulic controls over ecosystem responses to climate-enhanced disturbances

    NASA Astrophysics Data System (ADS)

    Mackay, D. S.; Ewers, B. E.; Reed, D. E.; Pendall, E.; McDowell, N. G.

    2012-12-01

    Climate-enhanced disturbances such as drought and insect infestation range in severity, contributing minor to severe stress to forests including forest mortality. While neither form of disturbance has been unambiguously implicated as a mechanism of mortality, both induce changes in water, carbon, and nutrient cycling that are key to understanding forest ecosystem response to, and recovery from, disturbance. Each disturbance type has different biophysical, ecohydrological, and biogeochemical signatures that potentially complicate interpretation and development of theory. Plant hydraulic function is arguably a unifying control over these responses to disturbance because it regulates stomatal conductance, leaf biochemistry, carbon (C) uptake and utilization, and nutrient cycling. We demonstrated this idea by focusing on water and C, including non-structural (NSC), resources, and nitrogen (N) uptake across a spectrum of forest ecosystems (e.g., northern temperate mixed forests, lodgepole pine forests in the Rocky Mountains, and pinon pine - juniper woodlands in New Mexico) using the Terrestrial Regional Ecosystem Exchange Simulator (TREES). TREES is grounded in the biophysics of water movement through soil and plants, respectively via hydraulic conductivity of the soil and cavitation of xylem. It combines this dynamic plant hydraulic conductance with canopy biochemical controls over photosynthesis, and the dynamics of structural and non-structural carbon through a carbon budget that responds to plant hydraulic status. As such, the model can be used to develop testable hypotheses on a multitude of disturbance and recovery responses including xylem dysfunction, stomatal and non-stomatal controls on photosynthesis and carbon allocation, respiration, and allocation to defense compounds. For each of the ecosystems we constrained and evaluated the model with allometry, sap flux and/or eddy covariance data, leaf gas exchange measurements, and vulnerability to cavitation data

  6. Virus-like nanostructures for tuning immune response

    NASA Astrophysics Data System (ADS)

    Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

    2015-11-01

    Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.

  7. Virus-like nanostructures for tuning immune response

    PubMed Central

    Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

    2015-01-01

    Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system. PMID:26577983

  8. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  9. Responses of seagrass to anthropogenic and natural disturbances do not equally translate to its consumers.

    PubMed

    Tomas, Fiona; Martínez-Crego, Begoña; Hernán, Gema; Santos, Rui

    2015-11-01

    Coastal communities are under threat from many and often co-occurring local (e.g., pollution, eutrophication) and global stressors (e.g., climate change), yet understanding the interactive and cumulative impacts of multiple stressors in ecosystem function is far from being accomplished. Ecological redundancy may be key for ecosystem resilience, but there are still many gaps in our understanding of interspecific differences within a functional group, particularly regarding response diversity, that is, whether members of a functional group respond equally or differently to anthropogenic stressors. Herbivores are critical in determining plant community structure and the transfer of energy up the food web. Human disturbances may alter the ecological role of herbivory by modifying the defense strategies of plants and thus the feeding patterns and performance of herbivores. We conducted a suite of experiments to examine the independent and interactive effects of anthropogenic (nutrient and CO2 additions) and natural (simulated herbivory) disturbances on a seagrass and its interaction with two common generalist consumers to understand how multiple disturbances can impact both a foundation species and a key ecological function (herbivory) and to assess the potential existence of response diversity to anthropogenic and natural changes in these systems. While all three disturbances modified seagrass defense traits, there were contrasting responses of herbivores to such plant changes. Both CO2 and nutrient additions influenced herbivore feeding behavior, yet while sea urchins preferred nutrient-enriched seagrass tissue (regardless of other experimental treatments), isopods were deterred by these same plant tissues. In contrast, carbon enrichment deterred sea urchins and attracted isopods, while simulated herbivory only influenced isopod feeding choice. These contrasting responses of herbivores to disturbance-induced changes in seagrass help to better understand the ecological

  10. Proteomic contributions to our understanding of vaccine and immune responses

    PubMed Central

    Galassie, Allison C.; Link, Andrew J.

    2015-01-01

    Vaccines are one of the greatest public health successes; yet, due to the empirical nature of vaccine design, we have an incomplete understanding of how the genes and proteins induced by vaccines contribute to the development of both protective innate and adaptive immune responses. While the advent of genomics has enabled new vaccine development and facilitated understanding of the immune response, proteomics identifies potentially new vaccine antigens with increasing speed and sensitivity. In addition, as proteomics is complementary to transcriptomic approaches, a combination of both approaches provides a more comprehensive view of the immune response after vaccination via systems vaccinology. This review details the advances that proteomic strategies have made in vaccine development and reviews how proteomics contributes to the development of a more complete understanding of human vaccines and immune responses. PMID:26172619

  11. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    2005-09-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system’s search for antibodies, a balance has evolved between binding affinity and specificity.

  12. DNA Damage Response and Immune Defense: Links and Mechanisms.

    PubMed

    Nakad, Rania; Schumacher, Björn

    2016-01-01

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

  13. DNA Damage Response and Immune Defense: Links and Mechanisms

    PubMed Central

    Nakad, Rania; Schumacher, Björn

    2016-01-01

    DNA damage plays a causal role in numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signaling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signaling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signaling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans. PMID:27555866

  14. [Defects in immune system response by our organisms].

    PubMed

    Español, Teresa

    2005-09-01

    When some of the mechanisms in our immune response system fail, this can be due to external problems such as infections or transplants or due to congenital errors, known as Primary Immunologic Deficiencies. Dr. Español briefly reviews the most important characteristics of our immune response system, and then continues with an analysis of the defects of this system, especially those defects which are classified as Primary Immunologic Deficiencies.

  15. Maternal antibodies and infant immune responses to vaccines.

    PubMed

    Edwards, Kathryn M

    2015-11-25

    Infants are born with immature immune systems, making it difficult for them to effectively respond to the infectious pathogens encountered shortly after birth. Maternal antibody is actively transported across the placenta and serves to provide protection to the newborn during the first weeks to months of life. However, maternal antibody has been shown repeatedly to inhibit the immune responses of young children to vaccines. The mechanisms for this inhibition are presented and the impact on ultimate immune responses is discussed. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  16. Demographic response of a shrubland bird to habitat creation, succession, and disturbance in a dynamic landscape

    Treesearch

    Michael E. Akresh; David I. King; Robert T. Brooks

    2015-01-01

    Shrubland birds have experienced widespread declines in the eastern United States. Habitat for shrubland birds is typically dynamic, in which available habitat changes temporally and spatially in response to disturbance and succession. Despite widespread concerns among conservationists about shrubland birds, much is still poorly understood regarding fundamental...

  17. High Risk Behaviors in Marine Mammals: Linking Behavioral Responses to Anthropogenic Disturbance to Biological Consequences

    DTIC Science & Technology

    2015-09-30

    Locomotion and the cost of hunting in large, stealthy marine carnivores. Integrative and Comparative Biology : doi:10.1093/icb/icv025. [published...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. High Risk Behaviors in Marine Mammals: Linking...Behavioral Responses to Anthropogenic Disturbance to Biological Consequences Terrie M. Williams Center for Ocean Health- Long Marine Lab Department of

  18. Capturing community context of human response to forest disturbance by insects: a multi-method assessment

    Treesearch

    Hua Qin; Courtney G. Flint

    2010-01-01

    The socioeconomic and environmental features of local places (community context) influence the relationship between humans and their physical environment. In times of environmental disturbance, this community context is expected to influence human perceptual and behavioral responses. Residents from nine Colorado communities experiencing a large outbreak of mountain...

  19. Vegetation response to natural and anthropogenic disturbances in the Larrea-Ambrosia and Coleogyne shrublands

    Treesearch

    Simon A. Lei

    2001-01-01

    Vegetation response to various types of disturbances was quantitatively investigated in the Larrea tridentata-Ambrosia dumosa (creosote bush-white bursage) and Coleogyne ramosissima (blackbrush) shrublands of southern Nevada. Between the two control (undisturbed) habitats, the Larrea-Ambrosia vegetation zone had a greater plant species richness, but had a lower percent...

  20. Antigen processing and immune regulation in the response to tumours.

    PubMed

    Reeves, Emma; James, Edward

    2017-01-01

    The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8(+) cytotoxic and CD4(+) helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8(+) cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4(+) T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8(+) cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets.

  1. Memory immune response: a major challenge in vaccination.

    PubMed

    Prisco, Antonella; De Berardinis, Piergiuseppe

    2012-10-01

    Abstract A crucial challenge for vaccine development is to design vaccines that induce a long-lasting protective immune response, i.e., immune memory. The persistence of antigen-specific antibody titers over a protective threshold, and the ability to exibit a 'recall response' to a subsequent encounter with an antigen have long been the only measurable correlates of vaccine take and immune memory development, suffering from the disadvantage of relying on long-term monitoring of the immune response. In the last few years, advances in the technologies for the identification and characterization of the cell subsets and molecular pathways involved in the immune response to vaccination have allowed innovative approaches to the identification of early correlates of immune memory. In this review, we discuss recent data and hypotheses on early correlates of the development of immune memory, with special emphasis on the gene expression signatures that underlie the self-renewal ability of some lymphocyte subsets, and their similarities with gene expression signatures in stem cells.

  2. Circadian rhythm and the immune response: a review.

    PubMed

    Habbal, O A; Al-Jabri, A A

    2009-01-01

    For long, the immune system has been thought of as an effector mechanism reacting to antigenic challenge with defensive responses designed to eliminate 'foreign' material and return to a standby or surveillance mode. However, the recent concept now supported by substantial evidence suggests that immunity is not effector biased but is also a sensory organ and forms part of an integrated homeostatic network. The bidirectional information flow between the neuroendocrine and immune systems functions to maintain and protect the internal homeostasis of the organism. The paradox of this interwined function is that homeostasis may require the neuroendocrine system to work for or against the immune system, as is the case in infection. Potential dangers necessitate activation of the immune system, and such a response may pose risks to the integrity of the host. This occurs when an overly vigorous response may be detrimental and kill the host, as is the case of toxic shock syndrome. Therefore, the constant monitoring role of the neuroendocrine system to control and, when necessary, regulate the function of the immune system is crucial for the homeostatic integrity of the host. This reciprocity of functional need determines the mode of action to determine the context of a perceived threat and the best way to respond. Any breakdown in this two-way communication may manifest itself in problems such as autoimmunity, septic shock, or chronic infection. In this article, we review our current knowledge of circadian rhythm and its relation to the immune response.

  3. Measles virus-induced suppression of immune responses

    PubMed Central

    Griffin, Diane E.

    2010-01-01

    Summary Measles is an important cause of child mortality that has a seemingly paradoxical interaction with the immune system. In most individuals, the immune response is successful in eventually clearing measles virus (MV) infection and in establishing life-long immunity. However, infection is also associated with persistence of viral RNA and several weeks of immune suppression, including loss of delayed type hypersensitivity responses and increased susceptibility to secondary infections. The initial T-cell response includes CD8+ and T-helper 1 CD4+ T cells important for control of infectious virus. As viral RNA persists, there is a shift to a T-helper 2 CD4+ T-cell response that likely promotes B-cell maturation and durable antibody responses but may suppress macrophage activation and T-helper 1 responses to new infections. Suppression of mitogen-induced lymphocyte proliferation can be induced by lymphocyte infection with MV or by lymphocyte exposure to a complex of the hemagglutinin and fusion surface glycoproteins without infection. Dendritic cells are susceptible to infection and can transmit infection to lymphocytes. MV-infected dendritic cells are unable to stimulate a mixed lymphocyte reaction and can induce lymphocyte unresponsiveness through expression of MV glycoproteins. Thus, multiple factors may contribute both to measles-induced immune suppression and to the establishment of durable protective immunity. PMID:20636817

  4. Advances in Overcoming Immune Responses following Hemophilia Gene Therapy

    PubMed Central

    Miao, Carol H.

    2012-01-01

    Both Clinical trials and pre-clinical experiments for hemophilia gene therapy showed that it is important to overcome potential immune responses against gene transfer vectors and/or transgene products to ensure the success of gene therapy. Recently various approaches have been investigated to prevent or modulate such responses. Gene transfer vectors have been specifically engineered and immunosuppressive regimens have been administered to avoid or manipulate the immune responses against the vectors. In order to prevent cytotoxic lymphocyte or antibody formation induced by transgene expression, novel approaches have been developed, including methods to manipulate antigen presentation, development of variant genes encoding less immunogenic proteins or gene transfer protocols to evade immune responses, as well as immunosuppressive strategies to target either T and/or B cell responses. Most of these successful protocols involve the induction of activated regulatory T cells to create a regulatory immune environment during tolerance induction. Recent development of these strategies to evade vector-specific immune responses and induce long-term immune tolerance specific to the transgene product will be discussed. PMID:22737594

  5. Modeling the interactions between pathogenic bacteria, bacteriophage and immune response

    NASA Astrophysics Data System (ADS)

    Leung, Chung Yin (Joey); Weitz, Joshua S.

    The prevalence of antibiotic-resistant strains of pathogenic bacteria has led to renewed interest in the use of bacteriophage (phage), or virus that infects bacteria, as a therapeutic agent against bacterial infections. However, little is known about the theoretical mechanism by which phage therapy may work. In particular, interactions between the bacteria, the phage and the host immune response crucially influences the outcome of the therapy. Few models of phage therapy have incorporated all these three components, and existing models suffer from unrealistic assumptions such as unbounded growth of the immune response. We propose a model of phage therapy with an emphasis on nonlinear feedback arising from interactions with bacteria and the immune response. Our model shows a synergistic effect between the phage and the immune response which underlies a possible mechanism for phage to catalyze the elimination of bacteria even when neither the immune response nor phage could do so alone. We study the significance of this effect for different parameters of infection and immune response, and discuss its implications for phage therapy.

  6. Protective immune responses to fungal infections.

    PubMed

    Rivera, A

    2014-09-01

    The incidence of fungal infections has been on the rise over several decades. Fungal infections threaten animals, plants and humans alike and are thus of significant concern to scientists across disciplines. Over the last decade, significant advances on fungal immunology have lead to a better understanding of important mechanisms of host protection against fungi. In this article, I review recent advances of relevant mechanisms of immune-mediated protection to fungal infections.

  7. Innate Immune Response to Burkholderia mallei

    DTIC Science & Technology

    2017-02-16

    infections. Lipopolysaccharide (LPS) is a major component of the outer membrane of gram- negative bacteria , and a potent stimulator of host innate...relapse or reinfection. Bacteria can become quiescent and subclinical to avoid host immune mechanisms of clearance. An earlier report indicated that non...autophagy correlate with intracellular persistence of bacteria with aerosol exposure not only of B. pseudomallei but also B. mallei in spleens of TR-17-034

  8. Mucosal immune responses following intestinal nematode infection

    PubMed Central

    Zaph, C; Cooper, P J; Harris, N L

    2014-01-01

    In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1–2 years) 1. Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2·5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) 2. Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host–helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed. PMID:25201407

  9. Animal temperament and human disturbance: implications for the response of wildlife to tourism.

    PubMed

    Martin, J G A; Réale, D

    2008-01-01

    Studies on the response of wildlife to human disturbance generally focus on demographic changes or on physiological and behavioural modifications directly related to stress response. Yet fewer studies have explored whether the distribution of individual animals in response to human disturbance is influenced by temperament. Temperament represents the consistency of responses of individuals in reaction to novel or challenging situations. Individuals are thus assumed to express highly consistent behaviour-hormonal response under specific stress conditions. In this study, we investigate the relations between exploration, grooming-scanning continuum, emotionality, and docility of individual Eastern chipmunks (Tamias striatus) and location of their burrow respective to frequentation by humans. We then assess the relationship between cortisol accumulated in the hair and both temperament and frequentation by humans. Explorative or docile chipmunks were more common in frequented areas. Hair cortisol increased with docility, but was not related to human frequentation. These results indicate that temperament may cause animals to distribute themselves in a non-random way in response to human disturbance. Integrating temperament into studies of the stress response of wildlife to humans could therefore help us understand the impact of tourism on wildlife.

  10. Sex differences in immune responses and immune reactivity to stress in adolescents.

    PubMed

    Kang, Duck-Hee; Kim, Chun-Ja; Suh, Yeonok

    2004-04-01

    The immune system is the body's major defense mechanism against disease. However, psychosocial factors, such as stress, can modulate various immune responses. Although they have been examined in adult humans and other animals, sex differences in immune responses and immune reactivity to stress have rarely been examined in adolescents, particularly comparing healthy and asthmatic adolescents. In 151 healthy and asthmatic high school adolescents (91 females and 60 males), natural killer cell (NK) cytotoxicity, polymorphonuclear leukocyte (PMN) superoxide release, lymphocyte proliferative responses, and CD subsets were measured twice: once during mid-semester and again during final examinations. There was little difference in these measures between healthy and asthmatic adolescents. Similarly, only sex difference was noted in NK cytotoxicity at a 25:1 effector-to-target cell ratio, with males showing significantly higher responses than females. For PMN superoxide release, females significantly increased their responses during final examinations, whereas males demonstrated no changes. For lymphocyte proliferative responses, both females and males increased their responses during final examinations, but the magnitude of increase was much greater in males. Furthermore, racial comparisons indicated that African American adolescents (n = 16), as compared with Caucasian adolescents (n = 128), had significantly higher responses in PMN superoxide release to N-Formyl-Met-Leu-Phe (FMLP) activation during mid-semester and lymphocyte proliferative responses at both time points. Nevertheless, the overall findings indicate limited differences in immune responses and immune reactivity to stress in adolescents between males and females, healthy and asthmatic adolescents, and Caucasians and African Americans. However, further investigations with larger samples are warranted.

  11. Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines.

    PubMed

    Duryee, Michael J; Bevins, Rick A; Reichel, Carmela M; Murray, Jennifer E; Dong, Yuxiang; Thiele, Geoffrey M; Sanderson, Sam D

    2009-05-14

    Vaccines to methamphetamine (meth) were designed by covalently attaching a meth hapten (METH) to peptide constructs that contained a conformationally biased, response-selective molecular adjuvant, YSFKPMPLaR (EP54). Rats immunized with EP54-containing meth vaccines generated serum antibody titers to authentic meth, an immune outcome that altered meth self-administration. Immunization increased meth self-administration suggesting pharmacokinetic antagonism. The ability of immune sera to bind a METH-modified target protein dramatically decreased during and shortly after the meth self-administration assay, suggesting effective sequestration of free meth. However, the binding ability of immune sera to the METH-modified target protein was recovered 34 days after meth-free clearance time.

  12. Selenium influence in the poultry immune response--review.

    PubMed

    Saad, Marina B; Gertner, Luiz R; Bona, Tania D M M; Santin, Elizabeth

    2009-11-01

    Selenium is an essential mineral for organic function on animal and human body. This mineral is important due to its function as antioxidant in organism, it neutralizes the free radicals that are resultant from many factors but especially by immune response. Diet is the major source of selenium. In poultry, the nutritional requirements for all nutrients and even selenium was normally calculated based on experimental trial using health animal in very low challenge conditions. However, on practical way animals are continually exposed to different infection challenges and intense vaccine program increasing immune system activation. On this aspect, there are studies that show that immune activation response increases the necessity of nutrients, vitamins and minerals. The objective of this review is to present recent patents information about the influence of selenium on immune response and practices applied on poultry production.

  13. Characterization of host immune responses in Ebola virus infections.

    PubMed

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

    2014-06-01

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

  14. Autophagy-associated immune responses and cancer immunotherapy.

    PubMed

    Pan, Hongming; Chen, Liuxi; Xu, Yinghua; Han, Weidong; Lou, Fang; Fei, Weiqiang; Liu, Shuiping; Jing, Zhao; Sui, Xinbing

    2016-04-19

    Autophagy is an evolutionarily conserved catabolic process by which cellular components are sequestered into a double-membrane vesicle and delivered to the lysosome for terminal degradation and recycling. Accumulating evidence suggests that autophagy plays a critical role in cell survival, senescence and homeostasis, and its dysregulation is associated with a variety of diseases including cancer, cardiovascular disease, neurodegeneration. Recent studies show that autophagy is also an important regulator of cell immune response. However, the mechanism by which autophagy regulates tumor immune responses remains elusive. In this review, we will describe the role of autophagy in immune regulation and summarize the possible molecular mechanisms that are currently well documented in the ability of autophagy to control cell immune response. In addition, the scientific and clinical hurdles regarding the potential role of autophagy in cancer immunotherapy will be discussed.

  15. Sex Drives Dimorphic Immune Responses to Viral Infections.

    PubMed

    Ghosh, Soumitra; Klein, Robyn S

    2017-03-01

    New attention to sexual dimorphism in normal mammalian physiology and disease has uncovered a previously unappreciated breadth of mechanisms by which females and males differentially exhibit quantitative phenotypes. Thus, in addition to the established modifying effects of hormones, which prenatally and postpubertally pattern cells and tissues in a sexually dimorphic fashion, sex differences are caused by extragonadal and dosage effects of genes encoded on sex chromosomes. Sex differences in immune responses, especially during autoimmunity, have been studied predominantly within the context of sex hormone effects. More recently, immune response genes have been localized to sex chromosomes themselves or found to be regulated by sex chromosome genes. Thus, understanding how sex impacts immunity requires the elucidation of complex interactions among sex hormones, sex chromosomes, and immune response genes. In this Brief Review, we discuss current knowledge and new insights into these intricate relationships in the context of viral infections.

  16. Systems level immune response analysis and personalized medicine.

    PubMed

    Brodin, Petter; Valentini, Davide; Uhlin, Michael; Mattsson, Jonas; Zumla, Alimuddin; Maeurer, Markus J

    2013-04-01

    The immune system is an anatomically structured, orchestrated interaction of different cell types that communicate via a large number of receptors recognizing both soluble and cellular ligands. Recent technological advances now allow large-scale measurements for better appreciation of this complexity. Despite these advances, only a few immunological parameters are routinely measured in clinical practice. The authors believe that these measurements are insufficient to describe the immune function of individual patients and thus cannot be used to evaluate immune-mediated diseases or response to therapy. Our current knowledge of immunology comes largely from work in murine model systems where the immune system has been characterized in great detail. This impressive volume of knowledge has proven to be difficult to translate into novel therapies in humans; one reason for this is the lack of large-scale immune monitoring allowing for systems-wide analysis of the human immune system. The authors propose a systems approach to immunology, where the focus is moved from analysis of individual cell types towards more integrated studies of the entire immune system. Exercising 'systems immunology' in preclinical research, during drug development and in patients undergoing therapies affecting the immune system, will enable us to improve clinical results through personalized medicine and help to define clinically relevant patterns of immune reactivity.

  17. Charon Mediates Immune Deficiency-Driven PARP-1-Dependent Immune Responses in Drosophila.

    PubMed

    Ji, Yingbiao; Thomas, Colin; Tulin, Nikita; Lodhi, Niraj; Boamah, Ernest; Kolenko, Vladimir; Tulin, Alexei V

    2016-09-15

    Regulation of NF-κB nuclear translocation and stability is central to mounting an effective innate immune response. In this article, we describe a novel molecular mechanism controlling NF-κB-dependent innate immune response. We show that a previously unknown protein, termed as Charon, functions as a regulator of antibacterial and antifungal immune defense in Drosophila Charon is an ankyrin repeat-containing protein that mediates poly(ADP-ribose) polymerase-1 (PARP-1)-dependent transcriptional responses downstream of the innate immune pathway. Our results demonstrate that Charon interacts with the NF-κB ortholog Relish inside perinuclear particles and delivers active Relish to PARP-1-bearing promoters, thus triggering NF-κB/PARP-1-dependent transcription of antimicrobial peptides. Ablating the expression of Charon prevents Relish from targeting promoters of antimicrobial genes and effectively suppresses the innate immune transcriptional response. Taken together, these results implicate Charon as an essential mediator of PARP-1-dependent transcription in the innate immune pathway. Thus, to our knowledge, our results are the first to describe the molecular mechanism regulating translocation of the NF-κB subunit from cytoplasm to chromatin.

  18. Male genital tract immune response against Chlamydia trachomatis infection.

    PubMed

    Mackern-Oberti, Juan Pablo; Motrich, Rubén Darío; Damiani, Maria Teresa; Saka, Héctor Alex; Quintero, Cristian Andrés; Sánchez, Leonardo Rodolfo; Moreno-Sosa, Tamara; Olivera, Carolina; Cuffini, Cecilia; Rivero, Virginia Elena

    2017-10-01

    Chlamydia trachomatis is the most commonly reported agent of sexually transmitted bacterial infections worldwide. This pathogen frequently leads to persistent, long-term, subclinical infections, which in turn may cause severe pathology in susceptible hosts. This is in part due to the strategies that Chlamydia trachomatis uses to survive within epithelial cells and to evade the host immune response, such as subverting intracellular trafficking, interfering signaling pathways and preventing apoptosis. Innate immune receptors such as toll-like receptors expressed on epithelial and immune cells in the genital tract mediate the recognition of chlamydial molecular patterns. After bacterial recognition, a subset of pro-inflammatory cytokines and chemokines are continuously released by epithelial cells. The innate immune response is followed by the initiation of the adaptive response against Chlamydia trachomatis, which in turn may result in T helper 1-mediated protection or in T helper 2-mediated immunopathology. Understanding the molecular mechanisms developed by Chlamydia trachomatis to avoid killing and host immune response would be crucial for designing new therapeutic approaches and developing protective vaccines. In this review, we focus on chlamydial survival strategies and the elicited immune responses in male genital tract infections. © 2017 Society for Reproduction and Fertility.

  19. A cognitive computational model inspired by the immune system response.

    PubMed

    Abdo Abd Al-Hady, Mohamed; Badr, Amr Ahmed; Mostafa, Mostafa Abd Al-Azim

    2014-01-01

    The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective.

  20. A Cognitive Computational Model Inspired by the Immune System Response

    PubMed Central

    Abdo Abd Al-Hady, Mohamed; Badr, Amr Ahmed; Mostafa, Mostafa Abd Al-Azim

    2014-01-01

    The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective. PMID:25003131

  1. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

    Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

    2007-01-01

    Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

  2. Methylglyoxal modulates immune responses: relevance to diabetes.

    PubMed

    Price, Claire L; Hassi, Hafid O S Al; English, Nicholas R; Blakemore, Alexandra I F; Stagg, Andrew J; Knight, Stella C

    2010-06-01

    Increased methylglyoxal (MG) concentrations and formation of advanced glycation end-products (AGEs) are major pathways of glycaemic damage in diabetes, leading to vascular and neuronal complications. Diabetes patients also suffer increased susceptibility to many common infections, the underlying causes of which remain elusive. We hypothesized that immune glycation damage may account for this increased susceptibility. We previously showed that the reaction mixture (RM) for MG glycation of peptide blocks up regulation of CD83 in myeloid cells and inhibits primary stimulation of T cells. Here, we continue to investigate immune glycation damage, assessing surface and intracellular cytokine protein expression by flow cytometry, T-cell proliferation using a carboxyfluorescein succinimidyl ester assay, and mRNA levels by RT-PCR. We show that the immunomodulatory component of this RM was MG itself, with MG alone causing equivalent block of CD83 and loss of primary stimulation. Block of CD83 expression could be reversed by MG scavenger N-acetyl cysteine. Further, MG within RM inhibited stimulated production of interleukin (IL)-10 protein from myeloid cells plus interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha from T cells. Loss of IL-10 and IFN-gamma was confirmed by RT-PCR analysis of mRNA, while TNF-alpha message was raised. Loss of TNF-alpha protein was also shown by ELISA of culture supernatants. In addition, MG reduced major histocompatibility complex (MHC) class I expression on the surface of myeloid cells and increased their propensity to apoptose. We conclude that MG is a potent suppressor of myeloid and T-cell immune function and may be a major player in diabetes-associated susceptibility to infection.

  3. The Ionospheric Responses to the Lower-atmosphere Disturbances Associated with Typhoon

    NASA Astrophysics Data System (ADS)

    Xiao, Sai-Guan; Xiao, Zuo; Zhang, Dong-He; Hao, Yong-Qiang

    2014-05-01

    The coupling between ionosphere and lower atmosphere is one of the important subjects in the space physics. A large number studies have shown that there is a close relation between the ionosphere and lower-atmosphere disturbances which can be caused by severe weather activities. Typhoon is one of the important sources in the lower-atmosphere. By the use of the continuous HF Doppler shift observation data in time, a study of ionospheric response to typhoon has been carried out. The results of analyses showed that the significant wave-like disturbances (in general, medium scale acoustic-gravity waves (AGWs)) appeared firstly and always formed the medium-scale traveling ionospheric disturbances (TIDs) in the ionosphere; Then these TIDs showed quite clear periodicity and their periods varied with time and gradually grew longer; After sunset, the wave-like disturbances with large magnitudes often excited the mid-latitude Spread-F; And the sunrise-like phenomena often appear in non-sunrise time during the period the typhoon exists, and so on. This study has important scientific significance for the further studying of the coupling between ionosphere and the disturbances of lower-atmosphere.

  4. The Ionospheric Responses to the Lower-atmosphere Disturbances Associated with Typhoon

    NASA Astrophysics Data System (ADS)

    Xiao, Sai-Guan; Xiao, Zuo; Shi, Jian-Kui; Zhang, Dong-He; Hao, Yong-Qiang

    2016-04-01

    The coupling between ionosphere and lower atmosphere is one of the important subjects in the space physics. A large number studies have shown that there is a close relation between the ionosphere and lower-atmosphere disturbances which can be caused by severe weather activities. Typhoon is one of the important sources in the lower-atmosphere. By the use of the continuous HF Doppler shift observation data in time, a study of ionospheric response to typhoon has been carried out. The results of analyses showed that the significant wave-like disturbances (in general, medium scale acoustic-gravity waves (AGWs)) appeared firstly and always formed the medium-scale traveling ionospheric disturbances (TIDs) in the ionosphere; Then these TIDs showed quite clear periodicity and their periods varied with time and gradually grew longer; After sunset, the wave-like disturbances with large magnitudes often excited the mid-latitude Spread-F; And the sunrise-like phenomena often appear in non-sunrise time during the period the typhoon exists, and so on. This study has important scientific significance for the further studying of the coupling between ionosphere and the disturbances of lower-atmosphere.

  5. [Effect of anabolic steroid on immune response].

    PubMed

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin.

  6. Immune allergic response in Asperger syndrome.

    PubMed

    Magalhães, Elizabeth S; Pinto-Mariz, Fernanda; Bastos-Pinto, Sandra; Pontes, Adailton T; Prado, Evandro A; deAzevedo, Leonardo C

    2009-11-30

    Asperger's syndrome is a subgroup of autism characterized by social deficits without language delay, and high cognitive performance. The biological nature of autism is still unknown but there are controversial evidence associating an immune imbalance and autism. Clinical findings, including atopic family history, serum IgE levels as well as cutaneous tests showed that incidence of atopy was higher in the Asperger group compared to the healthy controls. These findings suggest that atopy is frequent in this subgroup of autism implying that allergic inflammation might be an important feature in Asperger syndrome.

  7. The immune and inflammatory response to orf virus.

    PubMed

    Haig, D M; McInnes, C; Deane, D; Reid, H; Mercer, A

    1997-06-01

    Orf virus is a zoonotic, epitheliotropic DNA parapox virus that principally infects sheep and goats. The fact that the virus can repeatedly reinfect sheep has provoked an interest in the underlying cellular, virological and molecular mechanisms for its apparent escape from the host protective immune response. The local immune and inflammatory response in skin and the cell phenotype and cytokine response in lymph analysed around a single lymph node are characteristic of an anti-viral response. An unusual feature is the dense accumulation of MHC Class II+ dendritic cells in the skin lesion. The function of these cells is not known. Orf virus virulence genes and activities have been identified that may interfere with the development of the host protective immune and inflammatory response.

  8. Forest Canopy Water Cycling Responses to an Intermediate Disturbance Revealed Through Stable Water Vapor Isotopes

    NASA Astrophysics Data System (ADS)

    Fiorella, R.; Poulsen, C. J.; Matheny, A. M.; Rey Sanchez, C.; Fotis, A. T.; Morin, T. H.; Vogel, C. S.; Gough, C. M.; Aron, P.; Bohrer, G.

    2016-12-01

    Forest structure, age, and species composition modulate fluxes of carbon and water between the land surface and the atmosphere. The response of forests to intermediate disturbances such as ecological succession, species-specific insect invasion, or selective logging that disrupt the canopy but do not promote complete stand replacement, shape how these fluxes evolve through time. We investigate the impact of an intermediate disturbance to water cycling processes by comparing vertical profiles of stable water isotopes in two closely located forest canopies in the northern lower peninsula of Michigan using cavity ring-down spectroscopy. In one of the canopies, an intermediate disturbance was prescribed in 2008 by inducing mortality in all canopy-dominant early successional species. Isotopic compositions of atmospheric water vapor are measured at six heights during two time periods (summer and early fall) at two flux towers and compared with local meteorology and calculated atmospheric back-trajectories. Disturbance has little impact on low-frequency changes in isotopic composition (e.g., >1 day); at these timescales, isotopic composition is strongly related to large-scale moisture transport. In contrast, disturbance has substantial impacts on the vertical distribution of water isotopes throughout the canopy when transpiration rates are high during the summer, but impact is muted during early fall. Sub-diurnal differences in canopy water vapor cycling are likely related to differences in species composition and response to disturbance and changes in canopy structure. Predictions of transpiration fluxes by land-surface models that do not account species-specific relationships and canopy structure are unlikely to capture these relationships, but addition of stable isotopes to land surface models may provide a useful parameter to improve these predictions.

  9. Productivity, mortality, and response to disturbance of nesting Swainson's hawks on the Hanford Site

    SciTech Connect

    Poole, L.D.; Marr, N.V.; McCorquodale, S.M.

    1988-03-01

    The objectives of this study were to characterize Swainson's hawk (Buteo swainson) use of the US Department of Energy (DOE) Hanford Site and to evaluate the potential for engineering and other human activities on the Hanford Site to negatively affect the nesting Swainson's hawk population. Activities associated with the Basalt Waste Isolation Project (BWIP) were used as the primary external stimuli in studying hawk responses to potential human disturbance. Parked and moving vehicles were the most common disturbance sources observed in Swainson's hawk territories. Hawks appeared to be sensitive to disturbance from pedestrians and slow-moving vehicles near nests. Novel stimuli were much more likely to evoke strong responses than were recurring events. Adult hawks reacted more frequently and vigorously than did juveniles. When disturbed, adult hawks usually flew toward the location of the disturbance; juvenile hawks usually flew away from disturbances. Human activity associated with BWIP may have had negative on one pair of nesting Swainson's hawks and may have precluded the use of an additional traditional nesting territory. Negative impacts to nesting Swainson's hawks from human activity could be minimized by confining activities to the non-nesting period or to distances greater than 2.2 km from nest sites. Tree groves and elevated perches, including utility poles, across the Hanford Site are probably critical to the success of nesting Swainson's hawks. Potential mitigation strategies associated with energy research and development activities on the Hanford Site could include provisions for maintenance and establishment of drought-tolerant trees and native vegetation. 22 refs., 5 figs., 3 tabs.

  10. Forest response to increased disturbance in the Central Amazon and comparison to Western Amazonian forests

    NASA Astrophysics Data System (ADS)

    Holm, J. A.; Chambers, J. Q.; Collins, W.; Higuchi, N.

    2014-12-01

    Uncertainties surrounding vegetation response to increased disturbance rates associated with climate change remains a major global change issue for Amazon forests. Additionally, turnover rates in the Western Amazon are doubled compared to the Central Amazon, and notable gradients currently exist in specific wood density and aboveground biomass (AGB). This study investigates the extent to which the variation in disturbance regimes contributes to these regional gradients. To address these issues, we evaluated disturbance-recovery processes under scenarios of increased disturbance rates in a Central Amazon forest using first ZELIG-TROP, a dynamic vegetation gap model which we calibrated using long-term inventory data, and second using the Community Land Model (CLM), a global land surface model. Upon doubling the mortality rate in the Central Amazon to mirror the disturbance regime in the Western Amazon of ~2% mortality, the two regions continued to differ in multiple forest processes. With the inclusion of elevated natural disturbances, at steady-state, AGB significantly decreased by 41.9% with no significant difference between modeled AGB and empirical AGB from the western Amazon datasets (104 vs. 107 Mg C ha-1). However, different processes were responsible for the reductions in AGB between the models and empirical dataset. The empirical dataset suggests that a decrease in wood density drives the reduction in AGB. While decreased stand basal area was the driver of AGB loss in ZELIG-TROP, and decreased leaf area index (LAI) was the driver in CLM, two forest attributes that do not significantly vary across the Amazon Basin. Further comparisons found that stem density, specific wood density, and growth rates differed between the two Amazonian regions. This suggests that: 1) the variability between regions cannot be entirely explained by the variability in disturbance regime, but rather potentially sensitive to intrinsic environmental factors; or 2) the models are not

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

    PubMed

    James, J S

    1998-06-19

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

  12. Water Table and Soil Gas Emission Responses to Disturbance in Northern Forested Wetlands

    NASA Astrophysics Data System (ADS)

    Pypker, T. G.; Van Grinsven, M. J.; Bolton, N. W.; Shannon, J.; Davis, J.; Wagenbrenner, J. W.; Sebestyen, S. D.; Kolka, R. K.

    2014-12-01

    Exotic pest infestations are increasingly common throughout North American forests. In forested wetlands, disturbance events may alter nutrient, carbon, and hydrologic pathways. Recently, ash (Fraxinus spp.) forests in North Central and Eastern North America have been exposed to the exotic emerald ash borer (EAB) (Burprestidae: Agrilus planipennis), and the rapid and extensive expansion of EAB populations since 2001 may soon eliminate most existing ash stands. Limited research has focused on post-establishment ecosystem impacts of an EAB disturbance, and to our knowledge, there are no studies that have evaluated the coupled response of black ash (Fraxinus nigra) wetland water tables, soil temperatures, and soil gas emissions to an EAB infestation. We present preliminary results that detail those responses to a simulated EAB disturbance. Water table position, soil temperature, and soil gas emissions (CO2 and CH4) were monitored in nine black ash wetlands in the Upper Peninsula of Michigan for three years, including one year of pre-treatment and two years of post-treatment data-collection. An EAB disturbance was simulated by girdling (Girdle) or felling (Clearcut) all black ash trees with diameters of 2.5 cm or greater within the wetland, and each treatment was applied to three sites. The results indicate that wetland water tables were insensitive to treatment effects, soil temperatures were significantly higher in the Clearcut treatment, soil gas flux was significantly higher in the Clearcut treatment, and the rate of soil gas flux was strongly regulated by water table position and temperature. No significant treatment effects were detected in the Girdle treatment during the first post-treatment year. Because water tables were insensitive to treatment, we concluded that water tables did not independently generate a soil gas flux response despite their strong regulatory influence. Furthermore, we concluded that the response of soil temperature to disturbance was

  13. Subverting the adaptive immune resistance mechanism to improve clinical responses to immune checkpoint blockade therapy

    PubMed Central

    Kim, Young J

    2015-01-01

    The correlation between tumor-infiltrating lymphocyte (TIL)-expression of programmed cell death ligand 1 (PD-L1) and clinical responsiveness to the PD-1 blocking antibody nivolumab implicates adaptive immune evasion mechanisms in cancer. We review our findings that tumor cell PD-L1 expression is induced by interferon γ (IFNγ) producing TILs. We provide a mechanistic rationale for combining IFNγ+ T helper type 1 (Th1)-inducing cancer vaccines with PD-1 immune checkpoint blockade. PMID:25964860

  14. Modulation of Primary Immune Response by Different Vaccine Adjuvants

    PubMed Central

    Ciabattini, Annalisa; Pettini, Elena; Fiorino, Fabio; Pastore, Gabiria; Andersen, Peter; Pozzi, Gianni; Medaglini, Donata

    2016-01-01

    Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Here early biomarkers of adjuvanticity after primary immunization were investigated using four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood, and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w squalene), but not aluminum hydroxide (alum) or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed toward a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w squalene or CpG adjuvants. Tested adjuvants promoted the germinal center reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime–boost vaccine immunization protocols. PMID:27781036

  15. Specific immune responses in mice following subchronic exposure to acetamiprid.

    PubMed

    Marzouki, Soumaya; Dhouib, Ines Bini; Benabdessalem, Chaouki; Rekik, Raja; Doghri, Raoudha; Maroueni, Ammar; Bellasfar, Zakaria; Fazaa, Saloua; Bettaieb, Jihene; Barbouche, Mohamed Ridha; Ahmed, Melika Ben

    2017-08-23

    Acetamiprid (ACE) is an insecticide of the neonicotinoid family, the most widely used in the world. Herein, we assessed the effect of ACE on either the humoral or cellular immune responses of rodents. We also evaluated the role of curcumin in the restoration of altered immune responses after ACE treatment. Five groups of five Swiss Albino mice were immunized intraperitoneally with the recombinant form of CFP32, a virulence factor of Mycobacterium tuberculosis. One group received ACE (5mg/kg) during 61days, a second one received ACE associated with curcumin (100mg/kg). Three control groups were included; one untreated, the second received corn oil and the third received curcumin alone. The humoral immune response was assessed by ELISA testing the anti-rCFP32 antibody concentrations in the serum. The cellular immune response was assessed by analyzing the cellular proliferation of the splenocytes stimulated in vitro by a mitogen or rCFP32. The ACE-treated mice showed a significant immunosuppression of the specific humoral response with a restorative effect of curcumin when administered with ACE. Similarly, ACE significantly decreased the level of splenocyte proliferation after either a non specific or a specific activation. Curcumin partially restores the antigen specific cellular immune response. Moreover, when administered alone, curcumin significantly inhibits the proliferative responses to the mitogen confirming its anti-mitogenic effect. Histological analysis showed alteration of spleens of mice exposed to ACE. Altogether, our data indicated that ACE could potentially be harmful to the immune system. Copyright © 2017. Published by Elsevier Inc.

  16. Trachoma: Protective and Pathogenic Ocular Immune Responses to Chlamydia trachomatis

    PubMed Central

    Hu, Victor H.; Holland, Martin J.; Burton, Matthew J.

    2013-01-01

    Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious blinding disease worldwide. Chronic conjunctival inflammation develops in childhood and leads to eyelid scarring and blindness in adulthood. The immune response to Ct provides only partial protection against re-infection, which can be frequent. Moreover, the immune response is central to the development of scarring pathology, leading to loss of vision. Here we review the current literature on both protective and pathological immune responses in trachoma. The resolution of Ct infection in animal models is IFNγ-dependent, involving Th1 cells, but whether this is the case in human ocular infection still needs to be confirmed. An increasing number of studies indicate that innate immune responses arising from the epithelium and other innate immune cells, along with changes in matrix metalloproteinase activity, are important in the development of tissue damage and scarring. Current trachoma control measures, which are centred on repeated mass antibiotic treatment of populations, are logistically challenging and have the potential to drive antimicrobial resistance. A trachoma vaccine would offer significant advantages. However, limited understanding of the mechanisms of both protective immunity and immunopathology to Ct remain barriers to vaccine development. PMID:23457650

  17. Transgenerational effects enhance specific immune response in a wild passerine.

    PubMed

    Broggi, Juli; Soriguer, Ramon C; Figuerola, Jordi

    2016-01-01

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

  18. Transgenerational effects enhance specific immune response in a wild passerine

    PubMed Central

    Soriguer, Ramon C.; Figuerola, Jordi

    2016-01-01

    Vertebrate mothers transfer diverse compounds to developing embryos that can affect their development and final phenotype (i.e., maternal effects). However, the way such effects modulate offspring phenotype, in particular their immunity, remains unclear. To test the impact of maternal effects on offspring development, we treated wild breeding house sparrows (Passer domesticus) in Sevilla, SE Spain with Newcastle disease virus (NDV) vaccine. Female parents were vaccinated when caring for first broods, eliciting a specific immune response to NDV. The immune response to the same vaccine, and to the PHA inflammatory test were measured in 11-day-old chicks from their following brood. Vaccinated chicks from vaccinated mothers developed a stronger specific response that was related to maternal NDV antibody concentration while rearing their chicks. The chicks’ carotenoid concentration and total antioxidant capacity in blood were negatively related to NDV antibody concentration, whereas no relation with PHA response was found. Specific NDV antibodies could not be detected in 11-day-old control chicks from vaccinated mothers, implying that maternally transmitted antibodies are not directly involved but may promote offspring specific immunity through a priming effect, while other immunity components remain unaffected. Maternally transmitted antibodies in the house sparrow are short-lived, depend on maternal circulation levels and enhance pre-fledging chick specific immunity when exposed to the same pathogens as the mothers. PMID:27069782

  19. Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses

    PubMed Central

    Oyewumi, Moses O; Kumar, Amit; Cui, Zhengrong

    2010-01-01

    The development of novel immune adjuvants is emerging as a significant area of vaccine delivery based on the continued necessity to amplify immune responses to a wide array of new antigens that are poorly immunogenic. This article specifically focuses on the application of nanoparticles and microparticles as vaccine adjuvants. Many investigators are in agreement that the size of the particles is crucial to their adjuvant activities. However, reports on correlating the size of particle-based adjuvants and the resultant immune responses have been conflicting, with investigators on both sides of the fence with impressive data in support of the effectiveness of particles with small sizes (submicron) over those with larger sizes (micron) and vice versa, while other investigators reported data that showed submicron- and micron-sized particles are effective to the same degree as immune adjuvants. We have generated a list of biological, immunological and, more importantly, vaccine formulation parameters that may have contributed to the inconsistency from different studies and made recommendations on future studies attempting to correlate the size of particulate adjuvants and the immune responses induced. The information gathered could lead to strategies to optimize the performance of nano-microparticles as immune adjuvants. PMID:20822351

  20. Semiquantitative measure of immune responses against erythropoietic stem cell antigens

    SciTech Connect

    Harrison, D.E.

    1987-01-01

    A semiquantitative assay was developed and used to measure the effects of immune responses against 16 independent non-H-2 antigenic loci on erythropoietic stem cells. The assay compares repopulation in genetically anemic WBB6F1-W/Wv recipients that have normal immune responses, and in lethally irradiated WBB6F1 +/+ mice whose immune responses are suppressed by the irradiation. The differences in repopulating ability between these two types of recipients measure how immune responses affect erythropoietic stem cells. Stem cell repopulating abilities for the cells with antigens specified by the Thy-1, H-1, H-24, Ly-1, H-37, and H-17 loci were affected slightly, if at all. Repopulating abilities were moderately reduced by responses against antigens specified by H-15, 16, Ea-2, and Ly-2, 3 loci, and against the differences between the B6 and B10 genotypes, although marrow of these types cured W/Wv recipients. A surprising result occurred for the antigen specified by the H-8 locus, in which immune responses strongly reduced repopulating abilities, although this type of marrow cell cured W/Wv recipients. A comparison of these results with skin graft survival times suggests that the antigens specified by the H-17 and H-24 loci are strongly immunogenic on skin but not on marrow stem cells, while those specified by the H-12 and H-8 loci are strongly immunogenic on marrow stem cells but not on skin.

  1. Modulation of immune response in experimental Chagas disease.

    PubMed

    Basso, Beatriz

    2013-02-20

    Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response (modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi

  2. Factors influencing innate immunity and vaccine responses in infancy

    PubMed Central

    Kampmann, Beate; Jones, Christine E

    2015-01-01

    Despite significant progress in reducing the burden of mortality in children under the age of five, reducing mortality in newborns remains a major challenge. Infection plays a significant role in infant deaths and interventions such as early vaccination or antenatal immunization could make a significant contribution to prevention of such deaths. In the last few years, we have gained new insights into immune ontogeny and are now beginning to understand the impact of vaccines, nutrition and environmental factors on ‘training′ of the immune response in early life. This review article sets out to explain why vaccine responses can be heterogeneous between populations and individuals by providing examples chosen to illustrate the impact of host, pathogen and environmental factors on shaping the immune ‘interactome′ in young children. PMID:25964459

  3. Activation and Regulation of DNA-Driven Immune Responses

    PubMed Central

    2015-01-01

    SUMMARY The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally, several reports have demonstrated how defects in DNA sensing, signaling, and regulation are associated with susceptibility to infections or inflammatory diseases in humans and model organisms. In this review, the current literature on DNA-stimulated innate immune activation is discussed, and important new questions facing this field are proposed. PMID:25926682

  4. Cytolytic toxins as triggers of plant immune response

    PubMed Central

    Küfner, Isabell; Ottmann, Christian

    2009-01-01

    NEP1-like proteins (NLPs) are secreted proteins from fungi, oomycetes and bacteria, triggering immune responses and cell death in dicotyledonous plants. It has been unclear for a long time, whether NLPs are toxins or triggers of plant immunity. In a recent study we report that NLPs are toxins that exert cytolytic activity on dicotyledonous plants. Mutational analysis revealed a causal link between membrane damaging, cell death inducing and virulence promoting properties of NLPs. Interestingly, also induction of immune responses by NLPs required the same protein fold, providing evidence for damage-induced immunity in plants. Structural similarity to pore forming toxins from marine invertebrates allows the proposal of a model for the mode of NLP interaction with the host's membrane. PMID:19826219

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

    PubMed

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

    1994-01-01

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

  6. Functional genomic analysis of the Drosophila immune response.

    PubMed

    Valanne, Susanna

    2014-01-01

    Drosophila melanogaster has been widely used as a model organism for over a century now, and also as an immunological research model for over 20 years. With the emergence of RNA interference (RNAi) in Drosophila as a robust tool to silence genes of interest, large-scale or genome-wide functional analysis has become a popular way of studying the Drosophila immune response in cell culture. Drosophila immunity is composed of cellular and humoral immunity mechanisms, and especially the systemic, humoral response pathways have been extensively dissected using the functional genomic approach. Although most components of the main immune pathways had already been found using traditional genetic screening techniques, important findings including pathway components, positive and negative regulators and modifiers have been made with RNAi screening. Additionally, RNAi screening has produced new information on host-pathogen interactions related to the pathogenesis of many microbial species. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Three-dimensional analysis of the anatomical growth response of European conifers to mechanical disturbance.

    PubMed

    Schneuwly, Dominique M; Stoffel, Markus; Dorren, Luuk K A; Berger, Frédéric

    2009-10-01

    Studies on tree reaction after wounding were so far based on artificial wounding or chemical treatment. For the first time, type, spread and intensity of anatomical responses were analyzed and quantified in naturally disturbed Larix decidua Mill., Picea abies (L.) Karst. and Abies alba Mill. trees. The consequences of rockfall impacts on increment growth were assessed at the height of the wounds, as well as above and below the injuries. A total of 16 trees were selected on rockfall slopes, and growth responses following 54 wounding events were analyzed on 820 cross-sections. Anatomical analysis focused on the occurrence of tangential rows of traumatic resin ducts (TRD) and on the formation of reaction wood. Following mechanical disturbance, TRD production was observed in 100% of L. decidua and P. abies wounds. The radial extension of TRD was largest at wound height, and they occurred more commonly above, rather than below, the wounds. For all species, an intra-annual radial shift of TRD was observed with increasing axial distance from wounds. Reaction wood was formed in 87.5% of A. alba following wounding, but such cases occurred only in 7.7% of L. decidua. The results demonstrate that anatomical growth responses following natural mechanical disturbance differ significantly from the reactions induced by artificial stimuli or by decapitation. While the types of reactions remain comparable between the species, their intensity, spread and persistence disagree considerably. We also illustrate that the external appearance of wounds does not reflect an internal response intensity. This study reveals that disturbance induced under natural conditions triggers more intense and more widespread anatomical responses than that induced under artificial stimuli, and that experimental laboratory tests considerably underestimate tree response.

  8. Autophagy as a Stress Response Pathway in the Immune System.

    PubMed

    Bhattacharya, Abhisek; Eissa, N Tony

    2015-01-01

    Macroautophagy, hereafter, referred to as autophagy, has long been regarded as a housekeeping pathway involved in intracellular degradation and energy recycling. These housekeeping and homeostatic functions are especially important during cellular stress, such as periods of nutrient deprivation. However, importance of autophagy extends far beyond its degradative functions. Recent evidence shows that autophagy plays an essential role in development, organization and functions of the immune system, and defects in autophagy lead to several diseases, including cancer and autoimmunity. In the immune system, autophagy is important in regulation of the innate and adaptive immune responses. This review focuses on the roles of autophagy in the adaptive immune system. We first introduce the autophagy pathway and provide a brief description of the major molecular players involved in autophagy. We then discuss the importance of autophagy as a stress integrator mechanism and provide relevant examples of this role of autophagy in adaptive immune cells. Then we proceed to describe how autophagy regulates development, activation and functions of different adaptive immune cells. In these contexts, we mention both degradative and non-degradative roles of autophagy, and illustrate their importance. We also discuss role of autophagy in antigen presenting cells, which play critical roles in the activation of adaptive immune cells. Further, we describe how autophagy regulates functions of different adaptive immune cells during infection, inflammation and autoimmunity.

  9. Chitin and Its Effects on Inflammatory and Immune Responses.

    PubMed

    Elieh Ali Komi, Daniel; Sharma, Lokesh; Dela Cruz, Charles S

    2017-03-01

    Chitin, a potential allergy-promoting pathogen-associated molecular pattern (PAMP), is a linear polymer composed of N-acetylglucosamine residues which are linked by β-(1,4)-glycosidic bonds. Mammalians are potential hosts for chitin-containing protozoa, fungi, arthropods, and nematodes; however, mammalians themselves do not synthetize chitin and thus it is considered as a potential target for recognition by mammalian immune system. Chitin is sensed primarily in the lungs or gut where it activates a variety of innate (eosinophils, macrophages) and adaptive immune cells (IL-4/IL-13 expressing T helper type-2 lymphocytes). Chitin induces cytokine production, leukocyte recruitment, and alternative macrophage activation. Intranasal or intraperitoneal administration of chitin (varying in size, degree of acetylation and purity) to mice has been applied as a routine approach to investigate chitin's priming effects on innate and adaptive immunity. Structural chitin present in microorganisms is actively degraded by host true chitinases, including acidic mammalian chitinases and chitotriosidase into smaller fragments that can be sensed by mammalian receptors such as FIBCD1, NKR-P1, and RegIIIc. Immune recognition of chitin also involves pattern recognition receptors, mainly via TLR-2 and Dectin-1, to activate immune cells to induce cytokine production and creation of an immune network that results in inflammatory and allergic responses. In this review, we will focus on various immunological aspects of the interaction between chitin and host immune system such as sensing, interactions with immune cells, chitinases as chitin degrading enzymes, and immunologic applications of chitin.

  10. The immune response against Candida spp. and Sporothrix schenckii.

    PubMed

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

    2014-01-01

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

  11. Linking soils and streams: Response of soil solution chemistry to simulated hurricane disturbance mirrors stream chemistry following a severe hurricane

    Treesearch

    William H. McDowell; Daniel Liptzin

    2014-01-01

    Understanding the drivers of forest ecosystem response to major disturbance events is an important topic in forest ecology and ecosystem management. Because of the multiple elements included in most major disturbances such as hurricanes, fires, or landslides, it is often difficult to ascribe a specific driver to the observed response. This is particularly true for the...

  12. Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

    PubMed Central

    Duan, Susu; Thomas, Paul G.

    2016-01-01

    Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity. PMID:26904022

  13. Modulation of Human Immune Response by Fungal Biocontrol Agents

    PubMed Central

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A.; Vannier-Santos, Marcos A.; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses. PMID:28217107

  14. Immune Response Modulation of Conjugated Agonists with Changing Linker Length.

    PubMed

    Ryu, Keun Ah; Slowinska, Katarzyna; Moore, Troy; Esser-Kahn, Aaron

    2016-12-16

    We report immune response modulation with linked Toll-like receptor (TLR) agonists. Conjugating two agonists of synergistic TLRs induce an increase in immune activity compared to equal molarity of soluble agonists. Additionally, varying the distance between the agonists by changing the linker length alters the level of macrophage NF-κB activity as well as primary bone marrow derived dendritic cell IL-6 production. This modulation is effected by the size of the agonists and the pairing of the stimulated TLRs. The sensitivity of linker-length-dependent immune activity of conjugated agonists provides the potential for developing application specific therapeutics.

  15. Modulation of Human Immune Response by Fungal Biocontrol Agents.

    PubMed

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A; Vannier-Santos, Marcos A; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses.

  16. The nature of immune responses to urinary tract infections

    PubMed Central

    Abraham, Soman N.; Miao, Yuxuan

    2016-01-01

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

  17. Emerging functions of the unfolded protein response in immunity

    PubMed Central

    Janssens, Sophie; Pulendran, Bali; Lambrecht, Bart N.

    2015-01-01

    The unfolded protein response (UPR) has traditionally been viewed as an adaptive response triggered upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), aimed at restoring ER function. The UPR can also be an anticipatory response that is activated well before the disruption of protein homeostasis. UPR signaling intersects at many levels with the innate and adaptive immune response. In some immune cell types like dendritic cells and B cells, particular UPR sensors appear constitutively active in the absence of traditional UPR gene program induction, necessary for antigen presentation and immunoglobulin synthesis. The UPR also influences Toll-like receptor signaling and NF-κB activation, and some pathogens subvert the UPR. This review summarizes these emerging non-canonical functions of the UPR in immunity. PMID:25232821

  18. Harnessing DNA-induced immune responses for improving cancer vaccines

    PubMed Central

    Herrada, Andrés A.; Rojas-Colonelli, Nicole; González-Figueroa, Paula; Roco, Jonathan; Oyarce, César; Ligtenberg, Maarten A.; Lladser, Alvaro

    2012-01-01

    DNA vaccines have emerged as an attractive strategy to promote protective cellular and humoral immunity against the encoded antigen. DNA vaccines are easy to generate, inexpensive to produce and purify at large-scale, highly stable and safe. In addition, plasmids used for DNA vaccines act as powerful “danger signals” by stimulating several DNA-sensing innate immune receptors that promote the induction of protective adaptive immunity. The induction of tumor-specific immune responses represents a major challenge for DNA vaccines because most of tumor-associated antigens are normal non-mutated self-antigens. As a consequence, induction of potentially self-reactive T cell responses against such poorly immunogenic antigens is controlled by mechanisms of central and peripheral tolerance as well as tumor-induced immunosuppression. Although several DNA vaccines against cancer have reached clinical testing, disappointing results have been observed. Therefore, the development of new adjuvants that strongly stimulate the induction of antitumor T cell immunity and counteract immune-suppressive regulation is an attractive approach to enhance the potency of DNA vaccines and overcome tumor-associated tolerance. Understanding the DNA-sensing signaling pathways of innate immunity that mediate the induction of T cell responses elicited by DNA vaccines represents a unique opportunity to develop novel adjuvants that enhance vaccine potency. The advance of DNA adjuvants needs to be complemented with the development of potent delivery systems, in order to step toward successful clinical application. Here, we briefly discuss recent evidence showing how to harness DNA-induced immune response to improve the potency of cancer vaccines and counteract tumor-associated tolerance. PMID:23111166

  19. SUMO-Enriched Proteome for Drosophila Innate Immune Response

    PubMed Central

    Handu, Mithila; Kaduskar, Bhagyashree; Ravindranathan, Ramya; Soory, Amarendranath; Giri, Ritika; Elango, Vijay Barathi; Gowda, Harsha; Ratnaparkhi, Girish S.

    2015-01-01

    Small ubiquitin-like modifier (SUMO) modification modulates the expression of defense genes in Drosophila, activated by the Toll/nuclear factor-κB and immune-deficient/nuclear factor-κB signaling networks. We have, however, limited understanding of the SUMO-modulated regulation of the immune response and lack information on SUMO targets in the immune system. In this study, we measured the changes to the SUMO proteome in S2 cells in response to a lipopolysaccharide challenge and identified 1619 unique proteins in SUMO-enriched lysates. A confident set of 710 proteins represents the immune-induced SUMO proteome and analysis suggests that specific protein domains, cellular pathways, and protein complexes respond to immune stress. A small subset of the confident set was validated by in-bacto SUMOylation and shown to be bona-fide SUMO targets. These include components of immune signaling pathways such as Caspar, Jra, Kay, cdc42, p38b, 14-3-3ε, as well as cellular proteins with diverse functions, many being components of protein complexes, such as prosß4, Rps10b, SmD3, Tango7, and Aats-arg. Caspar, a human FAF1 ortholog that negatively regulates immune-deficient signaling, is SUMOylated at K551 and responds to treatment with lipopolysaccharide in cultured cells. Our study is one of the first to describe SUMO proteome for the Drosophila immune response. Our data and analysis provide a global framework for the understanding of SUMO modification in the host response to pathogens. PMID:26290570

  20. Maximizing Immune Response to Carbohydrate Antigens on Breast Tumors

    DTIC Science & Technology

    2003-08-01

    antigens expressed on breast tumors. Towards this end we are developing peptide mimotopes of tumor associated carbohydrate antigens as they are T cell...dependent antigens. In our progress to date we have shown the 1) immunization with peptide mimotope activates a specific cellular response to a model murine...tumor cell line; 2) vaccination of mice with peptide eradicates established tumor; 3) Immunization with DNA format of the peptide suppresses tumor

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

    PubMed

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

    2014-07-01

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

  2. The architects of B and T cell immune responses.

    PubMed

    Lane, Peter J L

    2008-08-15

    Published work links adult lymphoid tissue-inducer cells (LTi) with T cell-dependent antibody responses. In this issue of Immunity, Tsuji et al. (2008) associate LTi with T cell-independent IgA antibody responses in the gut.

  3. Enhancing the Immune Response to Recombinant Plague Antigens

    DTIC Science & Technology

    2006-05-01

    parvovirus (CPMV). In those studies, animals primed IN and boosted SC developed significantly higher serum anti-CPMV IgG2a responses than did animals...Wakelin. 2003. Effect of priming/booster immunisation protocols on immune response to canine parvovirus peptide induced by vaccination with a chimaeric

  4. Innate immune responses of temperamental and calm cattle after transportation

    USDA-ARS?s Scientific Manuscript database

    The objective was to investigate measures of cellular innate immune responses among calm and temperamental Brahman bulls in response to handling and transportation. Sixteen Brahman bulls (344 ± 37 days of age; 271.6 ± 45.5 kg BW) classified as either calm (n = 8) or temperamental (n = 8) were loaded...

  5. Forest response to increased disturbance in the Central Amazon and comparison to Western Amazonian forests

    NASA Astrophysics Data System (ADS)

    Holm, J. A.; Chambers, J. Q.; Collins, W. D.; Higuchi, N.

    2014-05-01

    Uncertainties surrounding vegetation response to increased disturbance rates associated with climate change remains a major global change issue for Amazon forests. Additionally, turnover rates computed as the average of mortality and recruitment rates in the Western Amazon basin are doubled when compared to the Central Amazon, and notable gradients currently exist in specific wood density and aboveground biomass (AGB) between these two regions. This study investigates the extent to which the variation in disturbance regimes contributes to these regional gradients. To address these issues, we evaluated disturbance-recovery processes under two scenarios of increased disturbance rates in a complex Central Amazon forest using first ZELIG-TROP, a dynamic vegetation gap model which we calibrated using long-term inventory data, and second using the Community Land Model (CLM), a global land surface model that is part of the Community Earth System Model (CESM). Upon doubling the mortality rate in the Central Amazon to mirror the natural disturbance regime in the Western Amazon of ∼2% mortality, at steady-state, AGB significantly decreased by 41.9% and there was no significant difference between the modeled AGB of 104 Mg C ha-1 and empirical AGB from the western Amazon datasets of 107 Mg C ha-1. We confirm that increases in natural disturbance rates in the Central Amazon will result in terrestrial carbon loss associated with higher turnover. However, different processes were responsible for the reductions in AGB between the models and empirical datasets. We observed that with increased turnover, the subsequent decrease in wood density drives the reduction in AGB in empirical datasets. However, decrease in stand basal area was the driver of the drop in AGB in ZELIG-TROP, and decreased leaf area index (LAI) was the driver in CLM. Further comparisons found that stem density, specific wood density, and basal area growth rates differed between the two Amazonian regions. This

  6. Genetics of the immune response: identifying immune variation within the MHC and throughout the genome.

    PubMed

    Geraghty, Daniel E; Daza, Riza; Williams, Luke M; Vu, Quyen; Ishitani, Akiko

    2002-12-01

    With the advent of modern genomic sequencing technology the ability to obtain new sequence data and to acquire allelic polymorphism data from a broad range of samples has become routine. In this regard, our investigations have started with the most polymorphic of genetic regions fundamental to the immune response in the major histocompatibility complex (MHC). Starting with the completed human MHC genomic sequence, we have developed a resource of methods and information that provide ready access to a large portion of human and nonhuman primate MHCs. This resource consists of a set of primer pairs or amplicons that can be used to isolate about 15% of the 4.0 Mb MHC. Essentially similar studies are now being carried out on a set of immune response loci to broaden the usefulness of the data and tools developed. A panel of 100 genes involved in the immune response have been targeted for single nucleotide polymorphism (SNP) discovery efforts that will analyze 120 Mb of sequence data for the presence of immune-related SNPs. The SNP data provided from the MHC and from the immune response panel has been adapted for use in studies of evolution, MHC disease associations, and clinical transplantation.

  7. Antigen-specific immune responses to influenza vaccine in utero

    PubMed Central

    Rastogi, Deepa; Wang, Chaodong; Mao, Xia; Lendor, Cynthia; Rothman, Paul B.; Miller, Rachel L.

    2007-01-01

    Initial immune responses to allergens may occur before birth, thereby modulating the subsequent development of atopy. This paradigm remains controversial, however, due to the inability to identify antigen-specific T cells in cord blood. The advent of MHC tetramers has revolutionized the detection of antigen-specific T cells. Tetramer staining of cord blood after CMV infection has demonstrated that effective CD8+ antigen-specific immune responses can follow intrauterine viral infections. We hypothesized that sensitization to antigens occurs in utero in humans. We studied cord blood B and T cell immune responses following vaccination against influenza during pregnancy. Anti-Fluzone and anti-matrix protein IgM antibodies were detected in 38.5% (27 of 70) and 40.0% (28 of 70), respectively, of cord blood specimens. Using MHC tetramers, HA-specific CD4+ T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father. Matrix protein–specific CD8+ T cells were detected among 10.0% (2 of 20) of HLA-A*0201+ newborns. These results suggest that B and T cell immune responses occur in the fetus following vaccination against influenza and have important implications for determining when immune responses to environmental exposures begin. PMID:17549258

  8. TIGIT predominantly regulates the immune response via regulatory T cells.

    PubMed

    Kurtulus, Sema; Sakuishi, Kaori; Ngiow, Shin-Foong; Joller, Nicole; Tan, Dewar J; Teng, Michele W L; Smyth, Mark J; Kuchroo, Vijay K; Anderson, Ana C

    2015-11-02

    Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation of these receptors on effector T cells terminates T cell responses, while their expression on Tregs promotes their suppressor function. Understanding the function of coinhibitory receptors in effector T cells and Tregs is crucial, as therapies that target coinhibitory receptors are currently at the forefront of treatment strategies for cancer and other chronic diseases. T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitory receptor that is found on the surface of a variety of lymphoid cells, and its role in immune regulation is just beginning to be elucidated. We examined TIGIT-mediated immune regulation in different murine cancer models and determined that TIGIT marks the most dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly active and suppressive phenotype. We demonstrated that TIGIT signaling in Tregs directs their phenotype and that TIGIT primarily suppresses antitumor immunity via Tregs and not CD8+ T cells. Moreover, TIGIT+ Tregs upregulated expression of the coinhibitory receptor TIM-3 in tumor tissue, and TIM-3 and TIGIT synergized to suppress antitumor immune responses. Our findings provide mechanistic insight into how TIGIT regulates immune responses in chronic disease settings.

  9. Modulation of immune responses in stress by Yoga.

    PubMed

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-07-01

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

  10. TIGIT predominantly regulates the immune response via regulatory T cells

    PubMed Central

    Kurtulus, Sema; Sakuishi, Kaori; Ngiow, Shin-Foong; Joller, Nicole; Tan, Dewar J.; Teng, Michele W.L.; Smyth, Mark J.; Kuchroo, Vijay K.; Anderson, Ana C.

    2015-01-01

    Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation of these receptors on effector T cells terminates T cell responses, while their expression on Tregs promotes their suppressor function. Understanding the function of coinhibitory receptors in effector T cells and Tregs is crucial, as therapies that target coinhibitory receptors are currently at the forefront of treatment strategies for cancer and other chronic diseases. T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitory receptor that is found on the surface of a variety of lymphoid cells, and its role in immune regulation is just beginning to be elucidated. We examined TIGIT-mediated immune regulation in different murine cancer models and determined that TIGIT marks the most dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue Tregs with a highly active and suppressive phenotype. We demonstrated that TIGIT signaling in Tregs directs their phenotype and that TIGIT primarily suppresses antitumor immunity via Tregs and not CD8+ T cells. Moreover, TIGIT+ Tregs upregulated expression of the coinhibitory receptor TIM-3 in tumor tissue, and TIM-3 and TIGIT synergized to suppress antitumor immune responses. Our findings provide mechanistic insight into how TIGIT regulates immune responses in chronic disease settings. PMID:26413872

  11. Selection for avian immune response: a commercial breeding company challenge.

    PubMed

    Fulton, J E

    2004-04-01

    Selection for immune function in the commercial breeding environment is a challenging proposition for commercial breeding companies. Immune response is only one of many traits that are under intensive selection, thus selection pressure needs to be carefully balanced across multiple traits. The selection environment (single bird cages, biosecure facilities, controlled environment) is a very different environment than the commercial production facilities (multiple bird cages, potential disease exposure, variable environment) in which birds are to produce. The testing of individual birds is difficult, time consuming, and expensive. It is essential that the results of any tests be relevant to actual disease or environmental challenge in the commercial environment. The use of genetic markers as indicators of immune function is being explored by breeding companies. Use of genetic markers would eliminate many of the limitations in enhancing immune function currently encountered by commercial breeding companies. Information on genetic markers would allow selection to proceed without subjecting breeding stock to disease conditions and could be done before production traits are measured. These markers could be candidate genes with known interaction or involvement with disease pathology or DNA markers that are closely linked to genetic regions that influence the immune response. The current major limitation to this approach is the paucity of mapped chicken immune response genes and the limited number of DNA markers mapped on the chicken genome. These limitations should be eliminated once the chicken genome is sequenced.

  12. Modulation of immune responses in stress by Yoga

    PubMed Central

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-01-01

    Stress is a constant factor in today's fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress. PMID:21829284

  13. Reduced cellular immune response in social insect lineages

    PubMed Central

    Sconiers, Warren B.; Frank, Steven D.; Dunn, Robert R.; Tarpy, David R.

    2016-01-01

    Social living poses challenges for individual fitness because of the increased risk of disease transmission among conspecifics. Despite this challenge, sociality is an evolutionarily successful lifestyle, occurring in the most abundant and diverse group of organisms on earth—the social insects. Two contrasting hypotheses predict the evolutionary consequences of sociality on immune systems. The social group hypothesis posits that sociality leads to stronger individual immune systems because of the higher risk of disease transmission in social species. By contrast, the relaxed selection hypothesis proposes that social species have evolved behavioural immune defences that lower disease risk within the group, resulting in lower immunity at the individual level. We tested these hypotheses by measuring the encapsulation response in 11 eusocial and non-eusocial insect lineages. We built phylogenetic mixed linear models to investigate the effect of behaviour, colony size and body size on cellular immune response. We found a significantly negative effect of colony size on encapsulation response (Markov chain Monte Carlo generalized linear mixed model (mcmcGLMM) p < 0.05; phylogenetic generalized least squares (PGLS) p < 0.05). Our findings suggest that insects living in large societies may rely more on behavioural mechanisms, such as hygienic behaviours, than on immune function to reduce the risk of disease transmission among nest-mates. PMID:26961895

  14. Genetic control of the innate immune response

    PubMed Central

    Wells, Christine A; Ravasi, Timothy; Faulkner, Geoffrey J; Carninci, Piero; Okazaki, Yasushi; Hayashizaki, Yoshihide; Sweet, Matthew; Wainwright, Brandon J; Hume, David A

    2003-01-01

    Background Susceptibility to infectious diseases is directed, in part, by the interaction between the invading pathogen and host macrophages. This study examines the influence of genetic background on host-pathogen interactions, by assessing the transcriptional responses of macrophages from five inbred mouse strains to lipopolysaccharide (LPS), a major determinant of responses to gram-negative microorganisms. Results The mouse strains examined varied greatly in the number, amplitude and rate of induction of genes expressed in response to LPS. The response was attenuated in the C3H/HeJlpsd strain, which has a mutation in the LPS receptor Toll-like receptor 4 (TLR4). Variation between mouse strains allowed clustering into early (C57Bl/6J and DBA/2J) and delayed (BALB/c and C3H/ARC) transcriptional phenotypes. There was no clear correlation between gene induction patterns and variation at the Bcg locus (Slc11A1) or propensity to bias Th1 versus Th2 T cell activation responses. Conclusion Macrophages from each strain responded to LPS with unique gene expression profiles. The variation apparent between genetic backgrounds provides insights into the breadth of possible inflammatory responses, and paradoxically, this divergence was used to identify a common transcriptional program that responds to TLR4 signalling, irrespective of genetic background. Our data indicates that many additional genetic loci control the nature and the extent of transcriptional responses promoted by a single pathogen-associated molecular pattern (PAMP), such as LPS. PMID:12826024

  15. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    PubMed

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  16. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds

    PubMed Central

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J.

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a ‘wildlife photographer’, resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds. PMID:27293597

  17. Characterization of the immune response of domestic fowl following immunization with proteins extracted from Dermanyssus gallinae.

    PubMed

    Harrington, David; Din, Hatem Mohi El; Guy, Jonathan; Robinson, Karen; Sparagano, Olivier

    2009-03-23

    Dermanyssus gallinae is the most significant ectoparasite of European poultry egg laying production systems due to high costs of control and associated production losses as well as adverse effects on bird welfare. In this study, soluble proteins were extracted from unfed D. gallinae (DGE) using a urea-based detergent and ultra-filtration, passed through a 0.22 microm filter and blended aseptically with adjuvant. One group of laying hens was immunized with DGE and adjuvant (Montanide ISA 50 V) whilst another group (Control) received physiological saline and adjuvant. All birds were immunized on two occasions, 21 days apart. Antibody response to immunization was determined by ELISA and western blotting using immunoglobulins (Igs) extracted from egg yolk. DGE immunization of hens resulted in a significant (P<0.05) IgY response compared to controls, although there was no significant difference in IgM response between treatments. A number of proteins were identified by western blotting using IgY antibodies from DGE immunized birds, most prominently at 40 and 230kDa. Analysis of proteins from approximately corresponding bands on SDS-PAGE confirmed the identity of tropomyosin, whilst other proteins showed high sequence homology with myosin and actin from other arachnid and insect species. Immunization of hens with DGE resulted in a 50.6% increase in mite mortality (P<0.001) 17h after feeding when tested by an in vitro mite feeding model. Data in this study demonstrate that somatic antigens from D. gallinae can be used to stimulate a protective immune response in laying hens. Further work is needed to identify other proteins of interest that could confer higher protection against D. gallinae, as well as optimization of the vaccination and in vitro testing protocol.

  18. Innate and Adaptive Immune Responses in Wound Epithelialization

    PubMed Central

    Strbo, Natasa; Yin, Natalie; Stojadinovic, Olivera

    2014-01-01

    Significance: Over the years, it has become clear that, in addition to performing their regular duties in immune defense, the innate and adaptive arms of the immune system are important regulators of the complex series of events that lead to wound healing. Immune cells modulate wound healing by promoting cellular cross-talk; they secrete signaling molecules, including cytokines, chemokines, and growth factors. In line with the major effort in wound healing research to find efficient therapeutic agents for the constantly increasing number of patients with chronic wounds, findings regarding the contributions of innate and adaptive immune responses to the re-epithelialization of damaged skin may bring novel therapeutics. Recent Advances: Increasing evidence suggests that induction of the adaptive immune response requires activation of innate immunity and that there is a dependent relationship between the two systems. Consequently, the bridge between the innate and the acquired immune systems has become an area of emerging exploration. It is clear that a better understanding of the epithelial cells (keratinocytes), immune cells, and mechanisms that contribute to an effective wound healing process is necessary so that new strategies for successful wounds treatment can be devised. Critical Issues: A greater understanding of the biology of skin innate and adaptive immune cells during wound epithelialization may have an impact on development of novel strategies for significant improvements in the quality of tissue repair. Future Directions: Future studies should clarify the importance of particular molecules and mechanisms utilized for development and functions of skin-resident γδT and Langerhans cells, as well as identify therapeutic targets for manipulation of these cells to combat epithelial diseases. PMID:25032069

  19. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures.

    PubMed

    Gunn, Shelly R; Gunn, G Gibson; Mueller, Francis W

    2016-05-11

    Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient's water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient's symptoms resolved. He is off medications, back to work, and resuming normal exercise. This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and may represent a treatable underlying disease etiology in a subset of genetically susceptible patients with RUC, CFS, and other immune disorders.

  20. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

    PubMed Central

    Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

    2016-01-01

    Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and

  1. A basic mathematical model of the immune response

    NASA Astrophysics Data System (ADS)

    Mayer, H.; Zaenker, K. S.; an der Heiden, U.

    1995-03-01

    Interaction of the immune system with a target population of, e.g., bacteria, viruses, antigens, or tumor cells must be considered as a dynamic process. We describe this process by a system of two ordinary differential equations. Although the model is strongly idealized it demonstrates how the combination of a few proposed nonlinear interaction rules between the immune system and its targets are able to generate a considerable variety of different kinds of immune responses, many of which are observed both experimentally and clinically. In particular, solutions of the model equations correspond to states described by immunologists as ``virgin state,'' ``immune state'' and ``state of tolerance.'' The model successfully replicates the so-called primary and secondary response. Moreover, it predicts the existence of a threshold level for the amount of pathogen germs or of transplanted tumor cells below which the host is able to eliminate the infectious organism or to reject the tumor graft. We also find a long time coexistence of targets and immune competent cells including damped and undamped oscillations of both. Plausibly the model explains that if the number of transformed cells or pathogens exeeds definable values (poor antigenicity, high reproduction rate) the immune system fails to keep the disease under control. On the other hand, the model predicts apparently paradoxical situations including an increased chance of target survival despite enhanced immune activity or therapeutically achieved target reduction. A further obviously paradoxical behavior consists of a positive effect for the patient up to a complete cure by adding an additional target challenge where the benefit of the additional targets depends strongly on the time point and on their amount. Under periodically pulsed stimulation the model may show a chaotic time behavior of both target growth and immune response.

  2. Kill: boosting HIV-specific immune responses.

    PubMed

    Trautmann, Lydie

    2016-07-01

    Increasing evidence suggests that purging the latent HIV reservoir in virally suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV-infected cells ('Shock and Kill' strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in-vivo and in-silico models to accelerate the design of new clinical trials. New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment.

  3. [Human milk, immune responses and health effects].

    PubMed

    Løland, Beate Fossum; Baerug, Anne B; Nylander, Gro

    2007-09-20

    Besides providing optimal nutrition to infants, human milk contains a multitude of immunological components. These components are important for protection against infections and also support the development and maturation of the infant's own immune system. This review focuses on the function of some classical immunocomponents of human milk. Relevant studies are presented that describe health benefits of human milk for the child and of lactation for the mother. Relevant articles were found mainly by searching PubMed. Humoral and cellular components of human milk confer protection against infections in the respiratory--, gastrointestinal--and urinary tract. Human milk also protects premature children from neonatal sepsis and necrotizing enterocolitis. There is evidence that human milk may confer long-term benefits such as lower risk of certain autoimmune diseases, inflammatory bowel disease and probably some malignancies. Human milk possibly affects components of the metabolic syndrome. Recent studies demonstrate long-term health benefits of lactation also for the mother. A reduced incidence of breast cancer is best documented. An increasing number of studies indicate protection against ovarian cancer, rheumatoid arthritis and type II diabetes.

  4. Immune responses to chlamydial antigens in humans.

    PubMed

    Hanna, L; Kerlan, R; Senyk, G; Stites, D P; Juster, R P; Jawetz, E

    1982-01-01

    Antibody titer, lymphocyte stimulation and leukocyte migration inhibition with chlamydial antigens were determined repeatedly over many months on human subjects. The volunteers were retrospectively placed into four groups on the basis of clinical, laboratory and epidemiologic criteria. Group A consisted of persons with proven or probable chlamydial infection, including an illness confirmed by chlamydial isolation or seroconversion, or a clinically compatible illness with positive serologic results. Group B were sexual partners or close contacts of group A individuals. Group C were laboratory workers with prolonged exposure to viable chlamydiae or their antigens. Group D included persons of comparable age as those in groups A and B, but lacking a history of symptomatic chlamydial infection or of contact with chlamydiae. Individual cases illustrated the rise of antibody and some cell mediated immunity reactions (CMI) with active chlamydial infection. By contrast, laboratory exposure resulted in elevation of CMI but not of antibody. Statistical analysis of the results in 46 volunteers tested repeatedly indicated a strong association of specific antibody with lymphocyte stimulation, but not with leukocyte migration inhibition. Regression analysis suggested that the type of exposure markedly influenced the relationship between antibody and lymphocyte stimulation. Measurement of immunotype-specific antibody titer by microimmunofluorescence (or an equally sensitive method) remains the best laboratory indicator of past chlamydial infection. Neither antibody nor CMI can, as yet, be definitely related to resistance to re-infection in humans.

  5. Cellular immune response in multiple sclerosis plaques.

    PubMed Central

    Boyle, E. A.; McGeer, P. L.

    1990-01-01

    Multiple sclerosis plaques were immunohistochemically stained to exhibit cells expressing immune-system antigens. Human leukocyte antigen (HLA)-DR-positive cells formed dense rings around all plaque regions. The majority were reactive microglia/macrophages. Counterstaining with oil red O revealed heavy myelin debris within these cells. They were distinct from astrocytes, which were identified with an antibody to glial fibrillary acidic protein (GFAP) and which did not contain oil red O myelin debris. Numerous leukocytes and microglia were stained with antibody to leukocyte common antigen (LCA). Lymphocytes in cuffs around vessels, along the margins of capillary walls, and, sparingly, in the tissue matrix of affected areas, were stained with antibodies to CD4 (T-helper/inducer) and CD8 (T-cytotoxic/suppressor). In experimental allergic encephalomyelitis (EAE) induced in Lewis rats, a similar proliferation of Ia-positive (OX6, OX17) cells displaying reactive microglia/macrophage morphology was observed. These Ia-positive cells also were easily distinguished from GFAP-positive astrocytes. The results suggest that macrophages/reactive microglia, and not astrocytes, express class II MHC antigens in multiple sclerosis and EAE plaques. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:1698025

  6. Crosstalk between microbiota, pathogens and the innate immune responses.

    PubMed

    Günther, Claudia; Josenhans, Christine; Wehkamp, Jan

    2016-08-01

    Research in the last decade has convincingly demonstrated that the microbiota is crucial in order to prime and orchestrate innate and adaptive immune responses of their host and influence barrier function as well as multiple developmental and metabolic parameters of the host. Reciprocally, host reactions and immune responses instruct the composition of the microbiota. This review summarizes recent evidence from experimental and human studies which supports these arms of mutual relationship and crosstalk between host and resident microbiota, with a focus on innate immune responses in the gut, the role of cell death pathways and antimicrobial peptides. We also provide some recent examples on how dysbiosis and pathogens can act in concert to promote intestinal infection, inflammatory pathologies and cancer. The future perspectives of these combined research efforts include the discovery of protective species within the microbiota and specific traits and factors of microbes that weaken or enforce host intestinal homeostasis.

  7. Innate Immune Responses to Nanoparticle Exposure in the Lung.

    PubMed

    Thompson, Elizabeth A; Sayers, Brian C; Glista-Baker, Ellen E; Shipkowski, Kelly A; Taylor, Alexia J; Bonner, James C

    2014-01-01

    The nanotechnology revolution offers enormous societal and economic benefits for innovation in the fields of engineering, electronics, and medicine. Nevertheless, evidence from rodent studies show that biopersistent engineered nanomaterials (ENMs) stimulate immune, inflammatory, and fibroproliferative responses in the lung, suggesting possible risks for lung diseases or systemic immune disorders as a consequence of occupational, environmental, or consumer exposure. Due to their nanoscale dimensions and increased surface area per unit mass, ENMs have a much greater potential to reach the distal regions of the lung and generate ROS. High aspect ratio ENMs (e.g., nanotubes, nanofibers) activate inflammasomes in macrophages, triggering IL-1β release and neutrophilic infiltration into the lungs. Moreover, some ENMs alter allergen-induced eosinophilic inflammation by immunostimulation, immunosuppression, or modulating the balance between Th1, Th2, and Th17 cells, thereby influencing the nature of the inflammatory response. ENMs also migrate from the lungs across epithelial, endothelial, or mesothelial barriers to stimulate or suppress systemic immune responses.

  8. Determinants of early life immune responses to RSV infection.

    PubMed

    Ruckwardt, Tracy J; Morabito, Kaitlyn M; Graham, Barney S

    2016-02-01

    Respiratory syncytial virus causes significant morbidity and mortality in both developed and developing countries, and a vaccine that adequately protects from severe disease remains an important unmet need. RSV disease has an inordinate impact on the very young, and the physical and immunological immaturity of early life complicates vaccine design. Defining and targeting the functional capacities of early life immune responses and controlling responses during primary antigen exposure with selected vaccine delivery approaches will be important for protecting infants by active immunization. Alternatively, vaccination of older children and pregnant mothers may ameliorate disease burden indirectly until infants reach about six months of age, when they can generate more effective anti-RSV immune responses.

  9. Probiotics, antibiotics and the immune responses to vaccines

    PubMed Central

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

    2015-01-01

    Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. PMID:25964456

  10. Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

    PubMed

    Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

    2016-05-01

    Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions.

  11. The Gender Bender effect in Periodontal Immune Response.

    PubMed

    Grover, Vishakha; Jain, Ashish; Kapoor, Anoop; Malhotra, Ranjan; Chahal, Gurparkash Singh

    2016-01-01

    The gender and sex of an individual is known to have a significant bearing on the immune system, responsible for protection against infections and disease. Contemporary evidence suggests there exists a sexual dimorphism in the hetero immune as well as autoimmune responses in human beings and females show stronger and more vigorous immune responses to antigenic stimulations, e.g infectious diseases and vaccination. The evidence supportive to gender based heterogeneity in immune responses specifically in context of periodontal disease, is mounting in contemporary literature. A thorough and methodical search for related scientific publications have been accomplished by using different key words and terms like sex or gender based immune differences in periodontal disease, both by manual methods and on various electronic databases. Primary research articles, narrative and systematic reviews of good quality, relevant to the subject were included. The aggregate effects of the factors related to gender such as the steroid hormones as well as gene based differences in both sexes as supported by published literature are in line with the observed variation in susceptibility for chronic periodontitis in both genders , with males showing more risk for disease than women. Gender as a risk factor for periodontal disease needs to identified, its underlying mechanisms to contribute needs to be revealed, so that novel strategies for risk assessment, disease identification and individualized therapeutic approaches can be developed for optimized patient care.

  12. Probiotics, antibiotics and the immune responses to vaccines.

    PubMed

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

    2015-06-19

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

  13. Innate and Adaptive Immune Response to Apoptotic Cells

    PubMed Central

    Peng, YuFeng; Martin, David A; Kenkel, Justin; Zhang, Kang; Ogden, Carol Anne; Elkon, Keith B.

    2007-01-01

    The immune system is constantly exposed to dying cells, most of which arise during central tolerance and from effete circulating immune cells. Under homeostatic conditions, phagocytes (predominantly macrophages and dendritic cells) belonging to the innate immune system, rapidly ingest cells and their debris. Apoptotic cell removal requires recognition of altered self on the apoptotic membrane, a process which is facilitated by natural antibodies and serum opsonins. Recognition, may be site and context specific. Uptake and ingestion of apoptotic cells promotes an immunosuppressive environment that avoids inflammatory responses to self antigens. However, it does not preclude a T cell response and it is likely that constant exposure to self antigen, particularly by immature dendritic cells, leads to T cell tolerance. Tolerance occurs by several different mechanisms including anergy and deletion (for CD8+ T cells) and induction of T regulatory cells (for CD4+ T cells). Failed apoptotic cell clearance promotes immune responses to self antigens, especially when the cellular contents are leaked from the cell (necrosis). Inflammatory responses may be induced by nucleic acid stimulation of toll like receptors and other immune sensors, specific intracellular proteins and non protein (uric acid) stimulation of inflammasomes. PMID:17888627

  14. Readapting the adaptive immune response - therapeutic strategies for atherosclerosis.

    PubMed

    Sage, Andrew P; Mallat, Ziad

    2017-01-04

    Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis as a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past three decades, but much remains to be done reduce disease burden. Current priorities include reducing atherosclerosis advancement to clinically significant stages and preventing plaque rupture or erosion. Inflammation and involvement of the adaptive immune system influences all these aspects and therefore is one focus for future therapeutic development. The atherosclerotic vascular wall is now recognized to be invaded from both sides (arterial lumen and adventitia), for better or worse, by the adaptive immune system. Atherosclerosis is also affected at several stages by adaptive immune responses, overall providing many opportunities to target these responses and to reduce disease progression. Protective influences that may be defective in diseased individuals include humoral responses to modified LDL and regulatory T cell responses. There are many strategies in development to boost these pathways in humans, including vaccine-based therapies. The effects of various existing adaptive immune targeting therapies, such as blocking critical co-stimulatory pathways or B cell depletion, on cardiovascular disease are beginning to emerge with important consequences for both autoimmune disease patients and the potential for wider use of such therapies. Entering the translation phase for adaptive immune targeting therapies is an exciting and promising prospect.

  15. Secondary immune response of rainbow trout following repeated immersion vaccination.

    PubMed

    Jaafar, R M; Al-Jubury, A; Chettri, J K; Dalsgaard, I; Kania, P W; Buchmann, K

    2017-07-14

    Teleosts are able to raise a protective immune response, comprising both innate and adaptive elements, against various pathogens. This is the basis for a widespread use of vaccines, administered as injection or immersion, in the aquaculture industry. It has been described that repeated injection vaccination of fish raises a secondary immune response, consisting of rapid, accelerated and increased antibody reaction. This study reports how rainbow trout responds to repeated immersion vaccination against yersiniosis (ERM) caused by the bacterial pathogen Yersinia ruckeri. It was found that rainbow trout does not raise a classical secondary response following repeated immersion vaccination. Serum antibody titres were merely slightly increased even after three immunizations, using 30-s immersion into a bacterin consisting of formalin-inactivated Y. ruckeri (serotype O1, biotypes 1 and 2), performed over a 3-month period. The densities of IgM-positive lymphocytes in spleen of fish immunized three times were increased compared to control fish, but no general trend for an increase with the number of immunizations was noted. The lack of a classical secondary response following repeated immersion vaccination may partly be explained by limited uptake of antigen by immersion compared to injection. © 2017 John Wiley & Sons Ltd.

  16. Innate immune responses in hepatitis C virus infection.

    PubMed

    Li, Kui; Lemon, Stanley M

    2013-01-01

    Hepatitis C virus (HCV) is a major causative agent of chronic hepatitis and hepatocellular carcinoma worldwide and thus poses a significant public health threat. A hallmark of HCV infection is the extraordinary ability of the virus to persist in a majority of infected people. Innate immune responses represent the front line of defense of the human body against HCV immediately after infection. They also play a crucial role in orchestrating subsequent HCV-specific adaptive immunity that is pivotal for viral clearance. Accumulating evidence suggests that the host has evolved multifaceted innate immune mechanisms to sense HCV infection and elicit defense responses, while HCV has developed elaborate strategies to circumvent many of these. Defining the interplay of HCV with host innate immunity reveals mechanistic insights into hepatitis C pathogenesis and informs approaches to therapy. In this review, we summarize recent advances in understanding innate immune responses to HCV infection, focusing on induction and effector mechanisms of the interferon antiviral response as well as the evasion strategies of HCV.

  17. Nutrient responses to ecosystem disturbances from annual to multi-millennial timescales

    Treesearch

    B. Buma

    2014-01-01

    The Novus Network annual meeting was held at H. J. Andrews Experimental Forest in Oregon, USA, from 22 May to 24 May 2013. The topic was: ‘Nutrient responses to ecosystem disturbances from annual to multi-millennial timescales’. The 2013 workshop brought together 28 researchers from 21 institutions spread across three continents. The participants – 17 faculty members,...

  18. Immune Responses in Rhinovirus-Induced Asthma Exacerbations.

    PubMed

    Steinke, John W; Borish, Larry

    2016-11-01

    Acute asthma exacerbations are responsible for urgent care visits and hospitalizations; they interfere with school and work productivity, thereby driving much of the morbidity and mortality associated with asthma. Approximately 80 to 85 % of asthma exacerbations in children, adolescents, and less frequently adults are associated with viral upper respiratory tract viral infections, and rhinovirus (RV) accounts for ∼60-70 % of these virus-associated exacerbations. Evidence suggests that it is not the virus itself but the nature of the immune response to RV that drives this untoward response. In particular, evidence supports the concept that RV acts to exacerbate an ongoing allergic inflammatory response to environmental allergens present at the time of the infection. The interaction of the ongoing IgE- and T cell-mediated response to allergen superimposed on the innate and adaptive immune responses to the virus and how this leads to triggering of an asthma exacerbation is discussed.

  19. Effect of protein release rates from tablet formulations on the immune response after sublingual immunization.

    PubMed

    Borde, Annika; Ekman, Annelie; Holmgren, Jan; Larsson, Anette

    2012-11-20

    Dry vaccine formulations for sublingual administration would provide great advantages for public health use, especially in developing countries, since they are easy to administer and might also have improved stability properties. This study investigates the influence of protein release rate from mucoadhesive two-layer tablets on the elicited antibody responses after sublingual immunization. Two fast release tablets, one based on a mixture of lactose and microcrystalline cellulose (MCC) and one protein coated ethylcellulose (EC) tablet, and three hydrophilic matrix tablets with extended release (ER) properties based on HPMC 90 SH 100000 or Carbopol® 974-P NF were tested. The in vitro release profiles of the model protein ovalbumin (OVA) from these tablets were characterized and correlated to the in vivo potential of the tablets to induce an immune response after sublingual immunization in BALB/c mice. It could be concluded that a tablet with fast protein release elicits antibody titres not significantly different from titres obtained with OVA in solution, whereas low immune responses were observed with a slow release of OVA from the ER formulations. Thus, an ER tablet seems not favorable for vaccine delivery to the sublingual mucosa. Thus, we can present a fast releasing tablet formulation with attractive features for sublingual immunization, whereas the use of ER formulations for sublingual vaccination has to be investigated more in detail.

  20. Disturbance dynamo electric fields in response to geomagnetic storms occurring at different universal times

    NASA Astrophysics Data System (ADS)

    Huang, C.

    2013-12-01

    Perturbed electric fields in the earth's ionosphere, resulting from the penetration electric fields from high latitudes and/or from the dynamo mechanism driven by the neutral disturbances, occurr in the storm periods. In general, the identification of the penetration electric fields is easier than that of the dynamo electric fields. At times, the latter becomes unperceivable or difficult to identify. This is an interesting problem which motivates a model study to investigate the possible reasons. Model runs made with the National Center for Atmospheric Research Thermosphere Ionosphere Electrodynamics General Circulation Model (NCAR/TIEGCM) will be presented. Theoretical studies of ionospheric responses to geomagnetic storms with model simulations indicate that the intensities of disturbance dynamo electric fields are highly dependent on various parameters such as solar activities, seasonal effects and universal times, etc. When geomagnetic storms commence at 01~07 UT in summer solstices with low solar fluxes, the disturbance dynamo electric fields become very small. As compared with the general daily variations, they seem to be unperceivable. This phenomenon can be explained by the model results which show that the positive charge accumulation at low latitudes will be weakened when the equatward neutral disturbances penetrate into the opposite hemisphere in the storm time. For other cases, the magnitudes of the dynamo electric fields are relatively larger under the same geomagnetic activity.

  1. Acute psychological stress induces short-term variable immune response.

    PubMed

    Breen, Michael S; Beliakova-Bethell, Nadejda; Mujica-Parodi, Lilianne R; Carlson, Joshua M; Ensign, Wayne Y; Woelk, Christopher H; Rana, Brinda K

    2016-03-01

    In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of natural killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Correcting gene expression for an influx of NK cells revealed a molecular signature specific to the adrenal cortex. Subsequently, focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific.

  2. Microgravity and immune responsiveness: implications for space travel.

    PubMed

    Borchers, Andrea T; Keen, Carl L; Gershwin, M Eric

    2002-10-01

    To date, several hundred cosmonauts and astronauts have flown in space, yet knowledge about the adaptation of their immune system to space flight is rather limited. It is evident that a variety of immune parameters are changed during and after space flight, but the magnitude and pattern of these changes can differ dramatically between missions and even between crew members on the same mission. A literature search was conducted involving a total of 335 papers published between 1972 and 2002 that dealt with the key words immune response, microgravity and astronauts/cosmonauts, isolation, gravity, and human health. The data from multiple studies suggested that major discrepancies in outcome are due to methodologic differences. However, the data also suggested major factors that affect and modulate the immune response during space travel. In part at least, these discrepancies can be attributed to methodologic differences. In addition, a variety of other features, in particular the types and extent of stressors encountered during space missions, are likely to contribute to the variability of immune responses during and after space flight. That stress plays an important role in the effects of space flight on immunologic parameters is suggested by the frequent findings that stress hormones are upregulated during and after space flight. Unfortunately, however, the existing data on hormonal parameters are almost as varied as those on immunologic changes, and correlations between the two datasets have only rarely been attempted. The functional implications of space flight-induced alterations in immune response largely remain to be elucidated, but the data suggest that long-term travel will be associated with the development of immune-compromised hosts.

  3. Suppressive influences in the immune response to cancer.

    PubMed

    Bronte, Vincenzo; Mocellin, Simone

    2009-01-01

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

  4. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    PubMed Central

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

    2016-01-01

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

  5. The Xs and Y of immune responses to viral vaccines.

    PubMed

    Klein, Sabra L; Jedlicka, Anne; Pekosz, Andrew

    2010-05-01

    The biological differences associated with the sex of an individual are a major source of variation, affecting immune responses to vaccination. Compelling clinical data illustrate that men and women differ in their innate, humoral, and cell-mediated responses to viral vaccines. Sex affects the frequency and severity of adverse effects of vaccination, including fever, pain, and inflammation. Pregnancy can also substantially alter immune responses to vaccines. Data from clinical trials and animal models of vaccine efficacy lay the groundwork for future studies aimed at identifying the biological mechanisms that underlie sex-specific responses to vaccines, including genetic and hormonal factors. An understanding and appreciation of the effect of sex and pregnancy on immune responses might change the strategies used by public health officials to start efficient vaccination programmes (optimising the timing and dose of the vaccine so that the maximum number of people are immunised), ensure sufficient levels of immune responses, minimise adverse effects, and allow for more efficient protection of populations that are high priority (eg, pregnant women and individuals with comorbid conditions). Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Handling properties of diverse automobiles and correlation with full scale response data. [driver/vehicle response to aerodynamic disturbances

    NASA Technical Reports Server (NTRS)

    Hoh, R. H.; Weir, D. H.

    1973-01-01

    Driver/vehicle response and performance of a variety of vehicles in the presence of aerodynamic disturbances are discussed. Steering control is emphasized. The vehicles include full size station wagon, sedan, compact sedan, van, pickup truck/camper, and wagon towing trailer. Driver/vehicle analyses are used to estimate response and performance. These estimates are correlated with full scale data with test drivers and the results are used to refine the driver/vehicle models, control structure, and loop closure criteria. The analyses and data indicate that the driver adjusts his steering control properties (when he can) to achieve roughly the same level of performance despite vehicle variations. For the more disturbance susceptible vehicles, such as the van, the driver tightens up his control. Other vehicles have handling dynamics which cause him to loosen his control response, even though performance degrades.

  7. Effects of NO/sub 2/ on immune responses

    SciTech Connect

    Lefkowitz, S.S.; McGrath, J.J.; Lefkowitz, D.L.

    1986-01-01

    The effects of NO/sub 2/ on immune responses of mice were investigated. Mice were exposed to various concentrations of NO/sub 2/ in inhalation chambers. After exposure the following parameters were measured: phagocytosis of polystyrene beads by both peritoneal and alveolar macrophages, production of antibody-forming cells from mice immunized with sheep erythrocytes, lymphocyte blastogenesis of splenic cells, and susceptibility to influenza virus. The production of antibody-forming cells was reduced in mice that were exposed to 5 ppm NO/sub 2/. The serum antibody titers, phagocytosis, and other immune parameters measured were not affected. Exposure to NO/sub 2/ did not affect mortality to influenza virus. These data indicate that certain immune parameters were altered by exposure to NO/sub 2/; however, NO/sub 2/ does not appear to be a major immunosuppressive factor at the concentrations tested.

  8. Host cell autophagy in immune response to zoonotic infections.

    PubMed

    Skendros, Panagiotis; Mitroulis, Ioannis

    2012-01-01

    Autophagy is a fundamental homeostatic process in which cytoplasmic targets are sequestered within double-membraned autophagosomes and subsequently delivered to lysosomes for degradation. Accumulating evidence supports the pivotal role of autophagy in host defense against intracellular pathogens implicating both innate and adaptive immunity. Many of these pathogens cause common zoonotic infections worldwide. The induction of the autophagic machinery by innate immune receptors signaling, such as TLRs, NOD1/2, and p62/SQSTM1 in antigen-presenting cells results in inhibition of survival and elimination of invading pathogens. Furthermore, Th1 cytokines induce the autophagic process, whereas autophagy also contributes to antigen processing and MHC class II presentation, linking innate to adaptive immunity. However, several pathogens have developed strategies to avoid autophagy or exploit autophagic machinery to their advantage. This paper focuses on the role of host cell autophagy in the regulation of immune response against intracellular pathogens, emphasizing on selected bacterial and protozoan zoonoses.

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

    PubMed

    Fins, Joseph J

    2015-04-01

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

  10. MATURATION OF THE IMMUNE RESPONSE IN VITRO

    PubMed Central

    Macario, Alberto J. L.; de Macario, Everly Conway; Franceschi, Claudio; Celada, Franco

    1972-01-01

    We have cultivated lymph node microfragments from β-D-galactosidase (Escherichia coli) primed rabbits and have measured their secondary response directed towards the whole molecule (precipitating antibodies) and to a single determinant (activating antibodies) of the antigen. By decreasing the size of the fragments to 105 cells, we began to observe heterogeneity among identical cultures in terms of positivity of response, antibody specificity, and titers. The affinity of "early" activating antibodies was inversely proportional to the dose of challenge. While no maturation was seen in low and excessive challenge, in all cultures receiving intermediate doses the association constant was raised several orders of magnitude within periods of 20 days. The relevance of these data to the mechanism of affinity selection of antigen-sensitive cells is discussed. PMID:4557772

  11. Crohn's Disease Disturbs the Immune Properties of Human Adipose-Derived Stem Cells Related to Inflammasome Activation.

    PubMed

    Serena, Carolina; Keiran, Noelia; Madeira, Ana; Maymó-Masip, Elsa; Ejarque, Miriam; Terrón-Puig, Margarida; Espin, Eloy; Martí, Marc; Borruel, Natalia; Guarner, Francisco; Menacho, Margarida; Zorzano, Antonio; Millan, Monica; Fernández-Veledo, Sonia; Vendrell, Joan

    2017-08-09

    Crohn's disease (CD) is characterized by the expansion of mesenteric fat, also known as "creeping fat." We explored the plasticity and immune properties of adipose-derived stem cells (ASCs) in the context of CD as potential key players in the development of creeping fat. Mesenteric CD-derived ASCs presented a more proliferative, inflammatory, invasive, and phagocytic phenotype than equivalent cells from healthy donors, irrespective of the clinical stage. Remarkably, ASCs from the subcutaneous depot of patients with CD also showed an activated immune response that was associated with a reduction in their immunosuppressive properties. The invasive phenotype of mesenteric CD ASCs was governed by an inflammasome-mediated inflammatory state since blocking inflammasome signaling, mainly the secretion of interleukin-1β, reversed this characteristic. Thus, CD alters the biological functions of ASCs as adipocyte precursors, but also their immune properties. Selection of ASCs with the best immunomodulatory properties is advocated for the success of cell-based therapies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Quantitative measurement of the immune response and sleep in Drosophila.

    PubMed

    Kuo, Tzu-Hsing; Handa, Arun; Williams, Julie A

    2012-12-04

    A complex interaction between the immune response and host behavior has been described in a wide range of species. Excess sleep, in particular, is known to occur as a response to infection in mammals (1) and has also recently been described in Drosophila melanogaster(2). It is generally accepted that sleep is beneficial to the host during an infection and that it is important for the maintenance of a robust immune system(3,4). However, experimental evidence that supports this hypothesis is limited(4), and the function of excess sleep during an immune response remains unclear. We have used a multidisciplinary approach to address this complex problem, and have conducted studies in the simple genetic model system, the fruitfly Drosophila melanogaster. We use a standard assay for measuring locomotor behavior and sleep in flies, and demonstrate how this assay is used to measure behavior in flies infected with a pathogenic strain of bacteria. This assay is also useful for monitoring the duration of survival in individual flies during an infection. Additional measures of immune function include the ability of flies to clear an infection and the activation of NFκB, a key transcription factor that is central to the innate immune response in Drosophila. Both survival outcome and bacterial clearance during infection together are indicators of resistance and tolerance to infection. Resistance refers to the ability of flies to clear an infection, while tolerance is defined as the ability of the host to limit damage from an infection and thereby survive despite high levels of pathogen within the system(5). Real-time monitoring of NFκB activity during infection provides insight into a molecular mechanism of survival during infection. The use of Drosophila in these straightforward assays facilitates the genetic and molecular analyses of sleep and the immune response and how these two complex systems are reciprocally influenced.

  13. Photodynamic therapy for cancer and activation of immune response

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.

    2010-02-01

    Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.

  14. Quantitative Measurement of the Immune Response and Sleep in Drosophila

    PubMed Central

    Kuo, Tzu-Hsing; Handa, Arun; Williams, Julie A.

    2012-01-01

    A complex interaction between the immune response and host behavior has been described in a wide range of species. Excess sleep, in particular, is known to occur as a response to infection in mammals 1 and has also recently been described in Drosophila melanogaster2. It is generally accepted that sleep is beneficial to the host during an infection and that it is important for the maintenance of a robust immune system3,4. However, experimental evidence that supports this hypothesis is limited4, and the function of excess sleep during an immune response remains unclear. We have used a multidisciplinary approach to address this complex problem, and have conducted studies in the simple genetic model system, the fruitfly Drosophila melanogaster. We use a standard assay for measuring locomotor behavior and sleep in flies, and demonstrate how this assay is used to measure behavior in flies infected with a pathogenic strain of bacteria. This assay is also useful for monitoring the duration of survival in individual flies during an infection. Additional measures of immune function include the ability of flies to clear an infection and the activation of NFκB, a key transcription factor that is central to the innate immune response in Drosophila. Both survival outcome and bacterial clearance during infection together are indicators of resistance and tolerance to infection. Resistance refers to the ability of flies to clear an infection, while tolerance is defined as the ability of the host to limit damage from an infection and thereby survive despite high levels of pathogen within the system5. Real-time monitoring of NFκB activity during infection provides insight into a molecular mechanism of survival during infection. The use of Drosophila in these straightforward assays facilitates the genetic and molecular analyses of sleep and the immune response and how these two complex systems are reciprocally influenced. PMID:23242373

  15. The microbiota and immune response during Clostridium difficile infection.

    PubMed

    Buonomo, Erica L; Petri, William A

    2016-10-01

    Clostridium difficile is a gram-positive, spore forming anaerobe that infects the gut when the normal microbiota has been disrupted. C. difficile infection (CDI) is the most common cause of hospital acquired infection in the United States, and the leading cause of death due to gastroenteritis. Patients suffering from CDI have varying symptoms which range from mild diarrhea to pseudomembranous colitis and death. The involvement of the immune response to influence disease severity is just beginning to be investigated. There is evidence that the immune response can facilitate either protective or pathogenic phenotypes, suggesting it plays a multifaceted role during CDI. In addition to the immune response, the microbiota is pivotal in dictating the pathogenesis to CDI. A healthy microbiota effectively inhibits infection by restricting the ability of C. difficile to expand in the colon. Thus, understanding which immune mediators and components of the microbiota play beneficial roles during CDI will be important to future therapeutic developments. This review outlines how the microbiota can modulate specific immune mediators, such as IL-23 and others, to influence disease outcome. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The microbiota and immune response during Clostridium difficile infection

    PubMed Central

    Buonomo, Erica L; Petri, William A.

    2016-01-01

    Clostridium difficile is a gram-positive, spore forming anaerobe that infects the gut when the normal microbiota has been disrupted. C. difficile infection (CDI) in the United States is the most common cause of hospital acquired infection, and the leading cause of death due to gastroenteritis. Patients suffering from CDI have varying symptoms which range from mild diarrhea to pseudomembranous colitis and death. The involvement of the immune response to influence disease severity is just beginning to be investigated. There is evidence that the immune response can facilitate either protective or pathogenic phenotypes, suggesting it plays a multifaceted role during CDI. In addition to the immune response, the microbiota is pivotal in dictating the pathogenesis to CDI. A healthy microbiota effectively inhibits infection by restricting the ability of C. difficile to expand in the colon. Thus, understanding which immune mediators and components of the microbiota play beneficial roles during CDI will be important to future therapeutic developments. This review outlines how the microbiota can modulate specific immune mediators, such as IL-23 and others, to influence disease outcome. PMID:27212111

  17. CNS leptin action modulates immune response and survival in sepsis

    PubMed Central

    Tschöp, Johannes; Nogueiras, Ruben; Haas-Lockie, Sarah; Kasten, Kevin; Castañeda, Tamara R.; Huber, Nadine; Guanciale, Kelsey; Perez-Tilve, Diego; Habegger, Kirk; Ottaway, Nickki; Woods, Stephen C.; Oldfield, Brian; Clarke, Iain; Chua, Streamson; Farooqi, I. Sadaf; O'Rahilly, Stephen; Caldwell, Charles C.; Tschöp, Matthias H.

    2010-01-01

    Sepsis describes a complex clinical syndrome that results from an infection, setting off a cascade of systemic inflammatory responses that can lead to multiple organ failure and death. Leptin is a 16 kDa adipokine that, among its multiple known effects, is involved in regulating immune function. Here we demonstrate that leptin deficiency in ob/ob mice leads to higher mortality and more severe organ damage in a standard model of sepsis in mice (cecal ligation and puncture, CLP). Moreover, systemic leptin replacement improved the immune response to CLP. Based on the molecular mechanisms of leptin regulation of energy metabolism and reproductive function, we hypothesized that leptin acts in the central nervous system (CNS) to efficiently coordinate peripheral immune defense in sepsis. We now report that leptin signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenous CNS leptin action is required for an adequate systemic immune response. These findings reveal the existence of a relevant neuroendocrine control of systemic immune defense, and suggest a possible therapeutic potential for leptin analogues in infectious disease. PMID:20427662

  18. The host immune response to gastrointestinal nematode infection in sheep.

    PubMed

    McRae, K M; Stear, M J; Good, B; Keane, O M

    2015-12-01

    Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed. © 2015 John Wiley & Sons Ltd.

  19. Mosquito phenoloxidase and defensin colocalize in melanization innate immune responses.

    PubMed

    Hillyer, Julián F; Christensen, Bruce M

    2005-06-01

    Mosquitoes mount strong humoral and cellular immune responses against foreign organisms. Two components of the mosquito immune response that have received much attention are the phenoloxidase cascade that leads to melanization and antimicrobial peptides. The purpose of the current study was to use immunocytochemistry and transmission electron microscopy to identify the location of the melanization rate-limiting enzyme phenoloxidase and the antimicrobial peptide defensin in innate immune reactions against Escherichia coli and Micrococcus luteus by the mosquito Aedes aegypti. Our results show that both phenoloxidase and defensin are present at the sites of melanin biosynthesis in immune reactions against bacteria. Furthermore, both proteins are often present inside the same melanotic capsules. When hemocytes were analyzed, phenoloxidase was present in the cytosol of oenocytoids, but no significant amounts of defensin were detected inside any hemocytes. In summary, these data show that phenoloxidase and defensin colocalize in melanization reactions against bacteria and argue for further studies into the potential role of defensin in phenoloxidase-based melanization innate immune responses in mosquitoes.

  20. Environmental Toxicants-Induced Immune Responses in the Olfactory Mucosa

    PubMed Central

    Imamura, Fumiaki; Hasegawa-Ishii, Sanae

    2016-01-01

    Olfactory sensory neurons (OSNs) are the receptor cells for the sense of smell. Although cell bodies are located in the olfactory mucosa (OM) of the nasal cavity, OSN axons directly project to the olfactory bulb (OB) that is a component of the central nervous system (CNS). Because of this direct and short connection from this peripheral tissue to the CNS, the olfactory system has attracted attention as a port-of-entry for environmental toxicants that may cause neurological dysfunction. Selected viruses can enter the OB via the OM and directly affect the CNS. On the other hand, environmental toxicants may induce inflammatory responses in the OM, including infiltration of immune cells and production of inflammatory cytokines. In addition, these inflammatory responses cause the loss of OSNs that are then replaced with newly generated OSNs that re-connect to the OB after inflammation has subsided. It is now known that immune cells and cytokines in the OM play important roles in both degeneration and regeneration of OSNs. Thus, the olfactory system is a unique neuroimmune interface where interaction between nervous and immune systems in the periphery significantly affects the structure, neuronal circuitry, and immunological status of the CNS. The mechanisms by which immune cells regulate OSN loss and the generation of new OSNs are, however, largely unknown. To help develop a better understanding of the mechanisms involved, we have provided a review of key research that has investigated how the immune response in the OM affects the pathophysiology of OSNs. PMID:27867383

  1. Environmental Toxicants-Induced Immune Responses in the Olfactory Mucosa.

    PubMed

    Imamura, Fumiaki; Hasegawa-Ishii, Sanae

    2016-01-01

    Olfactory sensory neurons (OSNs) are the receptor cells for the sense of smell. Although cell bodies are located in the olfactory mucosa (OM) of the nasal cavity, OSN axons directly project to the olfactory bulb (OB) that is a component of the central nervous system (CNS). Because of this direct and short connection from this peripheral tissue to the CNS, the olfactory system has attracted attention as a port-of-entry for environmental toxicants that may cause neurological dysfunction. Selected viruses can enter the OB via the OM and directly affect the CNS. On the other hand, environmental toxicants may induce inflammatory responses in the OM, including infiltration of immune cells and production of inflammatory cytokines. In addition, these inflammatory responses cause the loss of OSNs that are then replaced with newly generated OSNs that re-connect to the OB after inflammation has subsided. It is now known that immune cells and cytokines in the OM play important roles in both degeneration and regeneration of OSNs. Thus, the olfactory system is a unique neuroimmune interface where interaction between nervous and immune systems in the periphery significantly affects the structure, neuronal circuitry, and immunological status of the CNS. The mechanisms by which immune cells regulate OSN loss and the generation of new OSNs are, however, largely unknown. To help develop a better understanding of the mechanisms involved, we have provided a review of key research that has investigated how the immune response in the OM affects the pathophysiology of OSNs.

  2. Effect of immunization route on mucosal and systemic immune response in Atlantic salmon (Salmo salar).

    PubMed

    Valdenegro-Vega, Victoria A; Crosbie, Philip; Vincent, Benita; Cain, Kenneth D; Nowak, Barbara F

    2013-01-15

    This study aimed to assess systemic and mucosal immune responses of Atlantic salmon (Salmo salar) exposed to two protein-hapten antigens - dinitrophenol (DNP) and fluorescein isothiocyanate (FITC) each conjugated with keyhole limpet haemocyanin (KLH) - administered using different delivery strategies. Fish were exposed to the antigens through different routes, and were given a booster 4 weeks post initial exposure. Both systemic and mucosal antibody responses were measured for a period of 12 weeks using an enzyme-linked immunosorbent assay (ELISA). Only fish exposed to both antigens via intraperitoneal (IP) injection showed increased systemic antibody response starting 6 weeks post immunization. No treatment was able to produce a mucosal antibody response; however there was an increase in antibody levels in the tissue supernatant from skin explants obtained 12 weeks post immunization from fish injected with FITC. Western blots probed with serum and culture supernatant from skin explants showed a specific response against the antigens. In conclusion, IP injection of hapten-antigen in Atlantic salmon was the best delivery route for inducing an antibody response against these antigens in this species. Even though IP injection did not induce an increase in antibody levels in the skin mucus, there was an increased systemic antibody response and an apparent increase of antibody production in mucosal tissues as demonstrated by the increased level of specific antibody levels in supernatants from the tissue explants.

  3. miRNAs associated with immune response in teleost fish.

    PubMed

    Andreassen, Rune; Høyheim, Bjørn

    2017-02-28

    MicroRNAs (miRNAs) have been identified as important post transcriptional regulators of gene expression. In higher vertebrates, a subset of miRNAs has been identified as important regulators of a number of key genes in immune system gene networks, and this paper review recent studies on miRNAs associated with immune response in teleost fish. Challenge studies conducted in several species have identified differently expressed miRNAs associated with viral or bacterial infection. The results from these studies point out several miRNAs that are likely to have evolutionary conserved functions that are related to immune response in teleost fish. Changed expression levels of mature miRNAs from the five miRNA genes miRNA-462, miRNA-731, miRNA-146, miRNA-181 and miRNA-223 are observed following viral as well as bacterial infection in several teleost fish. Furthermore, significant changes in expression of mature miRNAs from the five genes miRNA-21, miRNA-155, miRNA-1388, miRNA-99 and miRNA-100 are observed in multiple studies of virus infected fish while changes in expression of mature miRNA from the three genes miRNA-122, miRNA-192 and miRNA-451 are observed in several studies of fish with bacterial infections. Interestingly, some of these genes are not present in higher vertebrates. The function of the evolutionary conserved miRNAs responding to infection depends on the target gene(s) they regulate. A few target genes have been identified while a large number of target genes have been predicted by in silico analysis. The results suggest that many of the targets are genes from the host's immune response gene networks. We propose a model with expected temporal changes in miRNA expression if they target immune response activators/effector genes or immune response inhibitors, respectively. The best way to understand the function of a miRNA is to identify its target gene(s), but as the amount of genome resources for teleost fish is limited, with less well characterized genomes

  4. Prenatal fluoxetine exposure affects cytokine and behavioral response to an immune challenge.

    PubMed

    Avitsur, Ronit; Levy, Sigal; Grinshpahet, Rachel; Goren, Naama; Hirsh, Ofer; Zalko, Assaf

    2015-07-15

    Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) is a commonly prescribed antidepressant drug in pregnant women. FLX readily crosses the placenta, consequently altering serotonergic neurotransmission in the fetus and causing physiological and behavioral disturbances in the newborn. Studies have shown that serotonin plays a role in modulating immune signaling. Thus, the goal of this study was to assess the effects of prenatal exposure to FLX on the response to an immune challenge in offspring mice. Male and female mice were prenatally exposed to FLX and later injected with lipopolysaccharide (LPS) at different stages of development. Results indicated that prenatal FLX modulated aspects of the response to the endotoxin challenge. Prenatal FLX diminished the secretion of interleukin (IL)-6 in adult male and female mice. Prenatal exposure to FLX further suppressed TNFα and augmented IL-1β secretion in adult males. Early effects of LPS (within 24h of administration) on body weight and food consumption were diminished by prenatal exposure to FLX in adult mice. Delayed effects of LPS (within 60h of administration) were modulated by prenatal FLX in young animals. These results provide an indication that prenatal modulations of the serotonergic system had lasting implications for host response to an immune challenge. These findings may contribute to the understanding of the effects of prenatal environment on the development of physiological systems that are important to coping with infectious challenges, and assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy.

  5. Leukocyte infiltration in cancer creates an unfavorable environment for antitumor immune responses: a novel target for therapeutic intervention.

    PubMed

    Bronte, Vincenzo; Cingarlini, Sara; Marigo, Ilaria; De Santo, Carmela; Gallina, Giovanna; Dolcetti, Luigi; Ugel, Stefano; Peranzoni, Elisa; Mandruzzato, Susanna; Zanovello, Paola

    2006-01-01

    The interaction between tumor cells and the nearby environment is being actively investigated to explore how this interplay affects the initiation and progression of cancer. Host-tumor relationship results in the production of pro-inflammatory cytokines and chemokines that promote the recruitment of leukocytes within and around developing neoplasms. Cancer cells, together with newly recruited tumor-infiltrating cells, can also activate fibroblast and vascular responses, thus resulting in a chronic microenvironment perturbation. In this complex scenario, interactions between innate and adaptive immune cells can be disturbed, leading to a failure of immune-mediated tumor recognition and destruction. On the basis of the recent awareness about tumor promotion and immune deregulation by immune/inflammatory cells, novel anti-cancer strategies can be exploited.

  6. Structural damage in the C. elegans epidermis causes release of STA-2 and induction of an innate immune response.

    PubMed

    Zhang, Yun; Li, Wenna; Li, Linfeng; Li, Yuanbao; Fu, Rong; Zhu, Yi; Li, Jie; Zhou, Yanfeng; Xiong, Sidong; Zhang, Huimin

    2015-02-17

    The epidermis constantly encounters invasions that disrupt its architecture, yet whether the epidermal immune system utilizes damaged structures as danger signals to activate self-defense is unclear. Here, we used a C. elegans epidermis model in which skin-penetrating infection or injury activates immune defense and antimicrobial peptide (AMP) production. By systemically disrupting each architectural component, we found that only disturbance of the apical hemidesmosomes triggered an immune response and robust AMP expression. The epidermis recognized structural damage through hemidesmosomes associated with a STAT-like protein, whose disruption led to detachment of STA-2 molecules from hemidesmosomes and transcription of AMPs. This machinery enabled the epidermis to bypass certain signaling amplification and directly trigger AMP production when subjected to extensive architectural damage. Together, our findings uncover an evolutionarily conserved mechanism for the epithelial barriers to detect danger and activate immune defense. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Cytomegalovirus infection enhances the immune response to influenza.

    PubMed

    Furman, David; Jojic, Vladimir; Sharma, Shalini; Shen-Orr, Shai S; Angel, Cesar J L; Onengut-Gumuscu, Suna; Kidd, Brian A; Maecker, Holden T; Concannon, Patrick; Dekker, Cornelia L; Thomas, Paul G; Davis, Mark M

    2015-04-01

    Cytomegalovirus (CMV) is a β-herpesvirus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli, and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV status. In contrast, CMV-seropositive young adults exhibited enhanced antibody responses to influenza vaccination, increased CD8(+) T cell sensitivity, and elevated levels of circulating interferon-γ compared to seronegative individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the ubiquity of CMV infection in humans and many other species.

  8. Immune Responses to Low Back Pain Risk Factors

    PubMed Central

    Splittstoesser, Riley E.; Marras, William S.; Best, Thomas M.

    2013-01-01

    Objective Investigate effects of interactions between biomechanical, psychosocial and individual risk factors on the body’s immune inflammatory responses. Background Current theories for low back pain causation do not fully account for the body’s response to tissue loading and tissue trauma. Methods Two groups possessing a preference for the sensor or intuitor personality trait performed repetitive lifting combined with high or low mental workload on separate occasions. Spinal loading was assessed using an EMG-assisted subject-specific biomechanical model and immune markers were collected before and after exposure. Results Mental workload was associated with a small decrease in AP shear. Both conditions were characterized by a regulated time-dependent immune response making use of markers of inflammation, tissue trauma and muscle damage. Intuitors’ creatine kinase levels were increased following low mental workload compared to that observed in Sensors with the opposite trend occurring for high mental workload. Conclusions A temporally regulated immune response to lifting combined with mental workload exists. This response is influenced by personality and mental workload. PMID:22317743

  9. The host immune response to Clostridium difficile infection

    PubMed Central

    2013-01-01

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

  10. Immune Responses and Protection of Aotus Monkeys Immunized with Irradiated Plasmodium vivax Sporozoites

    PubMed Central

    Jordán-Villegas, Alejandro; Perdomo, Anilza Bonelo; Epstein, Judith E.; López, Jesús; Castellanos, Alejandro; Manzano, María R.; Hernández, Miguel A.; Soto, Liliana; Méndez, Fabián; Richie, Thomas L.; Hoffman, Stephen L.; Arévalo-Herrera, Myriam; Herrera, Sócrates

    2011-01-01

    A non-human primate model for the induction of protective immunity against the pre-erythrocytic stages of Plasmodium vivax malaria using radiation-attenuated P. vivax sporozoites may help to characterize protective immune mechanisms and identify novel malaria vaccine candidates. Immune responses and protective efficacy induced by vaccination with irradiated P. vivax sporozoites were evaluated in malaria-naive Aotus monkeys. Three groups of six monkeys received two, five, or ten intravenous inoculations, respectively, of 100,000 irradiated P. vivax sporozoites; control groups received either 10 doses of uninfected salivary gland extract or no inoculations. Immunization resulted in the production low levels of antibodies that specifically recognized P. vivax sporozoites and the circumsporozoite protein. Additionally, immunization induced low levels of antigen-specific IFN-γ responses. Intravenous challenge with viable sporozoites resulted in partial protection in a dose-dependent manner. These findings suggest that the Aotus monkey model may be able to play a role in preclinical development of P. vivax pre-erythrocytic stage vaccines. PMID:21292877

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

    PubMed Central

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

    1994-01-01

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

  12. Immune response of the Antarctic teleost Trematomus bernacchii to immunization with Psychrobacter sp. (TAD1).

    PubMed

    Buonocore, Francesco; Bernini, Chiara; Coscia, Maria Rosaria; Giacomelli, Stefano; de Pascale, Donatella; Randelli, Elisa; Stocchi, Valentina; Scapigliati, Giuseppe

    2016-09-01

    Adult Trematomus bernacchii have been immunized intraperitoneally with heat-killed cells of the Antarctic marine bacterium Psychrobacter sp. (TAD1) up to 60 days. After immunizations and sampling at various times, fish sera were tested for specific IgM by ELISA, and different tissues (head kidney and spleen) were investigated for transcription of master genes of the acquired immune response (IgM, IgT, TRβ, TRγ). Results from ELISA assays showed a time-dependent induction of specific serum anti-TAD1 IgM, and western blot analysis of TAD1 lysates probed with fish sera revealed enhanced immunoreactivity in immunized animals compared to controls. Quantitative PCR analysis of transcripts coding for IgM, IgT, TRβ, TRγ was performed in T. bernacchii tissues to assess basal expression, and then on cDNAs of cells from head kidney and spleen of fish injected for 8, 24, and 72 h with inactivated TAD1. The results showed a differential basal expression of transcripts in the examined tissues, and a time-dependent strong up-regulation of IgT, TRβ, TRγ genes upon in vivo stimulation with TAD1. These results represent a first in vivo study on the mounting of a specific immune response in an Antarctic teleost species. Copyright © 2016. Published by Elsevier Ltd.

  13. Radiation, Inflammation, and Immune Responses in Cancer

    PubMed Central

    Multhoff, Gabriele; Radons, Jürgen

    2012-01-01

    Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR. PMID:22675673

  14. Ubiquitin enzymes in the regulation of immune responses

    PubMed Central

    Ebner, Petra; Versteeg, Gijs A.; Ikeda, Fumiyo

    2017-01-01

    Abstract Ubiquitination plays a central role in the regulation of various biological functions including immune responses. Ubiquitination is induced by a cascade of enzymatic reactions by E1 ubiquitin activating enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligase, and reversed by deubiquitinases. Depending on the enzymes, specific linkage types of ubiquitin chains are generated or hydrolyzed. Because different linkage types of ubiquitin chains control the fate of the substrate, understanding the regulatory mechanisms of ubiquitin enzymes is central. In this review, we highlight the most recent knowledge of ubiquitination in the immune signaling cascades including the T cell and B cell signaling cascades as well as the TNF signaling cascade regulated by various ubiquitin enzymes. Furthermore, we highlight the TRIM ubiquitin ligase family as one of the examples of critical E3 ubiquitin ligases in the regulation of immune responses. PMID:28524749

  15. The humoral immune response induced by snake venom toxins.

    PubMed

    da Silva, Wilmar Dias; Tambourgi, Denise V

    2011-10-01

    This review summarizes the key contributions to our knowledge regarding the immune response induced by snake venom toxins, focusing particularly on the production of antibodies and their venom-neutralizing effects. We cover the past and present state of the art of anti-snake venom production, followed by an overview of the venomous snakes and their venoms. The toxic properties of relevant snake venom toxins are approached in some details, with particular emphasis on the molecular domains responsible for binding to cells or plasma components in victims. The interactions of these domains are also reviewed, particularly the putatively relevant epitopes, along with the immune system and the resulting antibodies. We also review trials aimed at reducing the quantities of non-relevant antibodies in the antivenoms by substituting whole venoms with purified toxins to immunize animals, or the immunogenicity of the heterologous antivenom antibodies by humanizing their molecules.

  16. Induction and detection of immune responses by photoimmunotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Bartels, Kenneth E.; Liu, Hong; Nordquist, Robert E.

    2005-06-01

    A specific method of photoimmunotherapy, using a combination of selective photothermal laser tissue interactions and an in situ immunoadjuvant, has showed promising results in pre-clinical studies. Its effect on untreated remote metastases is especially interesting. To understand the mechanism of the combination of laser therapy and immunotherapy, immune responses have been investigated. The following laser photoimmunotherapy-induced tumor-specific immunological activities have been observed in our studies. 1. The photoimmunotherapy-cured tumor-bearing animal could resist repeated, dose escalated tumor rechallenges. 2. The serum from cured animals showed tumor-specific antibodies to enhance the binding to the tumor cells. 3. The serum from cured animals could also serve as antibody sources to bind certain specific tumor proteins. 4. In vivo, the spleen cells from cured animals showed anti-tumor immunity that could be adoptively transferred. The methods and the results of these immune responses are summarized.

  17. Adjuvant effects of saponins on animal immune responses*

    PubMed Central

    Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

  18. Recent progress in HIV vaccines inducing mucosal immune responses.

    PubMed

    Pavot, Vincent; Rochereau, Nicolas; Lawrence, Philip; Girard, Marc P; Genin, Christian; Verrier, Bernard; Paul, Stéphane

    2014-07-31

    In spite of several attempts over many years at developing a HIV vaccine based on classical strategies, none has convincingly succeeded to date. As HIV is transmitted primarily by the mucosal route, particularly through sexual intercourse, understanding antiviral immunity at mucosal sites is of major importance. An ideal vaccine should elicit HIV-specific antibodies and mucosal CD8⁺ cytotoxic T-lymphocyte (CTL) as a first line of defense at a very early stage of HIV infection, before the virus can disseminate into the secondary lymphoid organs in mucosal and systemic tissues. A primary focus of HIV preventive vaccine research is therefore the induction of protective immune responses in these crucial early stages of HIV infection. Numerous approaches are being studied in the field, including building upon the recent RV144 clinical trial. In this article, we will review current strategies and briefly discuss the use of adjuvants in designing HIV vaccines that induce mucosal immune responses.

  19. Immune Responses and Protection of Aotus Monkeys Immunized with Irradiated Plasmodium vivax Sporozoites

    DTIC Science & Technology

    2011-01-01

    responses and protective efficacy induced by vacci- nation with irradiated P vivax sporozoites were evaluated in malaria-naive Aotus monkeys. Three groups...received either 10 doses of uninfected salivary gland extract or no inoculations. Immunization resulted in the production low levels of antibodies that...responses. Intravenous challenge with viable sporozoites resulted in partial protection in a dose-dependent manner.l11ese findings suggest that the

  20. Time dependent response of equatorial ionospheric electric fields to magnetospheric disturbances

    SciTech Connect

    Fejer, B.G.; Scherliess, L.

    1995-04-01

    The authors use extensive radar measurements of F region vertical plasma drifts and auroral electrojet indices to determine the storm time dependence of equatorial zonal electric fields. These disturbance drifts result from the prompt penetration of high latitude electric fields and from the dynamo action of storm time winds which produce the largest perturbations a few hours after the onset of magnetic activity. The signatures of the equatorial disturbance electric fields change significantly depending on the relative contributions of these two components. The prompt electric field responses, with lifetimes of about one hour, are in excellent agreement with results from global convection models. The electric fields generated by storm time winds have longer lifetimes, amplitudes proportional to the energy input into the high latitude ionosphere, and a daily variation which follows closely the disturbance dynamo pattern of Blanc and Richmond. The storm wind driven electric fields are responsible for the larger amplitudes and longer lifetimes of the drift perturbations following sudden decreases in convection compared to those associated with sudden convection enhancements. 14 refs., 6 figs., 1 tab.

  1. Rectification of age-associated deficiency in cytotoxic T cell response to influenza A virus by immunization with immune complexes.

    PubMed

    Zheng, Biao; Zhang, Yongxin; He, Hongxia; Marinova, Ekaterina; Switzer, Kirsten; Wansley, Daniel; Mbawuike, Innocent; Han, Shuhua

    2007-11-01

    Decline in cellular immunity in aging compromises protection against infectious diseases and leads to the increased susceptibility of the elderly to infection. In particular, Ag-specific cytotoxic T lymphocyte (CTL) response against virus is markedly reduced in an aged immune system. It is of great importance to explore novel strategy in eliciting effective antiviral CTL activity in the elderly. In this study, the efficacy and mechanisms of immunization with immune complexes in overcoming age-associated deficiency in cellular immunity were investigated. In this study, we show that the severely depressed CTL response to influenza A in aged mice can be significantly restored by immunization with immune complexes consisting of influenza A virus and mAb to influenza A nucleoprotein. The main mechanisms underlying this recovery of CTL response induced by immune complex immunization in aged mice are enhanced dendritic cell function and elevated production of IFN-gamma in both CD4(+) Th1 and CD8(+) CTLs. Thus, these results demonstrate that immune complex immunization may represent a novel strategy to elicit effective virus-specific cytotoxic response in an aged immune system, and possibly, to overcome age-related immune deficiency in general.

  2. Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses

    PubMed Central

    Kazi, Zoheb B.; Prater, Sean N.; Kobori, Joyce A.; Viskochil, David; Bailey, Carrie; Gera, Renuka; Stockton, David W.; McIntosh, Paul; Rosenberg, Amy S.; Kishnani, Priya S.

    2016-01-01

    BACKGROUND. Enzyme replacement therapy (ERT) has prolonged survival and improved clinical outcomes in patients with infantile Pompe disease (IPD), a rapidly progressive neuromuscular disorder. Yet marked interindividual variability in response to ERT, primarily attributable to the development of antibodies to ERT, remains an ongoing challenge. Immune tolerance to ongoing ERT has yet to be described in the setting of an entrenched immune response. METHODS. Three infantile Pompe patients who developed high and sustained rhGAA IgG antibody titers (HSAT) and received a bortezomib-based immune tolerance induction (ITI) regimen were included in the study and were followed longitudinally to monitor the long-term safety and efficacy. A trial to taper the ITI protocol was attempted to monitor if true immune tolerance was achieved. RESULTS. Bortezomib-based ITI protocol was safely tolerated and led to a significant decline in rhGAA antibody titers with concomitant sustained clinical improvement. Two of the 3 IPD patients were successfully weaned off all ITI protocol medications and continue to maintain low/no antibody titers. ITI protocol was significantly tapered in the third IPD patient. B cell recovery was observed in all 3 IPD patients. CONCLUSION. This is the first report to our knowledge on successful induction of long-term immune tolerance in patients with IPD and HSAT refractory to agents such as cyclophosphamide, rituximab, and methotrexate, based on an approach using the proteasome inhibitor bortezomib. As immune responses limit the efficacy and cost-effectiveness of therapy for many conditions, proteasome inhibitors may have new therapeutic applications. FUNDING. This research was supported by a grant from the Genzyme Corporation, a Sanofi Company (Cambridge, Massachusetts, USA), and in part by the Lysosomal Disease Network, a part of NIH Rare Diseases Clinical Research Network (RDCRN). PMID:27493997

  3. Disturbance of wildlife by outdoor winter recreation: allostatic stress response and altered activity-energy budgets.

    PubMed

    Arlettaz, Raphaël; Nusslé, Sébastien; Baltic, Marjana; Vogel, Peter; Palme, Rupert; Jenni-Eiermann, Susanne; Patthey, Patrick; Genoud, Michel

    2015-07-01

    Anthropogenic disturbance of wildlife is of growing conservation concern, but we lack comprehensive approaches of its multiple negative effects. We investigated several effects of disturbance by winter outdoor sports on free-ranging alpine Black Grouse by simultaneously measuring their physiological and behavioral responses. We experimentally flushed radio-tagged Black Grouse from their snow burrows, once a day, during several successive days, and quantified their stress hormone levels (corticosterone metabolites in feces [FCM] collected. from individual snow burrows). We also measured feeding time allocation (activity budgets reconstructed from radio-emitted signals) in response to anthropogenic disturbance. Finally, we estimated the related extra energy expenditure that may be incurred: based on activity budgets, energy expenditure was modeled from measures of metabolism obtained from captive birds subjected to different ambient temperatures. The pattern of FCM excretion indicated the existence of a funneling effect as predicted by the allostatic theory of stress: initial stress hormone concentrations showed a wide inter-individual variation, which decreased during experimental flushing. Individuals with low initial pre-flushing FCM values augmented their concentration, while individuals with high initial FCM values lowered it. Experimental disturbance resulted in an extension of feeding duration during the following evening foraging bout, confirming the prediction that Black Grouse must compensate for the extra energy expenditure elicited by human disturbance. Birds with low initial baseline FCM concentrations were those that spent more time foraging. These FCM excretion and foraging patterns suggest that birds with high initial FCM concentrations might have been experiencing a situation of allostatic overload. The energetic model provides quantitative estimates of extra energy expenditure. A longer exposure to ambient temperatures outside the shelter of snow

  4. A Drosophila immune response against Ras-induced overgrowth

    PubMed Central

    Hauling, Thomas; Krautz, Robert; Markus, Robert; Volkenhoff, Anne; Kucerova, Lucie; Theopold, Ulrich

    2014-01-01

    ABSTRACT Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12), both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria), which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity. PMID:24659248

  5. [Immune response of Hansen's disease. Review].

    PubMed

    Rada, Elsa; Aranzazu, Nacarid; Convit, Jacinto

    2009-12-01

    Hansen's disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to "resist" host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen's disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory.

  6. HTLV-1, Immune Response and Autoimmunity.

    PubMed

    Quaresma, Juarez A S; Yoshikawa, Gilberto T; Koyama, Roberta V L; Dias, George A S; Fujihara, Satomi; Fuzii, Hellen T

    2015-12-24

    Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren's Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4⁺ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4⁺ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.

  7. HTLV-1, Immune Response and Autoimmunity

    PubMed Central

    Quaresma, Juarez A S; Yoshikawa, Gilberto T; Koyama, Roberta V L; Dias, George A S; Fujihara, Satomi; Fuzii, Hellen T

    2015-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren’s Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity. PMID:26712781

  8. Ecomorphodynamic feedbacks and barrier island response to disturbance: Insights from the Virginia Barrier Islands, Mid-Atlantic Bight, USA

    Treesearch

    Catherine W.V. Wolner; Laura J. Moore; Donald R. Young; Steven T. Brantley; Spencer N. Bissett; Randolph A. McBride

    2013-01-01

    Ecomorphodynamic feedbacks play an important role in the susceptibility and response of barrier islands to disturbance by overwash. Dune-building grasses, like Ammophila breviligulata, can help to restore areas of high relief after overwash events (i.e., resist disturbance). If overwash recurs before dunes have reestablished, however, overwash-adapted “maintainer”...

  9. Cross-scale interactions, legacies, and spatial connectivity: integrating time and space to predict post-disturbance response across scales

    USDA-ARS?s Scientific Manuscript database

    Emergent properties and cross-scale interactions are important in driving landscape-scale dynamics during a disturbance event, such as wildfire. We used these concepts related to changing pattern-process relationships across scales to explain ecological responses following disturbance that resulted ...

  10. Geomorphic responses of lower Bega River to catchment disturbance, 1851?1926

    NASA Astrophysics Data System (ADS)

    Brooks, Andrew P.; Brierley, Gary J.

    1997-03-01

    Prior to significant European settlement of the area in the 1850s, lower Bega River on the South Coast of NSW had a narrow, relatively deep channel lined by river oaks. The river had a suspended or mixed load, with platypus habitat available in pools. Banks were fine-grained and relatively cohesive (silts and clays), as was the floodplain, which graded to a series of valley-marginal swamps and lakes. Extensive evidence from maps and portion plans, archival photographs, bridge surveys, and anecdotal sources, complemented by field analysis of floodplain sedimentology (including radiocarbon-dated samples) and vegetation remnants are used to document the dramatic metamorphosis in the character and behaviour of lower Bega River in the latter half of the nineteenth century. By 1926 the channel had widened extensively (up to 340%) and shallowed in association with bed aggradation by coarse sandy bedload. Floodplain accretion was dominated by fine to medium sands, with some coarse sand splays. In contrast with most other studies of channel metamorphosis in Australia, which have emphasised river responses to climatically-induced flood histories, relegating