WorldWideScience

Sample records for immune restoration diseases

  1. Tuberculoid leprosy and cytomegalovirus retinitis as immune restoration disease in a patient with AIDS.

    Science.gov (United States)

    Kumar, Shishir; Ghosh, Manab Kumar; Sarkar, Somenath; Mallik, Sudeshna; Biswas, Pradyot Narayan; Saha, Bibhuti

    2012-02-01

    Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis.

    Science.gov (United States)

    Magrone, Thea; Jirillo, Emilio

    2013-01-01

    Gut immune system is daily exposed to a plethora of antigens contained in the environment as well as in food. Both secondary lymphoid tissue, such as Peyer's patches, and lymphoid follicles (tertiary lymphoid tissue) are able to respond to antigenic stimuli releasing cytokines or producing antibodies (secretory IgA). Intestinal epithelial cells are in close cooperation with intraepithelial lymphocytes and possess Toll-like receptors on their surface and Nod-like receptors (NLRs) which sense pathogens or pathogen-associated molecular patterns. Intestinal microbiota, mainly composed of Bacteroidetes and Firmicutes, generates tolerogenic response acting on gut dendritic cells and inhibiting the T helper (h)-17 cell anti-inflammatory pathway. This is the case of Bacteroides fragilis which leads to the production of interleukin-10, an anti-inflammatory cytokine, from both T regulatory cells and lamina propria macrophages. Conversely, segmented filamentous bacteria rather induce Th17 cells, thus promoting intestinal inflammation. Intestinal microbiota and its toxic components have been shown to act on both Nod1 and Nod2 receptors and their defective signaling accounts for the development of inflammatory bowel disease (IBD). In IBD a loss of normal tolerance to intestinal microbiota seems to be the main trigger of mucosal damage. In addition, intestinal microbiota thanks to its regulatory function of gut immune response can prevent or retard neoplastic growth. In fact, chronic exposure to environmental microorganisms seems to be associated with low frequency of cancer risk. Major nutraceuticals or functional foods employed in the modulation of intestinal microbiota are represented by prebiotics, probiotics, polyunsaturated fatty acids, amino acids and polyphenols. The cellular and molecular effects performed by these natural products in terms of modulation of the intestinal microbiota and mostly attenuation of the inflammatory pathway are described.

  3. Immune restoration in the context of HAART | Martin | Southern ...

    African Journals Online (AJOL)

    HAART induces a sustained effective suppression of HIV replication in most patients and leads to a preservation or restoration of immune function. The restoration of an impaired immune system is assessed by clinical parameters, immunological changes which can be measured in the laboratory and a marked reduction in ...

  4. CLINICAL IMMUNE RESTORATION IN THE CONTEXT OF HAART

    African Journals Online (AJOL)

    Enrique

    immune system is related to the kinetics of viral replication. In most cases increased ... The restoration of an impaired immune system is assessed by clinical parameters, immunological changes which can be measured in the ..... Levy JA, Mackeviez CE, Barker E. Controlling HIV pathogenesis: the role of the noncytotoxic ...

  5. Immune Restoration Syndrome with disseminated Penicillium marneffei and Cytomegalovirus co-infections in an AIDS patient

    Directory of Open Access Journals (Sweden)

    Wig Naveet

    2007-10-01

    Full Text Available Abstract Background Penicillium marneffei is a dimorphic fungus, endemic in South-east Asia. The fungus causes severe disease in immunocompromised patients such as AIDS. However, no case of immune restoration disease of Penicillium marneffei is reported in literature from a non-endemic area. Case Presentation We report the first case of Penicillium marneffei and Cytomegalovirus infection manifesting as a result of immune restoration one month after initiating HAART. This severely immunocompromised patient had presented with multiple lymphadenopathy, massive hepatosplenomegaly, visual impairment and mild icterus, but no skin lesions. Penicillium marneffei was isolated from lymph node fine-needle aspirates and blood cultures. Conclusion In order to diagnose such rare cases, the clinicians, histopathologists and microbiologists alike need to maintain a strong index of suspicion for making initial diagnosis as well as for suspecting immune reconstitution syndrome (IRS with Penicillium marneffei.

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kathie Béland

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

  9. Cellular immunity and immunopathology in autoimmune Addison's disease.

    Science.gov (United States)

    Bratland, Eirik; Husebye, Eystein S

    2011-04-10

    Autoimmune adrenocortical failure, or Addison's disease, is a prototypical organ-specific autoimmune disorder. In common with related autoimmune endocrinopathies, Addison's disease is only manageable to a certain extent with replacement therapy being the only treatment option. Unfortunately, the available therapy does not restore the physiological hormone levels and biorhythm. The key to progress in treating and preventing autoimmune Addison's disease lies in improving our understanding of the predisposing factors, the mechanisms responsible for the progression of the disease, and the interactions between adrenal antigens and effector cells and molecules of the immune system. The aim of the present review is to summarize the current knowledge on the role of T cells and cellular immunity in the pathogenesis of autoimmune Addison's disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. The peritoneum: healing, immunity, and diseases.

    Science.gov (United States)

    Capobianco, Annalisa; Cottone, Lucia; Monno, Antonella; Manfredi, Angelo A; Rovere-Querini, Patrizia

    2017-10-01

    The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

    Science.gov (United States)

    David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

    2017-07-01

    Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

  12. Restoration of Immune Surveillance in Lung Cancer by Natural Killer Cells

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0400 TITLE: Restoration of Immune Surveillance in Lung Cancer by Natural Killer Cells PRINCIPAL INVESTIGATOR... cancer . However, its mechanism remains obscure, especially related to natural killer (NK) cells . The goal of this application is to uncover how a...explore the viability of targeting miR183 to restore NK cells as a new form of immunotherapy for early stage lung cancer . The specific aims are 1) to

  13. Cancer as an immune-mediated disease

    Directory of Open Access Journals (Sweden)

    Shurin MR

    2012-06-01

    Full Text Available Michael R ShurinDepartments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: The link between oncology and immunology has a long history and its development is forced by the necessity to develop innovative and highly efficient modalities for immunological destruction of malignant cells. The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, as these treatments do not eliminate all cancerous cells, do not address the immunosuppressive nature of the disease and can further impair the patient's immune response weakening patient's resistance to the cancer. Multidisciplinary analysis of the interaction between the immune system and cancer in preclinical and clinical settings suggests that the immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of malfunctions in immunity, as malignant cells manage to escape recognition and elimination by the immune system. Chronic infections and inflammation associated with limited or polarized immune responses also contribute to carcinogenesis and tumor progression. The tumor immunoenvironment represents specific conditions and elements that support cancerous cell survival, proliferation and spreading. On the other hand, the specificity and strength of antitumor immunity is a powerful and efficient tool that can be used to recognize and destroy neoplastic cells or their supporting microenvironment. Understanding the role of the immune system in controlling and supporting tumor initiation, formation, growth and progression has crucial implications for cancer therapy and will therefore guide the future development of cancer immunotherapy and its combination with conventional therapies to achieve optimal antitumor effects in patients with different types of cancer.Keywords: tumor immunology and immunotherapy, tumor immunoenvironment, cancer, immunosuppression

  14. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    Science.gov (United States)

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  15. Skin immune sentinels in health and disease.

    Science.gov (United States)

    Nestle, Frank O; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J

    2009-10-01

    Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.

  16. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  17. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  18. The role of the immune system in kidney disease.

    Science.gov (United States)

    Tecklenborg, J; Clayton, D; Siebert, S; Coley, S M

    2018-05-01

    The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. © 2018 British Society for Immunology.

  19. Interferon Lambda: Modulating Immunity in Infectious Diseases.

    Science.gov (United States)

    Syedbasha, Mohammedyaseen; Egli, Adrian

    2017-01-01

    Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis . Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage

  20. Immune-mediated diseases and microbial exposure in early life

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...

  1. Infectious Diseases and Immunizations in International Adoption.

    Science.gov (United States)

    Obringer, Emily; Walsh, Linda

    2017-02-01

    Children who are adopted internationally have an increased risk of infectious diseases due to endemic conditions and variable access to preventive health care, such as vaccines, in their country of origin. Pediatricians and other providers who care for children should be familiar with the recommended screening for newly arrived international adoptees. Testing for gastrointestinal pathogens, tuberculosis, hepatitis, syphilis, and HIV should be routinely performed. Other endemic diseases and common skin infections may need to be assessed. Evaluation of the child's immunization record is also important, as nearly all international adoptees will require catch-up vaccines. The provider may also be asked to review medical records prior to adoption, provide travel advice, and ensure that parents and other close contacts are up-to-date on immunizations prior to the arrival of the newest family member. The pediatrician serves a unique role in facilitating the evaluation, treatment, and prevention of infectious diseases in international adoptees. [Pediatr Ann. 2017;46(2):e56-e60.]. Copyright 2017, SLACK Incorporated.

  2. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  3. Immunization history of children with inflammatory bowel disease.

    Science.gov (United States)

    Soon, Ing Shian; deBruyn, Jennifer C C; Wrobel, Iwona

    2013-04-01

    Protection against vaccine-preventable diseases is important in children with inflammatory bowel disease (IBD) due to frequent immunosuppressive therapy use. The chronic relapsing nature and treatment regimen of IBD may necessitate modified timing of immunizations. To evaluate the completeness of immunizations in children with IBD. Immunization records of all children with IBD followed at the Alberta Children's Hospital (Calgary, Alberta) were reviewed. For children with incomplete immunization according to the province of Alberta schedule, the reasons for such were clarified. Demographic data and age at diagnosis were also collected. Immunization records were obtained from 145 (79%) children with IBD. Fifteen children had incomplete routine childhood immunizations, including two with no previous immunizations. The most common incomplete immunizations included hepatitis B (n=9), diphtheria, tetanus, acellular pertussis at 14 to 16 years of age (n=7), and diphtheria, tetanus, acellular pertussis, inactivated polio at four to six years of age (n=6). The reasons for incomplete immunization included use of immunosuppressive therapy at time of scheduled immunization; IBD-related symptoms at time of scheduled immunization; parental refusal; recent move from elsewhere with different immunization schedule; unawareness of routine immunization; and needle phobia. Although the majority of children with IBD had complete childhood immunizations, suboptimal immunizations were present in 10%. With increasing use of immunosuppressive therapy in IBD, physicians caring for children with IBD must periodically evaluate immunization status and ensure the completeness of childhood immunizations.

  4. Targeting cFMS signaling to restore immune function and eradicate HIV reservoirs

    Science.gov (United States)

    Gerngross, Lindsey

    -associated CNS injury and AIDS pathogenesis. Through immunohistochemical studies using a relevant animal model of HIV infection, SIV infected rhesus macaques, we reported the presence of M-CSF and IL-34 in the brains of seronegative and SIV+ animals, for the first time, and identified spatial differences in the expression of these ligands. Important to our interest in viral persistence in the CNS, we observed the predominance of M-CSF expression in brain to be by cells that comprise perivascular cuffs and nodular lesions, which contain monocytes/ macrophages that have migrated into the CNS. IL-34 appeared to be a tissue-specific ligand expressed by resident microglia. Like M-CSF, we found that IL-34 also increased the frequency of CD16 +CD163+ monocytes in vitro. We further investigated the potential of cFMS inhibition as a means to abrogate macrophage-2-like immune polarization using the small molecule tyrosine kinase inhibitor (TKI), GW2580. The addition of GW2580 abolished cFMS ligand-mediated increases in CD16+CD163+ monocyte frequency in human peripheral blood mononuclear cells (PBMC) as well as virus production in HIV infected primary human microglia. Furthermore, we found cFMS-mediated upregulation of CD16 and CD163 to be relevant to an additional disease process, high-grade astrocytomas, suggesting that M-CSF and IL-34 may be mediators of other neuroinflammatory diseases, as well. We hope these findings will provide insight into the role of altered monocyte/macrophage homeostasis in HIV disease and identify a novel strategy for targeting long-lived cellular reservoirs of HIV infection through restored immune homeostasis.

  5. In immune defense: redefining the role of the immune system in chronic disease.

    Science.gov (United States)

    Rubinow, Katya B; Rubinow, David R

    2017-03-01

    The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

  6. Helminthic therapy: using worms to treat immune-mediated disease.

    Science.gov (United States)

    Elliott, David E; Weinstock, Joel V

    2009-01-01

    There is an epidemic of immune-mediated disease in highly-developed industrialized countries. Such diseases, like inflammatory bowel disease, multiple sclerosis and asthma increase in prevalence as populations adopt modern hygienic practices. These practices prevent exposure to parasitic worms (helminths). Epidemiologic studies suggest that people who carry helminths have less immune-mediated disease. Mice colonized with helminths are protected from disease in models of colitis, encephalitis, Type 1 diabetes and asthma. Clinical trials show that exposure to helminths reduce disease activity in patients with ulcerative colitis or Crohn's disease. This chapter reviews some of the work showing that colonization with helminths alters immune responses, against dysregulated inflammation. These helminth-host immune interactions have potentially important implications for the treatment of immune-mediated diseases.

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

    Science.gov (United States)

    Kirchner, Elizabeth; Ruffing, Victoria

    2017-02-01

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

  8. IL-35, a hallmark of immune-regulation in cancer progression, chronic infections and inflammatory diseases.

    Science.gov (United States)

    Teymouri, Manouchehr; Pirro, Matteo; Fallarino, Francesca; Gargaro, Marco; Sahebkar, Amirhosein

    2018-03-25

    Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target. © 2018 UICC.

  9. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  10. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  11. Microparticles as immune regulators in infectious disease

    Directory of Open Access Journals (Sweden)

    Zheng Lung Ling

    2011-11-01

    Full Text Available Despite their clear relationship to immunology, few existing studies have examined potential role of microparticles (MP in infectious disease. Infection with pathogens usually leads to the expression of a range of inflammatory cytokines and chemokines, as well as significant stress in both infected and uninfected cells. It is thus reasonable to infer from studies to date that infection-associated inflammation also leads to MP production. MP are produced by most of the major cell types in the immune system, and appear to be involved at both the innate and adaptive levels, potentially serving different functions at each level. Thus, MP do not appear to have a universal function; instead their functions are source- or stimulus-dependent, although likely to be primarily either pro- or anti-inflammatory. Importantly, in infectious diseases MP may have the ability to deliver antigen to APC via the biological cargo acquired from their cells of origin. Another potential benefit of MP would be to transfer and/or disseminate phenotype and function to target cells. However, MP may also potentially be manipulated, particularly by intracellular pathogens for survival advantage.

  12. Immunity to community: what can immune pathways tell us about disease patterns in corals?

    Science.gov (United States)

    Mydlarz, L. D.; Fuess, L.; Pinzon, J. C.; Weil, E.

    2016-02-01

    Predicting species composition and abundances is one of the most fundamental questions in ecology. This question is even more pressing in marine ecology and coral reefs since communities are changing at a rapid pace due to climate-related changes. Increases in disease prevalence and severity are just some of the consequences of these environmental changes. Particularly in coral reef ecosystems, diseases are increasing and driving region-wide population collapses. It has become clear, however, that not all reefs or coral species are affected by disease equally. In fact, the Caribbean is a concentrated area for diseases. The patterns in which disease manifests itself on an individual reef are also proving interesting, as not all coral species are affected by disease equally. Some species are host to different diseases, but seem to successfully fight them reducing mortality. Other species are disproportionately infected on any given reef and experience high mortality due to disease. We are interested in the role immunity can play in directing these patterns and are evaluating coral immunity using several novel approaches. We exposed 4 species of corals with different disease susceptibilities to immune stimulators and quantified of coral immunity using a combination of full transcriptome sequencing and protein activity assays for gene to phenotype analysis. We also mapped gene expression changes onto immune pathways (i.e. melanin-cascade, antimicrobial peptide synthesis, complement cascade, lectin-opsonization) to evaluate expression of immune pathways between species. In our preliminary data we found many immune genes in the disease susceptible Orbicella faveolata underwent changes in gene expression opposite of the predictions and may disply `dysfunctional' patterns of expression. We will present expression data for 4 species of coral and assess how these transcriptional and protein immune responses are related to disease susceptibility in nature, thus scaling up

  13. Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM.

    Science.gov (United States)

    Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee; Yee, Sung-Tae

    2008-01-01

    The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-gamma and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans. Copyright (c) 2007 John Wiley & Sons, Ltd.

  14. Global Immunizations: Health Promotion and Disease Prevention Worldwide.

    Science.gov (United States)

    Macintosh, Janelle L B; Eden, Lacey M; Luthy, Karlen E; Schouten, Aimee E

    Immunizations are one of the most important health interventions of the 20th century, yet people in many areas of the world do not receive adequate immunizations. Approximately 3 million people worldwide die every year from vaccine-preventable diseases; about half of these deaths are young children and infants. Global travel is more common; diseases that were once localized now can be found in communities around the world. Multiple barriers to immunizations have been identified. Healthcare access, cost, and perceptions of safety and trust in healthcare are factors that have depressed global immunization rates. Several global organizations have focused on addressing these barriers as part of their efforts to increase immunization rates. The Bill and Melinda Gates Foundation, The World Health Organization, and the United Nations Children's Emergency Fund each have a part of their organization that is concentrated on immunizations. Maternal child nurses worldwide can assist in increasing immunization rates. Nurses can participate in outreach programs to ease the burden of patients and families in accessing immunizations. Nurses can work with local and global organizations to make immunizations more affordable. Nurses can improve trust and knowledge about immunizations in their local communities. Nurses are a powerful influence in the struggle to increase immunization rates, which is a vital aspect of global health promotion and disease prevention.

  15. Myocarditis in auto-immune or auto-inflammatory diseases.

    Science.gov (United States)

    Comarmond, Cloé; Cacoub, Patrice

    2017-08-01

    Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis.

    Science.gov (United States)

    Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT". © Society for Leukocyte Biology.

  17. The immune system, natural autoantibodies and general homeostasis in health and disease.

    Science.gov (United States)

    Poletaev, A; Boura, P

    2011-10-01

    It is generally accepted that the destination of the immune system is not only to discriminate between self and non-self but also to mount responses against non-self. During the last decades, it became evident that weak self-reactivity is a necessary condition for immune homeostasis. Natural self reactivity and the internal image created by autoantibodies, participate greatly to the maintenance of homeostasis. Under conditions of increased or altered antigenic pressure, the homeostatic status is disrupted and the organism becomes vulnerable to the emergence of diseases. "Immunculus" is the self-reactive and interconnected entity of the immune system, provided by a complicated network of natural autoantibobies of different specificity, as a mosaic picture. Quantitative changes in each part of the image are related to variations of expression of relative antigens. The immune system takes in account image information from the continuous screening of the antigenic status and compares between presented state and the desired (optimal) one. Substantial and prolonged deviations from the optimal state, triggers the induction of compensatory and reparative processes, aiming to restore molecular and functional homeostasis. So, natural autoimmunity through the ability of natural a-Abs to induce mechanisms of natural and acquired immunity, aims to prevent pathogenic processes and maintain or restore health status.

  18. Therapeutic potential of helminths in autoimmune diseases: helminth-derived immune-regulators and immune balance.

    Science.gov (United States)

    Wang, Meng; Wu, Linxiang; Weng, Rennan; Zheng, Weihong; Wu, Zhongdao; Lv, Zhiyue

    2017-08-01

    Helminths have accompanied human throughout history by releasing immune-evasion molecules that could counteract an aberrant immune response within the host. In the past decades, helminth infections are becoming less prevalent possibly due to the developed sanitation. Meanwhile, the incidence of autoimmune diseases is increasing, which cannot be exclusively explained by the changes of susceptibility genes. While the hygiene hypothesis casts light on the problem. The infections of helminths are believed to interact with and regulate human immunity with the byproduct of suppressing the autoimmune diseases. Thus, helminths are potential to treat or cure the autoimmune diseases. The therapeutic progresses and possible immune suppression mechanisms are illustrated in the review. The helminths that are studied most intensively include Heligmosomoides polygyrus, Hymenolepis diminuta, Schistosoma mansoni, Trichinella spiralis, and Trichuris suis. Special attentions are paid on the booming animal models and clinical trials that are to detect the efficiency of immune-modulating helminth-derived molecules on autoimmune diseases. These trials provide us with a prosperous clinical perspective, but the precise mechanism of the down-regulatory immune response remains to be clarified. More efforts are needed to be dedicated until these parasite-derived immune modulators could be used in clinic to treat or cure the autoimmune diseases under a standard management.

  19. Role of the Immune System in Diabetic Kidney Disease.

    Science.gov (United States)

    Hickey, Fionnuala B; Martin, Finian

    2018-03-12

    The purpose of this review is to examine the proposed role of immune modulation in the development and progression of diabetic kidney disease (DKD). Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies. In addition, increased levels of circulating pro-inflammatory cytokines have been linked to disease progression. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease. Although no current therapies for DKD are directly based on immune modulation many of the therapies in clinical use have anti-inflammatory effects along with their primary actions. Macrophages emerge as the most likely beneficial immune cell target and compounds which reduce macrophage infiltration to the kidney have shown potential in both animal models and clinical trials.

  20. The study on the immunity restoring function of cWPROL in treating experimental radiation esophagitis

    International Nuclear Information System (INIS)

    Shen Li; Shan Baoen; Zhang Li; Lu Fuhe; Guo Xiujuan

    2007-01-01

    Objective: To study the restorative function of compound white peony root oral liquids (cWPROL) in treating rats' experimental acute radiation-induced esophagitis from the aspect of immunodeficiency. Methods: 128 Wistar rats were divided into eight groups. The radiation esophagitis was induced by 43 Gy 60 Co. Then the rats were treated with medicine in different ways. On every experimental point the absolute number and percentage of T lymphocyte subsets were analyzed by flow cytometry. The changes of the leukocyte in number and differential count were detected by haemocyte counting instrument. IgG and C3 in rats' serum were analyzed by immunological turbidimetry. Results: Radiation brought on decrease of experimental rats 'leukocyte count, the lymphocyte differential count, absolute count and absolute T lymphocyte subsets in the blood and the content of IgG and C3 with radiation esophagitis. cWPROL could increase the lymphocyte percentage compared that in with the radiated group 2. The preventive (high dose) could increase lymphocyte count while Western medicine decreased rats' leukocyte count, lymphocyte percentage and absolute count (P<0.05). The absolute T lymphocyte subsets in rats' peripheral blood increased in the group infused with cWPROL (high dose) (P<0.001). Compared with the radiated group 2 the absolute T lymphocyte subsets decreased significantly(P<0.001), and the content of complement C3 increased in the group infused with cWPROL (high dose) (P<0.05) but decreased in the group infused with Western medicine (P<0.01). Conclusion: cWPROL plays the role of restoring the cytoimmunity and immunity damaged by radiation in rats with radiation esophagitis. (authors)

  1. Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

    Science.gov (United States)

    Xu, Joella; Huang, Guannan; Guo, Tai L.

    2016-01-01

    Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg) cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS), have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases. PMID:29051427

  2. Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

    Directory of Open Access Journals (Sweden)

    Joella Xu

    2016-09-01

    Full Text Available Bisphenol A (BPA, used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors, epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg cells and upregulated pro- and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS, have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases.

  3. Linking the microbiota, chronic disease and the immune system

    Science.gov (United States)

    Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

    2016-01-01

    Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

  4. PPARgamma in immunity and inflammation: cell types and diseases.

    Science.gov (United States)

    Széles, Lajos; Töröcsik, Dániel; Nagy, László

    2007-08-01

    The lipid activated transcription factor, PPARgamma appears to have multiple functions in the immune system. There are several cell types expressing the receptor, most prominently antigen presenting cells, such as macrophages and dendritic cells. The receptor's activation leads to primary transcriptional activation of many, mostly lipid metabolism-related genes. However, gene regulation also occurs on immunity and inflammation-related genes. Key questions are: in what way lipid metabolism and immune regulation are connected and how activation and/or repression of gene expression may modulate inflammatory and anti-inflammatory responses and in what way can these be utilized in therapy. Here we provide a cell type and disease centric review on the role of this lipid activated transcription factor in the various cells of the immune system it is expressed in, and in some major inflammatory diseases such as atherosclerosis, inflammatory bowel disease and rheumatoid arthritis.

  5. Mucosal immunity in HIV infection: what can be done to restore gastrointestinal-associated lymphoid tissue function?

    Science.gov (United States)

    George, Michael D; Asmuth, David M

    2014-06-01

    This review describes the impact of HIV infection on gut-associated lymphoid tissue, the mechanisms for persistent gut-associated lymphoid tissue dysfunction despite effective antiretroviral therapy, and potential strategies to restore gut-associated lymphoid tissue function and promote immune reconstitution. Recent studies indicate that unresolved microbial translocation and intestinal dysbiosis may continue to promote enteropathy as well as HIV-associated and non-HIV-associated conditions in many HIV patients who otherwise maintain therapeutic control of systemic viral replication. Several novel therapeutic approaches to reduce intestinal inflammation and mitigate microbial translocation may hold promise for restoring gastrointestinal health and thereby increasing the efficacy of immune reconstitution in HIV-infected patients undergoing antiretroviral therapy.

  6. For better or worse: Immune system involvement in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Emma L. Walton

    2018-02-01

    Full Text Available In this issue of the Biomedical Journal, we explore the key role of the immune system in the development of Alzheimer's disease. We also learn more about the link between two disorders related to metabolic imbalances, with findings that could help to inform future screening programs. Finally, we would like to highlight some big news for our journal: the Biomedical Journal will be indexed in the Science Citation Index and receive its first official impact factor from this year. Keywords: Alzheimer's disease, Tau, Immune responses, Subclinical hypothyroidism, Metabolic disease

  7. Immune Deficiency Disease' of Undetermined Aetiology in Infancy

    African Journals Online (AJOL)

    1974-04-06

    Apr 6, 1974 ... J., 48, 687 (1974). Immune deficiency diseases in infancy are best known as ... tion at the age of 10 months confirmed the mental retarda- tion, and on further ... Examination of other organ systems was non-contributory. Triple .... linked recessive transmitted disease, and has not been re- ported in females.

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

    Science.gov (United States)

    Deem, Michael

    2004-03-01

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

  9. Atomoxetine restores the response inhibition network in Parkinson's disease.

    Science.gov (United States)

    Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-08-01

    Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction

  10. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Science.gov (United States)

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Celiac Disease Presenting with Immune Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Hakan Sarbay

    2017-01-01

    Full Text Available Celiac disease (CD is an immunological disorder. Clinical manifestations occur as a result of intestinal mucosa damage and malabsorption. CD is also associated with extraintestinal manifestations and autoimmune disorders. The coexistence of CD and autoimmune diseases has been described before. In this article, a patient with CD presenting with thrombocytopenia is discussed.

  12. Natural immunity and HIV disease progression

    DEFF Research Database (Denmark)

    Ullum, H; Cozzi-Lepri, A; Aladdin, H

    1999-01-01

    OBJECTIVE: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1. DESIGN: Data used were from 172 individuals with an estimated measure of NK cell activity...... and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.0 years. METHODS: The lytic activity of NK cells and LAK cells, the CD4 T lymphocyte count, and the concentration of CD......16/CD56 NK cells were measured at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis was performed considering three main endpoints: CD4 cell counts below 100 x 10(6) cells/l, clinical AIDS, and death. RESULTS: In unadjusted analysis and after adjustment for age, CD4 T...

  13. Immune expulsion of Trichuris muris from resistant mice: suppression by irradiation and restoration by transfer of lymphoid cells

    International Nuclear Information System (INIS)

    Wakelin, D.; Selby, G.R.

    1976-01-01

    Lethal irradiation (850 rads of x rays) of mice made resistant to Trichuris muris markedly depressed their ability to expel a challenge infection. Expulsion was restored within 7 to 10 days when MLNC from uninfected mice were transferred on the day of infection, but no significant restoration was evident after transfer of immune serum. Transfer of Bm alone had no restorative effect within 10 days and no synergism was seen when both BM and MLNC were transferred. MLNC from uninfected donors did not restore challenge expulsion when transfer was delayed until day 7 and the mice were killed 3 days later, although MLNC from resistant donors were effective within this time. When irradiated mice were given BM and the challenge infection allowed to continue for 15 days expulsion was restored, as it was when challenge was delayed for 7 days after BM transfer in thymectomized mice. The results confirm that expulsion of T. muris involves both antibody-mediated and lymphoid cell-mediated phases and offer no evidence for the involvement of other cell types. (author)

  14. The role of acquired immunity and periodontal disease progression.

    Science.gov (United States)

    Teng, Yen-Tung A

    2003-01-01

    Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response-in particular, CD4+ T-cells-plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction. In particular, studies of the pathogen-specific CD4+ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4+ T-cell-mediated osteoclastogenic factor, 'RANK-L', which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8+ T-cells, and CD4+ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

  15. [Humoral immune diseases: Cutaneous vasculitis and auto-immune bullous dermatoses].

    Science.gov (United States)

    Wechsler, Janine

    2018-02-01

    Humoral immunity is the cause of multiple diseases related to antibodies (IgA, IgG, IgM) produced by the patient. Two groups of diseases are identified. The first group is related to circulating antigen-antibody complexes. The antigens are various. They are often unknown. These immune complexes cause a vascular inflammation due to the complement fixation. Consequently, this group is dominated by inflammatory vasculitis. In the second group, the pathology is due to the fixation in situ of antibodies to a target antigen of the skin that is no more recognized by the patient. This group is represented by the auto-immune bullous dermatoses. Copyright © 2017. Published by Elsevier Masson SAS.

  16. Immune-mediated rippling muscle disease and myasthenia gravis.

    Science.gov (United States)

    Bettini, Mariela; Gonorazky, Hernan; Chaves, Marcelo; Fulgenzi, Ernesto; Figueredo, Alejandra; Christiansen, Silvia; Cristiano, Edgardo; Bertini, Enrico S; Rugiero, Marcelo

    2016-10-15

    Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Small and long regulatory RNAs in the immune system and immune diseases

    NARCIS (Netherlands)

    Stachurska, Anna; Zorro, Maria M.; van der Sijde, Marijke R.; Withoff, Sebo

    2014-01-01

    Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation

  18. Immune evasion mechanisms of Entamoeba histolytica: progression to disease

    Directory of Open Access Journals (Sweden)

    Sharmin eBegum

    2015-12-01

    Full Text Available Entamoeba histolytica (Eh is a protozoan parasite that infects 10% of the world’s population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  19. Immune Evasion Mechanisms of Entamoeba histolytica: Progression to Disease.

    Science.gov (United States)

    Begum, Sharmin; Quach, Jeanie; Chadee, Kris

    2015-01-01

    Entamoeba histolytica (Eh) is a protozoan parasite that infects 10% of the world's population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO) production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells) that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  20. Gut microbiota, immunity and disease: a complex relationship

    Directory of Open Access Journals (Sweden)

    Michele M Kosiewicz

    2011-09-01

    Full Text Available Our immune system has evolved to recognize and eradicate pathogenic microbes. However, we have a symbiotic relationship with multiple species of bacteria that occupy the gut and comprise the natural commensal flora or microbiota. The microbiota is critically important for the breakdown of nutrients, and also assists in preventing colonization by potentially pathogenic bacteria. In addition, the gut commensal bacteria appears to be critical for the development of an optimally functioning immune system. Various studies have shown that individual species of the microbiota can induce very different types of immune cells (e.g., Th17 cells, Foxp3+ regulatory T cells and responses, suggesting that the composition of the microbiota can have an important influence on the immune response. Although the microbiota resides in the gut, it appears to have a significant impact on the systemic immune response. Indeed, specific gut commensal bacteria have been shown to affect disease development in organs other than the gut, and depending on the species, have been found to have a wide range of effects on diseases from induction and exacerbation to inhibition and protection. In this review, we will focus on the role that the gut microbiota plays in the development and progression of inflammatory/autoimmune disease, and we will also touch upon its role in allergy and cancer.

  1. [Immune response of Hansen's disease. Review].

    Science.gov (United States)

    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.

  2. Narcolepsy as an Immune-Mediated Disease

    Directory of Open Access Journals (Sweden)

    Alberto K. De la Herrán-Arita

    2014-01-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA and T cell receptor (TCR polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1 in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

  3. Prevention of edema disease in pigs by passive immunization

    DEFF Research Database (Denmark)

    Johansen, M.; Andresen, Lars Ole; Thomsen, L.K.

    2000-01-01

    The effect of treatment with verotoxin 2e (VT2e) specific antiserum was evaluated in 3 Danish pig herds with edema disease (ED). The antiserum was prepared by immunizing horses with a VT2e toroid. The study was performed as a randomized blind field trial with parallel treatment and control groups...

  4. Arthropod Innate Immune Systems and Vector-Borne Diseases

    OpenAIRE

    Baxter, Richard H. G.; Contet, Alicia; Krueger, Kathryn

    2017-01-01

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins ...

  5. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

    OpenAIRE

    Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains deb...

  6. Behcet's disease in acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Beenish Siddiqui

    2016-01-01

    Full Text Available HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.

  7. [Environmental pollutants as adjuvant factors of immune system derived diseases].

    Science.gov (United States)

    Lehmann, Irina

    2017-06-01

    The main task of the immune system is to protect the body against invading pathogens. To be able to do so, immune cells must be able to recognize and combat exogenous challenges and at the same time tolerate body-borne structures. A complex regulatory network controls the sensitive balance between defense and tolerance. Perturbation of this network ultimately leads to the development of chronic inflammation, such as allergies, autoimmune reactions, and infections, because the immune system is no longer able to efficiently eliminate invading pathogens. Environmental pollutants can cause such perturbations by affecting the function of immune cells in such a way that they would react hypersensitively against allergens and the body's own structures, respectively, or that they would be no longer able to adequately combat pathogens. This indirect effect is also known as adjuvant effect. For pesticides, heavy metals, wood preservatives, or volatile organic compounds such adjuvant effects are well known. Examples of the mechanism by which environmental toxins contribute to chronic inflammatory diseases are manifold and will be discussed along asthma and allergies.While the immune system of healthy adults is typically well able to distinguish between foreign and endogenous substances even under adverse environmental conditions, that of children would react much more sensible upon comparable environmental challenges. To prevent priming for diseases by environmental cues during that highly sensitive period of early childhood children are to be particularly protected.

  8. Restoration of Immune Surveillance in Lung Cancer by Natural Killer Cells

    Science.gov (United States)

    2016-10-01

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

  9. [Gut microbiota and immune crosstalk in metabolic disease].

    Science.gov (United States)

    Burcelin, Rémy

    2017-01-01

    The aim of the review is to discuss about the role played by the defence crosstalk between the gut microbiota and the intestinal immune system, in the development of metabolic disease focusing on obesity and diabetes. Starting from physiological and pathological stand points and based on the latest published data, this review is addressing how the concept of the hologenome theory of evolution can drive the fate of metabolic disease. The notion of "metabolic infection" to explain the "metabolic inflammation" is discussed. This imply comments about the process of bacterial translocation and impaired intestinal immune defense against commensals. Eventually this review sets the soil for personalized medicine. The monthly increase in the number of publications on the gut microbiota to intestinal immune defense and the control of metabolism demonstrate the importance of this field of investigation. The notion of commensal as "self or non-self" has to be reevaluated in the light of the current data. Furthermore, data demonstrate the major role played by short chain fatty acids, secondary bile acids, LPS, peptidoglycans, indole derivatives, and other bacteria-related molecules on the shaping of cells involved in the intestinal protection against commensals is now becoming a central player in the incidence of metabolic diseases. The literature demonstrates that the onset of metabolic diseases and some specific co-morbidities can be explained by a gut microbiota to intestinal immune system crosstalk. Therefore, one should now consider this avenue of investigation as a putative source of biomarkers and therapeutic targets to personalize the treatment of metabolic disease and its co-morbidities. Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes

  10. Small and Long Regulatory RNAs in the Immune System and Immune Diseases

    OpenAIRE

    Stachurska, Anna; Zorro, Maria M.; van der Sijde, Marijke R.; Withoff, Sebo

    2014-01-01

    Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs...

  11. Immune responses of poultry to Newcastle disease virus.

    Science.gov (United States)

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

    2013-11-01

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

  12. Arthropod Innate Immune Systems and Vector-Borne Diseases.

    Science.gov (United States)

    Baxter, Richard H G; Contet, Alicia; Krueger, Kathryn

    2017-02-21

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization, and agglutination. Effector responses are initiated by damage signals such as reactive oxygen species signaling from epithelial cells and recognized by cell surface receptors on hemocytes. Antiviral immunity is primarily mediated by siRNA pathways but coupled with interferon-like signaling, antimicrobial peptides, and thioester-containing proteins. Molecular mechanisms of immunity are closely linked to related traits of longevity and fertility, and arthropods have the capacity for innate immunological memory. Advances in understanding vector immunity can be leveraged to develop novel control strategies for reducing the rate of transmission of both ancient and emerging threats to global health.

  13. Impact of Bee Venom Enzymes on Diseases and Immune Responses.

    Science.gov (United States)

    Hossen, Md Sakib; Shapla, Ummay Mahfuza; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-12-27

    Bee venom (BV) is used to treat many diseases and exhibits anti-inflammatory, anti-bacterial, antimutagenic, radioprotective, anti-nociceptive immunity promoting, hepatocyte protective and anti-cancer activity. According to the literature, BV contains several enzymes, including phospholipase A2 (PLA2), phospholipase B, hyaluronidase, acid phosphatase and α-glucosidase. Recent studies have also reported the detection of different classes of enzymes in BV, including esterases, proteases and peptidases, protease inhibitors and other important enzymes involved in carbohydrate metabolism. Nevertheless, the physiochemical properties and functions of each enzyme class and their mechanisms remain unclear. Various pharmacotherapeutic effects of some of the BV enzymes have been reported in several studies. At present, ongoing research aims to characterize each enzyme and elucidate their specific biological roles. This review gathers all the current knowledge on BV enzymes and their specific mechanisms in regulating various immune responses and physiological changes to provide a basis for future therapies for various diseases.

  14. Impact of Bee Venom Enzymes on Diseases and Immune Responses

    Directory of Open Access Journals (Sweden)

    Md. Sakib Hossen

    2016-12-01

    Full Text Available Bee venom (BV is used to treat many diseases and exhibits anti-inflammatory, anti-bacterial, antimutagenic, radioprotective, anti-nociceptive immunity promoting, hepatocyte protective and anti-cancer activity. According to the literature, BV contains several enzymes, including phospholipase A2 (PLA2, phospholipase B, hyaluronidase, acid phosphatase and α-glucosidase. Recent studies have also reported the detection of different classes of enzymes in BV, including esterases, proteases and peptidases, protease inhibitors and other important enzymes involved in carbohydrate metabolism. Nevertheless, the physiochemical properties and functions of each enzyme class and their mechanisms remain unclear. Various pharmacotherapeutic effects of some of the BV enzymes have been reported in several studies. At present, ongoing research aims to characterize each enzyme and elucidate their specific biological roles. This review gathers all the current knowledge on BV enzymes and their specific mechanisms in regulating various immune responses and physiological changes to provide a basis for future therapies for various diseases.

  15. High-dose dexamethasone or all-trans-retinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia.

    Science.gov (United States)

    Feng, Q; Xu, M; Yu, Y Y; Hou, Y; Mi, X; Sun, Y X; Ma, S; Zuo, X Y; Shao, L L; Hou, M; Zhang, X H; Peng, J

    2017-09-01

    Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients. Background Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and have diverse immunologic functions. Objectives To investigate the M1/M2 imbalance in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans-retinoic acid (ATRA) could restore this imbalance. Methods The numbers of M1 and M2 macrophages in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence. Monocyte-derived macrophages were cultured and induced with cytokines and drugs. The expression of M1 and M2 markers and functions of M1 and M2 macrophages before and after modulation by HD-DXM or ATRA were evaluated with flow cytometry and ELISA. Results There was preferred M1 polarization in ITP spleens as compared with healthy controls. Monocyte-derived macrophages from ITP patients had increased expression of M1 markers and impaired immunosuppressive functions. Either HD-DXM or ATRA corrected this imbalance by decreasing the expression of M1 markers and increasing the expression of M2 markers. Moreover, HD-DXM-modulated or ATRA-modulated macrophages suppressed both CD4 + and CD8 + T-cell proliferation and expanded CD4 + CD49 + LAG3 + type 1 T-regulatory cells. HD-DXM or ATRA modulated macrophages to shift the T-cell cytokine profile towards Th2. Treating patients with HD-DXM or ATRA

  16. Verneuil's disease, innate immunity and vitamin D: a pilot study.

    Science.gov (United States)

    Guillet, A; Brocard, A; Bach Ngohou, K; Graveline, N; Leloup, A-G; Ali, D; Nguyen, J-M; Loirat, M-J; Chevalier, C; Khammari, A; Dreno, B

    2015-07-01

    Verneuil's disease is a chronic inflammatory skin disease of the follicles in apocrine glands rich area of the skin (axillary, inguinal, anogenital) and is associated with a deficient skin innate immunity. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. Recently, vitamin D has been shown to stimulate skin innate immunity. The primary objective of the study was to assess whether Verneuil's disease was associated with vitamin D deficiency. The secondary objective was to determine whether vitamin D supplementation could improve inflammatory lesions. First, 25(OH) vitamin D3 serum levels in patients with Verneuil's disease followed at Nantes University Hospital were compared to those of healthy donors from the French Blood Bank. Then, a pilot study was conducted in 14 patients supplemented with vitamin D according to their vitamin D level at baseline at months 3 and 6. The endpoints at 6 months were decreased by at least 20% in the number of nodules and in the frequency of flare-ups. Twenty-two patients (100%) had vitamin D deficiency (level vitamin D deficiency (91%) of whom 14% were severely deficient. In 14 patients, the supplementation significantly decreased the number of nodules at 6 months (P = 0.01133), and the endpoints were achieved in 79% of these patients. A correlation between the therapeutic success and the importance of the increase in vitamin D level after supplementation was observed (P = 0.01099). Our study shows that Verneuil's disease is associated with a major vitamin D deficiency, correlated with the disease severity. It suggests that vitamin D could significantly improve the inflammatory nodules, probably by stimulating the skin innate immunity. A larger randomized study is needed to confirm these findings. © 2014 European Academy of Dermatology and Venereology.

  17. Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention.

    Science.gov (United States)

    Nocera, Nadia F; Lee, M Catherine; De La Cruz, Lucy M; Rosemblit, Cinthia; Czerniecki, Brian J

    2016-01-01

    The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy. Interestingly, response to HER-2 targeted therapies correlates with presence of immune response genes in the breast. Th1 cell production of the cytokines interferon gamma (IFNγ) and TNFα can enhance MHC class I expression, PD-L1 expression, augment apoptosis and tumor senescence, and enhances growth inhibition of many anti-breast cancer agents, including anti-estrogens and HER-2 targeted therapies. Recently, we have identified that a loss of anti-HER-2 CD4 Th1 in peripheral blood occurs during breast tumorigenesis and is dramatically diminished, even in Stage I breast cancers. The loss of anti-HER-2 Th1 response is specific and not readily reversed by standard therapies. In fact, this loss of anti-HER-2 Th1 response in peripheral blood correlates with lack of complete response to neoadjuvant therapy and diminished disease-free survival. This defect can be restored with HER-2 vaccinations in both DCIS and IBC. Correcting the anti-HER-2 Th1 response may have significant impact in improving response to HER-2 targeted therapies. Development of immune monitoring systems for anti-HER-2 Th1 to identify patients at risk for recurrence could be critical to improving outcomes, since the anti-HER-2 Th1 response can be restored by vaccination. Correction of the cellular immune response against HER-2 may prevent recurrence in high-risk patients with DCIS and IBC at risk of developing new or recurrent breast cancer.

  18. Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches.

    Science.gov (United States)

    Penêda, José Ferreira; Lima, Nuno Barros; Monteiro, Francisco; Silva, Joana Vilela; Gama, Rita; Condé, Artur

    2018-03-07

    Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. A review of articles on IMIED from the last 10 years was conducted using PubMed ® database. IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Convergent genetic and expression data implicate immunity in Alzheimer's disease.

    Science.gov (United States)

    2015-06-01

    Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. Copyright © 2015. Published by Elsevier Inc.

  20. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy

    NARCIS (Netherlands)

    Pakker, NG; Otto, SA; Hall, D; Wit, FWNM; Hamann, D; van der Ende, Marchina E.; Claessen, FAP; Kauffmann, RH; Koopmans, PP; Sprenger, HG; Weigel, HM; Montaner, JSG; Lange, JMA; Reiss, P; Schellekens, PTA; Miedema, F; Ten Napel, Chris H. H.

    1999-01-01

    Background: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. Objectives: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  1. Shared genetics in coeliac disease and other immune-mediated diseases

    NARCIS (Netherlands)

    Gutierrez-Achury, J.; Coutinho de Almeida, R.; Wijmenga, C.

    Gutierrez-Achury J, Coutinho de Almeida R, Wijmenga C (University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands; University of Brasilia School of Health Sciences, Brasilia, DF, Brazil). Shared genetics in coeliac disease and other immune-mediated diseases

  2. Cesarean section and disease associated with immune function

    DEFF Research Database (Denmark)

    Kristensen, Kim; Henriksen, Lonny

    2016-01-01

    colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma. CONCLUSION: Children delivered by CS are at increased......BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought...... to further explore these associations using discrimination between the effects of acute versus elective CS. METHODS: We performed a population- and national register-based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated...

  3. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap.

    Science.gov (United States)

    Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 10(9)/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave's disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave's disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy.

  4. Disease dynamics and potential mitigation among restored and wild staghorn coral, Acropora cervicornis

    Science.gov (United States)

    Lohr, Kathryn E.; Cameron, Caitlin M.; Williams, Dana E.; Peters, Esther C.

    2014-01-01

    The threatened status (both ecologically and legally) of Caribbean staghorn coral, Acropora cervicornis, has prompted rapidly expanding efforts in culture and restocking, although tissue loss diseases continue to affect populations. In this study, disease surveillance and histopathological characterization were used to compare disease dynamics and conditions in both restored and extant wild populations. Disease had devastating effects on both wild and restored populations, but dynamics were highly variable and appeared to be site-specific with no significant differences in disease prevalence between wild versus restored sites. A subset of 20 haphazardly selected colonies at each site observed over a four-month period revealed widely varying disease incidence, although not between restored and wild sites, and a case fatality rate of 8%. A tropical storm was the only discernable environmental trigger associated with a consistent spike in incidence across all sites. Lastly, two field mitigation techniques, (1) excision of apparently healthy branch tips from a diseased colony, and (2) placement of a band of epoxy fully enclosing the diseased margin, gave equivocal results with no significant benefit detected for either treatment compared to controls. Tissue condition of associated samples was fair to very poor; unsuccessful mitigation treatment samples had severe degeneration of mesenterial filament cnidoglandular bands. Polyp mucocytes in all samples were infected with suspect rickettsia-like organisms; however, no bacterial aggregates were found. No histological differences were found between disease lesions with gross signs fitting literature descriptions of white-band disease (WBD) and rapid tissue loss (RTL). Overall, our results do not support differing disease quality, quantity, dynamics, nor health management strategies between restored and wild colonies of A. cervicornis in the Florida Keys. PMID:25210660

  5. Immune system participates in brain regeneration and restoration of reproduction in the earthworm Dendrobaena veneta.

    Science.gov (United States)

    Molnar, Laszlo; Pollak, Edit; Skopek, Zuzanna; Gutt, Ewa; Kruk, Jerzy; Morgan, A John; Plytycz, Barbara

    2015-10-01

    Earthworm decerebration causes temporary inhibition of reproduction which is mediated by certain brain-derived neurohormones; thus, cocoon production is an apposite supravital marker of neurosecretory center functional recovery during brain regeneration. The core aim of the present study was to investigate aspects of the interactions of nervous and immune systems during brain regeneration in adult Dendrobaena veneta (Annelida; Oligochaeta). Surgical brain extirpation was combined, either with (i) maintenance of immune-competent coelomic cells (coelomocytes) achieved by surgery on prilocaine-anesthetized worms or (ii) prior extrusion of fluid-suspended coelomocytes by electrostimulation. Both brain renewal and cocoon output recovery were significantly faster in earthworms with relatively undisturbed coelomocyte counts compared with individuals where coelomocyte counts had been experimentally depleted. These observations provide empirical evidence that coelomocytes and/or coelomocyte-derived factors (e.g. riboflavin) participate in brain regeneration and, by implication, that there is close functional synergy between earthworm neural and immune systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Genetic prion disease: no role for the immune system in disease pathogenesis?

    Science.gov (United States)

    Friedman-Levi, Yael; Binyamin, Orli; Frid, Kati; Ovadia, Haim; Gabizon, Ruth

    2014-08-01

    Prion diseases, which can manifest by transmissible, sporadic or genetic etiologies, share several common features, such as a fatal neurodegenerative outcome and the aberrant accumulation of proteinase K (PK)-resistant PrP forms in the CNS. In infectious prion diseases, such as scrapie in mice, prions first replicate in immune organs, then invade the CNS via ascending peripheral tracts, finally causing death. Accelerated neuroinvasion and death occurs when activated prion-infected immune cells infiltrate into the CNS, as is the case for scrapie-infected mice induced for experimental autoimmune encephalomyelitis (EAE), a CNS inflammatory insult. To establish whether the immune system plays such a central role also in genetic prion diseases, we induced EAE in TgMHu2ME199K mice, a line mimicking for late onset genetic Creutzfeldt Jacob disease (gCJD), a human prion disease. We show here that EAE induction of TgMHu2ME199K mice neither accelerated nor aggravated prion disease manifestation. Concomitantly, we present evidence that PK-resistant PrP forms were absent from CNS immune infiltrates, and most surprisingly also from lymph nodes and spleens of TgMHu2ME199K mice at all ages and stages of disease. These results imply that the mechanism of genetic prion disease differs widely from that of the infectious presentation, and that the conversion of mutant PrPs into PK resistant forms occurs mostly/only in the CNS. If the absence of pathogenic PrP forms form immune organs is also true for gCJD patients, it may suggest their blood is devoid of prion infectivity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. The Immune System: Basis of so much Health and Disease: 4. Immunocytes.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-05-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers cells of the immune system (immunocytes). Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  8. Developmental origin of immune diseases-Environmental influences

    DEFF Research Database (Denmark)

    Strom, M.; Halldorsson, T. I.; Hansen, S.

    2015-01-01

    (PCBs), organochlorine pesticides, andmorerecently perfluoroalkyl substances (PFAS). Developmental exposures to PCBs have, for example, been associated with both otitis media and lower respiratory infections. Evidence regarding asthma and allergic disease is less well established, partly due to lack......Experimental studies have shown that developmental exposures to environmental chemicals may have long lasting adverse consequences for the development of the immune system. In humans such findings have mostly been explored for persistent organic pollutants (POPs) including polychlorinated biphenyls...... years of age we have examined the long term consequences of in utero exposure to POPs on offspring use of asthma medication and biomarkers of allergic airway disease. Using registry based information on offspring use of asthma medication until 20 years of age, prenatal exposures to PCB-118...

  9. Restoring calcium homeostasis to treat Alzheimer's disease: a future perspective.

    Science.gov (United States)

    Popugaeva, Elena; Vlasova, Olga L; Bezprozvanny, Ilya

    2015-10-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that primarily compromises memory formation and storage. Several hypotheses regarding the pathogenesis of AD have been proposed; however, no cure is available to date. Here we describe the calcium hypothesis of AD, which is gaining popularity. We present data supporting this hypothesis and focus on a recently discovered calcium-signaling pathway that is dysregulated in AD and propose targets for the development of disease-modifying therapies.

  10. The role of the immune system in Alzheimer disease: Etiology and treatment.

    Science.gov (United States)

    Jevtic, Stefan; Sengar, Ameet S; Salter, Michael W; McLaurin, JoAnne

    2017-11-01

    The immune system is now considered a major factor in Alzheimer Disease (AD). This review seeks to demonstrate how various aspects of the immune system, both in the brain and peripherally, interact to contribute to AD. We highlight classical nervous system immune components, such as complement and microglia, as well as novel aspects of the peripheral immune system that can influence disease, such as monocytes and lymphocytes. By detailing the roles of various immune cells in AD, we summarize an emerging perspective for disease etiology and future therapeutic targets. Copyright © 2017. Published by Elsevier B.V.

  11. Immune Development and Intestinal Microbiota in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Tamara Pozo-Rubio

    2012-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding, infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.

  12. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. Immunization

    Science.gov (United States)

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

  14. The Innate Immune System in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Allal Boutajangout

    2013-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloid β (Aβ peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT. Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4 (Potter and Wisniewski (2012, and Verghese et al. (2011. Recently, it has been reported by two groups independently that a rare functional variant (R47H of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs and are the resident macrophages of the central nervous system (CNS. In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

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

    Science.gov (United States)

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

    2016-08-17

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

  16. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I.

    Science.gov (United States)

    Sippel, Trisha R; White, Jason; Nag, Kamalika; Tsvankin, Vadim; Klaassen, Marci; Kleinschmidt-DeMasters, B K; Waziri, Allen

    2011-11-15

    The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell-derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell-mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients.

  17. The innate immune signaling in cancer and cardiometabolic diseases: Friends or foes?

    Science.gov (United States)

    Wang, Weijun; Zhang, Yaxing; Yang, Ling; Li, Hongliang

    2017-02-28

    The innate immune system is responsible for sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) by several types of germline-encoded pattern-recognition receptors (PRRs). It has the capacity to help the human body maintain homeostasis under normal conditions. However, in pathological conditions, PAMPs or DAMPs trigger aberrant innate immune and inflammatory responses and thus negatively or positively influence the progression of cancer and cardiometabolic diseases. Interestingly, we found that some elements of innate immune signaling are involved in these diseases partially via immune-independent manners, indicating a deeper understanding of the function of innate immune signaling in these diseases is urgent. In this review, we summarize the primary innate immune signaling pathways and their association with cancer and cardiometabolic diseases, with the aim of providing effective therapies for these diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  19. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

    Science.gov (United States)

    Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

    1999-02-04

    Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

  20. DMPD: Peptidoglycan signaling in innate immunity and inflammatory disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15802263 Peptidoglycan signaling in innate immunity and inflammatory disease. McDon...ald C, Inohara N, Nunez G. J Biol Chem. 2005 May 27;280(21):20177-80. Epub 2005 Mar 31. (.png) (.svg) (.html) (.csml) Show Peptidog...lycan signaling in innate immunity and inflammatory disease. PubmedID 15802263 Title Peptidog

  1. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

    Science.gov (United States)

    Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

    2015-04-09

    Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Immunopathology of immune reconstitution inflammatory syndrome in Whipple's disease.

    Science.gov (United States)

    Moos, Verena; Feurle, Gerhard E; Schinnerling, Katina; Geelhaar, Anika; Friebel, Julian; Allers, Kristina; Moter, Annette; Kikhney, Judith; Loddenkemper, Christoph; Kühl, Anja A; Erben, Ulrike; Fenollar, Florence; Raoult, Didier; Schneider, Thomas

    2013-03-01

    During antimicrobial treatment of classic Whipple's disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4(+) T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3(+), predominantly CD45RO(+)CD4(+) T cells. In the periphery, initial reduction of CD4(+) cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4(+) T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4(+) T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei-specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4(+) T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.

  3. Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs?

    Directory of Open Access Journals (Sweden)

    Denise L. Bellinger

    2018-04-01

    . Using a rodent model of inflammatory arthritis as an IMID model, we report disease-specific maladaptive changes in β2-adrenergic receptor (AR signaling from protein kinase A (PKA to mitogen activated protein kinase (MAPK pathways in the spleen. Beta2-AR signal “shutdown” in the spleen and switching from PKA to G-coupled protein receptor kinase (GRK pathways in lymph node cells drives inflammation and disease advancement. Based on these findings and the existing literature in other IMIDs, we present and discuss relevant literature that support the hypothesis that unresolvable immune stimulation from chronic inflammation leads to a maladaptive disease-inducing and perpetuating sympathetic response in an attempt to maintain allostasis. Since the role of sympathetic dysfunction in IMIDs is best studied in RA and rodent models of RA, this IMID is the primary one used to evaluate data relevant to our hypothesis. Here, we review the relevant literature and discuss sympathetic dysfunction as a significant contributor to the pathophysiology of IMIDs, and then discuss a novel target for treatment. Based on our findings in inflammatory arthritis and our understanding of common inflammatory process that are used by the immune system across all IMIDs, novel strategies to restore SNS homeostasis are expected to provide safe, cost-effective approaches to treat IMIDs, lower comorbidities, and increase longevity.

  4. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  5. Role of the Innate Immune System in the Pathogenesis of Inflammatory Bowel Disease

    NARCIS (Netherlands)

    van Lierop, Pieter P. E.; Samsom, Janneke N.; Escher, Johanna C.; Nieuwenhuis, Edward E. S.

    Crohn disease and ulcerative colitis are chronic inflammatory diseases of the intestinal tract commonly denoted as inflammatory bowel diseases. It has been proposed that these diseases result from aberrant mucosal immune responses to nonpathogenic microbial residents of the intestines. Recently, it

  6. Immune System and Its Link to Rheumatic Diseases

    Science.gov (United States)

    ... system, which contributes to the illness. So therapy targeting our own immune system can help alleviate the ... by the American College of Rheumatology Communications and Marketing Committee. This information is provided for general education ...

  7. Molecular signaling networks in regulation of immunity and disease

    DEFF Research Database (Denmark)

    Laursen, Janne Marie; Jensen, Stina Rikke; Sørensen, Morten

    and dynamic microbial communities with the immune cell compartment in the gut, and therefore the interaction between components from different gut bacteria can efficiently shape the phenotype of the immune response. A specialized antigenpresenting cell present at mucosal surfaces, the dendritic cell (DC......), plays a crucial role in shaping the nature of the adaptive/memorybased immune response after encountering inflammatory compounds. In the gut, the DC is continuously exposed to microbial and dietary components that are recognized by its innate pattern recognition receptors, and the phenotype developed...... in the DC during activation is of profound importance for the state of immune response and thereby also affects the inflammatory and metabolic status in tissues. We have shown that specific fermentation products from gut bacteria have distinct immunoregulatory effects that effectively inhibit...

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Senescence of the adaptive immune system in health and aging-associated autoimmune disease

    NARCIS (Netherlands)

    van der Geest, Kornelis Stephan Mario

    2015-01-01

    Aging of the immune system may contribute to the development of aging-associated autoimmune diseases, such as giant cell arteritis, polymyalgia rheumatica and rheumatoid arthritis. The aim of this thesis was to identify aging-dependent changes of the adaptive immune system that promote autoimmunity

  10. A short history of research on immunity to infectious diseases in fish

    NARCIS (Netherlands)

    Muiswinkel, van W.B.; Nakao, M.

    2014-01-01

    This review describes the history of research on immunity to infectious diseases of fish in the period between 1965 and today. Special attention is paid to those studies, which are dealing with the interaction between immune system and invading pathogens in bony fish. Moreover, additional biographic

  11. Mechanisms regulating skin immunity and inflammation.

    Science.gov (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

    2014-05-01

    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  12. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs

    Directory of Open Access Journals (Sweden)

    Wen-I Lee

    2011-12-01

    Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively

  13. The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases

    Science.gov (United States)

    Liu, Meifang; Zhang, Cai

    2017-01-01

    Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases. Here, we review the relationships between the ILC subsets and their functions in immune-mediated liver diseases, and discuss their therapeutic potential based on current knowledge about the functional roles of these cells in liver diseases. PMID:28659927

  14. Boosting innate immunity to sustainably control diseases in crops.

    Science.gov (United States)

    Nicaise, Valerie

    2017-10-01

    Viruses cause epidemics in all major crops, threatening global food security. The development of efficient and durable resistance able to withstand viral attacks represents a major challenge for agronomy, and relies greatly on the understanding of the molecular dialogue between viral pathogens and their hosts. Research over the last decades provided substantial advances in the field of plant-virus interactions. Remarkably, the advent of studies of plant innate immunity has recently offered new strategies exploitable in the field. This review summarizes the recent breakthroughs that define the mechanisms underlying antiviral innate immunity in plants, and emphasizes the importance of integrating that knowledge into crop improvement actions, particularly by exploiting the insights related to immune receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer

    DEFF Research Database (Denmark)

    Siddle, Hannah V; Kreiss, Alexandre; Tovar, Cesar

    2013-01-01

    Contagious cancers that pass between individuals as an infectious cell line are highly unusual pathogens. Devil facial tumor disease (DFTD) is one such contagious cancer that emerged 16 y ago and is driving the Tasmanian devil to extinction. As both a pathogen and an allograft, DFTD cells should...... be rejected by the host-immune response, yet DFTD causes 100% mortality among infected devils with no apparent rejection of tumor cells. Why DFTD cells are not rejected has been a question of considerable confusion. Here, we show that DFTD cells do not express cell surface MHC molecules in vitro or in vivo......, MHC class I molecules can be restored to the surface of DFTD cells in vitro by using recombinant devil IFN-γ, which is associated with up-regulation of the MHC class II transactivator, a key transcription factor with deacetylase activity. Further, expression of MHC class I molecules by DFTD cells can...

  16. Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation.

    Science.gov (United States)

    Mehta, Minesh; Ahmed, Shifat; Dryden, Gerald

    2017-08-01

    Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

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

    Science.gov (United States)

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

    2005-01-01

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

  18. STN-stimulation in Parkinson's disease restores striatal inhibition of thalamocortical projection

    DEFF Research Database (Denmark)

    Geday, Jacob; Østergaard, Karen; Johnsen, Erik

    2009-01-01

    To test the hypothesis that deep brain stimulation of the subthalamic nucleus (STN) restores the inhibitory output to the striatothalamocortical loop in Parkinson's disease, we obtained functional brain images of blood flow in 10 STN-stimulated patients with Parkinson's disease. Patients were...... in the STN and in the left nucleus lentiformis. Conversely, flow declined in the left supplementary motor area (BA 6), ventrolateral nucleus of the left thalamus, and right cerebellum. Activation of the basal ganglia and deactivation of supplementary motor area and thalamus were both correlated...... with the improvement of motor function. The result is consistent with the explanation that stimulation in resting patients raises output from the STN with activation of the inhibitory basal ganglia output nuclei and subsequent deactivation of the thalamic anteroventral and ventrolateral nuclei and the supplementary...

  19. Roles and Regulation of Gastrointestinal Eosinophils in Immunity and Disease

    Science.gov (United States)

    Jung, YunJae; Rothenberg, Marc E.

    2014-01-01

    Eosinophils have been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergy reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system. PMID:25049430

  20. Immunizations

    Science.gov (United States)

    ... vaccine leaves a person unprotected and still at risk for getting a disease. Other vaccinations require a booster shot every few years to ... who get diseases like mumps may be at risk for side effects of the illness, such ... children). Vaccinations are about protecting you in the future, not ...

  1. A short history of research on immunity to infectious diseases in fish.

    Science.gov (United States)

    Van Muiswinkel, Willem B; Nakao, Miki

    2014-04-01

    This review describes the history of research on immunity to infectious diseases of fish in the period between 1965 and today. Special attention is paid to those studies, which are dealing with the interaction between immune system and invading pathogens in bony fish. Moreover, additional biographic information will be provided of people involved. In the 1960s and 1970s the focus of most studies was on humoral (Ig, B-cell) responses. Thorough studies on specific cellular (T-cell) responses and innate immunity (lectins, lysozyme, interferon, phagocytic cells) became available later. In the period between 1980 and today an overwhelming amount of data on regulation (e.g. cell cooperation, cytokines) and cell surface receptors (e.g. T-cell receptor; MHC) was published. It became also clear, that innate responses were often interacting with the acquired immune responses. Fish turned out to be vertebrates like all others with a sophisticated immune system showing specificity and memory. These basic data on the immune system could be applied in vaccination or in selection of disease resistant fish. Successful vaccines against bacterial diseases became available in the 1970s and 1980s. Effective anti-viral vaccines appeared from the 1980s onwards. There is no doubt, that Fish Immunology has become a flourishing science by the end of the 20th century and has contributed to our understanding of fish diseases as well as the success of aquaculture. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Crohn’s disease: Mucosal immunology and immune modulating therapy

    NARCIS (Netherlands)

    Peters, C.P.

    2014-01-01

    Crohn’s disease (CD) and ulcerative colitis (UC) are debilitating chronic diseases that affect millions of people worldwide, profoundly impacting patient quality of life and incurring large costs in terms of treatment and lost productivity. While current interventions ameliorate disease symptoms,

  3. Atomoxetine restores the response inhibition network in Parkinson’s disease

    Science.gov (United States)

    Rae, Charlotte L.; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E.; Jones, P. Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Parkinson’s disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson’s disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson’s disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson’s disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson’s disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced

  4. Social Immunity: Emergence and Evolution of Colony-Level Disease Protection.

    Science.gov (United States)

    Cremer, Sylvia; Pull, Christopher D; Fürst, Matthias A

    2018-01-07

    Social insect colonies have evolved many collectively performed adaptations that reduce the impact of infectious disease and that are expected to maximize their fitness. This colony-level protection is termed social immunity, and it enhances the health and survival of the colony. In this review, we address how social immunity emerges from its mechanistic components to produce colony-level disease avoidance, resistance, and tolerance. To understand the evolutionary causes and consequences of social immunity, we highlight the need for studies that evaluate the effects of social immunity on colony fitness. We discuss the roles that host life history and ecology have on predicted eco-evolutionary dynamics, which differ among the social insect lineages. Throughout the review, we highlight current gaps in our knowledge and promising avenues for future research, which we hope will bring us closer to an integrated understanding of socio-eco-evo-immunology.

  5. Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

    Science.gov (United States)

    Jafri, Salema; Ormiston, Mark L

    2017-12-01

    Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4 + helper T cell populations, defined by excessive Th17 responses and impaired T reg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8 + T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders. Copyright © 2017 the American Physiological Society.

  6. Effect of ionizing radiation on humoral and cellular immunity in pigs vaccinated against Aujeszky's disease

    International Nuclear Information System (INIS)

    Bartoszcze, M.; Roszkowski, J.

    1991-01-01

    An effect of ionizing radiation on the immune response in pigs of both sexes weighing 35 kg vaccinated with an attenuated Aujeszky's disease virus was investigated. Ionizing radiation in a dose of 200 or 400 r reduced the number of IgM and IgG antibodies produced in vaccinated pigs. Additionally, the 400 r dose delyed the cellular immune response. No effect of the radiation on a clinical course of postvaccinal reaction was found

  7. B-Cell Dysregulation in Crohn's Disease Is Partially Restored with Infliximab Therapy.

    Directory of Open Access Journals (Sweden)

    Wilhelmina M C Timmermans

    Full Text Available B-cell depletion can improve a variety of chronic inflammatory diseases, but does not appear beneficial for patients with Crohn's disease.To elucidate the involvement of B cells in Crohn's disease, we here performed an 'in depth' analysis of intestinal and blood B-cells in this chronic inflammatory disease.Patients with Crohn's disease were recruited to study B-cell infiltrates in intestinal biopsies (n = 5, serum immunoglobulin levels and the phenotype and molecular characteristics of blood B-cell subsets (n = 21. The effects of infliximab treatment were studied in 9 patients.Granulomatous tissue showed infiltrates of B lymphocytes rather than Ig-secreting plasma cells. Circulating transitional B cells and CD21low B cells were elevated. IgM memory B cells were reduced and natural effector cells showed decreased replication histories and somatic hypermutation (SHM levels. In contrast, IgG and IgA memory B cells were normally present and their Ig gene transcripts carried increased SHM levels. The numbers of transitional and natural effector cells were normal in patients who responded clinically well to infliximab.B cells in patients with Crohn's disease showed signs of chronic stimulation with localization to granulomatous tissue and increased molecular maturation of IgA and IgG. Therapy with TNFα-blockers restored the defect in IgM memory B-cell generation and normalized transitional B-cell levels, making these subsets candidate markers for treatment monitoring. Together, these results suggest a chronic, aberrant B-cell response in patients with Crohn's disease, which could be targeted with new therapeutics that specifically regulate B-cell function.

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

    Science.gov (United States)

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

    2009-12-01

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

  9. Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease by Inhibition of Mammalian Target of Rapamycin.

    Science.gov (United States)

    Mitani, Akihisa; Ito, Kazuhiro; Vuppusetty, Chaitanya; Barnes, Peter J; Mercado, Nicolas

    2016-01-15

    Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Several molecular mechanisms have been proposed, such as activations of the phosphoinositide-3-kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the mechanism for corticosteroid resistance is still not fully elucidated. To investigate the role of mammalian target of rapamycin (mTOR) in corticosteroid sensitivity in COPD. The corticosteroid sensitivity of peripheral blood mononuclear cells collected from patients with COPD, smokers, and nonsmoking control subjects, or of human monocytic U937 cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α-induced CXCL8 production in the presence or absence of the mTOR inhibitor rapamycin. mTOR activity was determined as the phosphorylation of p70 S6 kinase, using Western blotting. mTOR activity was increased in peripheral blood mononuclear cells from patients with COPD, and treatment with rapamycin inhibited this as well as restoring corticosteroid sensitivity. In U937 cells, CSE stimulated mTOR activity and c-Jun expression, but pretreatment with rapamycin inhibited both and also reversed CSE-induced corticosteroid insensitivity. mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD.

  10. Immune dysfunction in Niemann?Pick disease type C

    OpenAIRE

    Platt, Nick; Speak, Annelise O.; Colaco, Alexandria; Gray, James; Smith, David A.; Williams, Ian M.; Wallom, Kerri?Lee; Platt, Frances M.

    2015-01-01

    Abstract Lysosomal storage diseases are inherited monogenic disorders in which lysosome function is compromised. Although individually very rare, they occur at a collective frequency of approximately one in five thousand live births and usually have catastrophic consequences for health. The lysosomal storage diseases Niemann?Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral membrane protein NPC1 and clinically presents as a progressive neurodegenerative ...

  11. The immune response to Prevotella bacteria in chronic inflammatory disease

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura

    2017-01-01

    the hunt for disease-modulating bacteria. Emerging studies in humans have linked the increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders and low-grade systemic inflammation....... Intriguingly, Prevotella abundance is reduced within the lung microbiota of patients with asthma and chronic obstructive pulmonary disease. Increased Prevotella abundance is associated with augmented T helper type 17 (Th17) -mediated mucosal inflammation, which is in line with the marked capacity of Prevotella...... and various stromal cells. These findings indicate that some Prevotella strains may be clinically important pathobionts that can participate in human disease by promoting chronic inflammation....

  12. Review: Potential biotechnological assets related to plant immunity modulation applicable in engineering disease-resistant crops.

    Science.gov (United States)

    Silva, Marilia Santos; Arraes, Fabrício Barbosa Monteiro; Campos, Magnólia de Araújo; Grossi-de-Sa, Maira; Fernandez, Diana; Cândido, Elizabete de Souza; Cardoso, Marlon Henrique; Franco, Octávio Luiz; Grossi-de-Sa, Maria Fátima

    2018-05-01

    This review emphasizes the biotechnological potential of molecules implicated in the different layers of plant immunity, including, pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), effector-triggered susceptibility (ETS), and effector-triggered immunity (ETI) that can be applied in the development of disease-resistant genetically modified (GM) plants. These biomolecules are produced by pathogens (viruses, bacteria, fungi, oomycetes) or plants during their mutual interactions. Biomolecules involved in the first layers of plant immunity, PTI and ETS, include inhibitors of pathogen cell-wall-degrading enzymes (CWDEs), plant pattern recognition receptors (PRRs) and susceptibility (S) proteins, while the ETI-related biomolecules include plant resistance (R) proteins. The biomolecules involved in plant defense PTI/ETI responses described herein also include antimicrobial peptides (AMPs), pathogenesis-related (PR) proteins and ribosome-inhibiting proteins (RIPs), as well as enzymes involved in plant defensive secondary metabolite biosynthesis (phytoanticipins and phytoalexins). Moreover, the regulation of immunity by RNA interference (RNAi) in GM disease-resistant plants is also considered. Therefore, the present review does not cover all the classes of biomolecules involved in plant innate immunity that may be applied in the development of disease-resistant GM crops but instead highlights the most common strategies in the literature, as well as their advantages and disadvantages. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Up in arms: Immune and nervous system response to sea star wasting disease

    Science.gov (United States)

    Fuess, Lauren E; Eiselord, Morgan E.; Closek, Collin J.; Tracy, Allison M.; Mauntz, Ruth; Gignoux-Wolfsohn, Sarah; Moritsch, Monica M; Yoshioka, Reyn; Burge, Colleen A.; Harvell, Drew; Friedman, Carolyn S.; Hershberger, Paul K.; Roberts, Steven B.

    2015-01-01

    Echinoderms, positioned taxonomically at the base of deuterostomes, provide an important system for the study of the evolution of the immune system. However, there is little known about the cellular components and genes associated with echinoderm immunity. The 2013–2014 sea star wasting disease outbreak is an emergent, rapidly spreading disease, which has led to large population declines of asteroids in the North American Pacific. While evidence suggests that the signs of this disease, twisting arms and lesions, may be attributed to a viral infection, the host response to infection is still poorly understood. In order to examine transcriptional responses of the sea star Pycnopodia helianthoides to sea star wasting disease, we injected a viral sized fraction (0.2 μm) homogenate prepared from symptomatic P. helianthoides into apparently healthy stars. Nine days following injection, when all stars were displaying signs of the disease, specimens were sacrificed and coelomocytes were extracted for RNA-seq analyses. A number of immune genes, including those involved in Toll signaling pathways, complement cascade, melanization response, and arachidonic acid metabolism, were differentially expressed. Furthermore, genes involved in nervous system processes and tissue remodeling were also differentially expressed, pointing to transcriptional changes underlying the signs of sea star wasting disease. The genomic resources presented here not only increase understanding of host response to sea star wasting disease, but also provide greater insight into the mechanisms underlying immune function in echinoderms.

  14. Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy

    Directory of Open Access Journals (Sweden)

    De Taboada Luis

    2009-06-01

    Full Text Available Abstract Background It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD. Mitochondria supply the adenosine triphosphate (ATP needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT. The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT. Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm2 for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined. Results The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM was significantly reduced (p Conclusion The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.

  15. Immunization Documentation Practices and Vaccine-Preventable Disease Surveillance Capacity among Institutions of Higher Education in Indiana

    Science.gov (United States)

    Stevens, Taryn; Golwalkar, Mugdha

    2018-01-01

    ABSTRACTObjective: Complete and accurate documentation of immunization records and surveillance of disease transmission are critical to the public health response to outbreaks of communicable disease in institutions of higher education (IHEs). This study aims to describe immunization documentation practices and disease surveillance capacity among…

  16. SCT for severe autoimmune diseases: consensus guidelines of the European Society for Blood and Marrow Transplantation for immune monitoring and biobanking.

    Science.gov (United States)

    Alexander, T; Bondanza, A; Muraro, P A; Greco, R; Saccardi, R; Daikeler, T; Kazmi, M; Hawkey, C; Simoes, B P; Leblanc, K; Fibbe, W E; Moore, J; Snarski, E; Martin, T; Hiepe, F; Velardi, A; Toubert, A; Snowden, J A; Farge, D

    2015-02-01

    Over the past 15 years, SCT has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies recently provided the proof-of-concept that restoration of immunological tolerance can be achieved by haematopoietic SCT in chronic autoimmunity through eradication of the pathologic, immunologic memory and profound reconfiguration of the immune system, that is, immune 'resetting'. Nevertheless, a number of areas remain unresolved and warrant further investigation to refine our understanding of the underlying mechanisms of action and to optimize clinical SCT protocols. Due to the low number of patients transplanted in each centre, it is essential to adequately collect and analyse biological samples in a larger cohort of patients under standardized conditions. The European society for blood and marrow transplantation Autoimmune Diseases and Immunobiology Working Parties have, therefore, undertaken a joint initiative to develop and implement guidelines for 'good laboratory practice' in relation to procurement, processing, storage and analysis of biological specimens for immune reconstitution studies in AD patients before, during and after SCT. The aim of this document is to provide practical recommendations for biobanking of samples and laboratory immune monitoring in patients with ADs undergoing SCT, both for routine supportive care purposes and investigational studies.

  17. Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease.

    Science.gov (United States)

    de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M; Tiscornia, Gustavo; Sánchez-Alcázar, José A

    2017-02-06

    Gaucher disease (GD) is caused by mutations in the GBA1 gene which encodes lysosomal β-glucocerebrosidase (GCase). In GD, partial or complete loss of GCase activity causes the accumulation of the glycolipids glucosylceramide (GlcCer) and glucosylsphingosine in the lysosomes of macrophages. In this manuscript, we investigated the effects of glycolipids accumulation on lysosomal and mitochondrial function, inflammasome activation and efferocytosis capacity in a THP-1 macrophage model of Gaucher disease. In addition, the beneficial effects of coenzyme Q 10 (CoQ) supplementation on cellular alterations were evaluated. Chemically-induced Gaucher macrophages were developed by differentiateing THP-1 monocytes to macrophages by treatment with phorbol 12-myristate 13-acetate (PMA) and then inhibiting intracellular GCase with conduritol B-epoxide (CBE), a specific irreversible inhibitor of GCase activity, and supplementing the medium with exogenous GlcCer. This cell model accumulated up to 16-fold more GlcCer compared with control THP-1 cells. Chemically-induced Gaucher macrophages showed impaired autophagy flux associated with mitochondrial dysfunction and increased oxidative stress, inflammasome activation and impaired efferocytosis. All abnormalities were partially restored by supplementation with CoQ. These data suggest that targeting mitochondria function and oxidative stress by CoQ can ameliorate the pathological phenotype of Gaucher cells. Chemically-induced Gaucher macrophages provide cellular models that can be used to investigate disease pathogenesis and explore new therapeutics for GD.

  18. The impact of strain-specific immunity on Lyme disease incidence is spatially heterogeneous.

    Science.gov (United States)

    Khatchikian, Camilo E; Nadelman, Robert B; Nowakowski, John; Schwartz, Ira; Wormser, Gary P; Brisson, Dustin

    2017-12-01

    Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne infection in the US. Recent studies have demonstrated that the incidence of human Lyme disease would have been even greater were it not for the presence of strain-specific immunity, which protects previously infected patients against subsequent infections by the same B. burgdorferi strain. Here, spatial heterogeneity is incorporated into epidemiological models to accurately estimate the impact of strain-specific immunity on human Lyme disease incidence. The estimated reduction in the number of Lyme disease cases is greater in epidemiologic models that explicitly include the spatial distribution of Lyme disease cases reported at the county level than those that utilize nationwide data. strain-specific immunity has the greatest epidemiologic impact in geographic areas with the highest Lyme disease incidence due to the greater proportion of people that have been previously infected and have developed strain-specific immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Immune biomarkers in the spectrum of childhood noncommunicable diseases

    NARCIS (Netherlands)

    Skevaki, Chrysanthi; Van Den Berg, Jolice; Jones, Nicholas; Garssen, Johan; Vuillermin, Peter; Levin, Michael; Landay, Alan; Renz, Harald; Calder, Philip C.; Thornton, Catherine A.

    2016-01-01

    A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or

  20. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group

    NARCIS (Netherlands)

    Pakker, N. G.; Kroon, E. D.; Roos, M. T.; Otto, S. A.; Hall, D.; Wit, F. W.; Hamann, D.; van der Ende, M. E.; Claessen, F. A.; Kauffmann, R. H.; Koopmans, P. P.; Kroon, F. P.; ten Napel, C. H.; Sprenger, H. G.; Weigel, H. M.; Montaner, J. S.; Lange, J. M.; Reiss, P.; Schellekens, P. T.; Miedema, F.

    1999-01-01

    BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  1. Hericium erinaceus polysaccharide facilitates restoration of injured intestinal mucosal immunity in Muscovy duck reovirus-infected Muscovy ducklings.

    Science.gov (United States)

    Wu, Yijian; Jiang, Huihui; Zhu, Erpeng; Li, Jian; Wang, Quanxi; Zhou, Wuduo; Qin, Tao; Wu, Xiaoping; Wu, Baocheng; Huang, Yifan

    2018-02-01

    To elucidate the effect of Hericium erinaceus polysaccharide (HEP) on the intestinal mucosal immunity in normal and Muscovy duck reovirus (MDRV)-infected Muscovy ducklings, 1-day-old healthy Muscovy ducklings were pretreated with 0.2g/L HEP and/or following by MDRV infection in this study, duodenal samples were respectively collected at 1, 3, 6, 10, 15 and 21day post-infection, tissue sections were prepared for observation of morphological structure and determination of intestinal parameters (villus height/crypt depth ratio, villus surface area) as well as counts of intraepithelial lymphocytes (IELs), goblet cells, mast cells. Additionally, dynamics of secretory immunoglobin A (sIgA), interferon-γ (IFN-γ) and interleukin-4 (IL-4) productions in intestinal mucosa were measured with radioimmunoassay. Results showed that HEP significantly improved intestinal morphological structure and related indexes, and significantly inhibited the reduction of intestinal mucosal IELs, goblet cells and mast cells caused by MDRV infection. Furthermore, HEP significantly increased the secretion of sIgA, IFN-γ and IL-4 to enhance intestinal mucosal immune functions. Our findings indicate that HEP treatment can effectively repair MDRV-caused injures of small intestinal mucosal immune barrier, and improve mucosal immune function in sick Muscovy ducklings, which will provide valuable help for further application of HEP in prevention and treatment of MDRV infection. Copyright © 2017. Published by Elsevier B.V.

  2. UV and hydrogen peroxide treatment restores changes in innate immunity caused by exposure of fish to reuse water.

    Science.gov (United States)

    Singh, Arvinder; Havixbeck, Jeffrey J; Smith, Matthew K; Shu, Zengquan; Tierney, Keith B; Barreda, Daniel R; El-Din, Mohamed Gamal; Belosevic, Miodrag

    2015-03-15

    The purpose of this study was to assess the innate immunity of goldfish exposed to reuse water, and UV/H2O2-treated reuse water, using a real-time flow-through exposure system. The reuse water generated by ultrafiltration of finished wastewater from the municipal wastewater treatment plant was analyzed for the presence of a panel of 20 herbicides/fungicides and 46 pharmaceuticals and personal care products (PPCP). There was a seasonal variation in the profile and concentrations of xenobiotics in reuse water with lowest levels occurring in the summer. The innate immunity parameters assessed were cytokine (IFNγ, IL-1β, IL-10, TNFα2), and cytokine receptor (TNFR1, TNFR2, IFNGR1, IFNGR2) gene expression, and phagocytosis of kidney leukocyte subpopulations. Assessment of innate immunity parameters was done after acute (7 days) and sub chronic (30 and 60 days) exposure to reuse water, UV/H2O2-treated reuse water, and activated carbon-treated reuse water (ACT; control), during spring, summer and fall of 2012. Temporal (acute versus sub chronic) as well as seasonal differences in innate immunity of fish exposed to reuse water were observed. The acute exposure of fish to reuse water caused significant down-regulation in cytokine gene expression in different organs of fish (kidney, spleen, liver) and phagocytic ability of different kidney leukocyte subpopulations. The immune gene expression and phagocytosis of kidney leukocytes of fish returned to ACT control levels after sub chronic exposure suggesting that fish have habituated to the reuse water exposure. The changes in gene expression after acute exposure were related to variations in the profile of xenobiotics in reuse water during different seasons. The efficiency of xenobiotic removal using UV/H2O2 ranged between 1.6 and 100% indicating that treatment of reuse water using high dose UV/H2O2 was only partially effective in removing the xenobiotics, as assessed by both chemical analyses and measurement of innate immune

  3. The Microbiota Regulates Immunity and Immunologic Diseases in Dogs and Cats.

    Science.gov (United States)

    Tizard, Ian R; Jones, Sydney W

    2018-03-01

    The complex commensal microbiota found on body surfaces controls immune responses and the development of allergic and inflammatory diseases. New genetic technologies permit investigators to determine the composition of the complex microbial populations found on these surfaces. Changes in the microbiota (dysbiosis) as a result of antibiotic use, diet, or other factors thus influence the development of many diseases in the dog and cat. The most important of these include chronic gastrointestinal disease; respiratory allergies, such as asthma; skin diseases, especially atopic dermatitis; and some autoimmune diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. High-throughput Sequencing Based Immune Repertoire Study during Infectious Disease

    Directory of Open Access Journals (Sweden)

    Dongni Hou

    2016-08-01

    Full Text Available The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases that achieved by traditional techniques and high-throughput sequencing techniques. High-throughput sequencing techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge, and also provides a basis for further development of novel diagnostic markers, immunotherapies and vaccines.

  5. Immune defenses of healthy, bleached and diseased Montastraea faveolata during a natural bleaching event.

    Science.gov (United States)

    Mydlarz, Laura D; Couch, Courtney S; Weil, Ernesto; Smith, Garriet; Harvell, C Drew

    2009-11-16

    One prominent hypothesis regarding climate change and scleractinian corals is that thermal stress compromises immune competence. To test this hypothesis we tracked how the immune defenses of bleached, apparently healthy and yellow band disease (YBD) diseased Montastraea faveolata colonies varied with natural thermal stress in southwestern Puerto Rico. Colonies were monitored for 21 mo from the peak of the bleaching event in October 2005 to August 2007. Since sea surface temperature was significantly higher in summer and fall 2005 than 2006, year of collection was used as a proxy for temperature stress, and colony fragments collected in 2005 were compared with those collected in 2006. Mortality rate was high (43% overall) and all colonies (except one) either died or became infected with YBD by August 2007. YBD-infected tissue did not bleach (i.e. expel zooxanthellae) during the 2005 bleaching event, even when healthy tissue of these colonies bleached. Immune activity was assayed by measuring prophenoloxidase (PPO), peroxidase (POX), lysozyme-like (LYS) and antibacterial (AB) activity. Immune activity was variable between all coral samples, but there was a significant elevation of PPO activity in bleached colonies collected in 2005 relative to apparently healthy and YBD-diseased corals in 2006. In YBD-diseased colonies, LYS and AB activity were elevated in both healthy and infected tissue, indicating a systemic response; activity levels in these colonies were higher compared to those that appeared healthy. In both these immune parameters, there was a trend for suppression of activity in corals that were bleached in 2005. These data, while complicated by between-genet variability, illustrate the complex interaction between disease and temperature stress on immune function.

  6. The Emerging Role of TLR and Innate Immunity in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Rolf Spirig

    2012-01-01

    Full Text Available Cardiovascular disease is a complex disorder involving multiple pathophysiological processes, several of which involve activation of toll-like receptors (TLRs of the innate immune system. As sentinels of innate immunity TLRs are nonclonally germline-encoded molecular pattern recognition receptors that recognize exogenous as well as tissue-derived molecular dangers signals promoting inflammation. In addition to their expression in immune cells, TLRs are found in other tissues and cell types including cardiomyocytes, endothelial and vascular smooth muscle cells. TLRs are differentially regulated in various cell types by several cardiovascular risk factors such as hypercholesterolemia, hyperlipidemia, and hyperglycemia and may represent a key mechanism linking chronic inflammation, cardiovascular disease progression, and activation of the immune system. Modulation of TLR signaling by specific TLR agonists or antagonists, alone or in combination, may be a useful therapeutic approach to treat various cardiovascular inflammatory conditions such as atherosclerosis, peripheral arterial disease, secondary microvascular complications of diabetes, autoimmune disease, and ischemia reperfusion injury. In this paper we discuss recent developments and current evidence for the role of TLR in cardiovascular disease as well as the therapeutic potential of various compounds on inhibition of TLR-mediated inflammatory responses.

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

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    Abdul Salam Jarrah

    2014-01-01

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

  8. Mesenchymal Stem Cells in Restoration of Fertility at Experimental Pelvic Inflammatory Disease

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    Nataliia Volkova

    2017-01-01

    Full Text Available Inflammatory disorders account for a significant percentage of gynecologic diseases, particularly in women of reproductive age. It is known that stem cells have anti-inflammatory and regenerative properties. Based on this, we investigated the effect of intravenous administration of cryopreserved mesenchymal stem cells (cMSCs of bone marrow on experimental chronic inflammation of the ovaries. The paper shows that on the 21st day after cMSC therapy, leukocyte infiltration of ovaries was slightly relative to the control group without treatment, and the ratio of developing and atretic follicles in the animals with cMSC injection dramatically increased, while in the control, it still remained on the side of atretic forms. The number of apoptotic oocytes after stimulation of superovulation in the control group was significantly higher (85.3 ± 5.2% than that in the animals with therapy (5.7 ± 0.8%. Relative number of fertilized eggs in the group with cMSC therapy was higher by 40% compare to that in the control. Pregnancy rate in natural estrous cycle after cell administration increased by 20%, and average number of litters in this group was two times significantly higher than that in the control. So the intravenous injection of cMSCs has the restorative effect on the fertility at experimental pelvic inflammatory disease.

  9. Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

    Science.gov (United States)

    Kawarazaki, Hiroo; Shibagaki, Yugo; Kido, Ryo; Nakajima, Ichiro; Fuchinoue, Shohei; Ando, Katsuyuki; Fujita, Toshiro; Fukagawa, Masafumi; Teraoka, Satoshi; Fukumoto, Seiji

    2012-07-01

    While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

  10. The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease.

    Science.gov (United States)

    Filyk, Heather A; Osborne, Lisa C

    2016-11-01

    Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Role of the peripheral innate immune system in the development of Alzheimer's disease.

    Science.gov (United States)

    Le Page, Aurélie; Dupuis, Gilles; Frost, Eric H; Larbi, Anis; Pawelec, Graham; Witkowski, Jacek M; Fulop, Tamas

    2017-12-21

    Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression. Microglia in the brain are innate immune cells, and brain-initiated inflammatory responses reflected in the periphery suggests that Alzheimer's disease is to some extent also a systemic inflammatory disease. Greater permeability of the blood brain barrier facilitates the transport of peripheral immune cells to the brain and vice versa so that a vicious circle originating on the periphery may contribute to the development of overt clinical AD. Persistent inflammatory challenges by pathogens in the periphery, increasing with age, may also contribute to the central propagation of the pathological changes seen clinically. Therefore, the activation status of peripheral innate immune cells may represent an early biomarker of the upcoming impact on the brain. The modulation of these cells may thus become a useful mechanism for modifying disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Haemophilus responses to nutritional immunity: epigenetic and morphological contribution to biofilm architecture, invasion, persistence and disease severity.

    Directory of Open Access Journals (Sweden)

    Blake R Szelestey

    Full Text Available In an effort to suppress microbial outgrowth, the host sequesters essential nutrients in a process termed nutritional immunity. However, inflammatory responses to bacterial insult can restore nutritional resources. Given that nutrient availability modulates virulence factor production and biofilm formation by other bacterial species, we hypothesized that fluctuations in heme-iron availability, particularly at privileged sites, would similarly influence Haemophilus biofilm formation and pathogenesis. Thus, we cultured Haemophilus through sequential heme-iron deplete and heme-iron replete media to determine the effect of transient depletion of internal stores of heme-iron on multiple pathogenic phenotypes. We observed that prior heme-iron restriction potentiates biofilm changes for at least 72 hours that include increased peak height and architectural complexity as compared to biofilms initiated from heme-iron replete bacteria, suggesting a mechanism for epigenetic responses that participate in the changes observed. Additionally, in a co-infection model for human otitis media, heme-iron restricted Haemophilus, although accounting for only 10% of the inoculum (90% heme-iron replete, represented up to 99% of the organisms recovered at 4 days. These data indicate that fluctuations in heme-iron availability promote a survival advantage during disease. Filamentation mediated by a SulA-related ortholog was required for optimal biofilm peak height and persistence during experimental otitis media. Moreover, severity of disease in response to heme-iron restricted Haemophilus was reduced as evidenced by lack of mucosal destruction, decreased erythema, hemorrhagic foci and vasodilatation. Transient restriction of heme-iron also promoted productive invasion events leading to the development of intracellular bacterial communities. Taken together, these data suggest that nutritional immunity, may, in fact, foster long-term phenotypic changes that better equip

  13. Looking a Gift Horse in the Mouth: 2014 Farm Bill Insect and Disease Restoration Provision -- True Gift or False Hope?

    OpenAIRE

    Holmstead, Jamilee E.

    2015-01-01

    Congress passed a revised Farm Bill in 2014 that amended the Healthy Forest Restoration Act (HFRA) to, hopefully, increase the speed with which natural resource issues could be addressed. Federal land management has often been condemned for being time-consuming and burdensome, chiefly in situations that require rapid response, such as insect disease and fire. The amendment in the 2014 Farm Bill is meant to address this concern. The amendment would allow for the insect and disease restorati...

  14. Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

    Science.gov (United States)

    Bergman, P; Seyedoleslami Esfahani, S; Engström, Y

    2017-01-01

    Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer. © 2017 Elsevier Inc. All rights reserved.

  15. Prenatal diethylstilbestrol exposure and self-reported immune-related diseases

    NARCIS (Netherlands)

    Vingerhoets, A. J.; Assies, J.; Goodkin, K.; van Heck, G. L.; Bekker, M. H.

    1998-01-01

    To compare self-reports of immune-related diseases in diethylstilbestrol (DES) daughters and controls. Prenatal exposure to DES has been associated with several malformations in the lower genital tract, a higher prevalence of adenosis, and increased risk of clear cell adenocarcinoma, and

  16. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

    NARCIS (Netherlands)

    Z. Zelinkova (Zuzana); E. Bultman (Evelien); L. Vogelaar (Lauran); C. Bouziane (Cheima); E.J. Kuipers (Ernst); C.J. van der Woude (Janneke)

    2012-01-01

    textabstractAIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identifed through the electronic diagnosis

  17. Probiotics cultures in animal feed: Effects on ruminal fermentation, immune responses, and resistance to infectious diseases

    Science.gov (United States)

    We evaluated the effects of probiotics included in dairy cattle and mice feed on ruminal fermentation, immune responses, and resistance to Johne’s disease. To unveil the underlying mechanisms, dairy cattle were either fed Bovamine (1.04 x 10**9 cfu of Lactobacillus acidophilus NP51 plus 2.04 x 10**...

  18. Stress-induced modulation of the innate immune system in cardiovascular disease

    NARCIS (Netherlands)

    Lagraauw, Hendrik Maxime

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease in which lipids and cells of the immune system accumulate in the vessel wall. Clinical complications, such as a myocardial infarction or stroke may occur when advanced atherosclerotic lesions become unstable and rupture. In this thesis, the influence

  19. The Role of CD39 in Modulating Effector Immune Responses in Inflammatory Bowel Disease

    OpenAIRE

    Huang, Huang

    2015-01-01

    Inflammatory bowel disease is associated with excessive inflammation of the bowel and intestinal tissues in genetically susceptible individuals. IBD can manifest in two major forms, ulcerative colitis and Crohn’s disease. T helper type 17 cells (Th17) are effector lymphocytes that have been linked to intestinal inflammation in both mice and humans. Effector Th17 cells and regulatory T cells (Treg) – a subset pivotal to immune-tolerance maintenance – derive from the same CD4 progenitors. Our i...

  20. Comparative analysis of the effectiveness of three immunization strategies in controlling disease outbreaks in realistic social networks.

    Directory of Open Access Journals (Sweden)

    Zhijing Xu

    Full Text Available The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies-acquaintance immunization, community-bridge immunization, and ring vaccination-were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures. However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice.

  1. Comparative analysis of the effectiveness of three immunization strategies in controlling disease outbreaks in realistic social networks.

    Science.gov (United States)

    Xu, Zhijing; Zu, Zhenghu; Zheng, Tao; Zhang, Wendou; Xu, Qing; Liu, Jinjie

    2014-01-01

    The high incidence of emerging infectious diseases has highlighted the importance of effective immunization strategies, especially the stochastic algorithms based on local available network information. Present stochastic strategies are mainly evaluated based on classical network models, such as scale-free networks and small-world networks, and thus are insufficient. Three frequently referred stochastic immunization strategies-acquaintance immunization, community-bridge immunization, and ring vaccination-were analyzed in this work. The optimal immunization ratios for acquaintance immunization and community-bridge immunization strategies were investigated, and the effectiveness of these three strategies in controlling the spreading of epidemics were analyzed based on realistic social contact networks. The results show all the strategies have decreased the coverage of the epidemics compared to baseline scenario (no control measures). However the effectiveness of acquaintance immunization and community-bridge immunization are very limited, with acquaintance immunization slightly outperforming community-bridge immunization. Ring vaccination significantly outperforms acquaintance immunization and community-bridge immunization, and the sensitivity analysis shows it could be applied to controlling the epidemics with a wide infectivity spectrum. The effectiveness of several classical stochastic immunization strategies was evaluated based on realistic contact networks for the first time in this study. These results could have important significance for epidemic control research and practice.

  2. Oxidative Stress and Immune System in Vitiligo and Thyroid Diseases

    Science.gov (United States)

    Colucci, Roberta; Dragoni, Federica

    2015-01-01

    Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo. PMID:25838868

  3. Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?

    Science.gov (United States)

    Alcaïs, Alexandre; Quintana-Murci, Lluis; Thaler, David S; Schurr, Erwin; Abel, Laurent; Casanova, Jean-Laurent

    2010-12-01

    The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably among diseases and among studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline; (ii) theoretical modeling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age; (iii) available molecular evidence from both monogenic and complex genetics of infectious diseases in children and adults; (iv) current knowledge of immunity to primary and secondary or latent infections; (v) the state of the art in the clinical genetics of noninfectious pediatric and adult diseases; and (vi) evolutionary data for the genes underlying single-gene and complex disease risk. With the recent advent of new-generation deep resequencing, this model of single-gene variations underlying severe pediatric infectious diseases is experimentally testable. © 2010 New York Academy of Sciences.

  4. Acne: a new model of immune-mediated chronic inflammatory skin disease.

    Science.gov (United States)

    Antiga, E; Verdelli, A; Bonciani, D; Bonciolini, V; Caproni, M; Fabbri, P

    2015-04-01

    Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

  5. Innate immune responses against foot-and-mouth disease virus: current understanding and future directions.

    Science.gov (United States)

    Summerfield, Artur; Guzylack-Piriou, Laurence; Harwood, Lisa; McCullough, Kenneth C

    2009-03-15

    Foot-and-mouth disease (FMD) represents one of the most economically important diseases of farm animals. The basis for the threat caused by this virus is the high speed of replication, short incubation time, high contagiousness, and high mutation rate resulting in constant antigenic changes. Thus, although protective immune responses against FMD virus (FMDV) can be efficacious, the rapidity of virus replication and spread can outpace immune defence development and overrun the immune system. FMDV can also evade innate immune responses through its ability to shut down cellular protein synthesis, including IFN type I, in susceptible epithelial cells. This is important for virus evolution, as FMDV is quite sensitive to the action of IFN. Despite this, innate immune responses are probably induced in vivo, although detailed studies on this subject are lacking. Accordingly, this interaction of FMDV with cells of the innate immune system is of particular interest. Dendritic cells (DC) can be infected by FMDV and support viral RNA replication, and viral protein synthesis but the latter is inefficient or abortive, leading most often to incomplete replication and progeny virus release. As a result DC can be activated, and particularly in the case of plasmacytoid DC (pDC), this is manifest in terms of IFN-alpha release. Our current state of knowledge on innate immune responses induced by FMDV is still only at a relatively early stage of understanding. As we progress, the investigations in this area will help to improve the design of current vaccines and the development of novel control strategies against FMD.

  6. Rabbit haemorrhagic disease: advantages of cELISA in assessing immunity in wild rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Zheng, Tao; Parkes, John P

    2011-12-15

    Rabbit haemorrhagic disease (RHD) is an acute fatal disease of domestic and wild European rabbits (Oryctolagus cuniculus) caused by RHD virus (RHDV). Accurate assessment of immunity is of great importance for the conservation and control of wild rabbits. We evaluated a competitive ELISA (cELISA) against isotype ELISAs for assessing the protective immunity against the disease by challenging 50 wild-caught rabbits with a lethal dose of RHDV. Death or survival to the challenge was used as a criterion to determine the performance characteristics of the assay for the assessment of immunity in rabbits. At 1:10 dilution, a serum exhibiting ≥ 25% inhibition (1:10(25)) was regarded as the presence of RHDV-specific antibodies. Eleven of 16 (68.8%) rabbits with antibodies at 1:10(25) (<1:40) died of RHD. When the cut-off was moved from 25% to 50% inhibition (1:10(50)) at 1:10 serum dilution, the assay sensitivity, specificity and accuracy for the protective immunity were improved from 84%, 54.2% and 69.4% to 84%, 100% and 91.8%, respectively. We also demonstrated at the epitope amino acid sequence level why the presence of the RHDV-cross reactive benign rabbit calicivirus, which interfered with isotype ELISAs, had little impact on the specificity of the cELISA for the diagnosis of RHDV infection. The presence of RHDV-specific antibody at 1:10(50) by the cELISA is a reliable indicator for the protective immunity. In contrast to isotype ELISAs, the cELISA is a valuable specific tool for monitoring the herd immunity to RHD for the conservation and management of wild rabbits in the field. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

    Science.gov (United States)

    Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

    2018-01-01

    Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions

  8. Immunizations for Preterm Babies

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Immunizations For Preterm Babies Safety & ...

  9. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  10. Immunizations: Active vs. Passive

    Science.gov (United States)

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

  11. IMMUNOPATHOLOGIC SYNDROMES: IMMUNE AUTOAGGRESSION DISEASES, PATHOLOGIC TOLERANCE, «TRANSPLANT AGAINST HOST» REACTIONS

    Directory of Open Access Journals (Sweden)

    P.F. Litvitsky

    2007-01-01

    Full Text Available This publication is the fourth and last in the series of the brief lectures devoted to the role of the system, exercising the immunobiological supervision over the individual and continuous antigenic contents of the body both in normal conditions and in the event of the pathology. It reviews the etiology, pathogenesis and main manifestations of the immune auto aggression diseases, pathologic tolerance and «transplant against host» reactions.Key words: immune auto aggression, idiotype, antigenic mimicry, tolerance, «transplant against host» reactions.

  12. Tracking Restoration of Park and Urban Street Settings in Coronary Artery Disease Patients

    Directory of Open Access Journals (Sweden)

    Regina Grazuleviciene

    2016-05-01

    Full Text Available The physiological effects of natural and urban environments on the cardiovascular system of coronary artery disease (CAD patients are not fully understood. This controlled field study examines the effects of restorative walking in a park vs. in an urban street environment on CAD patients’ stress parameters and cardiac function. Methods: Twenty stable CAD patients were randomly allocated to 7 days controlled walking in a city park or in an urban street environment group. The relationship between different environmental exposures and health effects was analyzed using Wilcoxon signed-rank test and exact Mann-Whitney U test. Results: The mean reduction in cortisol levels and negative effects after the walk on the first day was greater in the city park than in the urban street exposed group, while a reduction in negative effects in the urban group were greater after seven days. The reduction in diastolic blood pressure (DBP in the park group was evident on the seventh day before the walk (−4 mm Hg, p = 0.031 and 60 min after the walk (−6.00 mm Hg, p = 0.002. The cortisol slope was negatively associated with the DBP changes (r = −0.514, p < 0.05. Conclusions: Physical activity in a green environment with noise and air pollution levels lower than in an urban environment has a greater positive effect on CAD patients’ stress level and hemodynamic parameters. Mitigating green environmental influences may allow urban residents to maintain health and reduce disability.

  13. Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease.

    Science.gov (United States)

    Middeldorp, Jaap M

    2015-01-01

    Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

  14. SAP: structure, function, and its roles in immune-related diseases.

    Science.gov (United States)

    Xi, Dan; Luo, TianTian; Xiong, Haowei; Liu, Jichen; Lu, Hao; Li, Menghao; Hou, Yuqing; Guo, Zhigang

    2015-01-01

    Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Extracellular cell stress (heat shock) proteins-immune responses and disease: an overview.

    Science.gov (United States)

    Pockley, A Graham; Henderson, Brian

    2018-01-19

    Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory 'danger signals' for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. © 2017 The Author(s).

  16. Steroid sparing regimens for management of oral immune-mediated diseases

    Directory of Open Access Journals (Sweden)

    Arti Agrawal

    2014-01-01

    Full Text Available Immune-mediated mucocutaneous disease may present oral symptoms as a first sign of the disease. The primary etiology could be the cellular and/or humoral immune responses directed against epithelial or connective tissue, in a chronic and recurrent pattern. Lichen planus, pemphigus vulgaris and bullous pemphigoid are the most frequent immunologically mediated mucocutaneous diseases. More often than not, patients present with complaints of blisters, oral ulcers, pain, burning sensation, and bleeding from the various oral sites. Steroids, whether topical or systemic, are the treatment of choice as they have both anti-inflammatory and immune-suppressant properties; however, challenges in the treatment of autoimmune diseases are the complexity of symptoms, the need to manage long-term medications for preserving organ function, and the long-term adverse effects of steroids. In such situations steroid sparing agents, such as, tacrolimus, dapsone, azathioprine, cyclosporine, and so on, may be helpful. Here an attempt is made to review various treatment regimens that could be used as alternatives to steroids for management of such diseases.

  17. Exxon Valdez oil spill restoration project final report: Prince William Sound Herring disease program (HDP), restoration project 070819

    Science.gov (United States)

    Hershberger, Paul; Elliott, Diane G.; Emmenegger, Eveline J.; Hansen, John D.; Kurath, Gael; Winton, James R.; Kocan, Richard; LaPatra, Scott

    2011-01-01

    Surveys of pathogens in Pacific herring from 2007 – 2010 indicated that Ichthyophonus, viral hemorrhagic septicemia virus, and erythrocytic necrosis virus are endemic in Prince William Sound and throughout the NE Pacific. Laboratory studies with VHSV indicated that multiple herring stocks are equally susceptible to the resulting disease, Pacific herring shed copious levels of VHSV (as high at 5x108 plaque-forming units/day) shortly after exposure, chronic and persistent infections can occur in Pacific herring, susceptibility of Pacific herring to VHS extends to the larval life stages but not the embryonic stages, and the prior exposure history of Pacific herring to VHSV can be determined post hoc. Laboratory studies involving Ichthyophonus indicated that schizonts can be inactivated with chlorine and iodine solutions, the parasite can survive for extended periods in saltwater but not freshwater, a low potential exists for cross contamination between in vitro explant cultures, infectious schizonts are released from the skin surface of infected herring, schizonts are not uniformly distributed throughout the skeletal muscle of infected Pacific herring, multiple types of Ichthyophonus exist with different genotypes and phenotypic traits, and temperature is an important factor influencing the infectivity of Ichthyophonus. Additional field and laboratory studies indicated that Ichthyophonus negatively influences the swimming performance of infected hosts and the negative impacts effects are exacerbated by increasing temperatures, American shad are an important reservoir of Ichthyophonus in the NE Pacific, Pacific herring are not susceptible to infectious hematopoietic necrosis (IHN), and Pacific herring will accept surgically implanted acoustic tags with negligible impacts on survival.

  18. Restoring the basal ganglia in Parkinson's disease to normal via multi-input phase-shifted deep brain stimulation.

    Science.gov (United States)

    Agarwal, Rahul; Sarma, Sridevi V

    2010-01-01

    Deep brain stimulation (DBS) injects a high frequency current that effectively disables the diseased basal ganglia (BG) circuit in Parkinson's disease (PD) patients, leading to a reversal of motor symptoms. Though therapeutic, high frequency stimulation consumes significant power forcing frequent surgical battery replacements and causing widespread influence into other brain areas which may lead to adverse side effects. In this paper, we conducted a rigorous study to assess whether low frequency signals can restore behavior in PD patients by restoring neural activity in the BG to the normal state. We used a biophysical-based model of BG nuclei and motor thalamus whose parameters can be set to simulate the normal state and the PD state with and without DBS. We administered pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies ranging from 1-150Hz. For each DBS frequency, we computed statistics on the simulated neural activity to assess whether it is restored to the normal state. In particular, we searched for DBS waveforms that suppress pathological bursting, oscillations, correlations and synchronization prevalent in the PD state and that enable thalamic cells to relay cortical inputs reliably. We found that none of the tested waveforms restores neural activity to the normal state. However, our simulations led us to construct a novel DBS strategy involving low frequency multi-input phaseshifted DBS to be administered into the STN. This strategy successfully suppressed all pathological symptoms in the BG in addition to enabling thalamic cells to relay cortical inputs reliably.

  19. Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis.

    Directory of Open Access Journals (Sweden)

    Ting-Wei Mu

    2008-02-01

    Full Text Available A lysosomal storage disease (LSD results from deficient lysosomal enzyme activity, thus the substrate of the mutant enzyme accumulates in the lysosome, leading to pathology. In many but not all LSDs, the clinically most important mutations compromise the cellular folding of the enzyme, subjecting it to endoplasmic reticulum-associated degradation instead of proper folding and lysosomal trafficking. A small molecule that restores partial mutant enzyme folding, trafficking, and activity would be highly desirable, particularly if one molecule could ameliorate multiple distinct LSDs by virtue of its mechanism of action. Inhibition of L-type Ca2+ channels, using either diltiazem or verapamil-both US Food and Drug Administration-approved hypertension drugs-partially restores N370S and L444P glucocerebrosidase homeostasis in Gaucher patient-derived fibroblasts; the latter mutation is associated with refractory neuropathic disease. Diltiazem structure-activity studies suggest that it is its Ca2+ channel blocker activity that enhances the capacity of the endoplasmic reticulum to fold misfolding-prone proteins, likely by modest up-regulation of a subset of molecular chaperones, including BiP and Hsp40. Importantly, diltiazem and verapamil also partially restore mutant enzyme homeostasis in two other distinct LSDs involving enzymes essential for glycoprotein and heparan sulfate degradation, namely alpha-mannosidosis and type IIIA mucopolysaccharidosis, respectively. Manipulation of calcium homeostasis may represent a general strategy to restore protein homeostasis in multiple LSDs. However, further efforts are required to demonstrate clinical utility and safety.

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

    Directory of Open Access Journals (Sweden)

    Ruth Pye

    2018-02-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  2. Innate Immunity and Saliva in Candida albicans–mediated Oral Diseases

    Science.gov (United States)

    Salvatori, O.; Puri, S.; Tati, S.; Edgerton, M.

    2016-01-01

    The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals. PMID:26747422

  3. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  4. Herd immunity to Newcastle disease virus in broiler flocks in Israel.

    Science.gov (United States)

    Wiseman, Anat; Berman, Elyakum M

    2017-08-01

    Due to the ongoing need to protect poultry from virulent Newcastle disease virus, all commercial poultry flocks in Israel are vaccinated according to a defined programme using a combination of live and inactivated vaccines. The vaccination protocol for broilers during the years of the study comprised a live vaccine administered by spray on the day of hatching, inactivated vaccine by subcutaneous injection at 10-12 days of age, and another live vaccine given by aerosol at 17-21 days of age. A cross-sectional study was designed in order to examine the influence of herd immunity on the risk of Newcastle disease outbreak in broiler flocks. The study was based on the extensive field data kept in the Poultry Health Laboratories database. The results of serology tests employing haemagglutination inhibition for Newcastle disease virus were analysed and crossed with the list of flocks that had been diagnosed with ND in the years 2007-2014. At the peak of induced immunization (fifth week of growth), 87.5% of the tested flocks had achieved herd immunity (≥85% of birds in the flock with an HI titre ≥4). Based on a logistic regression model, the odds ratio for ND in flocks without herd immunity was 3.7 (95% CI 1.8-7.3, P-value < 0.001). The higher the percentage of birds with low HI titres the higher the risk of ND outbreak. Under field conditions, herd immunity is an important indicator for the risk of ND outbreak.

  5. Harnessing what lies within: Programming immunity with biocompatible devices to treat human disease

    Science.gov (United States)

    Roberts, Reid Austin

    Advances in our mechanistic insight of cellular function and how this relates to host physiology have revealed a world which is intimately connected at the macro and micro level. Our increasing understanding of biology exemplifies this, where cells respond to environmental cues through interconnected networks of proteins which function as receptors and adaptors to elicit gene expression changes that drive appropriate cellular programs for a given stimulus. Consequently, our deeper molecular appreciation of host homeostasis implicates aberrations of these pathways in nearly all major human disease categories, including those of infectious, metabolic, neurologic, oncogenic, and autoimmune etiology. We have come to recognize the mammalian immune system as a common network hub among all these varied pathologies. As such, the major goal of this dissertation is to identify a platform to program immune responses in mammals so that we may enhance our ability to treat disease and improve health in the 21st century. Using advances in materials science, in particular a recently developed particle fabrication technology termed Particle Replication in Non-wetting Templates (PRINT), our studies systematically assess the murine and human immune response to precisely fabricated nano- and microscale particles composed of biodegradable and biocompatible materials. We then build on these findings and present particle design parameters to program a number of clinically attractive immune responses by targeting endogenous cellular signaling pathways. These include control of particle uptake through surface modification, design parameters that modulate the magnitude and kinetics of biological signaling dynamics that can be used to exacerbate or dampen inflammatory responses, as well as particle designs which may be of use in treating allergies and autoimmune disorders. In total, this dissertation provides evidence that rational design of biocompatible nano- and microparticles is a viable

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

    Science.gov (United States)

    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.

  7. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease?

    Science.gov (United States)

    Colbeck, Emily Jayne; Ager, Ann; Gallimore, Awen; Jones, Gareth Wyn

    2017-01-01

    Secondary lymphoid organs are integral to initiation and execution of adaptive immune responses. These organs provide a setting for interactions between antigen-specific lymphocytes and antigen-presenting cells recruited from local infected or inflamed tissues. Secondary lymphoid organs develop as a part of a genetically preprogrammed process during embryogenesis. However, organogenesis of secondary lymphoid tissues can also be recapitulated in adulthood during de novo lymphoid neogenesis of tertiary lymphoid structures (TLSs). These ectopic lymphoid-like structures form in the inflamed tissues afflicted by various pathological conditions, including cancer, autoimmunity, infection, or allograft rejection. Studies are beginning to shed light on the function of such structures in different disease settings, raising important questions regarding their contribution to progression or resolution of disease. Data show an association between the tumor-associated TLSs and a favorable prognosis in various types of human cancer, attracting the speculation that TLSs support effective local antitumor immune responses. However, definitive evidence for the role for TLSs in fostering immune responses in vivo are lacking, with current data remaining largely correlative by nature. In fact, some more recent studies have even demonstrated an immunosuppressive, tumor-promoting role for cancer-associated TLSs. In this review, we will discuss what is known about the development of cancer-associated TLSs and the current understanding of their potential role in the antitumor immune response. PMID:29312327

  8. Rebuilding immunity with Remune.

    Science.gov (United States)

    Whitfield, L

    1998-01-01

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

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  10. Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems

    Science.gov (United States)

    Dusi, Veronica; Ghidoni, Alice; Ravera, Alice; De Ferrari, Gaetano M.; Calvillo, Laura

    2016-01-01

    Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a “working-network” in deep linkage with the autonomic nervous system. In this paper we will describe the single chemokines more involved in heart diseases; then we will present a comprehensive perspective of them as a complex network connecting the cardiovascular system to both the immune and the autonomic nervous systems. Finally, some recent evidences indicating chemokines as a possible new tool to predict cardiovascular risk will be described. PMID:27242392

  11. Restorative neuroscience

    DEFF Research Database (Denmark)

    Andres, Robert H; Meyer, Morten; Ducray, Angélique D

    2008-01-01

    There is increasing interest in the search for therapeutic options for diseases and injuries of the central nervous system (CNS), for which currently no effective treatment strategies are available. Replacement of damaged cells and restoration of function can be accomplished by transplantation of...

  12. Behavioral immune system and ingroup derogation: the effects of infectious diseases on ingroup derogation attitudes.

    Directory of Open Access Journals (Sweden)

    Qi Wu

    Full Text Available From evolutionary reasoning, we derived a novel hypothesis that ingroup derogation is an evolved response of behavioral immune system which follows the smoke detector principle and the functional flexibility principle. This hypothesis was tested and supported across three experiments. In Experiment 1, participants' group membership was manipulated by using a minimal group paradigm. The results indicated that mere social categorization alone - a heuristic cue that implies the differentiation between "us" and "them" - was sufficient to elicit ingroup derogation among Chinese participants, and, such an intergroup bias was positively associated with the perceived vulnerability to diseases, which was also more consistently associated with ingroup attitudes. Experiment 2 extended and partially replicated Experiment 1 by showing that when there were cues of diseases in the immediate physical environment, Chinese participants exaggerated their attitudes of ingroup derogation. The results also showed that this effect was mainly driven by outgroup attraction. Experiment 3 changed the method of disease manipulation, and found that Chinese participants responded more strongly to disease cues originating from ingroup members and that they endorsed more ingroup derogation attitudes even when the ingroup and outgroup members were both displaying cues of diseases. Taken together, these results reveal the previously unexplored effects of infectious diseases on ingroup derogation attitudes, and suggest an interesting linkage between the evolved behavioral immune system and the ingroup derogation.

  13. Severe infectious diseases of childhood as monogenic inborn errors of immunity

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-01-01

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications. PMID:26621750

  14. Severe infectious diseases of childhood as monogenic inborn errors of immunity.

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-12-22

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

  15. Childhood Immunization

    Science.gov (United States)

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  16. Transcriptional Innate Immune Response of the Developing Chicken Embryo to Newcastle Disease Virus Infection

    Science.gov (United States)

    Schilling, Megan A.; Katani, Robab; Memari, Sahar; Cavanaugh, Meredith; Buza, Joram; Radzio-Basu, Jessica; Mpenda, Fulgence N.; Deist, Melissa S.; Lamont, Susan J.; Kapur, Vivek

    2018-01-01

    Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust. The expression of CCL5, Mx1, and TLR3 in lung tissues of NDV challenged chicken embryos from the outbred Kuroiler and Tanzanian local ecotype lines showed that their expression was several orders of magnitude higher in the Kuroiler than in the local ecotypes. Next, the expression patterns of three additional innate-immunity related genes, IL-8, IRF-1, and STAT1, were examined in the highly congenic Fayoumi (M5.1 and M15.2) and Leghorn (Ghs6 and Ghs13) sublines that differ only at the microchromosome bearing the major histocompatibility locus. The results show that the Ghs13 Leghorn subline had a consistently higher expression of all genes except IL-8 and expression seemed to be subline-dependent rather than breed-dependent, suggesting that the innate immune response of chicken embryos to NDV infection may be genetically controlled by the MHC-locus. Taken together, the results suggest that the chicken embryo may represent a promising model to studying the patterns and sources of variation of the avian innate immune response to infection with NDV and related pathogens. PMID:29535762

  17. Clinical use of enteral immune nutrition in patients with acute exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Zhi-cheng ZHANG

    2015-06-01

    Full Text Available Objective To investigate the use of enteral immune nutrition preparation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD, regard its efficacy in improving nutritional status, and its influence on immunity and the status of acute inflammatory reaction of the patients. Methods Sixty-two AECOPD patients requiring mechanical ventilation in ICU of our hospital were randomly divided into two groups: immune nutrition group [study group, n=32, receiving Ruineng (a product of Huarui Pharmaceutical Ltd., which contained essential fatty acids, Omega-3 fatty acids, and energy 1.3 kcal/ml] and conventional nutrition group (control group, n=30, receiving the hospital self-made homogenized diet with 1.2 kal/ml. Patients in the two groups took enteral nutrition of equal calorie, and it was given by nasointestinal tube. On the day of admission and the 14th and 18th after admission, venous blood was obtained for the determination of serum albumin, prealbumin, transferrin, C reactive protein (CRP, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6. At the same time upper arm muscle circumference (MAMC was measured at the bed side. The 14-day off-respirator rate and mechanical ventilation time within 28 days were compared between the two groups. Results The 14-day off-respirator rate was higher in study group than in control group (P0.05. Conclusions Compared with homogenized diet, immune enteral nutrition could better improve the nutritional status and immune function, lower the acute inflammatory response level, increase the success rate of early off-respirator in AECOPD patients, therefore, enteral immune nutrition preparation is a better nutrition support solution for AECOPD. DOI: 10.11855/j.issn.0577-7402.2015.05.17

  18. Transcriptional Innate Immune Response of the Developing Chicken Embryo to Newcastle Disease Virus Infection

    Directory of Open Access Journals (Sweden)

    Megan A. Schilling

    2018-02-01

    Full Text Available Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust. The expression of CCL5, Mx1, and TLR3 in lung tissues of NDV challenged chicken embryos from the outbred Kuroiler and Tanzanian local ecotype lines showed that their expression was several orders of magnitude higher in the Kuroiler than in the local ecotypes. Next, the expression patterns of three additional innate-immunity related genes, IL-8, IRF-1, and STAT1, were examined in the highly congenic Fayoumi (M5.1 and M15.2 and Leghorn (Ghs6 and Ghs13 sublines that differ only at the microchromosome bearing the major histocompatibility locus. The results show that the Ghs13 Leghorn subline had a consistently higher expression of all genes except IL-8 and expression seemed to be subline-dependent rather than breed-dependent, suggesting that the innate immune response of chicken embryos to NDV infection may be genetically controlled by the MHC-locus. Taken together, the results suggest that the chicken embryo may represent a promising model to studying the patterns and sources of variation of the avian innate immune response to infection with NDV and related pathogens.

  19. Short communication: Association of disease incidence and adaptive immune response in Holstein dairy cows.

    Science.gov (United States)

    Thompson-Crispi, K A; Hine, B; Quinton, M; Miglior, F; Mallard, B A

    2012-07-01

    The objective of this study was to use previously calculated estimated breeding values for cell- (CMIR) and antibody-mediated immune responses (AMIR) to determine associations between immune response (IR) and economically important diseases of dairy cattle. In total, 699 Holsteins were classified as high, average, or low for CMIR, AMIR, and overall IR (combined CMIR and AMIR), and associations with mastitis, metritis, ketosis, displaced abomasums, and retained fetal membranes were determined. The incidence of mastitis was higher among average cows as compared with cows classified as high AMIR [odds ratio (OR)=2.5], high CMIR (OR=1.8), or high IR (OR=1.8). Low-CMIR cows had a higher incidence of metritis (OR=11.3) and low-IR cows had a higher incidence of displaced abomasum (OR=4.1) and retained fetal membrane (OR=2.8) than did average responders. Results of this study show that cows classified as high immune responders have lower occurrence of disease, suggesting that breeding cattle for enhanced IR may be a feasible approach to decrease the incidence of infectious and metabolic diseases in the dairy industry. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

    Science.gov (United States)

    Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash; Kothary, Rashmi

    2017-02-15

    Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. © The Author 2017. Published by Oxford University Press.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sanjay H. Chotirmall

    2013-01-01

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

  3. GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases

    Institute of Scientific and Technical Information of China (English)

    Yin Yao Shugart; Ying Wang; Wei-Hua Jia; Yi-Xin Zeng

    2011-01-01

    Increasing evidence suggests that multiple genes in the human leukocyte antigen (HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

  4. Association of immune response to endothelial cell growth factor with early disseminated and late manifestations of Lyme disease but not posttreatment Lyme disease syndrome.

    Science.gov (United States)

    Tang, Kevin S; Klempner, Mark S; Wormser, Gary P; Marques, Adriana R; Alaedini, Armin

    2015-12-01

    Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Intermittent Fasting Protects against Alzheimer's Disease Possible through Restoring Aquaporin-4 Polarity.

    Science.gov (United States)

    Zhang, Jingzhu; Zhan, Zhipeng; Li, Xinhui; Xing, Aiping; Jiang, Congmin; Chen, Yanqiu; Shi, Wanying; An, Li

    2017-01-01

    The impairment of amyloid-β (Aβ) clearance in the brain plays a causative role in Alzheimer's disease (AD). Polarity distribution of aquaporin-4 (AQP4) is important to remove Aβ from brain. AQP4 polarity can be influenced by the ratio of two AQP4 isoforms M1 and M23 (AQP4-M1/M23), however, it is unknown whether the ratio of AQP4-M1/M23 changes in AD. Histone deacetylase 3 has been reported to be significantly increased in AD brain. Moreover, evidence indicated that microRNA-130a (miR-130a) possibly mediates the regulation of histone deacetylase 3 on AQP4-M1/M23 ratio by repressing the transcriptional activity of AQP4-M1 in AD. This study aimed to investigate whether intermittent fasting (IF), increasing the level of an endogenous histone deacetylases inhibitor β-hydroxybutyrate, restores AQP4 polarity via miR-130a mediated reduction of AQP4-M1/M23 ratio in protection against AD. The results showed that IF ameliorated cognitive dysfunction, prevented brain from Aβ deposition, and restored the AQP4 polarity in a mouse model of AD (APP/PS1 double-transgenic mice). Additionally, IF down-regulated the expression of AQP4-M1 and histone deacetylase 3, reduced AQP4-M1/M23 ratio, and increased miR-130a expression in the cerebral cortex of APP/PS1 mice. In vitro , β-hydroxybutyrate was found to down-regulate the expression of AQP4-M1 and histone deacetylase 3, reduce AQP4-M1/M23 ratio, and increase AQP4-M23 and miR-130a expression in 2 μM Aβ-treated U251 cells. Interestingly, on the contrary to the result observed in 2 μM Aβ-treated cells, AQP4 expression was obviously decreased in cells exposed to 10 μM Aβ. miR-130a mimic decreased the expression of AQP4-M1 and the ratio of AQP4-M1/M23, as well as silencing histone deacetylase 3 caused the up-regulation of AQP4 and miR-130a, and the reduction of AQP4-M1/M23 ratio in U251 cells. In conclusion, IF exhibits beneficial effects against AD. The mechanism may be associated with recovery of AQP4 polarity, resulting from

  6. Intermittent Fasting Protects against Alzheimer’s Disease Possible through Restoring Aquaporin-4 Polarity

    Directory of Open Access Journals (Sweden)

    Jingzhu Zhang

    2017-11-01

    Full Text Available The impairment of amyloid-β (Aβ clearance in the brain plays a causative role in Alzheimer’s disease (AD. Polarity distribution of aquaporin-4 (AQP4 is important to remove Aβ from brain. AQP4 polarity can be influenced by the ratio of two AQP4 isoforms M1 and M23 (AQP4-M1/M23, however, it is unknown whether the ratio of AQP4-M1/M23 changes in AD. Histone deacetylase 3 has been reported to be significantly increased in AD brain. Moreover, evidence indicated that microRNA-130a (miR-130a possibly mediates the regulation of histone deacetylase 3 on AQP4-M1/M23 ratio by repressing the transcriptional activity of AQP4-M1 in AD. This study aimed to investigate whether intermittent fasting (IF, increasing the level of an endogenous histone deacetylases inhibitor β-hydroxybutyrate, restores AQP4 polarity via miR-130a mediated reduction of AQP4-M1/M23 ratio in protection against AD. The results showed that IF ameliorated cognitive dysfunction, prevented brain from Aβ deposition, and restored the AQP4 polarity in a mouse model of AD (APP/PS1 double-transgenic mice. Additionally, IF down-regulated the expression of AQP4-M1 and histone deacetylase 3, reduced AQP4-M1/M23 ratio, and increased miR-130a expression in the cerebral cortex of APP/PS1 mice. In vitro, β-hydroxybutyrate was found to down-regulate the expression of AQP4-M1 and histone deacetylase 3, reduce AQP4-M1/M23 ratio, and increase AQP4-M23 and miR-130a expression in 2 μM Aβ-treated U251 cells. Interestingly, on the contrary to the result observed in 2 μM Aβ-treated cells, AQP4 expression was obviously decreased in cells exposed to 10 μM Aβ. miR-130a mimic decreased the expression of AQP4-M1 and the ratio of AQP4-M1/M23, as well as silencing histone deacetylase 3 caused the up-regulation of AQP4 and miR-130a, and the reduction of AQP4-M1/M23 ratio in U251 cells. In conclusion, IF exhibits beneficial effects against AD. The mechanism may be associated with recovery of AQP4 polarity

  7. Fatigue in patients with inflammatory bowel disease is associated with distinct differences in immune parameters

    Directory of Open Access Journals (Sweden)

    Vogelaar L

    2017-05-01

    Full Text Available Lauran Vogelaar, 1,* Colin de Haar,2,* Bas RJ Aerts,1 Maikel P Peppelenbosch,1 Reinier Timman,3 Bettina E Hanssen,1 C Janneke van der Woude1 1Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, 2Applied Tumor Immunology, Laboratory of Translational Immunology, UMC Utrecht, Utrecht, 3Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus MC, Rotterdam, the Netherlands *These authors contributed equally to this work Background: Although it is well recognized that fatigue is an important problem in many of the quiescent inflammatory bowel disease (IBD patients, it is unknown whether the immune status is different in fatigued versus non-fatigued patients. In this study, we contrasted various characteristics of the immune system in fatigued against non-fatigued patients with IBD in clinical remission.Patients and methods: Patients with IBD in clinical remission were phenotyped according to the Montreal classification, and the checklist individual strength-fatigue (CIS-fatigue was used to assess fatigue (CIS-fatigue ≥ 35. Flow cytometry on peripheral blood samples was used to investigate differences in leukocyte subsets. The expression of various cytokines was determined in stimulated whole blood and serum samples using enzyme-linked immunosorbent assay. Differences between fatigued and non-fatigued patients with IBD were assessed.Results: In total, 55 patients were included in the fatigue group (FG and 29 patients in the non-fatigue group (NFG. No differences in demographic and clinical characteristics were observed between the groups. Flow cytometry data showed a significantly lower percentage of monocytes (p = 0.011 and a higher percentage of memory T-cells (p = 0.005 and neutrophils (p = 0.033 in the FG compared with the NFG. Whole blood stimulation showed increased TNF-α (p = 0.022 and IFN-γ (p = 0.047 in the FG. The median serum level was significantly higher for IL-12 (p < 0.001 and IL-10 (p

  8. Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

    Directory of Open Access Journals (Sweden)

    Gideon Steinbach

    Full Text Available Severe intestinal graft-vs-host disease (GVHD after allogeneic hematopoietic cell transplantation (HCT causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3, would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury. We conducted an observational pilot study to provide data for the potential design of a randomized study of lithium. Twenty patients with steroid refractory intestinal GVHD meeting enrollment criteria were given oral lithium carbonate. GVHD was otherwise treated per current practice, including 2 mg/kg per day of prednisone equivalent. Seventeen patients had extensive mucosal denudation (extreme endoscopic grade 3 in the duodenum or colon. We observed that 8 of 12 patients (67% had a complete remission (CR of GVHD and survived more than 1 year (median 5 years when lithium administration was started promptly within 3 days of endoscopic diagnosis of denuded mucosa. When lithium was started promptly and less than 7 days from salvage therapy for refractory GVHD, 8 of 10 patients (80% had a CR and survived more than 1 year. In perspective, a review of 1447 consecutive adult HCT patients in the preceding 6 years at our cancer center showed 0% one-year survival in 27 patients with stage 3-4 intestinal GVHD and grade 3 endoscopic appearance in the duodenum or colon. Toxicities included fatigue, somnolence, confusion or blunted affect in 50% of the patients. The favorable outcomes in patients who received prompt lithium therapy appear to support the future conduct of a randomized study of lithium for management of severe GVHD with

  9. Reuma.pt contribution to the knowledge of immune-mediated systemic rheumatic diseases.

    Science.gov (United States)

    Santos, Maria José; Canhão, Helena; Mourão, Ana Filipa; Oliveira Ramos, Filipa; Ponte, Cristina; Duarte, Cátia; Barcelos, Anabela; Martins, Fernando; Melo Gomes, José António

    2017-01-01

    Patient registries are key instruments aimed at a better understanding of the natural history of diseases, at assessing the effectiveness of therapeutic interventions, as well as identifying rare events or outcomes that are not captured in clinical trials. However, the potential of registries goes far beyond these aspects. For example, registries promote the standardization of clinical practice, can also provide information on domains that are not routinely collected in clinical practice and can support decision-making. Being aware of the importance of registries, the Portuguese Society of Rheumatology developed the Rheumatic Diseases Portuguese Register- Reuma.pt - which proved to be an innovative instrument essential to a better understanding of systemic immune-mediated rheumatic diseases. To describe the contribution of Reuma.pt to the knowledge of systemic immune-mediated rheumatic diseases. Reuma.pt is widely implemented, with 77 centres actively contributing to the recruitment and follow-up of patients. Reuma.pt follows in a standardized way patients with the following systemic inflammatory rheumatic diseases: rheumatoid arthritis (n=6218), psoriatic arthritis (n=1498), spondyloarthritis (n=2529), juvenile idiopathic arthritis (n =1561), autoinflammatory syndromes (n=122), systemic lupus erythematosus (n =1718), systemic sclerosis (n=180) and vasculitis (n=221). This platform is intended for use as an electronic medical record, provides standardized assessment of patients and support to the clinical decision, thereby contributing to a better quality of care of rheumatic patients. The research based on Reuma.pt identified genetic determinants of susceptibility and response to therapy, characterized in detail systemic rheumatic diseases and their long-term impact, critically appraised the performance of instruments for monitoring the disease activity, established the effectiveness and safety of biologic therapies and identified predictors of response, and

  10. The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases.

    Science.gov (United States)

    Yin, Jinghua; Zhang, Jian; Lu, Qianjin

    2017-07-01

    Basic leucine zipper transcription factor E4BP4 (also known as NFIL3) has been implicated in the molecular and cellular mechanisms of functions and activities in mammals. The interactions between E4BP4 and major regulators of cellular processes have triggered significant interest in the roles of E4BP4 in the pathogenesis of certain chronic diseases. Indeed, novel discoveries have been emerging to illustrate the involvement of E4BP4 in multiple disorders. It is recognized that E4BP4 is extensively involved in some immune-mediated diseases, but the mechanisms of E4BP4 involvement in these complex diseases remain poorly defined. Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies. Copyright © 2017. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2014-07-01

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

  12. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases.

    Science.gov (United States)

    García Bueno, B; Caso, J R; Madrigal, J L M; Leza, J C

    2016-05-01

    The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Regulation of the Immune Response to α-Gal and Vector-borne Diseases.

    Science.gov (United States)

    Cabezas-Cruz, Alejandro; Mateos-Hernández, Lourdes; Pérez-Cruz, Magdiel; Valdés, James J; Mera, Isabel G Fernández de; Villar, Margarita; de la Fuente, José

    2015-10-01

    Vector-borne diseases (VBD) challenge our understanding of emerging diseases. Recently, arthropod vectors have been involved in emerging anaphylactic diseases. In particular, the immunoglobulin E (IgE) antibody response to the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-gal) following a tick bite was associated with allergies to red meat, cetuximab, and gelatin. By contrast, an anti-α-gal IgM antibody response was shown to protect against mosquito-borne malaria. Herein, we highlight the interplay between the gut microbiota, vectors, transmitted pathogens, and the regulation of the immune response as a model to understand the protective or allergic effect of α-gal. Establishing the source of α-gal in arthropod vectors and the immune response to vector bites and transmitted pathogens will be essential for diagnosing, treating, and ultimately preventing these emerging anaphylactic and other vector-borne diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Innate immune signalling at the intestinal epithelium in homeostasis and disease

    Science.gov (United States)

    Pott, Johanna; Hornef, Mathias

    2012-01-01

    The intestinal epithelium—which constitutes the interface between the enteric microbiota and host tissues—actively contributes to the maintenance of mucosal homeostasis and defends against pathogenic microbes. The recognition of conserved microbial products by cytosolic or transmembrane pattern recognition receptors in epithelial cells initiates signal transduction and influences effector cell function. However, the signalling pathways, effector molecules and regulatory mechanisms involved are not yet fully understood, and the functional outcome is poorly defined. This review analyses the complex and dynamic role of intestinal epithelial innate immune recognition and signalling, on the basis of results in intestinal epithelial cell-specific transgene or gene-deficient animals. This approach identifies specific epithelial cell functions within the diverse cellular composition of the mucosal tissue, in the presence of the complex and dynamic gut microbiota. These insights have thus provided a more comprehensive understanding of the role of the intestinal epithelium in innate immunity during homeostasis and disease. PMID:22801555

  15. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

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

    Science.gov (United States)

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

    2012-08-01

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

  17. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice.

    Science.gov (United States)

    Ohlmann, Andreas; Scholz, Michael; Goldwich, Andreas; Chauhan, Bharesh K; Hudl, Kristiane; Ohlmann, Anne V; Zrenner, Eberhart; Berger, Wolfgang; Cvekl, Ales; Seeliger, Mathias W; Tamm, Ernst R

    2005-02-16

    Norrie disease is an X-linked retinal dysplasia that presents with congenital blindness, sensorineural deafness, and mental retardation. Norrin, the protein product of the Norrie disease gene (NDP), is a secreted protein of unknown biochemical function. Norrie disease (Ndp(y/-)) mutant mice that are deficient in norrin develop blindness, show a distinct failure in retinal angiogenesis, and completely lack the deep capillary layers of the retina. We show here that the transgenic expression of ectopic norrin under control of a lens-specific promoter restores the formation of a normal retinal vascular network in Ndp(y/-) mutant mice. The improvement in structure correlates with restoration of neuronal function in the retina. In addition, lenses of transgenic mice with ectopic expression of norrin show significantly more capillaries in the hyaloid vasculature that surrounds the lens during development. In vitro, lenses of transgenic mice in coculture with microvascular endothelial cells induce proliferation of the cells. Transgenic mice with ectopic expression of norrin show more bromodeoxyuridine-labeled retinal progenitor cells at embryonic day 14.5 and thicker retinas at postnatal life than wild-type littermates, indicating a putative direct neurotrophic effect of norrin. These data provide direct evidence that norrin induces growth of ocular capillaries and that pharmacologic modulation of norrin might be used for treatment of the vascular abnormalities associated with Norrie disease or other vascular disorders of the retina.

  18. Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2016-11-01

    Full Text Available Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer’s disease (AD. Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host’s adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions. In periodontitis, this bacterium inhibits the synthesis of IL-2 and increases humoral responses. This reduces the inflammatory responses related to T- and B-cell activation, and subsequent IFN-γ secretion by a subset of T cells. The T cells further suppress upregulation of programmed cell death-1 (PD-1-receptor on CD+cells and its ligand PD-L1 on CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response and induces a cytokine pattern in which the Th17 lineage is favored, thereby modulating the Th17/T-regulatory cell (Treg imbalance. The suppression of IFN-γ-stimulated release of interferon-inducible protein-10 (IP-10 chemokine ligands [ITAC (CXCL11 and Mig (CXCL9] by P. gingivalis capsular serotypes triggers distinct T cell responses and contributes to local immune evasion by release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces Tregs, transforms growth factor beta-1 (TGFβ-1, and causes imbalance in the Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood–brain barrier permeability and inhibit local IFN-γ response by preventing entry of immune cells into the brain. The scarcity of adaptive immune cells in AD neuropathology implies P. gingivalis infection of the brain likely causing impaired clearance of insoluble amyloid and inducing immunosuppression. By the effective manipulation of

  19. Diagnosis of acute radiation disease by Enzyme Immune-Assay (EIA)

    International Nuclear Information System (INIS)

    Popov, D.; Maliev, V.; Jones, J.; Gonta, S.; Prasad, K.; Rachal, C.

    2006-01-01

    Diagnosis of the acute radiation disease by the method of immune enzyme assay is a simple and efficient tool of evaluating and biological dosimetry and forecasting of development of the acute radiation defeats as at group of population so at individuals locating in the zone polluted by the radiation. We use as biological markers the group of essential radiotoxins - high molecular mass glycoprotein ( molecular mass - 200 - 250 kDa ) - radiation antigens (S.D.R. - specific radiation determinant ) accumulated in the lymphoid system, with epitopes specific to each form of radiation syndrome, after animals have been irradiated in doses inducing the development of the cerebral (1), toxic ( 2), gastrointestinal ( 3 ) and typical ( 4 ) forms of acute radiation sickness. These two phenomena allowed us to develop a technologies for diagnosis, prophylaxis and therapy of radiation disease - enzyme immune assay ( EIA ), anti radiation vaccine, anti radiation serum, method of immune - lymph - plasma-sorption. The important first step in effectiveness of therapy is an accurate assessment of severity of disease in early period after irradiation. The ideal markers for early and accurate assessment is high weight glycoprotein with specifics radiation induced features (S.D.R.) mentioned above. This biology active substance isolated from lymph can induct the symptoms of radiation syndrome without previously radiation when it is administrated intra-muscularly or intravenously to healthy animals. Enzyme immune assay (EIA) allowed researchers to indicate the significant levels of different forms of S.D.R. in peripheral blood of animals in first 24 hours after radiation. Indication of high level of S.D.R. -1 allowed to forecast a fast development of cerebral form of acute radiation disease. Determination of high levels of S.D.R.-2, S.D.R.-3 and S.D.R.-4 in peripheral blood allowed to recognize early periods of toxic, gastrointestinal and typical forms of acute radiation sickness

  20. Diagnosis of acute radiation disease by Enzyme Immune-Assay (EIA)

    Energy Technology Data Exchange (ETDEWEB)

    Popov, D.; Maliev, V. [Russian Academy of Science, Vladicaukas (Russian Federation); Jones, J.; Gonta, S. [NASA -Johnson Spa ce Center, Houston (United States); Prasad, K. [Antioxidant Research Institute, Premier Micrinutrient corporation, Novato (United States); Rachal, C. [Univercity Space Research Assotiation, Colorado (United States)

    2006-07-01

    Diagnosis of the acute radiation disease by the method of immune enzyme assay is a simple and efficient tool of evaluating and biological dosimetry and forecasting of development of the acute radiation defeats as at group of population so at individuals locating in the zone polluted by the radiation. We use as biological markers the group of essential radiotoxins - high molecular mass glycoprotein ( molecular mass - 200 - 250 kDa ) - radiation antigens (S.D.R. - specific radiation determinant ) accumulated in the lymphoid system, with epitopes specific to each form of radiation syndrome, after animals have been irradiated in doses inducing the development of the cerebral (1), toxic ( 2), gastrointestinal ( 3 ) and typical ( 4 ) forms of acute radiation sickness. These two phenomena allowed us to develop a technologies for diagnosis, prophylaxis and therapy of radiation disease - enzyme immune assay ( EIA ), anti radiation vaccine, anti radiation serum, method of immune - lymph - plasma-sorption. The important first step in effectiveness of therapy is an accurate assessment of severity of disease in early period after irradiation. The ideal markers for early and accurate assessment is high weight glycoprotein with specifics radiation induced features (S.D.R.) mentioned above. This biology active substance isolated from lymph can induct the symptoms of radiation syndrome without previously radiation when it is administrated intra-muscularly or intravenously to healthy animals. Enzyme immune assay (EIA) allowed researchers to indicate the significant levels of different forms of S.D.R. in peripheral blood of animals in first 24 hours after radiation. Indication of high level of S.D.R. -1 allowed to forecast a fast development of cerebral form of acute radiation disease. Determination of high levels of S.D.R.-2, S.D.R.-3 and S.D.R.-4 in peripheral blood allowed to recognize early periods of toxic, gastrointestinal and typical forms of acute radiation sickness

  1. Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

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    Juan Marcos Mucci

    2015-01-01

    Full Text Available Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

  2. Attention deficit hyperactivity disorder may be a highly inflammation and immune-associated disease (Review).

    Science.gov (United States)

    Zhou, Rong-Yi; Wang, Jiao-Jiao; Sun, Ji-Chao; You, Yue; Ying, Jing-Nang; Han, Xin-Min

    2017-10-01

    Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder. Previous research has indicated that genetic factors, family education, environment and dietary habits are associated with ADHD. It has been determined that in China many children with ADHD also have allergic rhinitis or asthma. These children are more susceptible to the common cold or upper respiratory infections compared with normal healthy children. Additionally, the common cold or an upper respiratory infection may lead to disease recurrence or worsen the symptoms in these children. Previous studies have determined that ADHD may have a close association with allergic disease. Based on the clinically observed phenomenon and previous studies, it was hypothesized that ADHD is a high inflammation and immune‑associated disease. Therefore, the authors designed clinical and animal experiments to test this hypothesis in the future. Immune system disorders may be a novel part of the etiology of ADHD. The current report may have implications for future clinical practice.

  3. Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease

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    Crompton, Peter D.; Moebius, Jacqueline; Portugal, Silvia; Waisberg, Michael; Hart, Geoffrey; Garver, Lindsey S.; Miller, Louis H.; Barillas, Carolina; Pierce, Susan K.

    2014-01-01

    Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa family, the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world’s most vulnerable populations, claiming the lives of nearly a million children and pregnant women each year in Africa alone. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite’s complex life cycle with a view towards developing the tools that will contribute to the prevention of disease and death and ultimately the goal of malaria eradication. In so doing we hope to inspire immunologists to participate in defeating this devastating disease. PMID:24655294

  4. Maternal Infectious Diseases, Antimicrobial Therapy or Immunizations: Very few Contraindications to Breastfeeding

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    Noni E Macdonald

    2006-01-01

    Full Text Available The Canadian Paediatric Society recommends exclusive breastfeeding as the optimal method of infant feeding for the first six months of life for healthy, term infants (1. There are many benefits associated with breastfeeding, including nutritional, immunological, psychological, developmental, environmental, social, economic and health (eg, decrease in infectious diseases (2-4. To promote, protect and support breastfeeding, every effort must be made to minimize contraindications to breastfeeding, particularly unnecessary ones. The present article summarizes the maternal infectious diseases in which continuing breastfeeding is recommended, the very few infectious diseases in which it is not recommended, the rare instances in which maternal antimicrobial therapy indicates a caution for breastfeeding, and the continuation of breastfeeding when a mother or her infant is receiving a routine recommended immunization.

  5. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.

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    Lesley Jones

    2010-11-01

    Full Text Available Late Onset Alzheimer's disease (LOAD is the leading cause of dementia. Recent large genome-wide association studies (GWAS identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.

  6. Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease

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    Nath KD

    2013-12-01

    Full Text Available Karthik D Nath,1,2 Julie G Burel,1 Viswanathan Shankar,3 Antonia L Pritchard,1 Michelle Towers,2 David Looke,1,2 Janet M Davies,1 John W Upham1,2 1The University of Queensland (School of Medicine, Brisbane, QLD, Australia; 2Princess Alexandra Hospital, Brisbane, QLD, Australia; 3Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA Background and objective: Individuals with chronic obstructive pulmonary disease (COPD are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine. Methods: In this observational study, 34 subjects (20 COPD, 14 healthy received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline and the fold increase in antibody titer after vaccination. Results: Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036. Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity. Conclusion: The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with

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

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

    2017-07-01

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

  8. Complement modulation of T cell immune responses during homeostasis and disease.

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    Clarke, Elizabeth V; Tenner, Andrea J

    2014-11-01

    The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders. © 2014 Society for Leukocyte Biology.

  9. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides

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    Jia, Haibo; Halilou, Amadou I.; Hu, Liang; Cai, Wenqian; Liu, Jing; Huang, Bo

    2011-01-01

    Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule. PMID:21969171

  10. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    Science.gov (United States)

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

  11. The immunization status of children with chronic neurological disease and serological assessment of vaccine-preventable diseases.

    Science.gov (United States)

    Dinleyici, Meltem; Carman, Kursat Bora; Kilic, Omer; Laciner Gurlevik, Sibel; Yarar, Coskun; Dinleyici, Ener Cagri

    2018-04-06

    The aim of this study was to evaluate the age-appropriate immunization coverage in 366 children with chronic neurological disease (CND), to evaluate the use of vaccines not included in routine program, to evaluate serological tests for vaccine-preventable diseases and to describe the related factors in unvaccinated children. 95.6% of all children with had received age-appropriate vaccinations according to the actual National Immunization Program (NIP) during childhood. 12 children (3.6%) had not received vaccines; only two had true contraindications. Because most of the vaccines have been implemented through the NIP for 10 years in Turkey, 88% of children required these new vaccines or booster doses. Moreover, 86.6% of the children and 92.6% of household contacts had no prior history of influenza vaccine. Furthermore, 88% of the patients had not received the varicella vaccine, and the anti-varicella IgG levels were only negative in 27.9%. In addition, 18.6% of the children were negative for anti-mumps IgG, 23.7% for anti-measles IgG, and 6.3% for anti-rubella IgG. Anti-HBs IgG level was 0-10 IU/L in 45.6% of the patients (most of them previously vaccinated) and 79.8% were negative for hepatitis A IgG antibodies. For pertussis infection, the antibody titers of 54.1% of patients were below the protective level, and 10% of patients had a prior acute pertussis infection. Therefore, it is suggested that children with CND should be evaluated for their vaccination status during their first and follow-up visits at certain intervals, and their primary immunization should be completed; moreover, many will need revaccination or booster doses.

  12. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    International Nuclear Information System (INIS)

    Park, J.E.S.; Beal, I.; Dilworth, J.P.; Tormey, V.; Haddock, J.

    2005-01-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly

  13. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.E.S. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Beal, I. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Dilworth, J.P. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Tormey, V. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom); Haddock, J. [Royal Free and Hampstead NHS Trust, Pond Street, London NW3 2QG (United Kingdom)]. E-mail: jamandahaddock@royalfree.nhs.uk

    2005-06-01

    Approximately 10% of patients with common variable immune deficiency have systemic granulomatous disease with associated interstitial lung disease. From a population of patients with CVID attending a large tertiary referral clinic for primary immunodeficiency diseases we selected a cohort who had a restrictive defect or impaired gas transfer on pulmonary function testing and/or histologically proven granulomatous disease. HRCT scans of the thorax were reviewed retrospectively in 18 patients by two radiologists. Thirteen patients had diffuse reticulation, which varied from fine to coarse with features of fibrosis. Nodules were found in eight patients. In seven, these were associated with reticulation and in one they were an isolated finding. Bronchiectasis was found as the only abnormality in three and in addition to diffuse reticulation or nodules in another three patients. Greater appreciation of the spectrum of the radiological abnormalities in CVID patients with interstitial lung disease is important. Deteriorating lung function in patients with granulomatous CVID may be secondary to interstitial lung disease rather than bronchiectasis, and treatment should be tailored accordingly.

  14. Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

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    Deanna L. Gibson

    2012-08-01

    Full Text Available The gastrointestinal (GI microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.

  15. Codevelopment of Microbiota and Innate Immunity and the Risk for Group B Streptococcal Disease

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    Julia Kolter

    2017-11-01

    Full Text Available The pathogenesis of neonatal late-onset sepsis (LOD, which manifests between the third day and the third month of life, remains poorly understood. Group B Streptococcus (GBS is the most important cause of LOD in infants without underlying diseases or prematurity and the third most frequent cause of meningitis in the Western world. On the other hand, GBS is a common intestinal colonizer in infants. Accordingly, despite its adaption to the human lower gastrointestinal tract, GBS has retained its potential virulence and its transition from a commensal to a dangerous pathogen is unpredictable in the individual. Several cellular innate immune mechanisms, in particular Toll-like receptors, the inflammasome and the cGAS pathway, are engaged by GBS effectors like nucleic acids. These are likely to impact on the GBS-specific host resistance. Given the long evolution of streptococci as a normal constituent of the human microbiota, the emergence of GBS as the dominant neonatal sepsis cause just about 50 years ago is remarkable. It appears that intensive usage of tetracycline starting in the 1940s has been a selection advantage for the currently dominant GBS clones with superior adhesive and invasive properties. The historical replacement of Group A by Group B streptococci as a leading neonatal pathogen and the higher frequency of other β-hemolytic streptococci in areas with low GBS prevalence suggests the existence of a confined streptococcal niche, where locally competing streptococcal species are subject to environmental and immunological selection pressure. Thus, it seems pivotal to resolve neonatal innate immunity at mucous surfaces and its impact on microbiome composition and quality, i.e., genetic heterogeneity and metabolism, at the microanatomical level. Then, designer pro- and prebiotics, such as attenuated strains of GBS, and oligonucleotide priming of mucosal immunity may unfold their potential and facilitate adaptation of potentially

  16. Codevelopment of Microbiota and Innate Immunity and the Risk for Group B Streptococcal Disease.

    Science.gov (United States)

    Kolter, Julia; Henneke, Philipp

    2017-01-01

    The pathogenesis of neonatal late-onset sepsis (LOD), which manifests between the third day and the third month of life, remains poorly understood. Group B Streptococcus (GBS) is the most important cause of LOD in infants without underlying diseases or prematurity and the third most frequent cause of meningitis in the Western world. On the other hand, GBS is a common intestinal colonizer in infants. Accordingly, despite its adaption to the human lower gastrointestinal tract, GBS has retained its potential virulence and its transition from a commensal to a dangerous pathogen is unpredictable in the individual. Several cellular innate immune mechanisms, in particular Toll-like receptors, the inflammasome and the cGAS pathway, are engaged by GBS effectors like nucleic acids. These are likely to impact on the GBS-specific host resistance. Given the long evolution of streptococci as a normal constituent of the human microbiota, the emergence of GBS as the dominant neonatal sepsis cause just about 50 years ago is remarkable. It appears that intensive usage of tetracycline starting in the 1940s has been a selection advantage for the currently dominant GBS clones with superior adhesive and invasive properties. The historical replacement of Group A by Group B streptococci as a leading neonatal pathogen and the higher frequency of other β-hemolytic streptococci in areas with low GBS prevalence suggests the existence of a confined streptococcal niche, where locally competing streptococcal species are subject to environmental and immunological selection pressure. Thus, it seems pivotal to resolve neonatal innate immunity at mucous surfaces and its impact on microbiome composition and quality, i.e., genetic heterogeneity and metabolism, at the microanatomical level. Then, designer pro- and prebiotics, such as attenuated strains of GBS, and oligonucleotide priming of mucosal immunity may unfold their potential and facilitate adaptation of potentially hazardous streptococci as

  17. Insight into the mechanisms regulating immune homeostasis in health and disease.

    Science.gov (United States)

    Sirisinha, Stitaya

    2011-03-01

    Innate and adaptive immune systems consist of cells and molecules that work together in concert to fight against microbial infection and maintain homeostasis. Hosts encounter microbes / exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) all the time and they must have proper mechanisms to counteract the danger such that appropriate responses (e.g., degree of inflammation and types of mediators induced) can be mounted in different scenarios. Increasing numbers of endogenous danger signals of host origin are being identified including, for example, uric acid and cholesterol crystals, high mobility group box1 (HMGB1) protein, oxidized LDL, vesicans, heat shock proteins (HSPs) and self DNA. Many of these endogenous ligands have been shown to be associated with inflammation-related diseases like atherosclerosis, gout and type 2 diabetes. Several DAMPs appear to have the ability to interact with more than one receptor. We are now beginning to understand how the immune system can distinguish infection from endogenous ligands elaborated following cellular insults and tissue damage. Appropriate responses to maintain the homeostatic state in health and disease depend largely on the recognition and response to these stimuli by germline encoded pattern-recognition receptors (PRRs) present on both immune and non-immune cells. These receptors are, for example, Toll-like receptors (TLRs), C-type lectin receptors (CLRs) and cytosolic receptors (e.g., RLRs, NLRs and some intracellular DNA sensors). Atypical PRR "danger" receptors, like the receptor for advanced glycation end products (RAGE) and their ligands have been identified. A proper response to maintain homeostasis relies on specific negative regulators and regulatory pathways to dampen its response to tissue injury while maintaining the capacity to eliminate infection and induce proper tissue repair. Moreover, some PRRs (e.g., TLR2,TLR4 and NLRP3) and atypical

  18. Dietary supplementation of probiotics affects growth, immune response and disease resistance of Cyprinus carpio fry.

    Science.gov (United States)

    Gupta, Akhil; Gupta, Paromita; Dhawan, Asha

    2014-12-01

    The effects of dietary Bacillus coagulans (MTCC 9872), Bacillus licheniformis (MTCC 6824) and Paenibacillus polymyxa (MTCC 122) supplementation on growth performance, non-specific immunity and protection against Aeromonas hydrophila infection were evaluated in common carp, Cyprinus carpio fry. Laboratory maintained B. coagulans, B. licheniformis and P. polymyxa were used to study antagonistic activity against fish pathogenic bacteria by agar well diffusion assay. Healthy fish fry were challenged by this bacterium for determination of its safety. Fish were fed for 80 days with control basal diet (B0) and experimental diets containing B. coagulans (B1), B. licheniformis (B2) and P. polymyxa (B3) at 10(9) CFU/g diet. Fish fry (mean weight 0.329 ± 0.01 g) were fed these diets and growth performance, various non-specific immune parameters and disease resistance study were conducted at 80 days post-feeding. The antagonism study showed inhibition zone against A. hydrophila and Vibrio harveyi. All the probiotic bacterial strains were harmless to fish fry as neither mortality nor morbidities were observed of the challenge. The growth-promoting influences of probiotic supplemented dietary treatments were observed with fish fry and the optimum survival, growth and feed utilization were obtained with P. polymyxa (B3) supplemented diet. Study of different non-specific innate immunological parameters viz. lysozyme activity, respiratory burst assay and myeloperoxidase content showed significant (p growth, feed utilization, non-specific immune responses and disease resistance of fry common carp, C. carpio. Copyright © 2014. Published by Elsevier Ltd.

  19. Diagnosis of acute radiation disease by enzyme immune-assay (EIA)

    International Nuclear Information System (INIS)

    Popov, D.; Maliev, V.

    2005-01-01

    Full text: Multifactor fundamental research under experimental and industrial conditions on farm and laboratory animals and also on humans blood serum of Chernobyl NPP clean-up workers conducted within 1982 - 2002 have enabled us to establish the existence of two previously unknown phenomena: the phenomenon of reversible redistribution of cytobiochemical parameters in the blood-interstices-lymph-blood system of irradiated animals, which supports compensatory maintenance of homeostasis. The phenomenon of specific immunochemical reactions to the radiological effect, involving the formation of high molecular mass glycoprotein (molecular mass - 200 - 250 kDa) - radiation antigens (SDR - specific radiation determinant) in the lymphoid system with epitopes specific to each form of radiation syndrome, after animals have been irradiated in doses inducing the development of the cerebral (1) , toxic (2) gastrointestinal (3) and typical (4) forms of acute radiation sickness. These two phenomena allowed us to develop a technologies for diagnosis, prophylaxis and therapy of radiation disease - enzyme immune assay (EIA), antiradiation vaccine, antiradiation serum, method of immune-lymph-plasmosorption. The important first step in effectiveness of therapy is an accurate assessment of severity of disease in early period after irradiation. The ideal markers for early and accurate assessment is high weight glycoprotein with specifics radiation induced features (SDR) mentioned above. This biology active substance isolated from lymph can induct the symptoms of radiation syndrome without previously radiation when it is administrated intramuscularly or intravenously to healthy animals. Enzyme immune assay (EIA) allowed researchers to indicate the significant levels of different forms of SDR in peripheral blood of animals in first 24 hours after radiation. Indication of high level of SDR -1 allowed to forecast a fast development of cerebral form of acute radiation disease. Determination

  20. Cardiovascular disease in haemodialysis: role of the intravascular innate immune system.

    Science.gov (United States)

    Ekdahl, Kristina N; Soveri, Inga; Hilborn, Jöns; Fellström, Bengt; Nilsson, Bo

    2017-05-01

    Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.

  1. ENHANCED IMMUNIZATION COVERAGE THROUGH INTERVENTIONS FOR CHILDHOOD CLUSTER DISEASES IN DEVELOPING COUNTRIES.

    Science.gov (United States)

    Mureed, Sheh; Somronghtong, Ratana; Kumar, Ramesh; Ghaffar, Abdul; Chapman, Robert S

    2015-01-01

    Globally immunisation has to be considered as a most effective and efficient public health intervention to reduce morbidity and mortality among children. Most of the children from developing countries are still not fully immunized due to multiple factors including lack of interventions, awareness, and financial constraints and due to limited resource. Conversely, this review has identified the effectiveness of interventions to increase the immunisation coverage among children of developing countries. Systematic review by using PRISMA statement ("preferred reporting items for systematic reviews and meta-analyses") has been conducted in English. published articles on Pub Med, Scopus, Cochrane, Medline and ISI by searching keywords like immunizations, childhood vaccination and developing countries has been accessed. Only randomised controlled trial and quasi-experimental studies designs were included in the final analysis based on quality assessment by adopting the Down and Black checklist and finally pooled analysis was done by random effect model. This systematic review has been approved and registered by University of York. A total of 16,570 published articles were accessed and finally 10 fulfilled our criteria that were analysed and interpreted. It demonstrated that the interventions has shown significantly increase vaccine coverage for childhood cluster diseases (OR 2.136 and p 0.05) and full vaccination schedule (OR 1.342 and p>0.05). Systematic review has concluded that the professional interventions are an effective while in improving the child immunisation coverage for cluster diseases in developing countries, major effect on DTP an.d measles.

  2. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice.

    Directory of Open Access Journals (Sweden)

    Trevor D Lawley

    Full Text Available Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

  3. Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

    Directory of Open Access Journals (Sweden)

    Christopher Beirne

    Full Text Available Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells', stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles. Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations.

  4. The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment.

    Directory of Open Access Journals (Sweden)

    James T Rosenbaum

    Full Text Available Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray.An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED, 25 patients with nonspecific orbital inflammation (NSOI, 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA. Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets.Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED.This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.

  5. Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?

    Science.gov (United States)

    Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Blandizzi, Corrado; Fornai, Matteo

    2018-05-24

    Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.

  6. Passive immunization of guinea-pigs with llama single-domain antibody fragments against foot-and-mouth disease

    NARCIS (Netherlands)

    Harmsen, M.M.; Solt, van C.B.; Fijten, H.P.D.; Keulen, van L.; Rosalia, R.A.; Weerdmeester, K.; Cornelissen, A.H.M.; Bruin, de M.G.M.; Eble, P.L.; Dekker, A.

    2007-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease that occasionally causes outbreaks in Europe. There is a need for therapies that provide rapid protection against FMD in outbreak situations. We aim to provide such rapid protection by passive immunization with llama single-domain antibody

  7. Early Nutrition as a Major Determinant of 'Immune Health': Implications for Allergy, Obesity and Other Noncommunicable Diseases.

    Science.gov (United States)

    Prescott, Susan L

    2016-01-01

    Early-life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. Dietary changes are at the center of the emerging epigenetic paradigms that underpin the rise in many modern inflammatory and metabolic diseases. There is growing evidence that exposures in pregnancy and the early postnatal period can modify gene expression and disease susceptibility. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients. Oligosaccharides (soluble fiber), antioxidants, polyunsaturated fatty acids, folate and other vitamins have documented effects on immune function as well as metabolism. Some have also been implicated in modified risk of allergic diseases in observational studies. Intervention studies are largely limited to trials with polyunsaturated fatty acids and oligosaccharides, showing preliminary but yet unconfirmed benefits in allergy prevention. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programming is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While an epigenetic mechanism provides a strong explanation of how nutritional exposures can affect fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function--including diet-induced changes in the microbiome. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures early in life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the

  8. The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.

    Science.gov (United States)

    Ostrovskaya, Rita U; Gruden, Marina A; Bobkova, Natalya A; Sewell, Robert D E; Gudasheva, Tatyana A; Samokhin, Alexander N; Seredinin, Sergey B; Noppe, Wim; Sherstnev, Vladimir V; Morozova-Roche, Ludmilla A

    2007-08-01

    The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Abeta peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Abeta((25-35)) peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Abeta((25-35)) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Abeta((25-35)) peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Abeta((25-35)) peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with its previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.

  9. The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

    Science.gov (United States)

    Luan, Y Y; Yao, Y M; Sheng, Z Y

    2013-01-01

    Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

  10. Hyperthermia on skin immune system and its application in the treatment of HPV-infected skin diseases

    Institute of Scientific and Technical Information of China (English)

    Gao Xinghua; Chen Hongduo

    2014-01-01

    In this paper, the effects of hyperthermia on cells and immune system are introduced briefly. The mechanism of action of hyperthermia on human papilloma virus (HPV)-infected skin diseases was elaborated as an example in this paper. Many studies have proved that hyperthermia affects a number of cellular and molecu- lar constitutes in the skin immune system, involving both innate and adaptive immune responses; the efficacy of hyperthermia in treating some infectious and cancerous conditions has been validated and applied in clinics, while molecular mechanisms of hyperthermia affecting the immunereaction is still unclear.

  11. Genome-Wide Association Studies Suggest Limited Immune Gene Enrichment in Schizophrenia Compared to 5 Autoimmune Diseases

    DEFF Research Database (Denmark)

    Pouget, Jennie G; Gonçalves, Vanessa F; Spain, Sarah L

    2016-01-01

    There has been intense debate over the immunological basis of schizophrenia, and the potential utility of adjunct immunotherapies. The major histocompatibility complex is consistently the most powerful region of association in genome-wide association studies (GWASs) of schizophrenia and has been...... in immune genes contributes to schizophrenia. We show that there is no enrichment of immune loci outside of the MHC region in the largest genetic study of schizophrenia conducted to date, in contrast to 5 diseases of known immune origin. Among 108 regions of the genome previously associated...

  12. Immunological regulation of metabolism--a novel quintessential role for the immune system in health and disease.

    Science.gov (United States)

    Schaefer, Jeremy S; Klein, John R

    2011-01-01

    The hypothalamus-pituitary-thyroid (HPT) axis is an integrated hormone network that is essential for maintaining metabolic homeostasis. It has long been known that thyroid stimulating hormone (TSH), a central component of the HPT axis, can be made by cells of the immune system; however, the role of immune system TSH remains enigmatic and most studies have viewed it as a cytokine used to regulate immune function. Recent studies now indicate that immune system-derived TSH, in particular, a splice variant of TSHβ that is preferentially made by cells of the immune system, is produced by a subset of hematopoietic cells that traffic to the thyroid. On the basis of these and other findings, we propose the novel hypothesis that the immune system is an active participant in the regulation of basal metabolism. We further speculate that this process plays a critical role during acute and chronic infections and that it contributes to a wide range of chronic inflammatory conditions with links to thyroid dysregulation. This hypothesis, which is amenable to empirical analysis, defines a previously unknown role for the immune system in health and disease, and it provides a dynamic connection between immune-endocrine interactions at the organismic level.

  13. Prospects for treatment of Porphyromonas gingivalis-mediated diseaseimmune-based therapy

    Directory of Open Access Journals (Sweden)

    Eric C. Reynolds

    2015-09-01

    Full Text Available Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with a polymicrobial biofilm (subgingival plaque accreted to the tooth which results in destruction of the tooth's supporting tissues. A characteristic feature of the disease-associated plaque is the emergence of proteolytic species. One of these species, Porphyromonas gingivalis has recently been described as a keystone pathogen as it dysregulates the host immune response to favour the polymicrobial biofilm disrupting homeostasis to cause dysbiosis and disease. The level of P. gingivalis in subgingival plaque above threshold levels (~10% of total bacterial cell load has been demonstrated to predict imminent clinical attachment loss (disease progression in humans. Porphyromonas gingivalis is found as microcolonies in the superficial layers of subgingival plaque adjacent to the periodontal pocket epithelium which helps explain the strong association with underlying tissue inflammation and disease at relatively low proportions (10% of the total bacterial cell load of the plaque. The mouse periodontitis model has been used to show that inflammation is essential to allow establishment of P. gingivalis at the levels in plaque (10% or greater of total bacterial cell load necessary to produce dysbiosis and disease. The extracellular proteinases “gingipains” (RgpA/B and Kgp of P. gingivalis have been implicated as major virulence factors that are critical for dysbiosis and disease. This has resulted in the strategy of targeting the gingipains by vaccination. We have produced a recombinant immunogen which induces an immune response in mice that neutralises the proteolytic and host/bacterial binding functions of the gingipains. Using this immunogen as a therapeutic vaccine in mice already infected with P. gingivalis, we have shown that inflammation and alveolar bone loss can be substantially reduced. The protection was characterised by a predominant Th2

  14. Nutrition and Helicobacter pylori: Host Diet and Nutritional Immunity Influence Bacterial Virulence and Disease Outcome

    Directory of Open Access Journals (Sweden)

    Kathryn P. Haley

    2016-01-01

    Full Text Available Helicobacter pylori colonizes the stomachs of greater than 50% of the world’s human population making it arguably one of the most successful bacterial pathogens. Chronic H. pylori colonization results in gastritis in nearly all patients; however in a subset of people, persistent infection with H. pylori is associated with an increased risk for more severe disease outcomes including B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma and invasive adenocarcinoma. Research aimed at elucidating determinants that mediate disease progression has revealed genetic differences in both humans and H. pylori which increase the risk for developing gastric cancer. Furthermore, host diet and nutrition status have been shown to influence H. pylori-associated disease outcomes. In this review we will discuss how H. pylori is able to create a replicative niche within the hostile host environment by subverting and modifying the host-generated immune response as well as successfully competing for limited nutrients such as transition metals by deploying an arsenal of metal acquisition proteins and virulence factors. Lastly, we will discuss how micronutrient availability or alterations in the gastric microbiome may exacerbate negative disease outcomes associated with H. pylori colonization.

  15. Interaction of Streptococcus agalactiae and cellular innate immunity in colonization and disease

    Directory of Open Access Journals (Sweden)

    Sybille eLandwehr-Kenzel

    2014-10-01

    Full Text Available Streptococcus agalactiae (Group B streptococcus, GBS is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis and death at the beginning of life, in the elderly and in diabetic patients. Thus GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days seven and 90 of life are at risk of a particularly striking sepsis manifestation (late onset disease, LOD, where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases is caused by one clone, GBS ST-17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like GAPDH-dependent induction of IL-10 and β-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors (TLRs and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are just

  16. Feeding frequency affects stress, innate immunity and disease resistance of juvenile blunt snout bream Megalobrama amblycephala.

    Science.gov (United States)

    Li, Xiang-Fei; Tian, Hong-Yan; Zhang, Ding-Dong; Jiang, Guang-Zhen; Liu, Wen-Bin

    2014-05-01

    This study aimed to evaluate the effects of feeding frequency on stress, innate immunity and disease resistance of juvenile blunt snout bream Megalobrama amblycephala (average weight: 9.92 ± 0.06 g). Fish were randomly assigned to one of six feeding frequencies (1, 2, 3, 4, 5 and 6 times/day) following the same ration size for 8 weeks. After the feeding trial, fish were challenged by Aeromonas hydrophila and cumulative mortality was recorded for the next 10 days. Daily gain index of fish fed 3-5 times/day was significantly higher than that of the other groups. High feeding frequencies induced significantly elevated plasma levels of both cortisol and lactate. Fish fed 3-4 times/day exhibited relatively low liver catalase and glutathione peroxidase activities as well as malondialdehyde contents, but obtained significantly higher reduced glutathione levels and post-challenged haemato-immunological parameters (include blood leukocyte and erythrocyte counts as well as plasma lysozyme, alternative complement, acid phosphatase and myeloperoxidase activities) compared with that of the other groups. After challenge, the lowest mortality was observed in fish fed 4 times/day. It was significantly lower than that of fish fed 1-3 times/day, but exhibited no statistical difference with that of the other groups. In conclusion, both low and high feeding frequencies could cause oxidative stress of juvenile M. amblycephala, as might consequently lead to the depressed immunity and reduced resistance to A. hydrophila infection. The optimal feeding frequency to enhance growth and boost immunity of this species at juvenile stage is 4 times/day. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. [Human papillomavirus vaccine. Statement of the Advisory Committee of Immunizations on behalf of the Chilean Infectious Diseases Society. September 2008].

    Science.gov (United States)

    Abarca, Katia; Valenzuela, M Teresa; Vergara, Rodrigo; Luchsinger, Vivian; Muñoz, Alma; Jiménez de la J, Jorge; Ripoll, Erna; O'Ryan, Miguel

    2008-11-01

    This article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases globally and in Chile, and the scientific information of the licensed HPV vaccines: Gardasil and Cervari. Considering the available information, the Advisory Committee on Immunizations of the Chilean Society of Infectious Diseases recommends vaccination of teenage girls, ideally before initiating sexual activity, i.e., approximately at the age of 12 to 13 years and vaccination of women of any age if they have not started sexual activity. If women are vaccinated after initiating sexual activity, they should be informed of the lower efficacy of immunization if HPV infection has occurred. Education on responsible sexuality and sexually transmitted diseases should be maintained as a priority. Vaccination should be highly considered for inclusion in the National Immunization Program.

  18. The road to restoring neural circuits for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Canter, Rebecca G; Penney, Jay; Tsai, Li-Huei

    2016-11-10

    Alzheimer's disease is a progressive loss of memory and cognition, for which there is no cure. Although genetic studies initially suggested a primary role for amyloid-in Alzheimer's disease, treatment strategies targeted at reducing amyloid-have failed to reverse cognitive symptoms. These clinical findings suggest that cognitive decline is the result of a complex pathophysiology and that targeting amyloid-alone may not be sufficient to treat Alzheimer's disease. Instead, a broad outlook on neural-circuit-damaging processes may yield insights into new therapeutic strategies for curing memory loss in the disease.

  19. Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

    Science.gov (United States)

    Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

    2016-02-04

    Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.

  20. Serum levels of innate immunity cytokines are elevated in dogs with metaphyseal osteopathy (hypertrophic osteodytrophy) during active disease and remission.

    Science.gov (United States)

    Safra, Noa; Hitchens, Peta L; Maverakis, Emanual; Mitra, Anupam; Korff, Courtney; Johnson, Eric; Kol, Amir; Bannasch, Michael J; Pedersen, Niels C; Bannasch, Danika L

    2016-10-15

    Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as chronic recurrent multifocal osteomyelitis (CRMO), and deficiency of interleukin-1 receptor antagonist (DIRA), involve impaired innate immunity pathways and aberrant cytokine production. Given the similarities between these diseases, we hypothesize that MO is an autoinflammatory disease mediated by cytokines involved in innate immunity. To characterize immune dysregulation in MO dogs we measured serum levels of inflammatory markers in 26 MO and 102 control dogs. MO dogs had significantly higher levels (pg/ml) of serum Interleukin-1beta (IL-1β), IL-18, IL-6, Granulocyte-macrophage colony stimulating factor (GM-CSF), C-X-C motif chemokine 10 (CXCL10), tumor necrosis factor (TNF), and IL-10. Notably, recovered MO dogs were not different from dogs during active MO disease, providing a suggestive mechanism for disease predisposition. This is the first documentation of elevated immune markers in MO dogs, uncovering an immune profile similar to comparable autoinflammatory disorders in children. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. An MHC class I immune evasion gene of Marek׳s disease virus.

    Science.gov (United States)

    Hearn, Cari; Preeyanon, Likit; Hunt, Henry D; York, Ian A

    2015-01-15

    Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198-205 (2001)), but the gene(s) involved have not been identified. Here we demonstrate that an MDV gene, MDV012, is capable of reducing surface expression of MHC class I on chicken cells. Co-expression of an MHC class I-binding peptide targeted to the endoplasmic reticulum (bypassing the requirement for the TAP peptide transporter) partially rescued MHC class I expression in the presence of MDV012, suggesting that MDV012 is a TAP-blocking MHC class I immune evasion protein. This is the first unique non-mammalian MHC class I immune evasion gene identified, and suggests that α-herpesviruses have conserved this function for at least 100 million years. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Humoral Immune Response Induced by PLGA Micro Particle Coupled Newcastle Disease Virus Vaccine in Chickens

    Directory of Open Access Journals (Sweden)

    Sanganagouda K

    2014-02-01

    Full Text Available This experiment was conducted for evaluating the humoral immune responses induced by Poly Lactide-co-Glycolide Acid (PLGA microspheres coupled inactivated Newcastle Disease Virus (NDV vaccine in comparison to an ‘in-house’ prepared inactivated and a live commercial vaccine. PLG microparticles containing inactivated NDV were prepared by a double emulsion technique based on solvent evaporation method. The size of the NDV coupled PLG microparticles was determined by Electron Microscopy. NDV coupled PLG microparticles were spherical having smooth surface, hollow core inside with no pores on the surface. The experiment was conducted in four groups of chickens (n=15. The encapsulation efficiency of NDV coupled PLG microparticles was determined by protein estimation and HA activity in elute. The mean (± SE size of PLG microspheres was found to be 2.409 ± 0.65 µm. The mean percent of encapsulation efficiency of PLG microspheres coupled to NDV was assessed based on the total protein content and HA activity in elute was found to be 8.03 ± 0.50 and 12.5 ± 0.00, respectively. In conclusion, the results of the experiment showed that PLGA coupled NDV vaccine elicited stronger and prolonged humoral immune response in chickens, in comparison to the other tested vaccines, as assessed by haemagglutination inhibition and enzyme linked immuno sorbent asaay titers.

  3. Association study of functional genetic variants of innate immunity related genes in celiac disease

    Directory of Open Access Journals (Sweden)

    Martín J

    2005-08-01

    Full Text Available Abstract Background Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. Methods We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. Results The TDT analysis for IL-1α, IL-1β, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. Conclusion Our results suggest that the analysed polymorphisms of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.

  4. Uncomplicated Diverticular Disease: Innate and Adaptive Immunity in Human Gut Mucosa before and after Rifaximin

    Directory of Open Access Journals (Sweden)

    Rossella Cianci

    2014-01-01

    Full Text Available Background/Aim. Uncomplicated diverticular disease (UDD is a frequent condition in adults. The pathogenesis of symptoms remains unknown. Bacteria are able to interact with Toll-like receptors (TLRs and to induce inflammation through both innate immunity and T-cell recruitment. We investigated the pattern of TLRs 2 and 4 and the intestinal homing in patients with UDD before and after a course of Rifaximin. Methods. Forty consecutive patients with UDD and 20 healthy asymptomatic subjects were enrolled. Among UDD patients, 20 were assigned to a 2-month course of treatment with Rifaximin 1.2 g/day for 15 days/month and 20 received placebo. Blood sample and colonic biopsies were obtained from patients and controls. The samples were collected and analyzed at baseline and at the end of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4, CD8, CD103, TCR-gamma/delta, CD14, TLR2, and TLR4. Results. In UDD, TLR2 and TLR4 expression on immune cell subpopulations from blood and mucosa of the affected colon are altered as compared with controls. Rifaximin treatment induced significant modifications of altered conditions. Conclusions. Our data show the role of TLRs in the development of inflammation in UDD. TLRs distribution is altered in UDD and these alterations are reversed after antibiotic treatment. This trial is registered with ClinicalTrials.gov: NCT02068482.

  5. Manufacturing immunity to disease in a test tube: the magic bullet realized.

    Science.gov (United States)

    Lerner, Richard A

    2006-12-11

    Although it took over one hundred years, Ehrlich's concept of the magic bullet is now a reality. Today, therapeutic antibodies are, arguably, the most important class of new drugs for the treatment of illnesses ranging from Alzheimer's disease to cancer. The emergence of therapeutic antibodies had to wait for advances in immunochemistry that allowed construction of antibodies in vitro. The centerpiece of the new technology is the combinatorial antibody library, which essentially allows one to synthesize an artificial immune system with a diversity that exceeds that of the natural repertoire. The construction of such libraries was perceived to be difficult because, if the natural immune system was to be used as the starting material, construction of the libraries would entail protocols that are the opposite of usual cloning. In gene cloning one starts with complexity and reduces it to a singularity. In the generation of diversity by construction of combinatorial antibody libraries, one starts with a collection of clones, randomly expands their complexity, and then returns them to recoverable singularities. The methods developed to accomplish this seemingly formidable task now allow construction of antibodies in a test tube to any antigen. These synthetic antibodies may be qualitatively and quantitatively superior to those of nature.

  6. Inhibition of Myeloperoxidase at the Peak of Experimental Autoimmune Encephalomyelitis Restores Blood-Brain-Barrier Integrity and Ameliorates Disease Severity.

    Science.gov (United States)

    Zhang, Hao; Ray, Avijit; Miller, Nichole M; Hartwig, Danielle; Pritchard, Kirkwood A; Dittel, Bonnie N

    2015-11-12

    Oxidative stress is thought to contribute to disease pathogenesis in the central nervous system (CNS) disease multiple sclerosis (MS). Myeloperoxidase (MPO), a potent peroxidase that generates toxic radicals and oxidants, is increased in the CNS during MS. However, the exact mechanism whereby MPO drives MS pathology is not known. We addressed this question by inhibiting MPO in mice with experimental autoimmune encephalomyelitis (EAE) using our non-toxic MPO inhibitor KYC. We found that therapeutic administration of KYC for five days starting at the peak of disease significantly attenuated EAE disease severity, reduced myeloid cell numbers and permeability of the blood-brain-barrier (BBB). These data indicate that inhibition of MPO by KYC restores BBB integrity thereby limiting migration of myeloid cells into the CNS that drive EAE pathogenesis. In addition, these observations indicate that KYC may be an effective therapeutic agent for the treatment of MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Linking susceptibility to infectious diseases to immune system abnormalities among HIV Exposed Uninfected Infants

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    Candice Ruck

    2016-08-01

    Full Text Available HIV exposed, uninfected (HEU infants have been shown to have an increase in overall mortality from infectious causes when compared to HIV unexposed, uninfected (HU infants. This is the case in both resource-rich and resource-limited settings. We explore here the concept that specific types of infectious diseases that are more common among HEU infants could provide clues as to the potential underlying immunological abnormalities. The most commonly reported infections in HEU vs. HU are caused by encapsulated bacteria; this suggests the existence of a less effective humoral (antibody, complement immune response. Decreased transplacental transfer of protective maternal antibodies has been seen consistently among HEU newborns, suggesting that this may indeed be one of the key drivers of their susceptibility to infections with encapsulated bacteria. Reassuringly, HEU humoral response to vaccination appears to be well conserved. While there appears to be an increase in overall incidence of acute viral infections, no specific pattern of acute viral infections has emerged; and while there is evidence of increased chronic viral infection from perinatal transmission of hepatitis C and CMV, no data exist to suggest an increase in adverse outcomes. Thus, no firm conclusions about anti-viral effector mechanisms can be drawn. However, the most unusual of reported infections among the HEU have been opportunistic infections, suggesting the possibility of underlying defects in CD4 helper and overall immune regulatory function. This may relate to the observation that the immunological profile of HEUs indicate more activated T cell profile as well as a more inflammatory innate immune response. However, both of these observations appear temporary, marked in early infancy, but no longer evident later in life. The causes of these changes in early life immune profile are likely multifactorial and may be related to in utero exposure to HIV, but also to increased

  8. Immune-mediated neuropathy with Epstein-Barr virus-positive T-cell lymphoproliferative disease.

    Science.gov (United States)

    Hattori, Takaaki; Arai, Ayako; Yokota, Takanori; Imadome, Ken-Ichi; Tomimitsu, Hiroyuki; Miura, Osamu; Mizusawa, Hidehiro

    2015-01-01

    A 47-year-old man with Epstein-Barr virus (EBV)-positive T/NK- cell lymphoproliferative disease (EBV-T/NK-LPD) developed acute-onset weakness. A nerve conduction study showed a conduction block in both the proximal and most distal segments. Although the patient's neuropathy transiently responded to intravenous immunoglobulin, it was progressive for at least 25 days until the start of prednisolone (PSL) administration, after which it remarkably improved. The neuropathy further improved after allogeneic bone marrow transplantation (BMT). The present patient's clinical course is not consistent with that of typical Guillain-Barré syndrome. This case suggests that EBV-T/NK-LPD can cause progressive immune-mediated neuropathy as a result of chronic EBV antigen presentation and can be treated with PSL and BMT.

  9. The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

    Directory of Open Access Journals (Sweden)

    MILENA B. P. SOARES

    2001-12-01

    Full Text Available Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC, the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.A doença de Chagas constitui um grave problema de saúde pública na América Latina, onde é uma das principais causas de problemas cardíacos. A cardiopatia chagásica crônica (CChC, forma mais grave da doença, manifesta-se em cerca de 25% dos indivíduos infectados pelo Trypanosoma cruzi, e é caracterizada, a nível histopatológico, pela presença de infiltrados

  10. Beta-endorphin and the immune system--possible role in autoimmune diseases

    DEFF Research Database (Denmark)

    Mørch, H; Pedersen, B K

    1995-01-01

    The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...... that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta......-endorphin-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative...

  11. Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

    Science.gov (United States)

    Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

    2012-06-01

    A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

  12. Mouse Model of Devil Facial Tumour Disease establishes that an effective immune response can be generated against the cancer cells

    Directory of Open Access Journals (Sweden)

    Terry L Pinfold

    2014-05-01

    Full Text Available The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus harrisii is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD. DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD recent evidence reveals that genetically diverse animals succumb to the disease. The lack of an immune response against the DFTD tumor cells may be due to a lack of immunogenicity of the tumor cells. This could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range of antibody isotypes against DFTD cells was detected, indicating that as DFTD cells can induce an immune response they are immunogenic. This was supported by cytokine production, when splenocytes from mice injected with DFTD cells were cultured in vitro with DFTD cells and the supernatant analyzed. There was a significant production of IFN-γ and TNF-α following the first injection with DFTD cells and a significant production of IL-6 and IL-10 following the second injection. Splenocytes from naïve or immunized mice killed DFTD cells in in vitro cytotoxicity assays. Thus they are also targets for immunological destruction. We conclude that as an immune response can be generated against DFTD cells they would be suitable targets for a vaccine.

  13. Co-immunization with DNA and protein mixture: a safe and efficacious immunotherapeutic strategy for Alzheimer's disease in PDAPP mice.

    Science.gov (United States)

    Liu, Si; Shi, DanYang; Wang, Hai-Chao; Yu, Yun-Zhou; Xu, Qing; Sun, Zhi-Wei

    2015-01-14

    Active immunotherapy targeting β-amyloid (Aβ) is the most promising strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical studies and clinical trials, a safe and effective AD vaccine requires a delicate balance between providing therapeutically adequate anti-Aβ antibodies and eliminating or suppressing unwanted adverse T cell-mediated inflammatory reactions. We describe here the immunological characterization and protective efficacy of co-immunization with a 6Aβ15-T DNA and protein mixture without adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization induced robust Th2-polarized Aβ-specific antibodies while simultaneously suppressed unwanted inflammatory T cell reactions and avoiding Aβ42-specific T cell-mediated autoimmune responses in immunized mice. Co-immunization with the DNA + protein vaccine could overcome Aβ42-associated hypo-responsiveness and elicit long-term Aβ-specific antibody responses, which helped to maintain antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce an anti-inflammatory Th2 immune response with high level Aβ-specific antibodies and low level IFN-γ production, also demonstrated the capacity to inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co-immunization with antigen-matched DNA and protein may represent a novel and efficacious strategy for AD immunotherapy to eliminate T cell inflammatory reactions while retaining high level antibody responses.

  14. Enhanced immunization coverage through interventions for childhood cluster diseases in developing countries

    International Nuclear Information System (INIS)

    Mureed, S.; Somronghtong, R.; Kumar, R.

    2015-01-01

    Globally immunisation has to be considered as a most effective and efficient public health intervention to reduce morbidity and mortality among children. Most of the children from developing countries are still not fully immunized due to multiple factors including lack of interventions, awareness, and financial constraints and due to limited resource. Conversely, this review has identified the effectiveness of interventions to increase the immunisation coverage among children of developing countries. Methods: Systematic review by using PRISMA statement (preferred reporting items for systematic reviews and meta-analyses) has been conducted in English published articles on Pub Med, Scopus, Cochrane, Medline and ISI by searching keywords like immunizations, childhood vaccination and developing countries has been accessed. Only randomised controlled trial and quasi-experimental studies designs were included in the final analysis based on quality assessment by adopting the Down and Black checklist and finally pooled analysis was done by random effect model. This systematic review has been approved and registered by University of York. Results: A total of 16,570 published articles were accessed and finally 10 fulfilled our criteria that were analysed and interpreted. It demonstrated that the interventions has shown significantly increase vaccine coverage for childhood cluster diseases (OR 2.136 and p <0.05).Furthermore, it has been proved that an effect was more prominent for DTP (OR 2.397 and p<0.05) and measles (OR 2.628 and p<0.05), not as much for polio (OR 2.284 and p>0.05) and full vaccination schedule (OR 1.342 and p>0.05). Conclusions: Systematic review has concluded that the professional interventions are an effective while in improving the child immunisation coverage for cluster diseases in developing countries, major effect on DTP and measles. (author)

  15. Immunity status of foot-and-mouth disease in the border districts of Peninsular Malaysia

    International Nuclear Information System (INIS)

    Palanisamy, K.; Daud, Z.M.; Seri Masran, M.S.

    2000-01-01

    A serological survey for the prevalence of protective level of antibody to Foot-and-mouth disease (FMD) was carried out in 10 border districts in Peninsular Malaysia. A liquid phase blocking ELISA kit prepared and standardized by World Reference Laboratory (WRL) for FMD was used for the testing. A total of 800 serum samples collected by a random process were tested for protective level of antibody for virus types O, A and Asia I. An overall mean prevalence for antibody to FMD in the 'immune-belt' region was found to be 51.0%, 37.3%, 53.6% for virus types Q, A, and Asia I respectively and 28.9% for all the three sero-types. The percentage of cattle population having protective level of antibody was too low to prevent active spread of FMD infection. There was also substantial variation in the prevalence of antibody detected at the district level and varied from a low mean of 18.8% for the State of Kedah and a high of 67.5% for the district of Besut. More than 70% of the population need to have protective level of antibody to effectively prevent disease spread. The States of Kedah and Kelantan had variable levels of vaccination coverage from 1994 and had less than 45% coverage for the year 1996. A coverage of more than 90% would be essential to maintain high herd immunity and the current high variability in the vaccination coverage at the district level will only favour a higher infection on rate in the field. (author)

  16. Extracts from Hericium erinaceus relieve inflammatory bowel disease by regulating immunity and gut microbiota.

    Science.gov (United States)

    Diling, Chen; Xin, Yang; Chaoqun, Zheng; Jian, Yang; Xiaocui, Tang; Jun, Chen; Ou, Shuai; Yizhen, Xie

    2017-10-17

    Hericium erinaceus (HE), a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. To investigate whether HE is clinically effective in alleviating inflammatory bowel disease (IBD), HE extracts (polysaccharide, alcoholic extracts and whole extracts were prepared using solvent extraction methods) were administrated for 2 weeks in rats with IBD induced by trinitro-benzene-sulfonic acid (TNBS) enema (150 mg/kg). Significant clinical and histological changes in IBD rats were identified, including damage activity, common morphous and tissue damage index scores in colonic mucosa and myeloperoxidase (MPO) activity. The damage activity, common morphous and tissue damage index scores in colonic mucosa ( P <0.05) were improved, MPO activities were decreased. Inflammatory factors were also differentially expressed in colonic mucosa in IBD rats, including serum cytokines, Foxp3 and interleukin (IL)-10 were increased while NF-κB p65 and tumor necrosis factor (TNF)-α were decreased ( P <0.05), and T cells were activated ( P <0.05), especially in the alcohol extracts-treated group. We also found that the structure of gut microbiota of the H. erinaceus extracts-treated groups changed significantly by compared with the model group. Further studies revealed that the polysaccharides in HE extracts may play a prebiotic role, whereas the alcoholic extracts show bactericidin-like and immunomodulatory effects. Taken together, we demonstrated that H. erinaceus extracts could promote the growth of beneficial gut bacteria and improve the host immunity in vivo IBD model, which shows clinical potential in relieving IBD by regulating gut microbiota and immune system.

  17. Vitamin D endocrine system and the immune response in rheumatic diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Plebani, M; Shoenfeld, Yehuda; Adorini, Luciano; Tincani, Angela

    2011-01-01

    Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors (VDRs) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immunomodulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Serum levels of vitamin D have been found to be significantly lower in patients with systemic lupus erythematosus, undifferentiated connective tissue disease, and type-1 diabetes mellitus than in the healthy population. In addition, it was also found that lower levels of vitamin D were associated with higher disease activity in rheumatoid arthritis. Promising clinical results together with evidence for the regulation of multiple immunomodulatory mechanisms by VDR agonists represent a sound basis for further exploration of their potential in the treatment of rheumatic autoimmune disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Association between Age at Diagnosis of Graves' Disease and Variants in Genes Involved in Immune Response

    Science.gov (United States)

    Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Krol, Aleksandra; Bednarczuk, Tomasz; Kolosza, Zofia; Tukiendorf, Andrzej; Szpak-Ulczok, Sylwia; Stanjek-Cichoracka, Anita; Polanska, Joanna; Jarzab, Barbara

    2013-01-01

    Background Graves' disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. The aim of the study was to examine the association between genetic variants in genes encoding proteins involved in immune response and the age at diagnosis of GD. Methods 735 GD patients and 1216 healthy controls from Poland were included into the study. Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD and the association with genotype was analysed. Results Polymorphism in the HLA-DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA DRB1*03 allele were more frequent in patients with age at GD diagnosis ≤30 years than in patients with older age at GD diagnosis. Conclusions HLADRB1*03 allele is associated with young age at diagnosis of Graves' disease in polish population. PMID:23544060

  19. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

    Science.gov (United States)

    Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

    2010-01-01

    Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

  20. Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases.

    Science.gov (United States)

    Martínez, A; Varadé, J; Márquez, A; Cénit, M C; Espino, L; Perdigones, N; Santiago, J L; Fernández-Arquero, M; de la Calle, H; Arroyo, R; Mendoza, J L; Fernández-Gutiérrez, B; de la Concha, E G; Urcelay, E

    2008-09-01

    The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interleukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases. The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type 1 diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test. The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 x 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1.36, 95% CI 1.07-1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82-1.28). The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.

  1. Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Crohn’s Disease: Current Status and Future Directions. A Review on Behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigators

    Directory of Open Access Journals (Sweden)

    Alan Graham Pockley

    2018-04-01

    Full Text Available Patients with treatment refractory Crohn’s disease (CD suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs. Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity via the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD—Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT.

  2. Direct restorative treatment of dental erosion caused by gastroesophageal reflux disease associated with bruxism: a case report.

    Science.gov (United States)

    Vidal, Cristina de Mattos Pimenta; Catelan, Anderson; Briso, André Luiz Fraga; dos Santos, Paulo Henrique

    2011-09-01

    Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach acids are chronically regurgitated into the esophagus and oral cavity. Continual exposure of the teeth to these acids can cause severe tooth wear. Dentists are often the first healthcare professionals to diagnose dental erosion in patients with GERD. This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism. After diagnosis, a multidisciplinary treatment plan was established. The initial treatment approach consisted of medical follow-up with counseling on dietary and smoking habits, as well as management of the gastric disorders with medication. GERD management and the dental treatment performed for the eroded dentition are described, including diagnosis, treatment planning, and restorative therapy.

  3. Literature-related discovery techniques applied to ocular disease : a vitreous restoration example

    NARCIS (Netherlands)

    Kostoff, Ronald N.; Los, Leonoor I.

    2013-01-01

    Purpose of reviewLiterature-related discovery and innovation (LRDI) is a text mining approach for bridging unconnected disciplines to hypothesize radical discovery. Application to medical problems involves identifying key disease symptoms, and identifying causes and treatments for those symptoms

  4. The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop

    Directory of Open Access Journals (Sweden)

    D. Pagliari

    2015-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

  5. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    P.J. Basso

    2014-09-01

    Full Text Available Inflammatory bowel disease (IBD, which includes Crohn's disease (CD and ulcerative colitis (UC, is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

  6. Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

    Science.gov (United States)

    Cuq, B; Blois, S L; Mathews, K A

    2017-06-01

    To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

  7. Immunization Schedules for Adults

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Adults (19 Years of Age and ... diseases that can be prevented by vaccines . 2018 Immunization Schedule Recommended Vaccinations for Adults by Age and ...

  8. Mucosal Immune Regulation in Intestinal Disease. The role of bacterial products, food components and drugs

    NARCIS (Netherlands)

    Bol-Schoenmakers, M.

    2009-01-01

    The challenge of the mucosal gut associated immune system is to remain unresponsive to food products and commensal microbiota, while mounting an appropriate immune response towards pathogens. This implicates the necessity of tight immune regulation within the gut associated lymphoid tissue (GALT).

  9. Viability and Risk Assessment in Species Restoration: Planning Reintroductions for the Wild Boar, a Potential Disease Reservoir

    Directory of Open Access Journals (Sweden)

    Néstor Fernández

    2006-06-01

    Full Text Available The reintroduction of large mammals is often considered a priority conservation action in highly industrialized countries in which many of these species have been depleted. However, species reintroduction after decades of absence may involve important risks for human activities and ecological communities, such as favoring the spread of diseases. An example of a potentially troublesome reintroduction is the wild boar, which may act as a reservoir of diseases, e.g., classical swine fever, and cause high economic losses, and has become a species of concern in several European countries for both ecological and recreational reasons. Failure to prevent the disease consequences of species restoration can negate its conservation benefits. Here we evaluated the probability of both successfully reintroducing wild boar into Denmark and limiting their contact with domestic pig farms to which they might spread disease. For this purpose, we developed a spatially explicit, individual-based population model that incorporates information on boar habitat and demography information from Central European populations. We then compared model predictions with the spatial distribution of farms to achieve a spatial assessment of the contact risk. The most restrictive model scenario predicted that nearly 6% of Denmark provides habitat conditions that would allow wild boar to reproduce. The best habitats for reintroduction were aggregated in seven different areas throughout the country in which the extinction probability was < 5%. However, the expected population expansion was very limited in most of these areas. Both the number of suitable areas and the potential for population expansion greatly increased when we relaxed our habitat assumptions about boar forest requirements; this provided a more conservative scenario for a cautious risk analysis. We additionally found that part of the risk of contact with piggeries was associated with the magnitude of the expansion

  10. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus.

    Science.gov (United States)

    Li, Feng-Yen; Chaigne-Delalande, Benjamin; Su, Helen; Uzel, Gulbu; Matthews, Helen; Lenardo, Michael J

    2014-04-03

    Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that infects and persists in 95% of adults worldwide and has the potential to cause fatal disease, especially lymphoma, in immunocompromised hosts. Primary immunodeficiencies (PIDs) that predispose to EBV-associated malignancies have provided novel insights into the molecular mechanisms of immune defense against EBV. We have recently characterized a novel PID now named "X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia" (XMEN) disease characterized by loss-of-function mutations in the gene encoding magnesium transporter 1 (MAGT1), chronic high-level EBV with increased EBV-infected B cells, and heightened susceptibility to EBV-associated lymphomas. The genetic etiology of XMEN disease has revealed an unexpected quantitative role for intracellular free magnesium in immune functions and has led to novel diagnostic and therapeutic strategies. Here, we review the clinical presentation, genetic mutation spectrum, molecular mechanisms of pathogenesis, and diagnostic and therapeutic considerations for this previously unrecognized disease.

  11. Month of birth, vitamin D and risk of immune-mediated disease: a case control study

    Directory of Open Access Journals (Sweden)

    Disanto Giulio

    2012-07-01

    Full Text Available Abstract Background A season of birth effect in immune-mediated diseases (ID such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB light exposure and vitamin D status during gestation. Methods The monthly distribution of births of patients with ID from the UK (n = 115,172 was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient. Results The distributions of ID births significantly differed from that of the general population (P = 5e-12 with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P P P = 0.00005 and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003. Conclusions The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.

  12. Diversity of aging of the immune system classified in the cotton rat (Sigmodon hispidus) model of human infectious diseases.

    NARCIS (Netherlands)

    Guichelaar, Teun; van Erp, Elisabeth A; Hoeboer, Jeroen; Smits, Noortje A M; van Els, Cécile A C M; Pieren, Daan K J; Luytjes, Willem

    2018-01-01

    Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed

  13. Specific immune responses against airway epithelial cells in a transgenic mouse-trachea transplantation model for obliterative airway disease

    NARCIS (Netherlands)

    Qu, N; de Haan, A; Harmsen, MC; Kroese, FGM; de Leij, LFMH; Prop, J

    2003-01-01

    Background. Immune injury to airway epithelium is suggested to play a central role in the pathogenesis of obliterative bronchiolitis (OB) after clinical lung transplantation. In several studies, a rejection model of murine trachea transplants is used, resulting in obliterative airway disease (OAD)

  14. Spitting Image: Tick Saliva Assists the Causative Agent of Lyme Disease in Evading Host Skin's Innate Immune Response

    NARCIS (Netherlands)

    Hovius, Joppe W. R.

    2009-01-01

    Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted through ticks. Inhibition of host skin's innate immune response might be instrumental to both tick feeding and B. burgdorferi transmission. The article by Marchal et al. describes how tick saliva suppresses B.

  15. Using Dutch elm disease-tolerant elm to restore floodplains impacted by emerald ash borer

    Science.gov (United States)

    Kathleen S. Knight; James M. Slavicek; Rachel Kappler; Elizabeth Pisarczyk; Bernadette Wiggin; Karen. Menard

    2012-01-01

    American elm (Ulmus Americana L.) was a dominant species in floodplains and swamps of the Midwest before Dutch elm disease (DED) (Ophiostoma ulmi and O.novo-ulmi) reduced its populations. In many areas, ash (Fraxinus spp.) became dominant in these ecosystems. Emerald ash borer (EAB) (...

  16. A pro-inflammatory effect of foot and mouth disease vírus on immune and non immune guinea pigs

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    Helio José Montassier

    1992-12-01

    Full Text Available The O1Campos strain of foot and mouth disease virus (FMDV used as inducing agent in the pleurisy model was able to trigger a pro-inflammatory effect on normal and immune guinea pigs. The proinflammatory activity which was detected at two times of the pleurisy (24 and 48 hours on normal guinea pigs was characterized only by mononuclear (MN cell influx, during the first interval of the reaction and by edematogenic effect, MN and polimorphonuclcar (PMN leucocyte migration, at the last time of the reaction. The inflammatory reaction profiles recorded on immune guinea pigs (vaccinated with anti-O1Campos oil adjuvanted vaccine, both after 7 and 30 days post vaccination (pv have showed, in both interval, lower intensities than that observed in normal guinea pigs, although in the 7 days PV guinea pigs the accumulations of total leucocytes and PMN were similar to that displayed by normal animals, after 48 hours of the reaction. Besides, on thirty days PV guinea pigs the FMDV induced a significant increase in volume of exudate and MN cell infiltration, after 24 hours, and all of the inflammatory parameters values dropped to normal levels, during the second interval of the reaction. It was found a negative association between the increase in serum neutralizing antibody titer, from 7 to 30 days PV and the intensities of pleural inflammatory parameters on the immune guinea pigs. The pleurisy test revealed itself feasible to evaluate the pro-inflammatory activity of FMDV.

  17. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    Science.gov (United States)

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.

    2009-01-01

    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  18. Diagnosis of Diabetes Diseases Using an Artificial Immune Recognition System2 (AIRS2) with Fuzzy K-nearest Neighbor

    OpenAIRE

    CHIKH, Mohamed Amine; SAIDI, Meryem; SETTOUTI, Nesma

    2012-01-01

    The use of expert systems and artificial intelligence techniques in disease diagnosis has been increasing gradually. Artificial Immune Recognition System (AIRS) is one of the methods used in medical classification problems. AIRS2 is a more efficient version of the AIRS algorithm. In this paper, we used a modified AIRS2 called MAIRS2 where we replace the K- nearest neighbors algorithm with the fuzzy K-nearest neighbors to improve the diagnostic accuracy of diabetes diseases. The diabetes disea...

  19. Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón).

    Science.gov (United States)

    Prieto, A; Reyes, E; Bernstein, E D; Martinez, B; Monserrat, J; Izquierdo, J L; Callol, L; de LUCAS, P; Alvarez-Sala, R; Alvarez-Sala, J L; Villarrubia, V G; Alvarez-Mon, M

    2001-06-01

    We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferón) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation was not mediated by an increase in CD3(-)CD56(+) NK cells. Further, glycophosphopeptical significantly increased the percentage of monocytes and PMNs that phagocytize Escherichia coli in vitro, as well as increased phagocytic indices. We conclude that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.

  20. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  1. Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

    Science.gov (United States)

    Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

    2017-02-01

    Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Necrotizing herpetic retinopathies. A spectrum of herpes virus-induced diseases determined by the immune state of the host.

    Science.gov (United States)

    Guex-Crosier, Y; Rochat, C; Herbort, C P

    1997-12-01

    Necrotizing herpetic retinopathies (NHR), a new spectrum of diseases induced by viruses of the herpes family (herpes simplex virus, varicella-zoster virus and cytomegalovirus), includes acute retinal necrosis (ARN) occurring in apparently immunocompetent patients and progressive outer retinal necrosis (PORN) described in severely immuno-compromised patients. Signs of impaired cellular immunity were seen in 16% of ARN patients in a review of 216 reported cases, indicating that immune dysfunction is not only at the origin of PORN but might also be at the origin of ARN. The aim of this study was to correlate clinical findings in NHR patients with their immunologic parameters. Charts from patients with the diagnosis of ARN or PORN seen from 1990 to 1995 were reviewed. Clinical characteristics and disease patterns were correlated with immunological parameters taking into account CD4 lymphocyte rate in AIDS patients and blood-lymphocyte subpopulation determination by flow cytometry, cutaneous delayed type hypersensitivity testing and lymphocytic proliferation rate to seven antigens in HIV-negative patients. During the period considered, 11 patients and 7 patients fulfilled the criteria of ARN and PORN respectively. Immune dysfunctions were identified in most patients. Mild type of ARN and classical ARN were associated with discrete immune dysfunctions, ARN with features of PORN was seen in more immunodepressed patients and classical PORN was always seen in severely immunodepressed HIV patients. Our findings suggest that NHR is a continuous spectrum of diseases induced by herpes viruses, whose clinical expression depends on the immune state of the host going from mild or classical ARN at one end in patients with non-detectable or slight immune dysfunction to PORN in severely immunodepressed patients at the other end and with intermediary forms between these extremes.

  3. The Effect of Tsukamurella inchonensis Bacterin on the Immune Response Against Influenza and Newcastle Disease Vaccines in Broiler Chickens

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    Forough Talazadeh

    2016-11-01

    Full Text Available Background: In poultry production, improving immunity is very important to prevent infectious diseases. One solution to improve the immunity of animals and to decrease their susceptibility to infectious disease is administration of immunostimulants. Surveys have indicated that some bacteria can work as immunomodulators such as Mycobacterium vaccae and can promote Th1-mediated mechanisms, and switch off pre-existing Th2 preponderance (1. Objectives: The aim of this study was to examine the effect of Tsukamurella inchonensis bacterin on the immune response against Influenza and Newcastle disease vaccine in broiler chickens . Materials and Methods: A total of 170 day-old broiler chicks were purchased and divided randomly into 5 equal groups. Chickens of group A received 106 bacterin subcutaneously on two days before vaccination against Newcastle disease and avian influenza. Chickens of group B received 106 bacterin subcutaneously on six days after the first injection of bacterin. Chickens of group C received 106bacterin subcutaneously on six days after the second injection of bacterin. Chickens of group D, vaccinated against Newcastle disease and avian influenza but did not receive bacterin. Chickens of group E, did not vaccinate against Newcastle disease and avian influenza and did not receive bacterin. All groups except group E, were vaccinated with live Newcastle vaccine and AI-ND killed vaccine (subtype H9N2. Blood samples were collected and antibody titer against Newcastle disease vaccine and avian influenza vaccine was determined by HI test. Results: The results of present study showed that receiving of Tsukamurella inchonensis bacterin for 3 times, significantly increased the specific antibody response to avian influenza subtype H9N2 vaccine. Also about Newcastle vaccine, significantly increased the specific antibody response to Newcastle vaccine at 21 and 28 days after vaccination. Conclusions: Receiving of Tsukamurella inchonensis bacterin

  4. ANTI-B-CELL THERAPY AT IMMUNE INFLAMMATORY RHEUMATIC DISEASES: EFFICACY AND TOLERABILITY IN 229 PATIENTS

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    L. P. Ananieva

    2014-01-01

    Full Text Available Objective: to assess the efficacy and tolerability of Rituximab treatment in patients with serious immune inflammatory rheumatic diseases (IRD like systemic lupus erythematosus (SLE, systemic sclerosis (SS, systemic vasculitis (SV, Sjogren syndrome (SjS, dermatomyositis/polymyositis (DM/PM.Subjects and methods. The clinical efficacy has been analyzed in 229 patients with IRD: SLE (n=97, SV (n=50, SS (n=40, SjS (n=23 and DM/PM (n=19. Rituximab treatment was accompanied by administration of glucocorticoids and/or immunosuppressive drugs. Most patients demonstrated resistance to or low tolerability of standard therapy. Efficacy of treatment was analyzed in each group with the criteria relevant for each disease. To compare clinical response to the treatment between the groups we used gradations accepted by international registries: complete (good response, partial response, no response. Average duration of monitoring comprised 72 (1–288 weeks after the first introduction of Rituximab. Average Rituximab dose administered to patients over the period of monitoring was low and varied from 1.6±0.84 in DM/PM to 3.1±1.75 in SV. About 80% of patients received one or two courses of Rituximab except for patients with SS (half of them received three and more courses.Results. «Complete response» was observed in 50.6%, «partial response» – in 35% of patients. Rituximab courses provided positive dynamics in clinical scores and allowed to reduce supportive dose of glucocorticoids and to lower the dose or withdraw of immune-stimulating drugs. Multiple Rituximab courses provided stable and longlasting effect. Recurrences were observed less frequently, whereas efficacy of the therapy increased during a year and longer. Occurrence of adverse events and mortality rate were comparable to data of other national Rituximab registries.Conclusion. The results of the study may prove administration of Rituximab in patients with resistance to standard

  5. TAM Receptor Signaling in Immune Homeostasis

    Science.gov (United States)

    Rothlin, Carla V.; Carrera-Silva, Eugenio A.; Bosurgi, Lidia; Ghosh, Sourav

    2015-01-01

    The TAM receptor tyrosine kinases (RTKs)—TYRO3, AXL, and MERTK—together with their cognate agonists GAS6 and PROS1 play an essential role in the resolution of inflammation. Deficiencies in TAM signaling have been associated with chronic inflammatory and autoimmune diseases. Three processes regulated by TAM signaling may contribute, either independently or collectively, to immune homeostasis: the negative regulation of the innate immune response, the phagocytosis of apoptotic cells, and the restoration of vascular integrity. Recent studies have also revealed the function of TAMs in infectious diseases and cancer. Here, we review the important milestones in the discovery of these RTKs and their ligands and the studies that underscore the functional importance of this signaling pathway in physiological immune settings and disease. PMID:25594431

  6. Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease

    Directory of Open Access Journals (Sweden)

    Cristen Chafin

    2010-10-01

    Full Text Available Cristen Chafin2, Sarah Muse2, Raquel Hontecillas5, Josep Bassaganya-Riera5, David L Caudell2, Samuel K Shimp III4, M Nichole Rylander4, John Zhang6, Liwu Li3, Christopher M Reilly1,21Virginia College of Osteopathic Medicine, 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 3Department of Biological Sciences, 4Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 5Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 6Medical University of SC, Charleston, SC, USAAbstract: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-γ has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-γ gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM mouse model. PPAR-γ+/+ and PPAR-γ-/- mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-γ+/+ and PPAR-γ-/- mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-γ-/- mice were significantly more severe compared with the PPAR-γ+/+ animals. We observed that the PPAR-γ-/- mice had decreased CD4+CD25+ regulatory T cells and an increased CD8+:CD4+ ratio as compared with the PPAR-γ+/+ mice, suggesting that PPAR-γ has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-γ-/- mice at two weeks as compared with the PPAR-γ+/+ animals. Taken together, these studies show that

  7. Immune and hormonal status of children at respiratory diseases have been born before and after the Chernobyl accident

    International Nuclear Information System (INIS)

    Lysenko, I.M.

    1997-01-01

    Immune- and hormonal status of preschool healthy children and of those often falling ill with respiratory diseases born of healthy mothers and of those with endocrine disorders before and after Chernobyl accident has been studied. The study has revealed evident deviation from the norm in the immune system and non-specific resistance indices of children from after 1986 and particularly of those living in the radionuclide contaminated areas as well as of children often falling ill. Breaks of correlation between separate hormonal systems have been found too

  8. Chemogenetic locus coeruleus activation restores reversal learning in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Rorabaugh, Jacki M; Chalermpalanupap, Termpanit; Botz-Zapp, Christian A; Fu, Vanessa M; Lembeck, Natalie A; Cohen, Robert M; Weinshenker, David

    2017-11-01

    See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer’s disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies. Here, a transgenic rat (TgF344-AD) expressing disease-causing mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1ΔE9) was characterized for histological and behavioural signs of locus coeruleus dysfunction reminiscent of mild cognitive impairment/early Alzheimer’s disease. In TgF344-AD rats, hyperphosphorylated tau was detected in the locus coeruleus prior to accrual in the medial entorhinal cortex or hippocampus, and tau pathology in the locus coeruleus was negatively correlated with noradrenergic innervation in the medial entorhinal cortex. Likewise, TgF344-AD rats displayed progressive loss of hippocampal norepinephrine levels and locus coeruleus fibres in the medial entorhinal cortex and dentate gyrus, with no frank noradrenergic cell body loss. Cultured mouse locus coeruleus neurons expressing hyperphosphorylation-prone mutant human tau had shorter neurites than control neurons, but similar cell viability, suggesting a causal link between pretangle tau accrual and altered locus coeruleus fibre morphology. TgF344-AD rats had impaired reversal learning in the Morris water maze compared to their wild-type littermates, which was rescued by chemogenetic locus coeruleus activation via designer receptors exclusively activated by designer drugs (DREADDs). Our results indicate that TgF344-AD rats uniquely meet several key criteria for a

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

    Science.gov (United States)

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

    2017-03-21

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

  10. Mycobacterium avium Subspecies paratuberculosis Infection in Cases of Irritable Bowel Syndrome and Comparison with Crohn's Disease and Johne's Disease: Common Neural and Immune Pathogenicities▿

    OpenAIRE

    Scanu, Antonio M.; Bull, Tim J.; Cannas, Sara; Sanderson, Jeremy D.; Sechi, Leonardo A.; Dettori, Giuseppe; Zanetti, Stefania; Hermon-Taylor, John

    2007-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacteri...

  11. Waning of maternal immunity and the impact of diseases: the example of myxomatosis in natural rabbit populations.

    Science.gov (United States)

    Fouchet, D; Marchandeau, S; Langlais, M; Pontier, D

    2006-09-07

    Myxomatosis is a leporipoxvirus that infects the european rabbit, inducing a high mortality rate. Observations lead us to hypothesize that a rabbit carrying maternal antibodies (or having recovered) can be infected (or re-infected) upon being exposed (or re-exposed) to the virus. Infection will lead to mild disease, boosting host immune protection. Using a modelling approach we show that this phenomenon may lead to a difference of impact of myxomatosis according to its transmission rate. Young are exposed when they still carry maternal antibodies and develop a mild disease in high transmission populations. Our results show that the impact of myxomatosis is generally higher in epidemic situations compared to populations where the virus circulates all the year. As a consequence, waning of acquired immunity and the continuous supply of newborn along the year may reduce the impact of the disease.

  12. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

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    Handel Adam E

    2011-01-01

    Full Text Available Abstract Background Venous thromboembolism (VTE is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT and pulmonary embolism (PE in people admitted to hospital with a range of immune-mediated diseases. Methods We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008 and the whole of England (1999 to 2008. Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. Results Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31 in the ORLS1 population, 4.60 (3.19 to 6.43 in ORLS2 and 3.71 (3.43 to 4.02 in the England dataset. Conclusions People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases.

  13. Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.

    Directory of Open Access Journals (Sweden)

    Rogier M Thurlings

    2009-11-01

    Full Text Available Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA, a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT. We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO. Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3 (0.95-5.1 x 10(-3 % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion.The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.

  14. Vascular consequences of passive Aβ immunization for Alzheimer's disease. Is avoidance of "malactivation" of microglia enough?

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    Barger Steven W

    2005-01-01

    Full Text Available Abstract The role of inflammation in Alzheimer's disease (AD has been controversial since its first consideration. As with most instances of neuroinflammation, the possibility must be considered that activation of glia and cytokine networks in AD arises merely as a reaction to neurodegeneration. Active, healthy neurons produce signals that suppress inflammatory events, and dying neurons activate phagocytic responses in microglia at the very least. But simultaneous with the arrival of a more complex view of microglia, evidence that inflammation plays a causal or exacerbating role in AD etiology has been boosted by genetic, physiological, and epidemiological studies. In the end, it may be that the semantics of "inflammation" and glial "activation" must be regarded as too simplistic for the advancement of our understanding in this regard. It is clear that elaboration of the entire repertoire of activated microglia – a phenomenon that may be termed "malactivation" – must be prevented for healthy brain structure and function. Nevertheless, recent studies have suggested that phagocytosis of Aβ by microglia plays an important role in clearance of amyloid plaques, a process boosted by immunization paradigms. To the extent that this clearance might produce clinical improvements (still an open question, this relationship thus obligates a more nuanced consideration of the factors that indicate and control the various activities of microglia and other components of neuroinflammation.

  15. IgG4-related disease and its pathogenesis—cross-talk between innate and acquired immunity

    Science.gov (United States)

    Nakajima, Akio; Nakamura, Takuji; Kawanami, Takafumi; Tanaka, Masao; Dong, Lingli; Kawano, Mitsuhiro

    2014-01-01

    IgG4-related disease (IgG4-RD) is a novel clinical entity proposed in Japan in the 21th century and is attracting strong attention over the world. The characteristic manifestations of IgG4-RD are increased serum IgG4 concentration and tumefaction by IgG4+ plasma cells. Although the clinical manifestations in various organs have been established, the pathogenesis of IgG4-RD is still unknown. Recently, many reports of aberrant acquired immunity such as Th2-diminated immune responses have been published. However, many questions still remain, including questions about the pathogenesis of IgG4-RD and the roles of IgG4. In this review, we discuss the pathogenesis of IgG4-RD by focusing on the cross-talk between innate and acquired immunity. PMID:25024397

  16. Different infective forms trigger distinct immune response in experimental Chagas disease.

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    Paula Melo de Abreu Vieira

    Full Text Available Although metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-α and later of IFN-γ by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-γ, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease.

  17. Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease.

    Science.gov (United States)

    Rizzello, Fernando; Olivieri, Ignazio; Armuzzi, Alessandro; Ayala, Fabio; Bettoli, Vincenzo; Bianchi, Luca; Cimino, Luca; Costanzo, Antonio; Cristaudo, Antonio; D'Angelo, Salvatore; Daperno, Marco; Fostini, Anna Chiara; Galeazzi, Mauro; Gilio, Michele; Gionchetti, Paolo; Gisondi, Paolo; Lubrano, Ennio; Marchesoni, Antonio; Offidani, Annamaria; Orlando, Ambrogio; Pugliese, Daniela; Salvarani, Carlo; Scarpa, Raffaele; Vecchi, Maurizio; Girolomoni, Giampiero

    2018-04-01

    Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis. A Delphi consensus-based approach was used to identify a core set of statements. The process included development of initial questions by a steering committee, an exhaustive search of the literature using complementary approaches to identify potential statements and two Delphi voting rounds for finalization of the statements. Consensus was achieved on the related nature of IMIDs, the existence of a high prevalence of multiple IMIDs in a single patient and the fact that a multidisciplinary approach can result in a more extensive evaluation and comprehensive approach to treatment. The goals of a multidisciplinary team should be to increase diagnosis of concomitant IMIDs, improve the decision-making process, and increase patient satisfaction and adherence. Early referral and diagnosis, early recognition of concomitant IMIDs and optimizing treatment to improve patient quality of life are some of the advantages of using multidisciplinary teams. To be effective, a multidisciplinary team should be equipped with the appropriate tools for diagnosis and follow-up, and at a minimum the multidisciplinary team should include a dermatologist, gastroenterologist and rheumatologist; providing psychologic support via a psychologist and involving an ophthalmologist, general practitioners and nurses in multidisciplinary care is also important. The present Delphi consensus identified a set of

  18. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2015-01-01

    Full Text Available Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants. Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators. The following terms were used: "inflammatory bowel disease (IBD" OR "Crohn′s disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine" AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]" AND "immunomodulators." Study Selection: The inclusion criteria of articles were that the studies: (1 Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria; (2 exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3 exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents. The exclusion criteria of articles were that the studies: (1 History of hepatitis B virus (HBV, influenza or streptococcus pneumoniae infection; (2 patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3 any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection; (4 individuals with positive hepatitis markers or liver cirrhosis; (5 patients with a known allergy to eggs or other components of the vaccines and (6 pregnancy. Results: Patients treated with immunomodulators were associated with lower response rates to

  19. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Maternal supplementation with LGG reduces vaccine-specific immune responses in infants at high-risk of developing allergic disease

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    Paul V Licciardi

    2013-11-01

    Full Text Available Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonisation at the mucosal surface as well as modulation of immune responses are widely recognised as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG on immune responses to tetanus, Haemophilus influenzae type b (Hib and pneumococcal conjugate (PCV7 vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib and pneumococcal serotypes contained in PCV7 (N=31 compared to placebo-treatment (N=30 but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific Treg in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.

  1. Restoring logic and data to phage-cures for infectious disease

    Directory of Open Access Journals (Sweden)

    Philip Serwer

    2017-08-01

    Full Text Available Antibiotic therapy for infectious disease is being compromised by emergence of multi-drug-resistant bacterial strains, often called superbugs. A response is to use a cocktail of several bacteria-infecting viruses (bacteriophages or phages to supplement antibiotic therapy. Use of such cocktails is called phage therapy, which has the advantage of response to bacterial resistance that is rapid and not exhaustible. A procedure of well-established success is to make cocktails from stockpiles of stored environmental phages. New phages are added to stockpiles when phage therapy becomes thwarted. The scientific subtext includes optimizing the following aspects: (1 procedure for rapidly detecting, purifying, storing and characterizing phages for optimization of phage cocktails, (2 use of directed evolution in the presence of bacteriostatic compounds to obtain phages that can be most efficiently used for therapy in the presence of these compounds, (3 phage genome sequencing technology and informatics to improve the characterization of phages, and (4 database technology to make optimal use of all relevant information and to rapidly retrieve phages for cocktails that will vary with the infection(s involved. The use of phage stockpiles has an established record, including a recent major human-therapy success by the US Navy. However, I conclude that most research is not along this track and, therefore, is not likely to lead to real world success. I find that a strong case exists for action to rectify this situation.

  2. Chlorophytum borivilianum Polysaccharide Fraction Provokes the Immune Function and Disease Resistance of Labeo rohita against Aeromonas hydrophila

    Directory of Open Access Journals (Sweden)

    Sib Sankar Giri

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of Chlorophytum borivilianum polysaccharide (CBP, as a dietary supplement administered at varying concentrations with feed (basal diet, on various cytokine-related responses in Labeo rohita fingerlings. Immune parameters and immune-related gene expressions were measured at 3rd, 4th, and 5th week after feeding. The results revealed that dietary administration of CBP at 0.2% and 0.4% for 4 weeks significantly upregulated serum lysozyme and phagocytic activity. Complement C3 and respiratory burst activity (RBA were significantly higher after 4 weeks of CBP feeding. The immune related genes IL-8, IL-1β, TNF-α, and iNOS were downregulated (P<0.05 in groups with 0.2% and 0.4% CBP supplemented diets at week 4. Expression of anti-inflammatory cytokines (IL-10 and TGF-β was also downregulated (P<0.5 after 4 weeks of feeding with 0.2% to 0.8% CBP. However, five weeks of CBP administration had no significant effect on immune gene expression, except TNF-α and IL-8. Fish fed with 0.4% CBP for 4 weeks showed maximum resistance against Aeromonas hydrophila (73.3% survival compared to control. From these results, we recommend that CBP administration at 0.4% for 4 weeks could effectively improve immune response and disease resistance in L. rohita.

  3. Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: Future therapeutic targets

    NARCIS (Netherlands)

    Kraneveld, A.D.; Rijnierse, A.; Nijkamp, F.P.; Garssen, J.

    2008-01-01

    The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory

  4. Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome : Future therapeutic targets

    NARCIS (Netherlands)

    Kraneveld, A.D.|info:eu-repo/dai/nl/126612838; Rijnierse, A.|info:eu-repo/dai/nl/304830224; Nijkamp, F.P.|info:eu-repo/dai/nl/067668852; Garssen, J.|info:eu-repo/dai/nl/086369962

    2008-01-01

    The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory

  5. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice.

    Science.gov (United States)

    Perusini, Jennifer N; Cajigas, Stephanie A; Cohensedgh, Omid; Lim, Sean C; Pavlova, Ina P; Donaldson, Zoe R; Denny, Christine A

    2017-10-01

    Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. APPswe/PS1dE9 (APP/PS1) mice have been developed as an AD model and are characterized by plaque formation at 4-6 months of age. Here, we sought to better understand AD-related cognitive decline by characterizing various types of memory. In order to better understand how memory declines with AD, APP/PS1 mice were bred with ArcCreER T2 mice. In this line, neural ensembles activated during memory encoding can be indelibly tagged and directly compared with neural ensembles activated during memory retrieval (i.e., memory traces/engrams). We first administered a battery of tests examining depressive- and anxiety-like behaviors, as well as spatial, social, and cognitive memory to APP/PS1 × ArcCreER T2 × channelrhodopsin (ChR2)-enhanced yellow fluorescent protein (EYFP) mice. Dentate gyrus (DG) neural ensembles were then optogenetically stimulated in these mice to improve memory impairment. AD mice had the most extensive differences in fear memory, as assessed by contextual fear conditioning (CFC), which was accompanied by impaired DG memory traces. Optogenetic stimulation of DG neural ensembles representing a CFC memory increased memory retrieval in the appropriate context in AD mice when compared with control (Ctrl) mice. Moreover, optogenetic stimulation facilitated reactivation of the neural ensembles that were previously activated during memory encoding. These data suggest that activating previously learned DG memory traces can rescue cognitive impairments and point to DG manipulation as a potential target to treat memory loss commonly seen in AD. © 2017 Wiley Periodicals, Inc.

  6. A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.

    Science.gov (United States)

    Spencer, Brian; Verma, Inder; Desplats, Paula; Morvinski, Dinorah; Rockenstein, Ed; Adame, Anthony; Masliah, Eliezer

    2014-06-20

    Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

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

    2016-10-10

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

  8. Immune phenotype in children with therapy-naïve remitted and relapsed Crohn’s disease

    Science.gov (United States)

    Cseh, Aron; Vasarhelyi, Barna; Molnar, Kriszta; Szalay, Balazs; Svec, Peter; Treszl, Andras; Dezsofi, Antal; Lakatos, Peter Laszlo; Arato, Andras; Tulassay, Tivadar; Veres, Gabor

    2010-01-01

    AIM: To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy-naïve childhood Crohn’s disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease. METHODS: We enrolled 26 pediatric patients with CD. 14 therapy-naïve CD children; of those, 10 children remitted on conventional therapy and formed the remission group. We also tested another group of 12 children who relapsed with conventional therapy and were given infliximab; and 15 healthy children who served as controls. The prevalence of Th1 and Th2, naïve and memory, activated and regulatory T cells, along with the members of innate immunity such as natural killer (NK), NK-T, myeloid and plasmocytoid dendritic cells (DCs), monocytes and Toll-like receptor (TLR)-2 and TLR-4 expression were determined in peripheral blood samples. RESULTS: Children with therapy-naïve CD and those in relapse showed a decrease in Th1 cell prevalence. Simultaneously, an increased prevalence of memory and activated lymphocytes along with that of DCs and monocytes was observed. In addition, the ratio of myeloid /plasmocytoid DCs and the prevalence of TLR-2 or TLR-4 positive DCs and monocytes were also higher in therapy-naïve CD than in controls. The majority of alterations diminished in remitted CD irrespective of whether remission was obtained by conventional or biological therapy. CONCLUSION: The finding that immune phenotype is normalized in remission suggests a link between immune phenotype and disease activity in childhood CD. Our observations support the involvement of members of the adaptive and innate immune systems in childhood CD. PMID:21157977

  9. Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

    Science.gov (United States)

    Bottaccioli, Anna Giulia; Bottaccioli, Francesco; Minelli, Andrea

    2018-05-15

    In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases. © 2018 New York Academy of Sciences.

  10. The novel KMO inhibitor CHDI-340246 leads to a restoration of electrophysiological alterations in mouse models of Huntington's disease.

    Science.gov (United States)

    Beaumont, Vahri; Mrzljak, Ladislav; Dijkman, Ulrike; Freije, Robert; Heins, Mariette; Rassoulpour, Arash; Tombaugh, Geoffrey; Gelman, Simon; Bradaia, Amyaouch; Steidl, Esther; Gleyzes, Melanie; Heikkinen, Taneli; Lehtimäki, Kimmo; Puoliväli, Jukka; Kontkanen, Outi; Javier, Robyn M; Neagoe, Ioana; Deisemann, Heike; Winkler, Dirk; Ebneth, Andreas; Khetarpal, Vinod; Toledo-Sherman, Leticia; Dominguez, Celia; Park, Larry C; Munoz-Sanjuan, Ignacio

    2016-08-01

    Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington's disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), an enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. In order to determine the role of KMO in the phenotype of mouse models of HD, we have developed a potent and selective KMO inhibitor termed CHDI-340246. We show that this compound, when administered orally to transgenic mouse models of HD, potently and dose-dependently modulates the Kyn pathway in peripheral tissues and in the central nervous system. The administration of CHDI-340246 leads to an inhibition of the formation of 3-OH-Kyn and Quin, and to an elevation of Kyn and Kynurenic acid (KynA) levels in brain tissues. We show that administration of CHDI-340246 or of Kyn and of KynA can restore several electrophysiological alterations in mouse models of HD, both acutely and after chronic administration. However, using a comprehensive panel of behavioral tests, we demonstrate that the chronic dosing of a selective KMO inhibitor does not significantly modify behavioral phenotypes or natural progression in mouse models of HD. Copyright © 2016. Published by Elsevier Inc.

  11. Engineered disulfide bonds restore chaperone-like function of DJ-1 mutants linked to familial Parkinson's disease.

    Science.gov (United States)

    Logan, Todd; Clark, Lindsay; Ray, Soumya S

    2010-07-13

    Loss-of-function mutations such as L166P, A104T, and M26I in the DJ-1 gene (PARK7) have been linked to autosomal-recessive early onset Parkinson's disease (PD). Cellular and structural studies of the familial mutants suggest that these mutations may destabilize the dimeric structure. To look for common dynamical signatures among the DJ-1 mutants, short MD simulations of up to 1000 ps were conducted to identify the weakest region of the protein (residues 38-70). In an attempt to stabilize the protein, we mutated residue Val 51 to cysteine (V51C) to make a symmetry-related disulfide bridge with the preexisting Cys 53 on the opposite subunit. We found that the introduction of this disulfide linkage stabilized the mutants A104T and M26I against thermal denaturation, improved their ability to scavenge reactive oxygen species (ROS), and restored a chaperone-like function of blocking alpha-synuclein aggregation. The L166P mutant was far too unstable to be rescued by introduction of the V51C mutation. The results presented here point to the possible development of pharmacological chaperones, which may eventually lead to PD therapeutics.

  12. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

    Science.gov (United States)

    Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

    2013-01-01

    Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes

  13. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    Science.gov (United States)

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  14. Disease susceptibiliy in the zig-zag model of host-microbe Interactions: only a consequence of immune suppression?

    OpenAIRE

    Keller, Harald; Boyer, Laurent; Abad, Pierre

    2016-01-01

    For almost ten years, the Zig-Zag model has provided a convenient framework for explaining the molecular bases of compatibility and incompatibility in plant-microbe interactions (Jones and Dangl, 2006). According to the Zig-Zag model, disease susceptibility is a consequence of the suppression of host immunity during the evolutionary arms race between plants and pathogens. The Zig-Zag model thus fits well with biotrophic interactions, but is less applicable to interactions involving pathogens ...

  15. Characterization of immune cell function in N-terminal fragment minipig model of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Valeková, Ivona; Butalová, N.; Vidinská, Daniela; Juhás, Štefan; Kovářová, Hana; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 24-25 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : neuroinflammation * innate immune system * microglia Subject RIV: FH - Neurology

  16. Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

    International Nuclear Information System (INIS)

    Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

    1979-01-01

    Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

  17. Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

    DEFF Research Database (Denmark)

    Rossin, Elizabeth J.; Hansen, Kasper Lage; Raychaudhuri, Soumya

    2011-01-01

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these r......Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed...... in rheumatoid arthritis (RA) and Crohn's disease (CD) GWAS, we build protein-protein interaction (PPI) networks for genes within associated loci and find abundant physical interactions between protein products of associated genes. We apply multiple permutation approaches to show that these networks are more...... that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non...

  18. Hashimoto's Thyroiditis Presenting as Acute Painful Thyroiditis and as a Manifestation of an Immune Reconstitution Inflammatory Syndrome in a Human Immunodeficiency Virus-Seropositive Patient.

    NARCIS (Netherlands)

    Visser, R.; Mast, Q. de; Netea-Maier, R.T.; Ven, A.J.A.M. van der

    2012-01-01

    Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby

  19. The Economic Impact of Biosimilars on Chronic Immune-Mediated Inflammatory Diseases.

    Science.gov (United States)

    Pentek, Marta; Zrubka, Zsombor; Gulacsi, Laszlo

    2017-01-01

    Biological drugs represent highly effective but costly treatments for chronic immunemediated inflammatory diseases posing substantial burden on health care budgets. Introduction of biosimilars since 2013 has brought forward the potential of market competition, and as a societal benefit, the hope of increased access at a lower cost. We aim to provide a descriptive review on economic aspects and market changes related to the introduction of biosimilar drugs. Our focus is on chronic immune-mediated inflammatory conditions in rheumatology, gastroenterology and dermatology. Based on available literature data, we discuss the determinants of access to biological treatment, summarize the available health economic evidences with special focus on cost-utility and budget impact analyses. Market penetration of biosimilars and their overall impact on biological markets are analyzed. Biosimilar markets are country specific due to differences in the regulatory and reimbursement systems. Cost-utility analyses suggest, that given the lower price of biosimilars, formerly established biological treatment sequence practices and the eligibility criteria for biological treatment deserve reconsideration. Budget impact analyses forecasted significant budget savings in various diagnoses and countries, providing opportunity for the treatment of more patients. Biosimilars may contribute to better patient-access and provide savings to governments. To increase their acceptability, further clinical evidences and real world experiences are needed, as well as education of physicians and patients. The high biosimilar penetration rates in Norway, Denmark and Poland suggest that policies which support interchanging from the reference product may be important drivers of biosimilar uptake. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.

    1977-01-01

    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  1. Epidemiology of Acquired Immune Deficiency Syndrome and Cerebrovascular Disease in a Post Antiretroviral Era.

    Science.gov (United States)

    Kucab, Phillip; Bhattacharya, Pratik

    2017-06-01

    People with acquired immune deficiency syndrome (AIDS) develop ischemic stroke through distinct mechanisms. These include infections such as syphilis, tuberculosis, varicella, and other conditions such as cocaine abuse, endocarditis, and hypercoagulability. The effect of improved awareness, detection, and treatment with highly active antiretroviral therapy (HAART) on the incidence and outcome of AIDS patients with stroke is unknown. Data from the Nationwide Inpatient Sample from 1995 to 2010 were analyzed. Patients with ischemic stroke and AIDS were identified using ICD-9 (International Classification of Diseases) codes. Time trends for demographics, survival, and frequency of AIDS-associated conditions were analyzed. Proportion of AIDS among stroke patients increased significantly during the study. Median age of all strokes decreased from 75 years in 1995 to 72 years in 2010. Conversely, median age for men with stroke and AIDS increased from 43 years to 53 years; and for women with stroke and AIDS, from 41 years to 51 years. Death rates from stroke in the AIDS patients declined. In recent years, the death rates from stroke are similar to patients without HIV/AIDS. Stroke patients with AIDS had increased odds of syphilis (odds ratio [OR]: 33.50), varicella (OR: 48.34), tuberculosis (OR: 137.48), endocarditis (OR: 5.19), cocaine abuse (OR: 26.05), and hypercoagulability (OR: 4.82). In the HAART era, the median age of incident stroke in AIDS has increased and the mortality from stroke has improved. Research should focus on optimal management of dyslipidemia while on HAART. Whether HAART can reduce the incidence and improve survival of stroke needs to be explored. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.

    Science.gov (United States)

    Scavella, Arnette; Leiva, Lily; Monjure, Hanh; Zea, Arnold H; Gardner, Renee V

    2010-08-01

    L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. (c) 2010 Wiley-Liss, Inc.

  3. The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease.

    Science.gov (United States)

    Iijima, Hideki; Shinzaki, Shinichiro; Takehara, Tetsuo

    2012-11-01

    This review summarizes the recent literature about the roles of vitamins D and K in bone metabolism and immunity-mediated inflammatory processes in inflammatory bowel diseases (IBDs). The levels of vitamins D and K are lower than normal in patients with IBD, especially in Crohn's disease. Although vitamins D and K are important for the maintenance of bone mineral density in non-IBD patients, an association between vitamins D or K and bone metabolism is not apparent in IBD patients. Recent studies showed that vitamins D and K are suggested to have immune-suppressive effects, both in animal models of colitis and human trials. In particular, vitamin D suppresses dendritic and T-cell functions by inhibiting the production of proinflammatory cytokines. Insufficiency of vitamin D is associated with the activated phenotype of IBD. Vitamins D and K potentially contribute to the maintenance of bone health in IBD, but this effect may be diminished by other factors such as steroid use, reduced exposure to sunlight, and inflammatory cytokines. Vitamin D and possibly vitamin K are suggested to be involved in the suppression of immune-mediated inflammation and modulation of disease activity.

  4. Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

    Science.gov (United States)

    Mohn, Kristin G.-I.; Cox, Rebecca Jane; Tunheim, Gro; Berdal, Jan Erik; Hauge, Anna Germundsson; Jul-Larsen, Åsne; Peters, Bjoern; Oftung, Fredrik

    2015-01-01

    Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza. PMID:26606759

  5. Omega-3 polyunsaturated fatty acids enrichment alters performance and immune response in infectious bursal disease challenged broilers

    Directory of Open Access Journals (Sweden)

    Maroufyan Elham

    2012-01-01

    Full Text Available Abstract Background Infectious bursal disease (IBD results in economic loss due to mortality, reduction in production efficiency and increasing the usage of antibiotics. This study was carried out to investigate the modulatory roles of dietary n-3 polyunsaturated fatty acids (PUFA enrichment in immune response and performance of IBD challenged broiler chickens. Methods A total of 300 day old male broiler chicks were assigned to four dietary n-3 PUFA ascending levels as the treatment groups (T1: 0.5; T2: 8.0; T3: 11.5; T4: 16.5 using combinations of tuna oil and sunflower oil. All diets were isocaloric and isonitrogenous. On day 28, all birds were challenged with IBD virus. Antibody titer, cytokine production, bursa lesion pre and post-challenge and lymphoid organ weight were recorded. Results On d 42 the highest body weight was observed in the T2 and T3 and the lowest in T4 chickens. Feed conversion ratio of the T2 broilers was significantly better than the other groups. Although productive parameters were not responded to the dietary n-3 PUFA in a dose-dependent manner, spleen weight, IBD and Newcastle disease antibody titers and IL-2 and IFN-γ concentrations were constantly elevated by n-3 PUFA enrichment. Conclusions Dietary n-3 PUFA enrichment may improve the immune response and IBD resistance, but the optimum performance does not coincide with the optimum immune response. It seems that dietary n-3 PUFA modulates the broiler chicken performance and immune response in a dose-dependent manner. Thus, a moderate level of dietary n-3 PUFA enrichment may help to put together the efficiency of performance and relative immune response enhancement in broiler chickens.

  6. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

    Directory of Open Access Journals (Sweden)

    Sina Moeller

    Full Text Available IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99, unaffected controls of similar age, gender, and race (n = 96, and patients with biopsy-proven celiac disease (n = 30. All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2. Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  7. Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

    Science.gov (United States)

    Moeller, Sina; Canetta, Pietro A; Taylor, Annette K; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H; Kiryluk, Krzysztof; Alaedini, Armin

    2014-01-01

    IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

  8. Transcriptional Profiling of Immune-Related Genes in Leishmania infantum-Infected Mice: Identification of Potential Biomarkers of Infection and Progression of Disease

    Directory of Open Access Journals (Sweden)

    Eduardo Ontoria

    2018-06-01

    Full Text Available Leishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease. In this large-scale analysis, differential expression of 112 immune-related genes has been analyzed using high-throughput qPCR in spleens of infected and naïve Balb/c mice at four different time points. This analysis revealed that early response against Leishmania infection is characterized by the upregulation of Th1 markers and M1-macrophage activation molecules such as Ifng, Stat1, Cxcl9, Cxcl10, Ccr5, Cxcr3, Xcl1, and Ccl3. This activation doesn't protect spleen from infection, since parasitic burden rises along time. This marked difference in gene expression between infected and control mice disappears during intermediate stages of infection, probably related to the strong anti-inflammatory and immunosuppresory signals that are activated early upon infection (Ctla4 or remain activated throughout the experiment (Il18bp. The overexpression of these Th1/M1 markers is restored later in the chronic phase (8 wpi, suggesting the generation of a classical “protective response” against leishmaniasis. Nonetheless, the parasitic burden rockets at this timepoint. This apparent contradiction can be explained by the generation of a regulatory immune response characterized by overexpression of Ifng, Tnfa, Il10, and downregulation Il4 that

  9. Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

    Science.gov (United States)

    Zhao, Yan-Jie; Jiang, Ni; Song, Qing-Kun; Wu, Jiang-Ping; Song, Yu-Guang; Zhang, Hong-Mei; Chen, Feng; Zhou, Lei; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Ren, Jun; Lyerly, Herbert Kim

    2015-01-01

    There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

  10. Lung Transcriptome Data from Chickens with Newcastle Disease Virus--Impact of Gender Immune Response

    Data.gov (United States)

    US Agency for International Development — To determine the gender impact on the immune response of chickens, the mRNA was isolated and sequenced from the lungs of 48 chickens of 2 lines as three time-points...

  11. Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis

    Science.gov (United States)

    2015-10-01

    cell function. Immune checkpoint blockade has been proven effective in recent clinical trials mostly in melanoma, lung and renal carcinomas. Our...noted between mice with ovarian and oviduct tumors, suggesting that both anatomical locations are similar in inducing an immune suppressive phenotype in...survival based on the anatomical site of mutation activation. (A) Nuclear grade of primary tumor tissues of the ovary, oviduct and the uterus

  12. Immune Memory to Sudan Virus: Comparison between Two Separate Disease Outbreaks

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    Ariel Sobarzo

    2015-01-01

    Full Text Available Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. However, a comprehensive protective immune profile has yet to be described. Here, we examine cellular memory immune responses among survivors of two separate Ebolavirus outbreaks (EVDs due to Sudan virus (SUDV infection in Uganda—Gulu 2000–2001 and Kibaale 2012. Freshly collected blood samples were stimulated with inactivated SUDV, as well as with recombinant SUDV or Ebola virus (EBOV GP (GP1–649. In addition, ELISA and plaque reduction neutralization assays were performed to determine anti-SUDV IgG titers and neutralization capacity. Cytokine expression was measured in whole blood cultures in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating recall responses that indicate immune memory. Cytokine responses between groups were similar but had distinct differences. Neutralizing, SUDV-specific IgG activity against irradiated SUDV and SUDV recombinant proteins were detected in both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to EBOV and EBOV recombinant GP1–649 was observed in both cohorts. In conclusion, immune responses in both groups of survivors demonstrate persistent recognition of relevant antigens, albeit larger cohorts are required in order to reach greater statistical significance. The differing cytokine responses between Gulu and Kibaale outbreak survivors suggests that each outbreak may not yield identical memory responses and promotes the merits of studying the immune responses among outbreaks of the same virus. Finally, our demonstration of cross-reactive immune recognition suggests that there is potential for developing cross

  13. The Role of the Immune System in Metabolic Health and Disease.

    Science.gov (United States)

    Zmora, Niv; Bashiardes, Stavros; Levy, Maayan; Elinav, Eran

    2017-03-07

    In addition to the immune system's traditional roles of conferring anti-infectious and anti-neoplastic protection, it has been recently implicated in the regulation of systemic metabolic homeostasis. This cross-talk between the immune and the metabolic systems is pivotal in promoting "metabolic health" throughout the life of an organism and plays fundamental roles in its adaptation to ever-changing environmental makeups and nutritional availability. Perturbations in this intricate immune-metabolic cross-talk contribute to the tendency to develop altered metabolic states that may culminate in metabolic disorders such as malnutrition, obesity, type 2 diabetes mellitus (T2DM), and other features of the metabolic syndrome. Regulators of immune-metabolic interactions include host genetics, nutritional status, and the intestinal microbiome. In this Perspective, we highlight current understanding of immune-metabolism interactions, illustrate differences among individuals and between populations in this respect, and point toward future avenues of research possibly enabling immune harnessing as means of personalized treatment for common metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Comparison of immune responses after intra-typic heterologous and homologous vaccination against foot-and-mouth disease virus infection in pigs

    NARCIS (Netherlands)

    Eble, P.L.; Bruin, de M.G.M.; Bouma, A.; Hemert-Kluitenberg, van F.; Dekker, A.

    2006-01-01

    This study compares the immune responses and protection induced by intra-typic heterologous vaccination with that induced by homologous vaccination against challenge with foot-and-mouth disease virus (FMDV). Humoral and cell-mediated immune responses and protection against challenge with FMDV O

  15. Immunity by equilibrium.

    Science.gov (United States)

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  16. Evaluation of traditional plant extracts for innate immune mechanisms and disease resistance against fish bacterial Aeromonas hydrophila and Pseudomonas sp.

    Science.gov (United States)

    Hardi, E. H.; Saptiani, G.; Kusuma, I. W.; Suwinarti, W.; Nugroho, R. A.

    2018-03-01

    The purposes of this study were to evaluate effect of ethanol herbal extracts of Boesenbergia pandurata, Solanum ferox and Zingimber zerumbet on Tilapia (Oreochromis nilaticus) innate immune mechanisms and disease resistance against Aeromonas hydrophila and Pseudomonas sp. Fish were intramuscularly injected with 0.1 mL/fish (1010 CFU mL-1) of each bacterium on the day 6th of post treatment using extract by several methods (injection, oral administration and immersion). The doses of extract were 600 ppm of B. pandurata, 900 ppm S. ferox and 200 ppm of Z. zerumbet. The percentage mortality, Relative Percent Survival (RPS) and innate immune response were assessed on weeks 1, 2, 3 and 4. All the methods were effective to enhance the immune parameters after 2 weeks application and the RPS of treatment reached more than 90 %. The results showed that the injection method of extracts was the most effective method to control A. hydrophila and Pseudomonas sp. The result indicated that all the doses of extracts could be significantly influence the immune response and protect the health status of tilapia against A. hydrophila and Pseudomonas sp. infections.

  17. Peripartum Antibiotics Promote Gut Dysbiosis, Loss of Immune Tolerance, and Inflammatory Bowel Disease in Genetically Prone Offspring.

    Science.gov (United States)

    Miyoshi, Jun; Bobe, Alexandria M; Miyoshi, Sawako; Huang, Yong; Hubert, Nathaniel; Delmont, Tom O; Eren, A Murat; Leone, Vanessa; Chang, Eugene B

    2017-07-11

    Factors affecting the developing neonatal gut microbiome and immune networks may increase the risk of developing complex immune disorders such as inflammatory bowel diseases (IBD). In particular, peripartum antibiotics have been suggested as risk factors for human IBD, although direct evidence is lacking. Therefore, we examined the temporal impact of the commonly used antibiotic cefoperazone on both maternal and offspring microbiota when administered to dams during the peripartum period in the IL-10-deficient murine colitis model. By rigorously controlling for cage, gender, generational, and murine pathobiont confounders, we observed that offspring from cefoperazone-exposed dams develop a persistent gut dysbiosis into adulthood associated with skewing of the host immune system and increased susceptibility to spontaneous and chemically dextran sodium sulfate (DSS)-induced colitis. Thus, early life exposure to antibiotic-induced maternal dysbiosis during a critical developmental window for gut microbial assemblage and immune programming elicits a lasting impact of increased IBD risk on genetically susceptible offspring. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-11-01

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

  19. Infection of goose with genotype VIId Newcastle disease virus of goose origin elicits strong immune responses at early stage

    Directory of Open Access Journals (Sweden)

    Qianqian Xu

    2016-10-01

    Full Text Available Newcastle disease (ND, caused by virulent strains of Newcastle disease virus (NDV, is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06. The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR1–3, 5, 7 and 15, avian β-defensin (AvBD 5–7, 10, 12 and 16, cytokines interleukin (IL-8, IL-18, IL-1β and interferon-γ, inducible NO synthase (iNOS, and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10 and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis.

  20. Our Immune System

    Science.gov (United States)

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  1. Effects of PM2.5 exposure on the Notch signaling pathway and immune imbalance in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Gu, Xing-yu; Chu, Xu; Zeng, Xiao-Li; Bao, Hai-Rong; Liu, Xiao-Ju

    2017-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure. PM2.5 exposure was performed by aerosol inhalation. γ-secretase inhibitor (GSI) was given using intraperitoneal injection. Splenic T lymphocytes were purified using a density gradient centrifugation method. CD4 + T lymphocyte subsets (Th1/Th2, Th17/Treg) were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5, and Hey1 were detected using RT-PCR and Western blot. Serum INF-γ, IL-4, IL-17 and IL-10 concentrations were measured using ELISA. The results showed that in COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of mRNA and protein in Notch1/2/3/4, Hes1/5, and Hey1 and serum INF-γ and IL-17 concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17-mediated immune disorder, and the Notch signaling pathway is in an overactivated state. PM2.5 promotes the overactivation of the Notch signaling pathway and aggravates the immune disorder of COPD. GSI can partially inhibit the activation of the Notch signaling pathway and alleviate the immune disorder under basal state and the immune disorder of COPD caused by PM2.5. This result suggests that PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch signaling pathway and that PM2.5 aggravates COPD. - Highlights: • The COPD mice demonstrated Th1 and Th17 dominant immune imbalance. • PM2.5 aggravates the Th1/Th2 and Th

  2. Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overview of the Experimental and Clinical Evidence.

    Science.gov (United States)

    Toussirot, Eric; Béreau, Matthieu; Vauchy, Charline; Saas, Philippe

    2018-01-01

    Immune mediated diseases (IMDs) are complex chronic inflammatory diseases involving genetic and environmental factors. Salt intake has been proposed as a diet factor that can influence the immune response. Indeed, experimental data report the influence of sodium chloride on the differentiation of naive CD4 + T cells into IL-17 secreting T helper (Th) cells (Th17 cells), by a mechanism involving the serum glucocorticoid kinase-1 (SGK1) that promotes the expression of the IL-23 receptor (IL-23R). The IL-23/IL-23R is critical for pathogenic inflammatory Th17 cell differentiation. Experimental data in murine models of arthritis, colitis and encephalomyelitis corroborate these findings. This manuscript reviews the current knowledge on the effects of sodium chloride on innate and adaptive immunity. We also performed a systematic literature review for clinical studies examining the relationships between salt consumption and the development or the activity/severity of the most common IMDs mediated by the IL-23/Th17 pathway, i.e., rheumatoid arthritis (RA), multiple sclerosis (MS), and Crohn's disease (CD). Nine studies were found, 4 in RA, 4 in MS and 1 in CD. An association was found between developments of anti-citrullinated protein antibody (ACPA) positive RA in smokers and salt intake, but these results were not confirmed in another study. For MS, no association was observed in pediatric subjects while in adult patients, a link was found between salt intake and disease activity. However, this result was not confirmed in another study. These conflicting results highlight the fact that further evaluation in human IMDs is required. Moreover, physicians need to develop clinical trials with diet interventions to evaluate the impact of low salt intake on disease activity/severity of IMDs.

  3. Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overview of the Experimental and Clinical Evidence

    Directory of Open Access Journals (Sweden)

    Eric Toussirot

    2018-04-01

    Full Text Available Immune mediated diseases (IMDs are complex chronic inflammatory diseases involving genetic and environmental factors. Salt intake has been proposed as a diet factor that can influence the immune response. Indeed, experimental data report the influence of sodium chloride on the differentiation of naive CD4+ T cells into IL-17 secreting T helper (Th cells (Th17 cells, by a mechanism involving the serum glucocorticoid kinase-1 (SGK1 that promotes the expression of the IL-23 receptor (IL-23R. The IL-23/IL-23R is critical for pathogenic inflammatory Th17 cell differentiation. Experimental data in murine models of arthritis, colitis and encephalomyelitis corroborate these findings. This manuscript reviews the current knowledge on the effects of sodium chloride on innate and adaptive immunity. We also performed a systematic literature review for clinical studies examining the relationships between salt consumption and the development or the activity/severity of the most common IMDs mediated by the IL-23/Th17 pathway, i.e., rheumatoid arthritis (RA, multiple sclerosis (MS, and Crohn's disease (CD. Nine studies were found, 4 in RA, 4 in MS and 1 in CD. An association was found between developments of anti-citrullinated protein antibody (ACPA positive RA in smokers and salt intake, but these results were not confirmed in another study. For MS, no association was observed in pediatric subjects while in adult patients, a link was found between salt intake and disease activity. However, this result was not confirmed in another study. These conflicting results highlight the fact that further evaluation in human IMDs is required. Moreover, physicians need to develop clinical trials with diet interventions to evaluate the impact of low salt intake on disease activity/severity of IMDs.

  4. Progress in Vaccine-Preventable and Respiratory Infectious Diseases-First 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006-2015.

    Science.gov (United States)

    Schuchat, Anne; Anderson, Larry J; Rodewald, Lance E; Cox, Nancy J; Hajjeh, Rana; Pallansch, Mark A; Messonnier, Nancy E; Jernigan, Daniel B; Wharton, Melinda

    2018-07-01

    The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006-2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus-associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful.

  5. Lipid reserves and immune defense in healthy and diseased migrating monarchs Danaus plexippus

    Directory of Open Access Journals (Sweden)

    Dara A. SATTERFIELD, Amy E. WRIGHT, Sonia ALTIZER

    2013-06-01

    Full Text Available Recent studies suggest that the energetic demands of long-distance migration might lower the pool of resources available for costly immune defenses. Moreover, migration could amplify the costs of parasitism if animals suffering from parasite-induced damage or depleted energy reserves are less able to migrate long distances. We investigated relationships between long-distance migration, infection, and immunity in wild fall-migrating monarch butterflies Danaus plexippus. Monarchs migrate annually from eastern North America to central Mexico, accumulating lipids essential for migration and winter survival as they travel southward. Monarchs are commonly infected by the debilitating protozoan parasite Ophryocystis elektroscirrha (OE. We collected data on lipid reserves, parasite loads, and two immune measures (hemocyte concentration and phenoloxidase activity from wild monarchs migrating through north GA (USA to ask whether (1 parasite infection negatively affects lipid reserves, and (2 greater investment in lipid reserves is associated with lower immune measures. Results showed that monarchs sampled later in the fall migration had lower but not significantly different immune measures and significantly higher lipid reserves than those sampled earlier. Lipid measures correlated negatively but only nearly significantly with one measure of immune defense (phenoloxidase activity in both healthy and infected monarchs, but did not depend on monarch infection status or parasite load. These results provide weak support for a trade-off between energy reserves and immune defense in migrants, and suggest that previously-demonstrated costs of OE infection for monarch migration are not caused by depleted lipid reserves [Current Zoology 59 (3: 393–402, 2013].

  6. Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

    Science.gov (United States)

    Rossin, Elizabeth J.; Lage, Kasper; Raychaudhuri, Soumya; Xavier, Ramnik J.; Tatar, Diana; Benita, Yair

    2011-01-01

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these risk variants. It has previously been observed that different genes harboring causal mutations for the same Mendelian disease often physically interact. We sought to evaluate the degree to which this is true of genes within strongly associated loci in complex disease. Using sets of loci defined in rheumatoid arthritis (RA) and Crohn's disease (CD) GWAS, we build protein–protein interaction (PPI) networks for genes within associated loci and find abundant physical interactions between protein products of associated genes. We apply multiple permutation approaches to show that these networks are more densely connected than chance expectation. To confirm biological relevance, we show that the components of the networks tend to be expressed in similar tissues relevant to the phenotypes in question, suggesting the network indicates common underlying processes perturbed by risk loci. Furthermore, we show that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute evidence that, for many of the complex diseases studied here, common genetic associations implicate regions encoding proteins that physically interact in a preferential manner, in

  7. A Novel Antagonist of the Immune Checkpoint Protein Adenosine A2a Receptor Restores Tumor-Infiltrating Lymphocyte Activity in the Context of the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Melanie Mediavilla-Varela

    2017-07-01

    Full Text Available BACKGROUND: Therapeutic strategies targeting immune checkpoint proteins have led to significant responses in patients with various tumor types. The success of these studies has led to the development of various antibodies/inhibitors for the different checkpoint proteins involved in immune evasion of the tumor. Adenosine present in high concentrations in the tumor microenvironment activates the immune checkpoint adenosine A2a receptor (A2aR, leading to the suppression of antitumor responses. Inhibition of this checkpoint has the potential to enhance antitumor T-cell responsiveness. METHODS: We developed a novel A2aR antagonist (PBF-509 and tested its antitumor response in vitro, in a mouse model, and in non-small cell lung cancer patient samples. RESULTS: Our studies showed that PBF-509 is highly specific to the A2aR as well as inhibitory of A2aR function in an in vitro model. In a mouse model, we found that lung metastasis was decreased after treatment with PBF-509 compared with its control. Furthermore, freshly resected tumor-infiltrating lymphocytes from lung cancer patients showed increased A2aR expression in CD4+ cells and variable expression in CD8+ cells. Ex vivo studies showed an increased responsiveness of human tumor-infiltrating lymphocytes when PBF-509 was combined with anti-PD-1 or anti-PD-L1. CONCLUSIONS: Our studies demonstrate that inhibition of the A2aR using the novel inhibitor PBF-509 could lead to novel immunotherapeutic strategies in non-small cell lung cancer.

  8. Supplemental effects of biofloc powder on growth performance, innate immunity, and disease resistance of Pacific white shrimp Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Chorong Lee

    2017-07-01

    Full Text Available Abstract An 8-week feeding trial was conducted to study the effect of dietary supplementation of a biofloc powder on growth performance and non-specific immune response of Litopenaeus vannamei. Seven experimental diets were prepared with supplementation of graded levels of dried biofloc powder by 0, 0.5, 1.0, 2.0, 4.0, 6.0, and 8.0% (designated as Con, BF0.5, BF1, BF2, BF4, BF6, and BF8, respectively. Triplicate groups of shrimp (1.01 ± 0.01 g were hand-fed with one of the diets four times a day. At the end of the feeding trial, significantly (P ˂ 0.05 higher growth performance and feed utilization were obtained in BF4 groups compared to those fed the Con diet. The innate immunity of shrimp was improved by the dietary supplementation of biofloc. Dietary inclusion of biofloc at the level of 4.0% significantly increased disease resistance of shrimp against Vibrio harveyi. The results indicate that biofloc might be used as a dietary supplement for growth performance, innate immunity and disease resistance of Pacific white shrimp.

  9. Need for immunization against hepatotropic viruses in children with chronic liver disease.

    Science.gov (United States)

    Srivastava, Anshu; Mathias, Amrita; Yachha, Surender Kumar; Agarwal, Jaya; Aggarwal, Rakesh

    2014-09-01

    Infection with hepatotropic viruses is a common cause of acute deterioration and adverse outcome in children with chronic liver disease (CLD). Such superimposed infections may be preventable through vaccination. The present study aimed to evaluate the exposure rates of hepatitis A, B, and E viruses in children with CLD and suggest an optimal vaccination strategy. Children with CLD were prospectively evaluated with a demographic, clinical, and investigative proforma. Hepatitis B surface antigen positive cases were labeled as hepatitis B virus-CLD, and all other etiologies as non-HBV-related CLD. Patients were tested for exposure to hepatitis A (total anti-hepatitis A virus [HAV], immunoglobulin M anti-HAV), hepatitis B (hepatitis B surface antigen, total anti-hepatitis B core, anti-hepatitis B surface), and hepatitis E (IgG anti-hepatitis E virus). A total of 142 children with CLD (age 9.1 ± 3.7 years, 83 [58.5%] boys) were enrolled. A total of 3.5% (5/142) and 38.7% (55/142) had received HAV and HBV vaccines, respectively. A total of 134 (94.4%) were total anti-HAV positive including 5 postimmunization patients, with higher positivity in those older than 5 years (19/25 vs 115/117; P = 0.001). Of the 115 patients with non-HBV-related CLD, 45 (39.1%) had exposure to HBV (40 total anti-hepatitis B core positive and 5 anti-HBs positive without immunization). Only 28 of 142 (19.7%) patients were IgG anti-HEV positive, with no difference across age. A total of 90.8%, 39.1%, and 19.7% of children with CLD from the developing world are exposed to hepatitis A, B, and E infections, respectively. Selective hepatitis A vaccination (patients younger than 5 years of age) and universal hepatitis B vaccination are required to protect children with CLD. Sanitation improvement and HEV vaccine trial are needed for prevention against HEV.

  10. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

    Directory of Open Access Journals (Sweden)

    Esposito Pasquale

    2011-03-01

    Full Text Available Abstract Background Celiac disease (CD is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders. Methods CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity. Results Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308, paralleled by significantly increased expression of claudin (CLDN 4 (P = 0.0286. Relative to controls, adaptive immunity markers interleukin (IL-6 (P = 0.0124 and IL-21 (P = 0.0572 were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR 2 was increased in GS but not in CD (P = 0.0295. Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325 and CD patients (P = 0.0293. Conclusions This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.

  11. Diversity of aging of the immune system classified in the cotton rat (Sigmodon hispidus) model of human infectious diseases.

    Science.gov (United States)

    Guichelaar, Teun; van Erp, Elisabeth A; Hoeboer, Jeroen; Smits, Noortje A M; van Els, Cécile A C M; Pieren, Daan K J; Luytjes, Willem

    2018-05-01

    Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed to define aging-related changes of the immune system of this species. Concomitantly, we asked whether the rate of immunological alterations may be stratified by physiological aberrations encountered during aging. With increasing age, cotton rats showed reduced frequencies of T cells, impaired induction of antibodies to RSV, higher incidence of aberrations of organs and signs of lipemia. Moreover, old animals expressed high biological heterogeneity, but the age-related reduction of T cell frequency was only observed in those specimens that displayed aberrant organs. Thus, cotton rats show age-related alterations of lymphocytes that can be classified by links with health status. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

    2015-06-01

    The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. The ABP Dendrimer, a Drug-Candidate against Inflammatory Diseases That Triggers the Activation of Interleukin-10 Producing Immune Cells.

    Science.gov (United States)

    Fruchon, Séverine; Poupot, Rémy

    2018-05-25

    The ABP dendrimer, which is built on a phosphorus-based scaffold and bears twelve azabisphosphonate groups at its surface, is one of the dendrimers that has been shown to display immuno-modulatory and anti-inflammatory effects towards the human immune system. Its anti-inflammatory properties have been successfully challenged in animal models of inflammatory disorders. In this review, we trace the discovery and the evaluation of the therapeutic effects of the ABP dendrimer in three different animal models of both acute and chronic inflammatory diseases. We emphasize that its therapeutic effects rely on the enhancement of the production of Interleukin-10, the paradigm of anti-inflammatory cytokines, by different subsets of immune cells, such as monocytes/macrophages and CD4+ T lymphocytes.

  14. Involvement of Innate Immunity in the Development of Inflammatory and Autoimmune Diseases

    Czech Academy of Sciences Publication Activity Database

    Tlaskalová, Helena; Tučková, Ludmila; Štěpánková, Renata; Hudcovic, Tomáš; Palová-Jelínková, Lenka; Kozáková, Hana; Rossmann, Pavel; Sánchez, Daniel; Cinová, Jana; Hrnčíř, Tomáš; Kverka, Miloslav; Frolová, Lenka; Uhlig, H.; Powrie, F.; Bland, P.

    2005-01-01

    Roč. 1051, - (2005), s. 787-798 ISSN 0077-8923 R&D Projects: GA AV ČR IAA5020205; GA AV ČR KJB5020407; GA ČR GA310/05/2245; GA ČR GD310/03/H147; GA ČR GP310/04/P242; GA AV ČR IBS5020203; GA MZd NR8356 Institutional research plan: CEZ:AV0Z50200510 Keywords : innate immunity * mucosal immunity * mucosal barrier Subject RIV: EE - Microbiology, Virology Impact factor: 1.971, year: 2005

  15. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

  16. Disease resistance or growth: the role of plant hormones in balancing immune responses and fitness costs

    NARCIS (Netherlands)

    Denance, N.; Sanchez Vallet, A.; Goffner, D.; Molina, A.

    2013-01-01

    Plant growth and response to environmental cues are largely governed by phytohormones. The plant hormones ethylene, jasmonic acid, and salicylic acid (SA) play a central role in the regulation of plant immune responses. In addition, other plant hormones, such as auxins, abscisic acid (ABA),

  17. Goblet cells contribute to ocular surface immune tolerance—implications for dry eye disease

    NARCIS (Netherlands)

    Barbosa, Flavia L.; Xiao, Yangyan; Bian, Fang; Coursey, Terry G.; Ko, Byung Yi; Clevers, Hans; de Paiva, Cintia S.; Pflugfelder, Stephen C.

    2017-01-01

    Conjunctival goblet cell (GC) loss in dry eye is associated with ocular surface inflammation. This study investigated if conjunctival GCs contribute to ocular surface immune tolerance. Antigens applied to the ocular surface, imaged by confocal microscopy, passed into the conjunctival stroma through

  18. Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease

    NARCIS (Netherlands)

    Barbosa, Flavia L; Xiao, Yangyan; Bian, Fang; Coursey, Terry G; Ko, Byung Yi; Clevers, Hans; de Paiva, Cintia S; Pflugfelder, Stephen C

    2017-01-01

    Conjunctival goblet cell (GC) loss in dry eye is associated with ocular surface inflammation. This study investigated if conjunctival GCs contribute to ocular surface immune tolerance. Antigens applied to the ocular surface, imaged by confocal microscopy, passed into the conjunctival stroma through

  19. Interactions between epithelial cells and dendritic cells in airway immune responses: lessons from allergic airway disease

    NARCIS (Netherlands)

    van Tongeren, J.; Reinartz, S. M.; Fokkens, W. J.; de Jong, E. C.; van Drunen, C. M.

    2008-01-01

    Micro-organisms constantly invade the human body and may form a threat to our health. Traditionally, concepts of defence mechanisms have included a protective outer layer of epithelia and a vigilant immune system searching for areas where the integrity of the outer layer may be compromised. Instead

  20. Diagnosis of diabetes diseases using an Artificial Immune Recognition System2 (AIRS2) with fuzzy K-nearest neighbor.

    Science.gov (United States)

    Chikh, Mohamed Amine; Saidi, Meryem; Settouti, Nesma

    2012-10-01

    The use of expert systems and artificial intelligence techniques in disease diagnosis has been increasing gradually. Artificial Immune Recognition System (AIRS) is one of the methods used in medical classification problems. AIRS2 is a more efficient version of the AIRS algorithm. In this paper, we used a modified AIRS2 called MAIRS2 where we replace the K- nearest neighbors algorithm with the fuzzy K-nearest neighbors to improve the diagnostic accuracy of diabetes diseases. The diabetes disease dataset used in our work is retrieved from UCI machine learning repository. The performances of the AIRS2 and MAIRS2 are evaluated regarding classification accuracy, sensitivity and specificity values. The highest classification accuracy obtained when applying the AIRS2 and MAIRS2 using 10-fold cross-validation was, respectively 82.69% and 89.10%.

  1. Challenges of Generating and Maintaining Protective Vaccine-Induced Immune Responses for Foot-and-Mouth Disease Virus in Pigs

    Science.gov (United States)

    Lyons, Nicholas A.; Lyoo, Young S.; King, Donald P.; Paton, David J.

    2016-01-01

    Vaccination can play a central role in the control of outbreaks of foot-and-mouth disease (FMD) by reducing both the impact of clinical disease and the extent of virus transmission between susceptible animals. Recent incursions of exotic FMD virus lineages into several East Asian countries have highlighted the difficulties of generating and maintaining an adequate immune response in vaccinated pigs. Factors that impact vaccine performance include (i) the potency, antigenic payload, and formulation of a vaccine; (ii) the antigenic match between the vaccine and the heterologous circulating field strain; and (iii) the regime (timing, frequency, and herd-level coverage) used to administer the vaccine. This review collates data from studies that have evaluated the performance of foot-and-mouth disease virus vaccines at the individual and population level in pigs and identifies research priorities that could provide new insights to improve vaccination in the future. PMID:27965966

  2. Effects of dietary nucleotides on growth, non-specific immune response and disease resistance of sea cucumber Apostichopus japonicas.

    Science.gov (United States)

    Wei, Zehong; Yi, Lina; Xu, Wei; Zhou, Huihui; Zhang, Yanjiao; Zhang, Wenbing; Mai, Kangsen

    2015-11-01

    A 9-week feeding trial was conducted to investigate the effects of dietary nucleotides (NT) on growth, immune response and disease resistance of sea cucumber Apostichopus japonicas (initial weight: 5.87 ± 0.03 g). Four graded levels of dietary NT were designed as 0, 150, 375 and 700 mg/kg, respectively. After the feeding trial, sea cucumbers were challenged with Vibrio splendidus for the determination of disease resistance. The results showed that the specific growth rates were significantly higher in sea cucumber fed the diet with 375 mg/kg NT than those fed the basal diet without NT supplementation (P sea cucumber fed diets with nucleotides (≥ 375 mg/kg) had significantly higher phagocytic activities in coelomic fluid (P 0.05). After being challenged with V. splendidus, the cumulative mortalities of sea cucumber fed diets with 150 and 375 mg/kg NT were significantly lower than that in the treatment without dietary nucleotide supplementation (P sea cucumber in vivo. In conclusion, it was showed that dietary NT does increase the growth performance, non-specific immunity and disease resistance of sea cucumber. The optimum dietary NT supplementation level for sea cucumber was found to be 375 mg/kg. The application of dietary NT may present a novel strategy for health management in sea cucumber's aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Dietary beta-1,3 glucan potentiates innate immunity and disease resistance of Asian catfish, Clarias batrachus (L.).

    Science.gov (United States)

    Kumari, J; Sahoo, P K

    2006-02-01

    This study investigated the effects of short and prolonged administration of a yeast beta-glucan on non-specific immune parameters, growth rate and the disease resistance of Asian catfish, Clarias batrachus. Fish fed with a basal diet (control) and test diet (basal diet supplemented with 0.1% glucan) for 1, 2 and 3 weeks were assayed for superoxide production, serum myeloperoxidase (MPO) content, natural haemagglutinin level, complement and lysozyme activities. Fish were weighed at weekly intervals and specific growth rate (SGR, % increase in body weight per day) was determined. After each week, fish were challenged with Aeromonas hydrophila to measure the level of protection. Results showed that glucan administration at 0.1% in feed, significantly (Pcomplement activity and SGR were not affected by the dietary supplementation of yeast glucan. As glucan feeding at 0.1% for 1 week is able to enhance the non-specific immunity and disease resistance of catfish efficiently, short-term feeding might be used in farmed catfish diets to enhance disease resistance.

  4. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    Science.gov (United States)

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  5. Immunizations for adult women.

    Science.gov (United States)

    Faubion, Stephanie S; Larkin, Lisa C

    2016-12-01

    Immunizations protect individual persons and contribute to public health by reducing morbidity and mortality associated with common infectious diseases. In this Practice Pearl, we review guidelines for adult immunizations and recent and potential changes in vaccines.

  6. SEVERAL MUCOSAL VACCINATION ROUTES CONFER IMMUNITY AGAINST ENTERIC REDMOUTH DISEASE IN RAINBOW TROUT, BUT THE PROTECTIVE MECHANISMS ARE DIFFERENT

    DEFF Research Database (Denmark)

    Neumann, Lukas; Villumsen, Kasper Rømer; Kragelund Strøm, Helene

    Vaccination is a keystone in prophylactic strategies preventing outbreaks of fish pathogenic bacterial diseases in aquaculture. The first commercial fish vaccine consisted of a bacterin of Yersinia ruckeri serotype O1 biotype 1. The vaccine has been very successful and has been used for more than...... cells and M-like cells have been found in fish, is it suggested that gut-associated lymphoid tissue (GALT) associated with the gastrointestinal tract are involved in antigen uptake and generation of a local protective immune response against Y. ruckeri....

  7. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease.

    Science.gov (United States)

    Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

    2011-04-29

    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB.

  8. Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease

    Directory of Open Access Journals (Sweden)

    Andrew S. Flies

    2017-05-01

    Full Text Available Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population. We have recently demonstrated that the inhibitory checkpoint molecule PD-L1 is upregulated on Tasmanian devil (Sarcophilus harrisii facial tumor cells in response to the interferon-gamma cytokine. As this could play a role in immune evasion by tumor cells, we performed a thorough comparative analysis of checkpoint molecule protein sequences among Tasmanian devils and eight other species. We report that many of the key signaling motifs and ligand-binding sites in the checkpoint molecules are highly conserved across the estimated 162 million years of evolution since the last common ancestor of placental and non-placental mammals. Specifically, we discovered that the CTLA-4 (MYPPPY ligand-binding motif and the CTLA-4 (GVYVKM inhibitory domain are completely conserved across all nine species used in our comparative analysis, suggesting that the function of CTLA-4 is likely conserved in these species. We also found that cysteine residues for intra- and intermolecular disulfide bonds were also highly conserved. For instance, all 20 cysteine residues involved in disulfide bonds in the human 4-1BB molecule were also present in devil 4-1BB. Although many key sequences were conserved, we have also identified immunoreceptor tyrosine-based inhibitory motifs (ITIMs and immunoreceptor tyrosine-based switch

  9. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

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

    Science.gov (United States)

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

    2018-01-01

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

  11. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

    Science.gov (United States)

    Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nöthen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cécile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Céline; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sánchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Longstreth, W T; Fairchild, Thomas J; Bossù, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairén, Mònica Díez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleó, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Muñoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stählbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, María J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-François; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D

    2017-09-01

    We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

  12. Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0

    Science.gov (United States)

    Arason, G J; Kolka, R; Hreidarsson, A B; Gudjonsson, H; Schneider, P M; Fry, L; Arnason, A

    2005-01-01

    Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0·50; P Grave's disease (0·30; P = 0·002) and insulin-dependent diabetes mellitus (0·23; P = 0·04) and in British patients with dermatitis herpetiformis (0·42; P = 0·002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0·51, P = 0·0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P cause of the PIP defect in autoimmune connective tissue disease. PMID:15932521

  13. Immune responses of mature chicken bone-marrow-derived dendritic cells infected with Newcastle disease virus strains with differing pathogenicity.

    Science.gov (United States)

    Xiang, Bin; Zhu, Wenxian; Li, Yaling; Gao, Pei; Liang, Jianpeng; Liu, Di; Ding, Chan; Liao, Ming; Kang, Yinfeng; Ren, Tao

    2018-06-01

    Infection of chickens with virulent Newcastle disease virus (NDV) is associated with severe pathology and increased morbidity and mortality. The innate immune response contributes to the pathogenicity of NDV. As professional antigen-presenting cells, dendritic cells (DCs) play a unique role in innate immunity. However, the contribution of DCs to NDV infection has not been investigated in chickens. In this study, we selected two representative NDV strains, i.e., the velogenic NDV strain Chicken/Guangdong/GM/2014 (GM) and the lentogenic NDV strain La Sota, to investigate whether NDVs could infect LPS-activated chicken bone-derived marrow DCs (mature chicken BM-DCs). We compared the viral titres and innate immune responses in mature chicken BM-DCs following infection with those strains. Both NDV strains could infect mature chicken BM-DC, but the GM strain showed stronger replication capacity than the La Sota strain in mature chicken BM-DCs. Gene expression profiling showed that MDA5, LGP2, TLR3, TLR7, IFN-α, IFN-β, IFN-γ, IL-1β, IL-6, IL-18, IL-8, CCL5, IL-10, IL-12, MHC-I, and MHC-II levels were altered in mature DCs after infection with NDVs at all evaluated times postinfection. Notably, the GM strain triggered stronger innate immune responses than the La Sota strain in chicken BM-DCs. However, both strains were able to suppress the expression of some cytokines, such as IL-6 and IFN-α, in mature chicken DCs at 24 hpi. These data provide a foundation for further investigation of the role of chicken DCs in NDV infection.

  14. Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes

    Directory of Open Access Journals (Sweden)

    Lin Na-Sheng

    2007-09-01

    Full Text Available Abstract Background Plant viruses can be employed as versatile vectors for the production of vaccines by expressing immunogenic epitopes on the surface of chimeric viral particles. Although several viruses, including tobacco mosaic virus, potato virus X and cowpea mosaic virus, have been developed as vectors, we aimed to develop a new viral vaccine delivery system, a bamboo mosaic virus (BaMV, that would carry larger transgene loads, and generate better immunity in the target animals with fewer adverse environmental effects. Methods We engineered the BaMV as a vaccine vector expressing the antigenic epitope(s of the capsid protein VP1 of foot-and-mouth disease virus (FMDV. The recombinant BaMV plasmid (pBVP1 was constructed by replacing DNA encoding the 35 N-terminal amino acid residues of the BaMV coat protein with that encoding 37 amino acid residues (T128-N164 of FMDV VP1. Results The pBVP1 was able to infect host plants and to generate a chimeric virion BVP1 expressing VP1 epitopes in its coat protein. Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies. Real-time PCR analysis of peripheral blood mononuclear cells from the BVP1-immunized swine revealed that they produced VP1-specific IFN-γ. Furthermore, all BVP1-immunized swine were protected against FMDV challenge. Conclusion Chimeric BaMV virions that express partial sequence of FMDV VP1 can effectively induce not only humoral and cell-mediated immune responses but also full protection against FMDV in target animals. This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.

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

    Science.gov (United States)

    Kaleeswaran, B; Ilavenil, S; Ravikumar, S

    2011-12-01

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

  16. The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease

    OpenAIRE

    Filyk, Heather A; Osborne, Lisa C

    2016-01-01

    Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the ‘multibiome’ to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine...

  17. Aflatoxin-Related Immune Dysfunction in Health and in Human Immunodeficiency Virus Disease

    Directory of Open Access Journals (Sweden)

    Yi Jiang

    2008-01-01

    Full Text Available Both aflatoxin and the human immunodeficiency virus (HIV cause immune suppression and millions of HIV-infected people in developing countries are chronically exposed to aflatoxin in their diets. We investigated the possible interaction of aflatoxin and HIV on immune suppression by comparing immune parameters in 116 HIV positive and 80 aged-matched HIV negative Ghanaians with high (≥0.91 pmol/mg albumin and low (<0.91 pmol/mg albumin aflatoxin B1 albumin adduct (AF-ALB levels. AF-ALB levels and HIV viral load were measured in plasma and the percentages of leukocyte immunophenotypes and cytokine expression were determined using flow cytometry. The cross-sectional comparisons found that (1 among both HIV positive and negative participants, high AF-ALB was associated with lower perforin expression on CD8+ T-cells (P=.012; (2 HIV positive participants with high AF-ALB had significantly lower percentages of CD4+ T regulatory cells (Tregs; P=.009 and naive CD4+ T cells (P=.029 compared to HIV positive participants with low AF-ALB; and (3 HIV positive participants with high AF-ALB had a significantly reduced percentage of B-cells (P=.03 compared to those with low AF-ALB. High AF-ALB appeared to accentuate some HIV associated changes in T-cell phenotypes and in B-cells in HIV positive participants.

  18. Isocitrate dehydrogenase of Helicobacter pylori potentially induces humoral immune response in subjects with peptic ulcer disease and gastritis.

    Directory of Open Access Journals (Sweden)

    M Abid Hussain

    Full Text Available BACKGROUND: H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD, an important house keeping protein of H. pylori. METHODOLOGY/PRINCIPAL FINDINGS: Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD. CONCLUSIONS/SIGNIFICANCE: ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1 and therefore, may not be a notable proinflammatory agent.

  19. Adherence to systemic therapies for immune-mediated inflammatory diseases in Lebanon: a physicians' survey from three medical specialties.

    Science.gov (United States)

    Ammoury, Alfred; Okais, Jad; Hobeika, Mireille; Sayegh, Raymond B; Shayto, Rani H; Sharara, Ala I

    2017-01-01

    Immune-mediated inflammatory diseases (IMIDs) are chronic conditions that may cause tissue damage and disability, reduced quality of life and increased mortality. Various treatments have been developed for IMIDs, including immune modulators and targeted biologic agents. However, adherence remains suboptimal. An adherence survey was used to evaluate physicians' beliefs about adherence to medication in IMID and to evaluate if and how they manage adherence. The survey was distributed to 100 randomly selected physicians from three different specialties. Results were analyzed by four academic experts commissioned to develop an action plan to address practical and perceptual barriers to adherence, integrating it into treatment goals to maximize outcomes in IMID, thereby elevating local standards of care. Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74%) did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Lack of time and specialized nursing support was reported as an important barrier to measuring adherence. The expert panel identified four key areas for action: 360° education (patient-nurse-physician), patient-physician communication, patient perception and concerns, and market access/cost. An action plan was developed centered on education and awareness, enhanced benefit-risk communication, development of adherence assessment tools and promotion of patient support programs. Nonadherence to medication is a commonly underestimated problem with important consequences. A customized target-based strategy to address the root causes of non-adherence is essential in the management of chronic immune-mediated diseases.

  20. Human Milk Oligosaccharides and Associations With Immune-Mediated Disease and Infection in Childhood: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Alice M. Doherty

    2018-04-01

    Full Text Available Complex sugars found in breastmilk, human milk oligosaccharides (HMOs, may assist in early-life immune programming and prevention against infectious diseases. This study aimed to systematically review the associations between maternal levels of HMOs and development of immune-mediated or infectious diseases in the offspring. PubMed and EMBASE databases were searched (last search on 22 February 2018 according to a predetermined search strategy. Original studies published in English examining the effect of HMOs on immune-mediated and infectious disease were eligible for inclusion. Of 847 identified records, 10 articles from 6 original studies were included, with study quality ranging from low to high. Of three studies to examine allergic disease outcomes, one reported a protective effect against cow’s milk allergy (CMA by 18 months of age associated with lower lacto-N-fucopentaose (LNFP III concentrations (OR: 6.7, 95% CI 2.0–22. Another study found higher relative abundance of fucosyloligosaccharides was associated with reduced diarrhea incidence by 2 years, due to (i stable toxin-E. coli infection (p = 0.04 and (ii “all causes” (p = 0.042. Higher LNFP-II concentrations were associated with (i reduced cases of gastroenteritis and respiratory tract infections at 6 weeks (p = 0.004, p = 0.010 and 12 weeks (p = 0.038, p = 0.038 and (ii reduced HIV transmission (OR: 0.45; 95% CI: 0.21–0.97 and mortality risk among HIV-exposed, uninfected infants (HR: 0.33; 95% CI: 0.14–0.74 by 24 months. Due to heterogeneity of the outcomes reported, pooling of results was not possible. There was limited evidence that low concentrations of LNFP-III are associated with CMA and that higher fucosyloligosaccharide levels protect infants against infectious disease. Further research is needed.

  1. Human Milk Oligosaccharides and Associations With Immune-Mediated Disease and Infection in Childhood: A Systematic Review.

    Science.gov (United States)

    Doherty, Alice M; Lodge, Caroline J; Dharmage, Shyamali C; Dai, Xin; Bode, Lars; Lowe, Adrian J

    2018-01-01

    Complex sugars found in breastmilk, human milk oligosaccharides (HMOs), may assist in early-life immune programming and prevention against infectious diseases. This study aimed to systematically review the associations between maternal levels of HMOs and development of immune-mediated or infectious diseases in the offspring. PubMed and EMBASE databases were searched (last search on 22 February 2018) according to a predetermined search strategy. Original studies published in English examining the effect of HMOs on immune-mediated and infectious disease were eligible for inclusion. Of 847 identified records, 10 articles from 6 original studies were included, with study quality ranging from low to high. Of three studies to examine allergic disease outcomes, one reported a protective effect against cow's milk allergy (CMA) by 18 months of age associated with lower lacto- N -fucopentaose (LNFP) III concentrations (OR: 6.7, 95% CI 2.0-22). Another study found higher relative abundance of fucosyloligosaccharides was associated with reduced diarrhea incidence by 2 years, due to (i) stable toxin- E. coli infection ( p  = 0.04) and (ii) "all causes" ( p  = 0.042). Higher LNFP-II concentrations were associated with (i) reduced cases of gastroenteritis and respiratory tract infections at 6 weeks ( p  = 0.004, p  = 0.010) and 12 weeks ( p  = 0.038, p  = 0.038) and (ii) reduced HIV transmission (OR: 0.45; 95% CI: 0.21-0.97) and mortality risk among HIV-exposed, uninfected infants (HR: 0.33; 95% CI: 0.14-0.74) by 24 months. Due to heterogeneity of the outcomes reported, pooling of results was not possible. There was limited evidence that low concentrations of LNFP-III are associated with CMA and that higher fucosyloligosaccharide levels protect infants against infectious disease. Further research is needed.

  2. The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

    Directory of Open Access Journals (Sweden)

    Elisa Ridolfi

    2013-01-01

    Full Text Available In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS. They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

  3. The role of the innate immune system in Alzheimer's disease and frontotemporal lobar degeneration: an eye on microglia.

    Science.gov (United States)

    Ridolfi, Elisa; Barone, Cinzia; Scarpini, Elio; Galimberti, Daniela

    2013-01-01

    In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

  4. Graves' Disease as a Manifestation of Immune Reconstitution in HIV-Infected Individuals after Initiation of Highly Active Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Samad Rasul

    2011-01-01

    Full Text Available Graves' disease after the initiation of highly active antiretroviral therapy (HAART in certain HIV-1-infected individuals has been described as an immune reconstitution inflammatory syndrome (IRIS. This phenomenon should be suspected in individuals who present with clinical deterioration and a presentation suggestive of hyperthyroidism despite good virological and immunological response to HAART. Signs and symptoms of hyperthyroidism may be discrete or overt and typically develop 8–33 months after initiating therapy. One to two percent of HIV-infected patients can present with overt thyroid disease. Relatively few cases of Graves' IRIS have been reported in the literature to date. We describe four cases of Graves' IRIS in HIV-infected patients who were started on HAART therapy.

  5. Variation in immune parameters and disease prevalence among Lesser Black-backed Gulls (Larus fuscus sp. with different migratory strategies.

    Directory of Open Access Journals (Sweden)

    Elena Arriero

    Full Text Available The ability to control infections is a key trait for migrants that must be balanced against other costly features of the migratory life. In this study we explored the links between migration and disease ecology by examining natural variation in parasite exposure and immunity in several populations of Lesser Black-backed Gulls (Larus fuscus with different migratory strategies. We found higher activity of natural antibodies in long distance migrants from the nominate subspecies L.f.fuscus. Circulating levels of IgY showed large variation at the population level, while immune parameters associated with antimicrobial activity showed extensive variation at the individual level irrespective of population or migratory strategy. Pathogen prevalence showed large geographical variation. However, the seroprevalence of one of the gull-specific subtypes of avian influenza (H16 was associated to the migratory strategy, with lower prevalence among the long-distance migrants, suggesting that migration may play a role in disease dynamics of certain pathogens at the population level.

  6. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis.

    Science.gov (United States)

    Zhou, Xiaopu; Chen, Yu; Mok, Kin Y; Zhao, Qianhua; Chen, Keliang; Chen, Yuewen; Hardy, John; Li, Yun; Fu, Amy K Y; Guo, Qihao; Ip, Nancy Y

    2018-02-20

    Alzheimer's disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10 -14 ), two common variants, GCH1 (rs72713460, P = 4.36 × 10 -5 ) and KCNJ15 (rs928771, P = 3.60 × 10 -6 ), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype-phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE , GCH1 , and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system. Copyright © 2018 the Author(s). Published by PNAS.

  7. Instream habitat restoration and stream temperature reduction in a whirling disease-positive Spring Creek in the Blackfoot River Basin, Montana

    Science.gov (United States)

    Pierce, Ron; Podner, Craig; Marczak, Laurie B; Jones, Leslie A.

    2014-01-01

    Anthropogenic warming of stream temperature and the presence of exotic diseases such as whirling disease are both contemporary threats to coldwater salmonids across western North America. We examined stream temperature reduction over a 15-year prerestoration and postrestoration period and the severity of Myxobolus cerebralisinfection (agent of whirling disease) over a 7-year prerestoration and postrestoration period in Kleinschmidt Creek, a fully reconstructed spring creek in the Blackfoot River basin of western Montana. Stream restoration increased channel length by 36% and reduced the wetted surface area by 69% by narrowing and renaturalizing the channel. Following channel restoration, average maximum daily summer stream temperatures decreased from 15.7°C to 12.5°C, average daily temperature decreased from 11.2°C to 10.0°C, and the range of daily temperatures narrowed by 3.3°C. Despite large changes in channel morphology and reductions in summer stream temperature, the prevalence and severity of M. cerebralis infection for hatchery Rainbow Trout Oncorhynchus mykiss remained high (98–100% test fish with grade > 3 infection) versus minimal for hatchery Brown Trout Salmo trutta (2% of test fish with grade-1 infection). This study shows channel renaturalization can reduce summer stream temperatures in small low-elevation, groundwater-dominated streams in the Blackfoot basin to levels more suitable to native trout. However, because of continuous high infections associated with groundwater-dominated systems, the restoration of Kleinschmidt Creek favors brown trout Salmo trutta given their innate resistance to the parasite and the higher relative susceptibility of other salmonids.

  8. Interim restorations.

    Science.gov (United States)

    Gratton, David G; Aquilino, Steven A

    2004-04-01

    Interim restorations are a critical component of fixed prosthodontic treatment, biologically and biomechanically. Interim restoration serves an important diagnostic role as a functional and esthetic try-in and as a blueprint for the design of the definitive prosthesis. When selecting materials for any interim restoration, clinicians must consider physical properties, handling properties, patient acceptance, and material cost. Although no single material meets all the requirements and material classification alone of a given product is not a predictor of clinical performance, bis-acryl materials are typically best suited to single-unit restorations, and poly(methylmethacrylate) interim materials are generally ideal for multi-unit, complex, long-term, interim fixed prostheses. As with most dental procedures, the technique used for fabrication has a greater effect on the final result than the specific material chosen.

  9. Restoring forests

    DEFF Research Database (Denmark)

    Jacobs, Douglass F.; Oliet, Juan A.; Aronson, James

    2015-01-01

    of land requiring restoration implies the need for spatial prioritization of restoration efforts according to cost-benefit analyses that include ecological risks. To design resistant and resilient ecosystems that can adapt to emerging circumstances, an adaptive management approach is needed. Global change......, in particular, imparts a high degree of uncertainty about the future ecological and societal conditions of forest ecosystems to be restored, as well as their desired goods and services. We must also reconsider the suite of species incorporated into restoration with the aim of moving toward more stress resistant...... and competitive combinations in the longer term. Non-native species may serve an important role under some circumstances, e.g., to facilitate reintroduction of native species. Propagation and field establishment techniques must promote survival through seedling stress resistance and site preparation. An improved...

  10. Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases.

    Science.gov (United States)

    Ouaissi, Ali; Ouaissi, Mehdi

    2005-01-01

    A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.

  11. Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers with immune-mediated rheumatic disease.

    Science.gov (United States)

    Bremer, Hanna Dorotea; Hillström, Anna; Kånåhols, Malin; Hagman, Ragnvi; Hansson-Hamlin, Helene

    2017-04-17

    Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to healthy dogs, but that the increase would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs and 19 healthy control NSDTRs using two different canine-specific CRP assays. Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but the concentrations were below the clinical decision limit for systemic inflammation for most of the IMRD dogs. These results indicate that CRP concentrations were increased in dogs with IMRD and ANA, but the increase was mild, similar to what has been observed in human SLE.

  12. Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis

    NARCIS (Netherlands)

    Evers, A.W.M.; Verhoeven, E.W.M.; Middendorp, H. van; Sweep, F.C.; Kraaimaat, F.W.; Donders, A.R.T.; Eijsbouts, A.E.; Laarhoven, A.I.M. van; Brouwer, S.J.M. de; Wirken, L.; Radstake, T.R.D.J.; Riel, P.L.C.M. van

    2014-01-01

    OBJECTIVES: Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present

  13. Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

    Science.gov (United States)

    Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

    2014-09-01

    Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Heterologous prime-boost immunization of Newcastle disease virus vectored vaccines protected broiler chickens against highly pathogenic avian influenza and Newcastle disease viruses.

    Science.gov (United States)

    Kim, Shin-Hee; Samal, Siba K

    2017-07-24

    Avian Influenza virus (AIV) is an important pathogen for both human and animal health. There is a great need to develop a safe and effective vaccine for AI infections in the field. Live-attenuated Newcastle disease virus (NDV) vectored AI vaccines have shown to be effective, but preexisting antibodies to the vaccine vector can affect the protective efficacy of the vaccine in the field. To improve the efficacy of AI vaccine, we generated a novel vectored vaccine by using a chimeric NDV vector that is serologically distant from NDV. In this study, the protective efficacy of our vaccines was evaluated by using H5N1 highly pathogenic avian influenza virus (HPAIV) strain A/Vietnam/1203/2004, a prototype strain for vaccine development. The vaccine viruses were three chimeric NDVs expressing the hemagglutinin (HA) protein in combination with the neuraminidase (NA) protein, matrix 1 protein, or nonstructural 1 protein. Comparison of their protective efficacy between a single and prime-boost immunizations indicated that prime immunization of 1-day-old SPF chicks with our vaccine viruses followed by boosting with the conventional NDV vector strain LaSota expressing the HA protein provided complete protection of chickens against mortality, clinical signs and virus shedding. Further verification of our heterologous prime-boost immunization using commercial broiler chickens suggested that a sequential immunization of chickens with chimeric NDV vector expressing the HA and NA proteins following the boost with NDV vector expressing the HA protein can be a promising strategy for the field vaccination against HPAIVs and against highly virulent NDVs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Prevalence of vaccine preventable diseases and utilization of routine immunizations services by parents of under‐one children in a semi‐urban community of Sokoto State, Nigeria

    Directory of Open Access Journals (Sweden)

    Kaoje AU

    2017-01-01

    Full Text Available Introduction Vaccine preventable diseases are categories of diseases that could be prevented by immunization. They affect children of less than five years of age. This study was conducted to determine the prevalence of vaccine preventable diseases and utilization of routine immunization services among parents/caregivers of under‐one children in Bodinga town of Sokoto State, Nigeria. Methods The study was community based and a descriptive cross sectional epidemiological study design was used. Four hundred households participated in the survey and were selected using a two stage sampling technique. A structured interviewer administered questionnaire with closed and some open‐ ended questions was used to collect the survey data through face‐to‐face interview. Data collected were entered into computer and analyzed using the SPSS version 23. Results were presented in simple tables for clarity. Results Measles was found to be the most prevalent vaccine preventable diseases in the community, while Hepatitis B has the least prevalence and mortality from these diseases was found to be 3%. Majority of the respondent were aware of Poliomyelitis as vaccine preventable disease and only few were aware of Hepatitis B vaccination. The percentage of fully vaccinated children was very low (4.75% while about one‐third of the children were not immunized at all. The socio‐cultural factors found to affect the utilization of routine immunization services includes: place of delivery (more for the hospital delivery, educational level and occupation of child’s parent affect positively more especially the mother. The major reason for not taking the children for immunization was Father’s refusal. Conclusion The study revealed that measles is the most prevalent vaccine preventable disease in the study area. The awareness of vaccine preventable diseases was found to be low except for poliomyelitis. Strengthening routine immunization including demand creation

  16. Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung's Disease.

    Directory of Open Access Journals (Sweden)

    Ankush Gosain

    Full Text Available Hirschsprung's disease (HSCR is characterized by aganglionosis from failure of neural crest cell (NCC migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC, with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/- resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P 21-24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer's Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer's Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted

  17. The role of nuclear medicine in the staging and management of human immune deficiency virus infection and associated diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ankrah, Alfred O.; Sathekge, Mike [Dept. of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria (South Africa); Glaudemans, Andor W. J. M.; Klein, Hans; Dierckx, Rudi A. J. O. [University of Groningen, University Medical Centre Groningen, Groningen (Netherlands)

    2017-06-15

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  18. The Role of Nuclear Medicine in the Staging and Management of Human Immune Deficiency Virus Infection and Associated Diseases.

    Science.gov (United States)

    Ankrah, Alfred O; Glaudemans, Andor W J M; Klein, Hans C; Dierckx, Rudi A J O; Sathekge, Mike

    2017-06-01

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  19. The role of nuclear medicine in the staging and management of human immune deficiency virus infection and associated diseases

    International Nuclear Information System (INIS)

    Ankrah, Alfred O.; Sathekge, Mike; Glaudemans, Andor W. J. M.; Klein, Hans; Dierckx, Rudi A. J. O.

    2017-01-01

    Human immune deficiency virus (HIV) is a leading cause of death. It attacks the immune system, thereby rendering the infected host susceptible to many HIV-associated infections, malignancies and neurocognitive disorders. The altered immune system affects the way the human host responds to disease, resulting in atypical presentation of these disorders. This presents a diagnostic challenge and the clinician must use all diagnostic avenues available to diagnose and manage these conditions. The advent of highly active antiretroviral therapy (HAART) has markedly reduced the mortality associated with HIV infection but has also brought in its wake problems associated with adverse effects or drug interaction and may even modulate some of the HIV-associated disorders to the detriment of the infected human host. Nuclear medicine techniques allow non-invasive visualisation of tissues in the body. By using this principle, pathophysiology in the body can be targeted and the treatment of diseases can be monitored. Being a functional imaging modality, it is able to detect diseases at the molecular level, and thus it has increased our understanding of the immunological changes in the infected host at different stages of the HIV infection. It also detects pathological changes much earlier than conventional imaging based on anatomical changes. This is important in the immunocompromised host as in some of the associated disorders a delay in diagnosis may have dire consequences. Nuclear medicine has played a huge role in the management of many HIV-associated disorders in the past and continues to help in the diagnosis, prognosis, staging, monitoring and assessing the response to treatment of many HIV-associated disorders. As our understanding of the molecular basis of disease increases nuclear medicine is poised to play an even greater role. In this review we highlight the functional basis of the clinicopathological correlation of HIV from a metabolic view and discuss how the use of

  20. Dietary administration of chitooligosaccharides to enhance growth, innate immune response and disease resistance of Trachinotus ovatus.

    Science.gov (United States)

    Lin, Shimei; Mao, Shuhong; Guan, Yong; Lin, Xin; Luo, Li

    2012-05-01

    The present study was conducted to investigate the effects of dietary chitooligosaccharides (COS) supplementation on the innate immune response and protection against Vibrio harveyi infection in Trachinotus ovatus. A basal diet was supplemented with 0.0 (control), 2.0, 4.0 and 6.0 g COS kg(-1) to formulate four experimental diets. Each diet was randomly allocated to triplicate groups of fish in floating sea cages (1.5 × 1.0 × 2.0 m), and each cage was stocked with 80 fish (initial average weight 10.8 ± 0.05 g). After 8 weeks of feeding trial, Both the final weight and specific growth rate (SGR) significantly increased with increasing dietary COS levels up to 4.0 g kg(-1), whereas there were no significant differences for COS levels from 4.0 to 6.0 g kg(-1). A decreased feed conversion ratio (FCR) was observed with increasing dietary COS levels. The total leukocyte counts (WBC), differential leukocyte counts, respiratory burst activity, lysozyme and superoxide dismutase (SOD) activity were significantly increased with the increased levels of dietary COS (P growth, survival and immune response of the fish. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

    Science.gov (United States)

    Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South Africa...

  2. Control of vector-borne infectious diseases by human immunity against α-Gal

    Czech Academy of Sciences Publication Activity Database

    Cabezas-Cruz, A.; Valdés, James J.; de la Fuente, J.

    2016-01-01

    Roč. 15, č. 8 (2016), s. 953-955 ISSN 1476-0584 EU Projects: European Commission(XE) 278976 - ANTIGONE Institutional support: RVO:60077344 Keywords : microbiota * probiotics * vaccine * α-Gal * vector-borne diseases Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 3.555, year: 2016

  3. The Association of the Immune Response Genes to Human Papillomavirus-Related Cervical Disease in a Brazilian Population

    Directory of Open Access Journals (Sweden)

    Amanda Vansan Marangon

    2013-01-01

    Full Text Available The genetic variability of the host contributes to the risk of human papillomavirus (HPV-related cervical disease. Immune response genes to HPV must be investigated to define patients with the highest risk of developing malignant disease. The aim of this study was to investigate the association of polymorphic immune response genes, namely KIR, HLA class I and II, and single-nucleotide polymorphisms (SNPs of cytokines with HPV-related cervical disease. We selected 79 non-related, admixed Brazilian women from the state of Paraná, southern region of Brazil, who were infected with high carcinogenic risk HPV and present cervical intraepithelial neoplasia grade 3 (CIN3, and 150 HPV-negative women from the same region matched for ethnicity. KIR genes were genotyped using an in-house PCR-SSP. HLA alleles were typed using a reverse sequence-specific oligonucleotide technique. SNPs of TNF −308G>A, IL6 −174G>C, IFNG +874T>A, TGFB1 +869T>C +915G>C, and IL10 −592C>A −819C>T −1082G>A were evaluated using PCR-SSP. The KIR genes were not associated with HPV, although some pairs of i(inhibitoryKIR-ligands occurred more frequently in patients, supporting a role for NK in detrimental chronic inflammatory and carcinogenesis. Some HLA haplotypes were associated with HPV. The associations of INFG and IL10 SNPs potentially reflect impaired or invalid responses in advanced lesions.

  4. Dietary Factors and Mucosal Immune Response in Celiac Disease Patients Having Persistent Symptoms Despite a Gluten-free Diet.

    Science.gov (United States)

    Laurikka, Pilvi; Lindfors, Katri; Oittinen, Mikko; Huhtala, Heini; Salmi, Teea; Lähdeaho, Marja-Leena; Ilus, Tuire; Mäki, Markku; Kaukinen, Katri; Kurppa, Kalle

    2018-03-02

    The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients. For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa. We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD. The density of CD3 and γδ intraepithelial lymphocytes (IELs), CD25 and FOXP3 regulatory T cells, and CD117 mast cells, and the expression of tight junction proteins claudin-3 and occludin, heat shock protein 60, interleukin 15, and Toll-like receptor 2 and 4 were evaluated in duodenal biopsies. All subjects kept a strict GFD and had negative celiac autoantibodies and recovered mucosal morphology. The asymptomatic patients had higher mean fiber intake (20.2 vs. 15.2 g/d, P=0.028) and density of CD3 IELs (59.3 vs. 45.0 cell/mm, P=0.045) than those with persistent symptoms. There was a similar but nonsignificant trend in γδ IELs (17.9 vs. 13.5, P=0.149). There were no differences between the groups in other parameters measured. Low fiber intake may predispose patients to persistent symptoms in celiac disease. There were no differences between the groups in the markers of innate immunity, epithelial stress or epithelial integrity. A higher number of IELs in asymptomatic subjects may indicate that the association between symptoms and mucosal inflammation is more complicated than previously thought.

  5. Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

    Science.gov (United States)

    Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

    2018-01-01

    Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

  6. The Association of the Immune Response Genes to Human Papillomavirus-Related Cervical Disease in a Brazilian Population

    Science.gov (United States)

    Marangon, Amanda Vansan; Guelsin, Gláucia Andreia Soares; Visentainer, Jeane Eliete Laguila; Borelli, Sueli Donizete; Watanabe, Maria Angélica Ehara; Consolaro, Márcia Edilaine Lopes; Caleffi-Ferracioli, Katiany Rizzieri; Rudnick, Cristiane Conceição Chagas; Sell, Ana Maria

    2013-01-01

    The genetic variability of the host contributes to the risk of human papillomavirus (HPV)-related cervical disease. Immune response genes to HPV must be investigated to define patients with the highest risk of developing malignant disease. The aim of this study was to investigate the association of polymorphic immune response genes, namely KIR, HLA class I and II, and single-nucleotide polymorphisms (SNPs) of cytokines with HPV-related cervical disease. We selected 79 non-related, admixed Brazilian women from the state of Paraná, southern region of Brazil, who were infected with high carcinogenic risk HPV and present cervical intraepithelial neoplasia grade 3 (CIN3), and 150 HPV-negative women from the same region matched for ethnicity. KIR genes were genotyped using an in-house PCR-SSP. HLA alleles were typed using a reverse sequence-specific oligonucleotide technique. SNPs of TNF −308G>A, IL6 −174G>C, IFNG +874T>A, TGFB1 +869T>C +915G>C, and IL10 −592C>A −819C>T −1082G>A were evaluated using PCR-SSP. The KIR genes were not associated with HPV, although some pairs of i(inhibitory)KIR-ligands occurred more frequently in patients, supporting a role for NK in detrimental chronic inflammatory and carcinogenesis. Some HLA haplotypes were associated with HPV. The associations of INFG and IL10 SNPs potentially reflect impaired or invalid responses in advanced lesions. PMID:23936772

  7. Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

    LENUS (Irish Health Repository)

    Guo, Yanxia

    2018-01-01

    Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA\\/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

  8. Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Balderacchi Jasminka

    2011-05-01

    Full Text Available Abstract Introduction Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. Case Presentation We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. Conclusion To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

  9. Plant innate immunity

    Indian Academy of Sciences (India)

    Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and ...

  10. A Comparative Clinicopathologic Study of Collagenous Gastritis in Children and Adults: The Same Disorder With Associated Immune-mediated Diseases.

    Science.gov (United States)

    Ma, Changqing; Park, Jason Y; Montgomery, Elizabeth A; Arnold, Christina A; McDonald, Oliver G; Liu, Ta-Chiang; Salaria, Safia N; Limketkai, Berkeley N; McGrath, Kevin M; Musahl, Tina; Singhi, Aatur D

    2015-06-01

    Collagenous gastritis is a rare condition characterized by surface epithelial damage, subepithelial collagen deposition, and a lamina propria inflammatory infiltrate. Previous studies have proposed 2 clinicopathologic subtypes: (1) children (18 y of age or younger) presenting with severe anemia, nodular gastric mucosa, and isolated gastric disease; and (2) adults with chronic watery diarrhea that is associated with diffuse collagenous involvement of the gastrointestinal tract. However, notable exceptions exist. In fact, broad variability in clinical presentation, etiology, treatment and disease course has been reported. To better define the clinicopathologic features of collagenous gastritis, we have collected 10 pediatric and 21 adult cases and describe their clinical, endoscopic, pathologic, and follow-up findings. Both children and adults presented with similar clinical symptoms such as anemia (50%, 35%, respectively), epigastric/abdominal pain (50%, 45%), and diarrhea (40%, 55%). Concomitant immune disorders were identified in 2 (20%) children and 3 (14%) adults. Further, 7 of 17 (41%) adults were taking medications associated with other immune-related gastrointestinal diseases including olmesartan and antidepressants. Histologically, there were no differences between children and adults with collagenous gastritis in the location of gastric involvement, mean collagenous layer thickness, and prominence of eosinophils (P>0.05). Extragastric collagenous involvement was also seen with comparable frequencies in each cohort (44%, 59%). Follow-up information was available for 22 of 31 (71%) patients and ranged from 2 to 122 months (mean, 33.6 mo). Despite medical management in most cases, persistence of symptoms or collagenous gastritis on subsequent biopsies was seen in 100% of children and 82% of adults. Of note, treatment for 1 adult patient involved cessation of olmesartan resulting in resolution of both symptoms and subepithelial collagen deposition on subsequent

  11. Adherence to systemic therapies for immune-mediated inflammatory diseases in Lebanon: a physicians’ survey from three medical specialties

    Directory of Open Access Journals (Sweden)

    Ammoury A

    2017-05-01

    Full Text Available Alfred Ammoury,1 Jad Okais,2 Mireille Hobeika,3 Raymond B Sayegh,4 Rani H Shayto,5 Ala I Sharara5 1Division of Dermatology, St George Hospital University Medical Center, 2Division of Rheumatology, St Joseph University, 3AbbVie Levant, 4Division of Gastroenterology, St Joseph University, 5Department of Internal Medicine, Division of Gastroenterology, American University of Beirut Medical Center, Beirut, Lebanon Background: Immune-mediated inflammatory diseases (IMIDs are chronic conditions that may cause tissue damage and disability, reduced quality of life and increased mortality. Various treatments have been developed for IMIDs, including immune modulators and targeted biologic agents. However, adherence remains suboptimal. Methods: An adherence survey was used to evaluate physicians’ beliefs about adherence to medication in IMID and to evaluate if and how they manage adherence. The survey was distributed to 100 randomly selected physicians from three different specialties. Results were analyzed by four academic experts commissioned to develop an action plan to address practical and perceptual barriers to adherence, integrating it into treatment goals to maximize outcomes in IMID, thereby elevating local standards of care. Results: Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74% did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Lack of time and specialized nursing support was reported as an important barrier to measuring adherence. The expert panel identified four key areas for action: 360° education (patient–nurse–physician, patient–physician communication, patient perception and concerns, and market access/cost. An action plan was developed centered on education and awareness

  12. Studies on comparative immune response of broiler chicken to different imported live infectious bursal disease vaccines

    International Nuclear Information System (INIS)

    Shoukat, T.M.; Sheikh, M.A.; Akhtar, S.S.; Hassan, S.S.

    2007-01-01

    In the present study the comparative efficacy of different vaccines was carried out. These include Gumbokal. Vaccine, IBA-Vac and IBD, Vac. The vaccines were evaluated on the basis of immure response developed by using indirect haemaggtutination (IHA) test in all the birds the presence of material antibodies on day first of their age by IHA. The titre varied from 1:4 to 1:6. All the vaccinated group and control group was examined for their immune response on the 7th and then gradual increase in titre occurred on day 15th and highest values were observed on 30th day post vaccination. All the three vaccines gave identical results as far as their efficacy against IBDV infection was concerned. (author)

  13. Immune complex modulation by plasma proteins. With special reference to the complement system and autoimmune diseases

    DEFF Research Database (Denmark)

    Baatrup, G

    1989-01-01

    The complement (C) system consists of two activation pathways, the classical and the alternative, which may both be activated by immune complexes (IC). C activation products become attached to the IC during activation leading to profound changes in the properties of the complexes. The common...... inflammation. 5) Tissue damage by activation and/or lysis of bystanding cells. 6) Modulation of B-cell proliferation and differentiation. Activation of the C system by IC is an essential normal component in the clearance of invading foreign material. However, in conditions with a persistent high concentration...... preformed, fluid phase IC (CMS assay). The CMS was found to be dependent upon the alternative pathway of C and facilitated by the classical. Further studies concerning the influence of C deficiencies or depletion of C factors, the concentration of divalent metallions, the temperature and the ionic strength...

  14. Sulphonylurea usage in melioidosis is associated with severe disease and suppressed immune response.

    Directory of Open Access Journals (Sweden)

    Xiang Liu

    2014-04-01

    Full Text Available BACKGROUND: Melioidosis is a problem in the developing tropical regions of Southeast Asia and Northern Australia where the the Gram negative saprophytic bacillus Burkholderia pseudomallei is endemic with the risk of fulminant septicaemia. While diabetes mellitus is a well-established risk factor for melioidiosis, little is known if specific hypoglycemic agents may differentially influence the susceptibility and clinical course of infection with B. pseudomallei (Bp. METHODOLOGY/PRINCIPAL FINDINGS: In this cohort study, patients with pre-existing diabetes and melioidosis were retrospectively studied. OUTCOME MEASURES: mortality, length of stay and development of complications (namely hypotension, intubation, renal failure and septicaemia were studied in relation to prior diabetic treatment regimen. Peripheral blood mononuclear cells (PBMC from diabetic patients and healthy PBMC primed with metformin, glyburide and insulin were stimulated with purified Bp antigens in vitro. Immune response and specific immune pathway mediators were studied to relate to the clinical findings mechanistically. Of 74 subjects, 44 (57.9% had sulphonylurea-containing diabetic regimens. Patient receiving sulphonylureas had more severe septic complications (47.7% versus 16.7% p = 0.006, in particular, hypotension requiring intropes (p = 0.005. There was also a trend towards increased mortality in sulphonylurea-users (15.9% versus 3.3% p = 0.08. In-vitro, glyburide suppressed inflammatory cytokine production in a dose-dependent manner. An effect of the drug was the induction of IL-1R-associated kinase-M at the level of mRNA transcription. CONCLUSION/SIGNIFICANCE: Sulphonylurea treatment results in suppression of host inflammatory response and may put patients at higher risk for adverse outcomes in melioidosis.

  15. Future oceanic warming and acidification alter immune response and disease status in a commercial shellfish species, Mytilus edulis L.

    Directory of Open Access Journals (Sweden)

    Clara L Mackenzie

    Full Text Available Increases in atmospheric carbon dioxide are leading to physical changes in marine environments including parallel decreases in ocean pH and increases in seawater temperature. This study examined the impacts of a six month exposure to combined decreased pH and increased temperature on the immune response and disease status in the blue mussel, Mytilus edulis L. Results provide the first confirmation that exposure to future acidification and warming conditions via aquarium-based simulation may have parallel implications for bivalve health. Collectively, the data suggests that temperature more than pH may be the key driver affecting immune response in M. edulis. Data also suggests that both increases in temperature and/or lowered pH conditions may lead to changes in parasite abundance and diversity, pathological conditions, and bacterial incidence in M. edulis. These results have implications for future management of shellfish under a predicted climate change scenario and future sustainability of shellfisheries. Examination of the combined effects of two stressors over an extended exposure period provides key preliminary data and thus, this work represents a unique and vital contribution to current research efforts towards a collective understanding of expected near-future impacts of climate change on marine environments.

  16. Propolis and Herba Epimedii extracts enhance the non-specific immune response and disease resistance of Chinese sucker, Myxocyprinus asiaticus.

    Science.gov (United States)

    Zhang, Guobin; Gong, Shiyuan; Yu, Denghang; Yuan, Hanwen

    2009-03-01

    The effect of traditional Chinese medicine (TCM) formulated from propolis and Herba Epimedii extracts at the ratio of 3:1 (w/w) on non-specific immune response of Chinese sucker (Myxocyprinus asiaticus) was investigated. Fish were fed diets containing 0 (control), 0.1%, 0.5% or 1.0% TCM extracts for five weeks. The respiratory burst and phagocytic activities of blood leukocytes, lysozyme and natural haemolytic complement activities in plasma were measured weekly. After five weeks of feeding, fish were infected with Aeromonas hydrophila and mortalities were recorded. Results of this study showed that feeding Chinese sucker with different dosage of TCM extracts stimulated respiratory burst activity, phagocytosis of phagocytic cells in blood and lysozyme activity in plasma. They had no effect on plasma natural haemolytic complement activity. All dosage of treated groups showed reduced mortality following A. hydrophila infection. Feed containing 0.5% TCM extracts was the most effective with the mortality of the fish significantly reduced by 35% compared to the control. The results indicate that propolis and Herba Epimedii extracts in combination enhances the non-specific immune response and disease resistance of Chinese sucker against A. hydrophila.

  17. Xenoepitope substitution avoids deceptive imprinting and broadens the immune response to foot-and-mouth disease virus.

    Science.gov (United States)

    Szczepanek, Steven M; Barrette, Roger W; Rood, Debra; Alejo, Diana; Silbart, Lawrence K

    2012-04-01

    Many RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as "decoy epitopes," which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates. A series of chimeric cyclic peptides resembling the type O G-H loop were prepared, each bearing a defined "B cell xenoepitope" from another virus in place of the native decoy epitope. These sequences were derived from porcine respiratory and reproductive syndrome virus (PRRSV), from HIV, or from a presumptively tolerogenic sequence from murine albumin and were subsequently used as immunogens in BALB/c mice. Cross-reactive antibody responses against all peptides were compared to a wild-type peptide and ovalbumin (OVA). A broadened antibody response was generated in animals inoculated with the PRRSV chimeric peptide, in which virus binding of serum antibodies was also observed. A B cell epitope mapping experiment did not reveal recognition of any contiguous linear epitopes, raising the possibility that the refocused response was directed to a conformational epitope. Taken together, these results indicate that xenoepitope substitution is a novel method for immune refocusing against decoy epitopes of RNA viruses such as FMDV as part of the rational design of next-generation vaccines.

  18. Oxidative damage and chemokine production dominate days before immune cell infiltration and EAE disease debut

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Rasmussen, Rune Skovgaard; Johansen, Flemming Fryd

    2016-01-01

    BACKGROUND: Multiple sclerosis is widely accepted as an inflammatory disease. However, studies indicate that degenerative processes in the CNS occur prior to inflammation. In the widely used animal model experimental autoimmune encephalomyelitis (EAE), we investigated the significance of degenera...

  19. Immunity of foot-and-mouth disease serotype Asia 1 by sublingual vaccination.

    Directory of Open Access Journals (Sweden)

    Hao-tai Chen

    Full Text Available Foot-and-mouth disease virus (FMDV causes vesicular disease of cloven-hoofed animals, with severe agricultural and economic losses. Here we present study using a sublingual (SL route with the killed serotype Asia 1 FMDV vaccine. Guinea pigs were vaccinated using a commercially available vaccine formulation at the manufacturer's recommended full, 1/4, and 1/16 antigen doses. Animals were challenged with homologous FMDV Asia1 strain at various times following vaccination. All control guinea pigs exhibited clinical disease, including fever, viremia, and lesions, specifically vesicle formation in feet. Animals vaccinated with the 1/16 and 1/4 doses were protected after challenge at days 7, 28, and 35 post vaccination. These data suggest that effective protection against foot-and-mouth disease can be achieved with 1/16 of the recommended vaccine dose using SL vaccination, indicating that the sublingual route is an attractive alternative for the administration of the FMDV vaccine.

  20. Dynamics of immune indices in patients with Hodgkin's disease following splenectomy and radiation therapy

    International Nuclear Information System (INIS)

    Ankudinov, V.A.; Aslyaev, L.A.; Khvorostenko, M.I.; Krugovov, B.A.; Kosse, V.A.

    1981-01-01

    The effect of splenectomy and radiation therapy on immunoreactivity in patients with Hodgkin's disease is studied. It is established that splenectomy and laparatomy are advisable prior to radiation therapy [ru

  1. ramic restorations

    Directory of Open Access Journals (Sweden)

    Ashish R Jain

    2013-01-01

    Full Text Available Rehabilitation of a patient with severely worn dentition after restoring the vertical dimension is a complex procedure and assessment of the vertical dimension is an important aspect in these cases. This clinical report describes the full mouth rehabilitation of a patient who was clinically monitored to evaluate the adaptation to a removable occlusal splint to restore vertical dimension for a period 1 month and provisional restorations to determine esthetic and functional outcome for a period of 3 months. It is necessary to recognizing that form follows function and that anterior teeth play a vital role in the maintenance of oral health. Confirmation of tolerance to changes in the vertical dimension of occlusion (VDO is of paramount importance. Articulated study casts and a diagnostic wax-up can provide important information for the evaluation of treatment options. Alteration of the VDO should be conservative and should not be changed without careful consideration.

  2. Hair restoration.

    Science.gov (United States)

    Rawnsley, Jeffrey D

    2008-08-01

    The impact of male hair loss as a personal and social marker of aging is tremendous and its persistence as a human concern throughout recorded history places it in the forefront of male concern about the physical signs of aging. Restoration of the frontal hairline has the visual effect of re-establishing facial symmetry and turning back time. Follicular unit transplantation has revolutionized hair restoration, with its focus on redistributing large numbers of genetically stable hair to balding scalp in a natural distribution. Follicular unit hair restoration surgery is a powerful tool for the facial plastic surgeon in male aesthetic facial rejuvenation because it offers high-impact, natural-appearing results with minimal downtime and risk for adverse outcome.

  3. Immune ablation and stem-cell therapy in autoimmune disease: Clinical experience

    OpenAIRE

    Tyndall, Alan; Gratwohl, Alois

    2000-01-01

    In the past 5 years, around 350 patients have received haematopoietic stem cell (HSC) transplantation for an autoimmune disease, with 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT). Most patients had either a progressive form of multiple sclerosis (MS; n = 88) or scleroderma (now called systemic sclerosis; n = 55). Other diseases were rheumatoi...

  4. Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease.

    Science.gov (United States)

    Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide

    2017-07-01

    The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1 H nuclear magnetic resonance. Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia . Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease. Published by the BMJ Publishing Group Limited

  5. Effect of Cucurbita mixta (L.) seed meal enrichment diet on growth, immune response and disease resistance in Oreochromis mossambicus.

    Science.gov (United States)

    Musthafa, Mohamed Saiyad; Jawahar Ali, Abdul Rahman; Arun Kumar, Meenatchi Sundaram; Paray, Bilal Ahmad; Al-Sadoon, Mohammad K; Balasundaram, Chellam; Harikrishnan, Ramasamy

    2017-09-01

    The impact of Cucurbita mixta (L.) seed meal enriched diet on growth performance, innate immune response, and disease resistance in Oreochromis mossambicus against Aeromonas hydrophila was investigated. O. mossambicus was fed with 2 g kg -1 , 4 g kg -1 , and 6 g kg -1  C. mixta seed meal diets for a period of 4 weeks. The results indicated that C. mixta seed meal diets at 4 g kg -1 and 6 g kg -1 significantly (P < 0.05) enhances the survival rate, weight gain (WG), protein efficiency ratio (PER), specific growth rate (SGR), feed conversion ratio (FCR), and feed efficiency (FE) from weeks 1-4 when compared to control. C. mixta seed meals administered as feed supplements significantly (P < 0.05) enhanced the complement activity, phagocytic activity, respiratory burst activity, and lysosome activity in infected fish fed with 4 g kg -1 and 6 g kg -1 of C. mixta seed meal enriched diet from weeks 2-4. The cumulative mortality was lower in the fish fed with 4 g kg -1 and 6 g kg -1 of C. mixta seed meal enriched diets (15% and 18%) than with 2 g kg -1 diet (26%). The present investigation suggested that C. mixta seed meal enriched diet at 4 g kg -1 and 6 g kg -1 enhance the better growth performance, innate immunity, and disease resistance against A. hydrophilla in O. mossambicus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The association of fatigue, pain, depression and anxiety with work and activity impairment in immune mediated inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Murray W Enns

    Full Text Available Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID, depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255, inflammatory bowel disease (n = 248, rheumatoid arthritis (n = 154 and a depression and anxiety group (n = 307, using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment (quantile regression standardized estimates ranging from 0.3 to 1.0. When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5. These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.

  7. 7a, 25-dihydroxycholesterol-mediated activation of EBI2 in immune regulation and diseases

    Directory of Open Access Journals (Sweden)

    Siquan eSun

    2015-03-01

    Full Text Available EBI2, aka GPR183, is a G-couple receptor originally identified in 1993 as one of main genes induced in Burkitt’s lymphoma cell line BL41 by Epstein-Barr virus (EBV infection. After it was reported in 2009 that the receptor played a key role in regulating B cell migration and responses, we initiated an effort in looking for its endogenous ligand. In 2011 we and another group reported the identification of 7a, 25-dihydroxyxcholesterol (7a, 25-OHC, an oxysterol, as the likely physiological ligand of EBI2. A few subsequently published studies further elucidated how 7a, 25-OHC bound to EBI2, and how a gradient of 7a, 25-OHC could be generated in vivo and regulated migration, activation, and functions of B cells, T cells, dendritic cells (DC, monocytes/macrophages and astrocytes. The identification of 7a, 25-OHC as a GPCR ligand revealed a previously unknown signaling system of oxysterols, a class of molecules which exert profound biological functions. Dysregulation of the synthesis or functions of these molecules is believed to contribute to inflammation and autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancer as well as metabolic diseases such as diabetes, obesity, and dyslipidemia. Therefore EBI2 may represent a promising target for therapeutic interventions for human diseases.

  8. Immune regulation in T1D and T2D: prospective role of Foxp3+ Treg cells in disease pathogenesis and treatment

    Directory of Open Access Journals (Sweden)

    Mara eKornete

    2013-06-01

    Full Text Available There is increasing evidence that dysregulated immune responses play key roles in the pathogenesis and complications of type 1 but also type 2 diabetes. Indeed, chronic inflammation and autoimmunity, which are salient features of type 1 diabetes, are now believed to actively contribute to the pathogenesis of type 2 diabetes. The accumulation of activated innate and adaptive immune cells in various metabolic tissues results in the release of inflammatory mediators, which promote insulin resistance and β-cell damage. Moreover, these dysregulated immune responses can also mutually influence the prevalence of both type 1 and 2 diabetes. In this review article, we discuss the central role of immune responses in the patho-physiology and complications of type 1 and 2 diabetes, and provide evidence that regulation of these responses, particularly through the action of regulatory T cells, may be a possible therapeutic avenue for the treatment of these disease and their respective complications.

  9. Interleukin 17A is an immune marker for chlamydial disease severity and pathogenesis in the koala (Phascolarctos cinereus).

    Science.gov (United States)

    Mathew, Marina; Waugh, Courtney; Beagley, Kenneth W; Timms, Peter; Polkinghorne, Adam

    2014-10-01

    The koala (Phascolarctos cinereus) is an iconic Australian marsupial species that is facing many threats to its survival. Chlamydia pecorum infections are a significant contributor to this ongoing decline. A major limiting factor in our ability to manage and control chlamydial disease in koalas is a limited understanding of the koala's cell-mediated immune response to infections by this bacterial pathogen. To identify immunological markers associated with chlamydial infection and disease in koalas, we used koala-specific Quantitative Real Time PCR (qrtPCR) assays to profile the cytokine responses of Peripheral Blood Mononuclear Cells (PBMCs) collected from 41 koalas with different stages of chlamydial disease. Target cytokines included the principal Th1 (Interferon gamma; IFNγ), Th2 (Interleukin 10; IL10), and pro-inflammatory cytokines (Tumor Necrosis Factor alpha; TNFα). A novel koala-specific IL17A qrtPCR assay was also developed as part of this study to quantitate the gene expression of this Th17 cytokine in koalas. A statistically significant higher IL17A gene expression was observed in animals with current chlamydial disease compared to animals with asymptomatic chlamydial infection. A modest up-regulation of pro-inflammatory cytokines, such as TNFα and IFNγ, was also observed in these animals with signs of current chlamydial disease. IL10 gene expression was not evident in the majority of animals from both groups. Future longitudinal studies are now required to confirm the role played by cytokines in pathology and/or protection against C. pecorum infection in the koala. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The Role of Innate and Adaptive Immune Cells in the Immunopathogenesis of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Nurwidya, Fariz; Damayanti, Triya; Yunus, Faisal

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic and progressive inflammatory disease of the airways and lungs that results in limitations of continuous airflow and is caused by exposure to noxious gasses and particles. A major cause of morbidity and mortality in adults, COPD is a complex disease pathologically mediated by many inflammatory pathways. Macrophages, neutrophils, dendritic cells, and CD8+ T-lymphocytes are the key inflammatory cells involved in COPD. Recently, the non-coding small RNA, micro-RNA, have also been intensively investigated and evidence suggest that it plays a role in the pathogenesis of COPD. Here, we discuss the accumulated evidence that has since revealed the role of each inflammatory cell and their involvement in the immunopathogenesis of COPD. Mechanisms of steroid resistance in COPD will also be briefly discussed.

  11. IMMUNIZATION OF CHILDREN AGAINST PNEUMOCOCCAL DISEASE: PRACTICAL ASPECTS FROM THE STANDPOINT OF AN OTOLARYNGOLOGIST

    Directory of Open Access Journals (Sweden)

    S. G. Gubanova

    2014-01-01

    Full Text Available The article describes the results of studying the effectiveness of vaccination of children with allergic disorders and frequently ill children against pneumococcal diseases. The effectiveness and good tolerability of the vaccine was detected. A follow-up study of the vaccinated children was performed. The positive effect of vaccination on the incidence of acute respiratory diseases, acute adenoiditis and acute otitis media in all groups of children was shown. The positive effect of vaccination on the degree of hyperplasia of adenoid tissue in the nasopharynx of frequently ill children was proved.

  12. Kidney and innate immunity.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  13. Transparent Restoration

    NARCIS (Netherlands)

    Barou, L.; Bristogianni, T.; Oikonomopoulou, F.

    2017-01-01

    This paper investigates the application of structural glass in restoration and conservation practices in order to highlight and safeguard our built heritage. Cast glass masonry is introduced in order to consolidate a half-ruined historic tower in Greece, by replacing the original parts of the façade

  14. Site Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Noynaert, L.; Bruggeman, A.; Cornelissen, R.; Massaut, V.; Rahier, A

    2001-04-01

    The objectives, the programme, and the achievements of the Site Restoration Department of SCK-CEN in 2000 are summarised. Main activities include the decommissioning of the BR3 PWR-reactor as well as other clean-up activities, projects on waste minimisation and activities related to the management of decommissioning projects. The department provides consultancy and services to external organisations.

  15. Site Restoration

    International Nuclear Information System (INIS)

    Noynaert, L.; Bruggeman, A.; Cornelissen, R.; Massaut, V.; Rahier, A.

    2001-01-01

    The objectives, the programme, and the achievements of the Site Restoration Department of SCK-CEN in 2000 are summarised. Main activities include the decommissioning of the BR3 PWR-reactor as well as other clean-up activities, projects on waste minimisation and activities related to the management of decommissioning projects. The department provides consultancy and services to external organisations

  16. Environmental Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Zeevaert, T.; Vanmarcke, H

    1998-07-01

    The objectives of SCK-CEN's programme on environmental restoration are (1) to optimize and validate models for the impact assessment from environmental, radioactive contaminations, including waste disposal or discharge; (2) to support the policy of national authorities for public health and radioactive waste management. Progress and achievements in 1997 are reported.

  17. AN MHC class I immune evasion gene of Marek's disease virus

    Science.gov (United States)

    Marek's disease virus (MDV) is a widespread a-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198–205 (2001)), but the gene(s) involved have not been identified. Here...

  18. Immune Evasion During Foot-and-Mouth Disease Virus (FMDV) Infection of Swine

    Science.gov (United States)

    The interface between successful pathogens and their hosts is often a tenuous balance. In acute viral infections, this involves induction and inhibition of innate responses. Foot-and-mouth disease virus (FMDV) is considered one of the most contagious viruses known and is characterized by rapid induc...

  19. Yogurt, immune function and infectious disease: can yogurt be used to protect the elderly against infections?

    Science.gov (United States)

    Systemic low-grade inflammation and immunosenescence occurs with aging, predisposing the elderly to myriad risk factors for infectious and chronic disease. Respiratory infections such as influenza and pneumonia are a leading cause of mortality in the elderly, and therefore of significant public hea...

  20. big bang gene modulates gut immune tolerance in Drosophila.

    Science.gov (United States)

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

    2013-02-19

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

  1. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  2. Acquired immune deficiency syndrome: specific aspects of the disease in Haiti.

    Science.gov (United States)

    Guerin, J M; Malebranche, R; Elie, R; Laroche, A C; Pierre, G D; Arnoux, E; Spira, T J; Dupuy, J M; Seemayer, T A; Pean-Guichard, C

    1984-01-01

    This paper presents clinical data on 41 patients (29 male and 12 female) from Haiti who presented with acquired immunedeficiency syndrome (AIDS). Their mean age was 32 years (range 17-61 years). 4 of thes cases were homosexual or bisexual; none was an illicit drug user or a hemophiliac. In addition, 3 of the female patients had sexual contact with a male partner with AIDS. 4 patients had received blood transfusions before their illness. The most prominent clinical symptom in this series was chronic diarrhea of 2-33 months' duration, which occurrred in 39 patients (95%). Also reporte were marked weight loss (95%), fatigue (95%), prolonger fever (90%), and nodular or maculopapular skin lesions (54%). Opportunistic infections in this series included oroesophageal candidiasis (88%) and intestinal cryptosporidiosis (31%). Tuberculosis developed in 22% of patients. Immunologic evaluation revealed profoundly depressed T-helper cells and an inverted T-helper/T-suppressor cell ratio. Biologic markers included elevated alpha-1 thymosin and beta-2 microglobulin levels, elevated immune complexes, and the presence of acid-labile interferon. Of interest were differences in the clinical expression of AIDS between this series and cases in the US. The Haitian data suggest a higher incidencs of female cases,a predominance of gastrointestinal symptoms rather than respiratory symptoms and lymphadenopathy, a frequent association with tuberculosis, and a relatively low incidence of Kaposi's sarcoma or P. carinii pneumonia compared to the situation in the US. As in the US, where most AIDS cases are concentrated in New York and California, most AIDS cases in Haiti are found in residents of Port-au-Prince and Carrefour, which are centers for male and female prostitution.

  3. Loss of population levels of immunity to malaria as a result of exposure-reducing interventions: consequences for interpretation of disease trends.

    Directory of Open Access Journals (Sweden)

    Azra C Ghani

    Full Text Available BACKGROUND: The persistence of malaria as an endemic infection and one of the major causes of childhood death in most parts of Africa has lead to a radical new call for a global effort towards eradication. With the deployment of a highly effective vaccine still some years away, there has been an increased focus on interventions which reduce exposure to infection in the individual and -by reducing onward transmission-at the population level. The development of appropriate monitoring of these interventions requires an understanding of the timescales of their effect. METHODS & FINDINGS: Using a mathematical model for malaria transmission which incorporates the acquisition and loss of both clinical and parasite immunity, we explore the impact of the trade-off between reduction in exposure and decreased development of immunity on the dynamics of disease following a transmission-reducing intervention such as insecticide-treated nets. Our model predicts that initially rapid reductions in clinical disease incidence will be observed as transmission is reduced in a highly immune population. However, these benefits in the first 5-10 years after the intervention may be offset by a greater burden of disease decades later as immunity at the population level is gradually lost. The negative impact of having fewer immune individuals in the population can be counterbalanced either by the implementation of highly-effective transmission-reducing interventions (such as the combined use of insecticide-treated nets and insecticide residual sprays for an indefinite period or the concurrent use of a pre-erythrocytic stage vaccine or prophylactic therapy in children to protect those at risk from disease as immunity is lost in the population. CONCLUSIONS: Effective interventions will result in rapid decreases in clinical disease across all transmission settings while population-level immunity is maintained but may subsequently result in increases in clinical disease many

  4. Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

    Science.gov (United States)

    Arru, G; Mameli, G; Deiana, G A; Rassu, A L; Piredda, R; Sechi, E; Caggiu, E; Bo, M; Nako, E; Urso, D; Mariotto, S; Ferrari, S; Zanusso, G; Monaco, S; Sechi, G; Sechi, L A

    2018-03-31

    Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su 19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su 19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. Increased circulating levels of Abs directed against the HERV-W env-su 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su 19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS. © 2018 EAN.

  5. Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

    Directory of Open Access Journals (Sweden)

    James E Peters

    2016-03-01

    Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

  6. Radiolabeled somatostatin analog scintigraphy in oncology and immune diseases: an overview

    International Nuclear Information System (INIS)

    Kwekkeboom, D.J.; Krenning, E.P.

    1997-01-01

    [ 111 In-DTPA-D-Phe 1 [-octreotide is a new radiopharmaceutical with a great potential for the visualization of somatostatin receptor-positive tumors, granulomas, and diseases in which activated leukocytes play a role. The overall sensitivity of [ 111 In-DTPA-D-Phe 1 [-octreotide scintigraphy to localize neuroendocrine tumors is high. In several neuroendocrine tumor types, inclusion of somatostatin receptor imaging in the localization or staging procedure may be very rewarding, either in terms of cost-effectiveness, patient management, or quality of life. In our opinion, this holds true for patients with carcinoids, gastrinomas, paragangliomas, small-cell lung carcinoma, and selected cases of patients with insulinomas. The value of [ 111 In-DTPA-D-Phe 1 [-octreotide scintigraphy in patients with other tumors, such as breast cancer, malignant lymphomas, or in patients with granulomatous diseases, has to be established. (orig.). With 4 figs., 1 tab

  7. Early-Onset Creutzfeldt-Jakob Disease Mimicking Immune-Mediated Encephalitis

    Directory of Open Access Journals (Sweden)

    Wietse A. Wiels

    2018-04-01

    Full Text Available ObjectivesThe objective of this study is to explore the clinical, radiological, and pathological manifestations of a rare subtype of prion disease and their implication for differential diagnosis in case of an early onset neuropsychiatric deterioration.MethodsWe discuss a patients’ clinical history, as well as the string of investigations and symptomatological evolution that finally led to a pathological diagnosis.ResultsOur patient had the extremely rare VV1 type sporadic Creutzfeldt-Jakob disease (sCJD. We explain the differential diagnosis of progressive encephalomyelitis with rigidity and myoclonus and its implications for treatment.ConclusionsCJD, especially the VV1 subtype, can present at an early age with an insidious psychiatric onset. Classical findings of prion disease—14-3-3 protein, PSWC on electroencephalography, and magnetic resonance imaging patterns—are not always present. The presence of neural autoantibodies does not always implicate pathogenicity in the presence of other neurological/neurodegenerative conditions.

  8. Maternal Infectious Diseases, Antimicrobial Therapy or Immunizations: Very few Contraindications to Breastfeeding

    OpenAIRE

    2006-01-01

    The Canadian Paediatric Society recommends exclusive breastfeeding as the optimal method of infant feeding for the first six months of life for healthy, term infants (1). There are many benefits associated with breastfeeding, including nutritional, immunological, psychological, developmental, environmental, social, economic and health (eg, decrease in infectious diseases) (2-4). To promote, protect and support breastfeeding, every effort must be made to minimize contraindications to breastfee...

  9. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema.

    Directory of Open Access Journals (Sweden)

    Sandra Grumelli

    2004-10-01

    Full Text Available Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear.We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4+ and CD8+ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells, but not CCR3 or CCR4 (markers of T helper 2 cells. Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma--often associated with T helper 1 cells--and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12, a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema.These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.

  10. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Andrew Kroger from CDC’s National Center for Immunization and Respiratory Diseases discusses simple, safe, and effective ways adults can help protect themselves, their family, and their community from serious and deadly diseases.

  11. Immune ablation and stem-cell therapy in autoimmune disease. Clinical experience.

    Science.gov (United States)

    Tyndall, A; Gratwohl, A

    2000-01-01

    In the past 5 years, around 350 patients have received haematopoietic stem cell (HSC) transplantation for an autoimmune disease, with 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT). Most patients had either a progressive form of multiple sclerosis (MS; n = 88) or scleroderma (now called systemic sclerosis; n = 55). Other diseases were rheumatoid arthritis (Ra n = 40), juvenile idiopathic arthritis (JIA; n = 30), systemic lupus erythematosus (SLE; n = 20), idiopathic thrombocytopenic purpura (ITP; n = 7) and others. The procedure-related mortality was around 9%, with between-disease differences, being higher in systemic sclerosis and JIA and lower in RA (one death only). Benefit has been seen in around two-thirds of cases. No one regimen was clearly superior to another, with a trend toward more infectious complications with more intense regimens. Prospective, controlled randomized trials are indicated and being planned.

  12. Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases: A systematic review and meta-analysis.

    Science.gov (United States)

    Franco, André Silva; Freitas, Thiago Quadrante; Bernardo, Wanderley M; Pereira, Rosa Maria R

    2017-06-01

    Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic. MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation. Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005). Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

  13. CD147 (EMMPRIN/Basigin) in kidney diseases: from an inflammation and immune system viewpoint.

    Science.gov (United States)

    Kosugi, Tomoki; Maeda, Kayaho; Sato, Waichi; Maruyama, Shoichi; Kadomatsu, Kenji

    2015-07-01

    The glycosylated transmembrane protein CD147/basigin, also known as extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), contributes to cell survival, migration and cancer invasion. In normal kidneys, high expression of CD147 is detected only in the basolateral side of tubular epithelial cells (TECs). The pathophysiological roles of CD147 in the kidneys are diverse, ranging from involvement in the occurrence of acute kidney injury (AKI) that is frequently accompanied by ischemia, inflammation and a loss of self-tolerance to the progression of chronic kidney disease (CKD) that is caused by an imbalance in extracellular matrix protein turnover. In AKI induced by ischemia, it is the CD147 on neutrophils, rather than that on TECs, that coordinately participates in massive neutrophil recruitment via acting as a physiological ligand for E-selectin, which is specifically enhanced in the endothelium upon inflammatory stimulation. In the CKD that follows AKI, a molecular circuit involving CD147, MMPs and transforming growth factor-β may be involved in the pathogenesis of progressive fibrosis through hyaluronan production and macrophage infiltration. Whereas CD147 thus plays deleterious roles in ischemic and fibrotic kidney injuries, CD147 expression on lymphocytes might decrease the disease activity of lupus nephritis (LN) by functioning as a potential negative regulator of the extraordinary proliferation of lymphocytes that occurs in this disease. In line with these basic studies, our clinical data indicate the potential of plasma CD147 to function as a critical biomarker for both ischemic AKI and LN. CD147 is also involved in crosstalk between the kidneys and distant organs, which may be mediated by chemotactic cytokines that are derived from circulating inflammatory cells and damaged organs. Disruption of such a vicious chain reaction involving CD147 would therefore be required in order to overcome kidney diseases. Multidisciplinary research regarding CD147

  14. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015.

    Science.gov (United States)

    Sureda, A; Bader, P; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Falkenburg, J H F; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Marsh, J C; Nagler, A; Peters, C; Velardi, A; Mohty, M; Madrigal, A

    2015-08-01

    This is the sixth special report that the European Society for Blood and Marrow Transplantation regularly publishes on the current practice and indications for haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred in the field of haematopoietic SCT over the last years. Cord blood units as well as haploidentical donors have been increasingly used as stem cell sources for allo-SCT, thus, augmenting the possibility of finding a suitable donor for a patient. Continuous refinement of conditioning strategies has also expanded not only the number of potential indications but also has permitted consideration of older patients or those with co-morbidity for a transplant. There is accumulating evidence of the role of haematopoietic SCT in non-haematological disorders such as autoimmune diseases. On the other hand, the advent of new drugs and very effective targeted therapy has challenged the role of SCT in some instances or at least, modified its position in the treatment armamentarium of a given patient. An updated report with revised tables and operating definitions is presented.

  15. Alzheimer’s Disease and HLA-A2: Linking Neurodegenerative to Immune Processes through an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Ricardo A. Cifuentes

    2014-01-01

    Full Text Available There is a controversial relationship between HLA-A2 and Alzheimer’s disease (AD. It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians, in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P = 0.02, which additionally encode truly interacting proteins. The network of proteins encoded by APP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, and CD8A linked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.

  16. [Impact of immunization measures by the Family Health Program on infant mortality from preventable diseases in Olinda, Pernambuco State, Brazil].

    Science.gov (United States)

    Guimarães, Tânia Maria Rocha; Alves, João Guilherme Bezerra; Tavares, Márcia Maia Ferreira

    2009-04-01

    This article analyzes the impact of the Family Health Program (FHP) on infant health in Olinda, Pernambuco State, Brazil, evaluating immunization and infant mortality from vaccine-preventable diseases. A time-series study was conducted with