WorldWideScience

Sample records for immune complexes c1q-ic

  1. Studies on pathogenesis and treatment of experimental immune complex glomerulonephrtis.

    NARCIS (Netherlands)

    Fleuren, Gerard Johannes Maria

    1976-01-01

    Chapter 1. In this thesis an investigation into pathogenetic mechanisms of epimembranous immune complex depostion in the glomeruli was described. For this study we used two related models of experimental immune complex glemerulonephritis: the heterologous and the autologous immune complex

  2. Immune Algorithm Complex Method for Transducer Calibration

    Directory of Open Access Journals (Sweden)

    YU Jiangming

    2014-08-01

    Full Text Available As a key link in engineering test tasks, the transducer calibration has significant influence on accuracy and reliability of test results. Because of unknown and complex nonlinear characteristics, conventional method can’t achieve satisfactory accuracy. An Immune algorithm complex modeling approach is proposed, and the simulated studies on the calibration of third multiple output transducers is made respectively by use of the developed complex modeling. The simulated and experimental results show that the Immune algorithm complex modeling approach can improve significantly calibration precision comparison with traditional calibration methods.

  3. Radioimmunological determination of soluble immune complexes

    Energy Technology Data Exchange (ETDEWEB)

    Falck, P; Meffert, H; Diezel, W; Schmidt, E; Soennichsen, N [Humboldt-Universitaet, Berlin (German Democratic Republic). Bereich Medizin (Charite)

    1979-04-01

    Soluble immune complexes were determined in sera from patients with systemic lupus erythematosus, using /sup 125/I-labelled anti-Ig-antibody and plastics-fixed C1q (component of complement). The detection limit of the method is 0.1 ..mu..g of aggregated human IgG and the range is between 0.1 ..mu..g and 10 ..mu..g per 0.5 ml serum. In 58% of the sera tested an increase of the number of immune complexes was found.

  4. Antigen Cross-Presentation of Immune Complexes

    Science.gov (United States)

    Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

    2014-01-01

    The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets. PMID:24744762

  5. Integration of the immune system: a complex adaptive supersystem

    Science.gov (United States)

    Crisman, Mark V.

    2001-10-01

    Immunity to pathogenic organisms is a complex process involving interacting factors within the immune system including circulating cells, tissues and soluble chemical mediators. Both the efficiency and adaptive responses of the immune system in a dynamic, often hostile, environment are essential for maintaining our health and homeostasis. This paper will present a brief review of one of nature's most elegant, complex adaptive systems.

  6. Circulating immune complexes – reviewing the biological roles in ...

    African Journals Online (AJOL)

    Circulating immune complexes – reviewing the biological roles in human immune function and exercise. ... studies that have investigated CIC's following exercise and proposes that a comprehensive understanding and interpretation of immune system responses to exercise should take these complexes into consideration.

  7. The deconvolution of complex spectra by artificial immune system

    Science.gov (United States)

    Galiakhmetova, D. I.; Sibgatullin, M. E.; Galimullin, D. Z.; Kamalova, D. I.

    2017-11-01

    An application of the artificial immune system method for decomposition of complex spectra is presented. The results of decomposition of the model contour consisting of three components, Gaussian contours, are demonstrated. The method of artificial immune system is an optimization method, which is based on the behaviour of the immune system and refers to modern methods of search for the engine optimization.

  8. Circulating Immune Complexes among Diabetic Children

    Directory of Open Access Journals (Sweden)

    George Nicoloff

    2004-01-01

    Full Text Available Insulin dependent diabetes mellitus (IDDM is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC. CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA. We studied the levels of CIC (IgG, IgM and IgA in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years, 29 of them had vascular complications (group 1 and the other 29 were without vascular complications (group 2. As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years. Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03 than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011 Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65% were positive for CIC IgG, 8/26 (31% for CIC IgM and 2/26 (8% for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005 and microalbuminuria (r=0.42, p=0.033. CIC IgA correlated with age (r=0.44, p=0.03. CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02. These

  9. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

    Directory of Open Access Journals (Sweden)

    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  10. Binding of properdin to solid-phase immune complexes

    DEFF Research Database (Denmark)

    Junker, A; Baatrup, G; Svehag, S E

    1998-01-01

    The capacity of serum to support deposition of C3, properdin and factor B was studied by enzyme-linked immunosorbent assay using solid-phase immune complexes (IC) for activation of complement. Deposition of C3 and properdin occurred in fairly dilute normal human serum (NHS), but factor B uptake...... fixed to IC was the principal ligand for properdin in the assay. The findings could have biological implications relating to complement-mediated modification of immune complexes in disease....

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

    Science.gov (United States)

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

    2016-03-01

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

  12. Two different mechanisms of immune-complex trapping in the mouse spleen during immune responses

    NARCIS (Netherlands)

    Yoshida, K.; van den Berg, T. K.; Dijkstra, C. D.

    1993-01-01

    The capacity of immune-complex (IC) trapping was examined using purified horse radish peroxidase (HRP)-anti-HRP (PAP) on frozen sections of mouse spleen in vitro. We investigated the trapping mechanisms by applying the IC with or without fresh mouse serum added on the spleen sections of naive as

  13. The function of the Mediator complex in plant immunity.

    Science.gov (United States)

    An, Chuanfu; Mou, Zhonglin

    2013-03-01

    Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

  14. Detection of circulating immune complexes in hepatitis by means of a new method employing /sup 125/I-antibody. Circulating immune complexes in hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Fresco, G F [Genoa Univ. (Italy). Dept. of Internal Medicine

    1978-06-01

    A new RIA method for the detection of circulating immune complexes and antibodies arising in the course of viral hepatitis is described. It involves the use of /sup 125/I-labeled antibodies and foresees the possibility of employing immune complex-coated polypropylene tubes. This simple and sensitive procedure takes into account the possibility that the immune complexes may be absorbed by the surface of polypropylene tubes during the period in which the serum remains there.

  15. Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana.

    Science.gov (United States)

    Phoolcharoen, Waranyoo; Bhoo, Seong H; Lai, Huafang; Ma, Julian; Arntzen, Charles J; Chen, Qiang; Mason, Hugh S

    2011-09-01

    Filoviruses (Ebola and Marburg viruses) cause severe and often fatal haemorrhagic fever in humans and non-human primates. The US Centers for Disease Control identifies Ebola and Marburg viruses as 'category A' pathogens (defined as posing a risk to national security as bioterrorism agents), which has lead to a search for vaccines that could prevent the disease. Because the use of such vaccines would be in the service of public health, the cost of production is an important component of their development. The use of plant biotechnology is one possible way to cost-effectively produce subunit vaccines. In this work, a geminiviral replicon system was used to produce an Ebola immune complex (EIC) in Nicotiana benthamiana. Ebola glycoprotein (GP1) was fused at the C-terminus of the heavy chain of humanized 6D8 IgG monoclonal antibody, which specifically binds to a linear epitope on GP1. Co-expression of the GP1-heavy chain fusion and the 6D8 light chain using a geminiviral vector in leaves of N. benthamiana produced assembled immunoglobulin, which was purified by ammonium sulphate precipitation and protein G affinity chromatography. Immune complex formation was confirmed by assays to show that the recombinant protein bound the complement factor C1q. Size measurements of purified recombinant protein by dynamic light scattering and size-exclusion chromatography also indicated complex formation. Subcutaneous immunization of BALB/C mice with purified EIC resulted in anti-Ebola virus antibody production at levels comparable to those obtained with a GP1 virus-like particle. These results show excellent potential for a plant-expressed EIC as a human vaccine. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  16. Clearing the complexity: immune complexes and their treatment in lupus nephritis

    Directory of Open Access Journals (Sweden)

    Catherine Toong

    2011-01-01

    Full Text Available Catherine Toong1, Stephen Adelstein1, Tri Giang Phan21Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; 2Immunology Program, Garvan Institute of Medical Research and St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaAbstract: Systemic lupus erythematosus (SLE is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.Keywords: immune complex, systemic lupus erythematosus, nephritis, therapy

  17. Dynamics of interaction between complement-fixing antibody/dsDNA immune complexes and erythrocytes. In vitro studies and potential general applications to clinical immune complex testing

    International Nuclear Information System (INIS)

    Taylor, R.P.; Horgan, C.; Hooper, M.; Burge, J.

    1985-01-01

    Soluble antibody/ 3 H-double-stranded PM2 DNA (dsDNA) immune complexes were briefly opsonized with complement and then allowed to bind to human erythrocytes (via complement receptors). The cells were washed and subsequently a volume of autologous blood in a variety of media was added, and the release of the bound immune complexes from the erythrocytes was studied as a function of temperature and time. After 1-2 h, the majority of the bound immune complexes were not released into the serum during blood clotting at either 37 degrees C or room temperature, but there was a considerably greater release of the immune complexes into the plasma of blood that was anticoagulated with EDTA. Similar results were obtained using various conditions of opsonization and also using complexes that contained lower molecular weight dsDNA. Thus, the kinetics of release of these antibody/dsDNA immune complexes differed substantially from the kinetics of release of antibody/bovine serum albumin complexes that was reported by others. Studies using the solution phase C1q immune complex binding assay confirmed that in approximately half of the SLE samples that were positive for immune complexes, there was a significantly higher level of detectable immune complexes in plasma vs. serum. Freshly drawn erythrocytes from some SLE patients exhibiting this plasma/serum discrepancy had IgG antigen on their surface that was released by incubation in EDTA plasma. Thus, the higher levels of immune complexes observed in EDTA plasma vs. serum using the C1q assay may often reflect the existence of immune complexes circulating in vivo bound to erythrocytes

  18. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Science.gov (United States)

    Deloumeau, Aude; Bayard, Sophie; Coquerel, Quentin; Déchelotte, Pierre; Bole-Feysot, Christine; Carlander, Bertrand; Cochen De Cock, Valérie; Fetissov, Sergueï O; Dauvilliers, Yves

    2010-10-13

    Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  19. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Aude Deloumeau

    Full Text Available BACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  20. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

    Science.gov (United States)

    Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

    2008-01-01

    Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

  1. A simple method for determining polymeric IgA-containing immune complexes.

    Science.gov (United States)

    Sancho, J; Egido, J; González, E

    1983-06-10

    A simplified assay to measure polymeric IgA-immune complexes in biological fluids is described. The assay is based upon the specific binding of a secretory component for polymeric IgA. In the first step, multimeric IgA (monomeric and polymeric) immune complexes are determined by the standard Raji cell assay. Secondly, labeled secretory component added to the assay is bound to polymeric IgA-immune complexes previously fixed to Raji cells, but not to monomeric IgA immune complexes. To avoid false positives due to possible complement-fixing IgM immune complexes, prior IgM immunoadsorption is performed. Using anti-IgM antiserum coupled to CNBr-activated Sepharose 4B this step is not time-consuming. Polymeric IgA has a low affinity constant and binds weakly to Raji cells, as Scatchard analysis of the data shows. Thus, polymeric IgA immune complexes do not bind to Raji cells directly through Fc receptors, but through complement breakdown products, as with IgG-immune complexes. Using this method, we have been successful in detecting specific polymeric-IgA immune complexes in patients with IgA nephropathy (Berger's disease) and alcoholic liver disease, as well as in normal subjects after meals of high protein content. This new, simple, rapid and reproducible assay might help to study the physiopathological role of polymeric IgA immune complexes in humans and animals.

  2. Immune complex-based vaccine for pig protection against parvovirus.

    Science.gov (United States)

    Roić, B; Cajavec, S; Ergotić, N; Lipej, Z; Madić, J; Lojkić, M; Pokrić, B

    2006-02-01

    The insoluble immune complexes (ICs) were prepared under the conditions of double immunodiffusion in gel, using the suspension of the ultrasound treated PK-15 cell-line infected with porcine parvovirus (PPV) containing both viral particles and viral proteins, as well as pig or rabbit anti-PPV polyclonal immune sera. The immunodiffusion performed in an agarose gel allows only viral subunits with a molecular mass equal to or less than 1000 kDa, rather than the viral particles, to diffuse through the gel and reach the point where the immunoprecipitate is to be formed. The immunoprecipitation under the conditions of the diffusion ensures the optimal, i.e. equimolar ratio of both immunoprecipitating components, antibody/antigen in the IC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Western blot analyses showed the ICs were composed of two proteins, a protein in which molecular mass corresponded to the VP2 of the PPV and a protein with a molecular mass of the IgG. This suggests that the ICs are mainly composed of the VP2 antigen and IgG class antibodies. The potency of the IC-vaccines prepared in the form of a water-in-oil-in-water emulsion was compared with that of a commercially available, inactivated oil vaccine. The vaccination of gilts, 6 weeks before mating, with the IC containing allogeneic pig antibodies, resulted in the development of high and long-lasting anti-PPV antibody titres, similar to those generated by the licenced vaccine (P > 0.01). The content of the virus material administered by the IC was twice lower than that in the licenced vaccine. Neither systemic nor local reactions were observed in the gilts during the period of the trial with the IC vaccine. The number of viable piglets per litter varied between 9 and 12 and no signs of the PPV infection were detected. Rabbits were used as one of the alternative laboratory animal models accepted for the testing of the vaccine against the PPV. The rabbit humoral immune response

  3. Complex pattern of immune evasion in MSI colorectal cancer.

    Science.gov (United States)

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

    2018-01-01

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

  4. Complex role for the immune system in initiation and progression of pancreatic cancer.

    Science.gov (United States)

    Inman, Kristin S; Francis, Amanda A; Murray, Nicole R

    2014-08-28

    The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.

  5. Focal glomerular immune complex deposition: possible role of periglomerular fibrosis/atubular glomeruli.

    Science.gov (United States)

    Satoskar, Anjali A; Calomeni, Edward; Bott, Cherri; Nadasdy, Gyongyi M; Nadasdy, Tibor

    2009-02-01

    Consensus exists among renal pathologists that, in biopsies with immune complex glomerulonephritis, even a single glomerulus with open capillary loops may be sufficient for immunofluorescence and/or electron microscopy evaluation because immune complex deposition is a diffuse phenomenon. However, we have encountered renal biopsies with focal absence of immune complexes in glomeruli on either immunofluorescence or electron microscopy examination despite presence of open glomerular capillary loops. To evaluate renal biopsies with focal immune complex deposition and look for any subtle or unusual morphologic changes in the glomeruli (and in the biopsy in general). Native and transplant renal biopsies were reviewed. All biopsies had been triaged and processed according to our routine protocol for light microscopy, immunofluorescence, and electron microscopy examination. Of 2018 renal biopsies from December 2005 to December 2007, we found 10 such biopsies; 5 native and 5 transplant kidney biopsies. We found that the glomeruli with absent immune complex deposits had periglomerular fibrosis with open, albeit, wrinkled appearing capillary loops but no glomerular sclerosis. We hypothesize that these histologic features are indicative of nonfunctional glomeruli and may be associated with disconnection between the Bowman capsule and proximal tubule (atubular glomeruli). These glomeruli may not have effective filtration, despite some degree of circulation through the open capillary loops, and therefore are unable to accumulate immune complex deposits. If biopsies are small and only such glomeruli are available for immunofluorescence or electron microscopy examination, the absence of immune complex deposition in them should be evaluated carefully.

  6. Complex Immune Evasion Strategies in Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Wein, Frederik; Weniger, Marc A; Höing, Benedikt; Arnolds, Judith; Hüttmann, Andreas; Hansmann, Martin-Leo; Hartmann, Sylvia; Küppers, Ralf

    2017-12-01

    The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T cells (Tregs), and cytotoxic T cells. Th cells and Tregs presumably provide essential survival signals for HRS cells. Tregs are also involved in rescuing HRS cells from antitumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only relevant for a characterization of the pathophysiology of cHL but is also clinically relevant, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4 + T-cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4 + Th cells and Tregs isolated from cHL lymph nodes and reactive tonsils revealed that Treg signatures were enriched in CD4 + Th cells of cHL. Hence, HRS cells may induce Treg differentiation in Th cells, a conclusion supported by in vitro studies with Th cells and cHL cell lines. We also found evidence for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs B- and T-cell lymphocyte attenuator-herpesvirus entry mediator and CD200R-CD200 in promoting immune evasion. Taken together, this study highlights the relevance of Treg induction and reveals new immune checkpoint-driven immune evasion strategies in cHL. Cancer Immunol Res; 5(12); 1122-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Circulating IgA immune complexes in patients with psoriasis

    International Nuclear Information System (INIS)

    Hall, R.P.; Peck, G.L.; Lawley, T.J.

    1983-01-01

    The sera of 21 patients with psoriasis were examined for the presence of IgA-containing circulating immune complexes (CIC) using the Raji IgA radioimmunoassay. In addition, the Raji IgG radioimmunoassay and 125I-Clq binding assay were used to detect IgG- and IgM-containing CIC. Twenty-five patients with other hyperkeratotic skin disorders were studied as controls. Patients were studied before institution of systemic therapy with etretinate (20 patients) or 13-cis-retinoic acid (1 patient). In addition, sera of 15 of the patients treated with etretinate were studied before, during, and after therapy. The extent of pretreatment disease involvement as well as response to therapy were evaluated in a blinded fashion. Fourteen of 21 (67%) patients with psoriasis had evidence of IgA-containing CIC at some time during the course of their disease, as compared to only 1 of 25 patients with other hyperkeratotic skin disorders. In contrast, only 2 of 19 (11%) had evidence of IgG-containing CIC using the Raji IgG assay, and only 1 of 19 (5%) had evidence of IgG- or IgM-containing CIC using the 125I-Clq binding assay. A positive correlation was found between the extent of pretreatment disease involvement and the level of IgA-containing CIC by linear regression analysis (p . 0.01). There was, however, no correlation between clinical improvement and the presence or level of IgA-containing CIC in 15 patients followed during therapy. Sucrose density gradient analysis of the IgA-containing CIC found in 2 of these patients demonstrated IgA-containing CIC in the 9S to 13S region. The finding of IgA-containing CIC in a significant number of patients with psoriasis and the relative absence of IgG- or IgM-containing CIC suggest that IgA-containing CIC may play a role in psoriasis

  8. 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.

  9. Acute lung injury in rat caused by immunoglobulin A immune complexes.

    OpenAIRE

    Johnson, K J; Wilson, B S; Till, G O; Ward, P A

    1984-01-01

    Mouse IgG and IgA, with reactivity to dinitrophenol conjugated to carrier protein, have been isolated from myeloma proteins by means of a variety of affinity techniques. The IgA was predominantly in the dimeric form. The in vitro and in vivo biological activities of IgA-containing immune complexes were assessed in the rat. IgA-containing immune complexes were demonstrated, in a dose-dependent manner in vitro, to activate neutrophils and to generate O.-2. In addition, these immune complexes sh...

  10. Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires

    Directory of Open Access Journals (Sweden)

    Enkelejda Miho

    2018-02-01

    Full Text Available The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV. Adaptive immune receptor repertoire sequencing (AIRR-seq has driven the quantitative and molecular-level profiling of immune repertoires, thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity and to understand the dynamics of adaptive immunity. Here, we review the current research on (i diversity, (ii clustering and network, (iii phylogenetic, and (iv machine learning methods applied to dissect, quantify, and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology toward coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.

  11. An immune stimulating complex (iscom) subunit rabies vaccine protects dogs and mice against street rabies challenge.

    NARCIS (Netherlands)

    M. Fekadu; J.H. Schaddock; J. Ekströ m; A.D.M.E. Osterhaus (Albert); D.W. Sanderlin; B. Sundquist; B. Morein (Bror)

    1992-01-01

    textabstractDogs and mice were immunized with either a rabies glycoprotein subunit vaccine incorporated into an immune stimulating complex (ISCOM) or a commercial human diploid cell vaccine (HDCV) prepared from a Pitman Moore (PM) rabies vaccine strain. Pre-exposure vaccination of mice with two

  12. Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system

    Directory of Open Access Journals (Sweden)

    Barbara Lukasch

    2017-08-01

    Full Text Available Background A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA or heterozygosity at the MHC are more important. Methods To do this we used captive house sparrows (Passer domesticus to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Results Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral were associated with several different alleles. Discussion We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

  13. Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system.

    Science.gov (United States)

    Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix; Hoi, Herbert

    2017-01-01

    A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. To do this we used captive house sparrows ( Passer domesticus ) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

  14. Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis

    International Nuclear Information System (INIS)

    Gelb, A.F.; Dreisen, R.B.; Epstein, J.D.; Silverthorne, J.D.; Bickel, Y.; Fields, M.; Border, W.A.; Taylor, C.R.

    1983-01-01

    We obtained results of lung immune complexes (LIC), circulating immune complexes (CIC), 48-hour gallium lung scans (scans), bronchoalveolar lavage (BAL), and pulmonary function tests in 20 patients with idiopathic interstitial pneumonitis-fibrosis. Sixteen patients had predominantly interstitial (13 cases UIP) and/or intraalveolar (3 cases DIP) cellular disease (group 1). Prior to corticosteroid therapy in group 1, scans were positive in 75 percent, CIC were elevated in 86 percent, LIC were present in 64 percent, and BAL was abnormal in 90 percent. Duration of follow-up after treatment was 3.5 +/- 1.0 year. In group 1 after treatment with corticosteroids in 13 patients and corticosteroids and penicillamine (three patients) and plasmapheresis (one patient), only four patients remain stable or improved. After corticosteroid therapy, elevated CIC returned to normal values despite progressive patient deterioration. In three patients, lung immune complexes were still detected after circulating immune complexes had returned to normal after corticosteroid therapy. In group 2 were four patients with fibrotic disease; scans and CIC were uniformly negative, LIC were weakly present in only one patient, and BAL was abnormal in all. Despite corticosteroid therapy, all have died or deteriorated. These results suggest that positive gallium lung scans, BAL, circulating immune complexes, and to a lesser extent, lung immune complexes are associated with the cellular phase of interstitial pneumonia, but do not reliably identify a corticosteroid-responsive group

  15. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Groothuis, D.R.; Mikhael, M.A.

    1986-06-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

  16. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    International Nuclear Information System (INIS)

    Groothuis, D.R.; Mikhael, M.A.

    1986-01-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system

  17. Global efficiency of local immunization on complex networks.

    Science.gov (United States)

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

    2013-01-01

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

  18. Global efficiency of local immunization on complex networks

    Science.gov (United States)

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

    2013-07-01

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

  19. Delivery route determines the presence of immune complexes on umbilical cord erythrocytes.

    Science.gov (United States)

    de Lima, Andrés; Franco, Luis C; Sarmiento, Andrés; González, John M

    2017-11-01

    Umbilical cord blood offers a unique opportunity to study the basal level of immunoglobulin complexes. This study aims to determine the presence of immune complexes and complement deposition on erythrocytes from umbilical cord blood from normal, full-term pregnancies. In vitro pre-formed IgA, IgG, and IgM complexes were used as positive control for flow cytometry detection, and for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal and cesarean deliveries were tested for the presence of immunoglobulin complexes. Fourteen samples from vaginal deliveries and 20 samples from cesarean deliveries were assessed. IgG and IgM complexes were detected on erythrocytes, whereas no IgA complexes or complement deposition was observed. Interestingly, the percentage of IgG complexes was higher on erythrocytes from vaginal delivery samples compared to those from cesarean deliveries. No other associations between immune complexes and other maternal or newborn variables were found. IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes. Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes present compared to that from cesarean deliveries. Since no C3d activity was detected, these complexes are non-pathological and should be part of the newborn's initial innate immune response.

  20. 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. ...

  1. 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...

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Canine Distemper Virus (CDV) immune-stimulating complexes (iscoms), but not measles virus iscoms, protect dogs against CDV infection.

    NARCIS (Netherlands)

    P. de Vries (Petra); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1988-01-01

    textabstractThe potential of immune-stimulating complexes (iscoms), a novel form of antigenic presentation, for the induction of protective immunity against morbillivirus infection was shown by immunizing dogs with canine distemper virus (CDV) iscoms, which contained the fusion (F) protein and a

  4. Complement fixation by solid phase immune complexes. Reduced capacity in SLE sera

    DEFF Research Database (Denmark)

    Baatrup, G; Jonsson, H; Sjöholm, A

    1988-01-01

    We describe an ELISA for assessment of complement function based on the capacity of serum to support fixation of complement components to solid phase immune complexes (IC). Microplates were coated with aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA IgG. The solid phase IC were...

  5. Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections

    NARCIS (Netherlands)

    P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2003-01-01

    textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

  6. Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections.

    NARCIS (Netherlands)

    Koraka, P.; Burghoorn-Maas, C.P.; Falconar, A.; Setiati, T.E.; Djamiatun, K.; Groen, J.; Osterhaus, A.D.

    2003-01-01

    Accurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot blot

  7. Circulating immune complexes, immunoglobulin classes (IgG, IgA ...

    African Journals Online (AJOL)

    Objective:- To evaluate serum levels of circulating immune complexes (CICs), immunoglobulin classes (IgG, IgA and IgM) and Complement Components (C3c, C4 and Factor B) in Nigerians with Type 1 or Type 2 diabetes mellitus. Design:- Case control study. Setting:- University College Hospital, Ibadan, Oyo State, Nigeria.

  8. Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Kappelgaard, E

    1984-01-01

    Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease g...

  9. Detection of circulating immune complexes in breast cancer and melanoma by three different methods

    Energy Technology Data Exchange (ETDEWEB)

    Krapf, F; Renger, D; Fricke, M; Kemper, A; Schedel, I; Deicher, H

    1982-08-01

    By the simultaneous application of three methods, C1q-binding-test (C1q-BA), a two antibody conglutinin binding ELISA and a polyethylene-glycol 6000 precipitation with subsequent quantitative determination of immunoglobulins and complement factors in the redissolved precipitates (PPLaNT), circulating immune complexes could be demonstrated in the sera of 94% of patients with malignant melanoma and of 75% of breast cancer patients. The specific detection rates of the individual methods varied between 23% (C1q-BA) and 46% (PPLaNT), presumably due to the presence of qualitatively different immune complexes in the investigated sera. Accordingly, the simultaneous use of the afore mentioned assays resulted in an increased diagnostic sensitivity and a duplication of the predictive value. Nevertheless, because of the relatively low incidence of malignant diseases in the total population, and due to the fact that circulating immune complexes occur in other non-malignant diseases with considerable frequency, tests for circulating immune complexes must be regarded as less useful parameters in the early diagnostic of cancer.

  10. Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: Involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes

    NARCIS (Netherlands)

    Claassen, I.J.T.M.; Osterhaus, A.D.M.E.; Claassen, E.

    1995-01-01

    Several mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system. However, until

  11. Antigen detection in vivo after immunization with different presentation forms of rabies virus antigen: involvement of marginal metallophilic macrophages in the uptake of immune-stimulating complexes.

    NARCIS (Netherlands)

    I.J.Th.M. Claassen (Ivo); A.D.M.E. Osterhaus (Albert); H.J.H.M. Claassen (Eric)

    1995-01-01

    textabstractSeveral mechanisms have been postulated to explain the relatively high immunogenicity of antigens presented in immune-stimulating complexes (iscom). Their potency can in part be explained by the specific targeting of these structures to cells presenting antigens to the immune system.

  12. The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

    Science.gov (United States)

    Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

    2013-11-01

    We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

  13. Massively Parallel RNA Sequencing Identifies a Complex Immune Gene Repertoire in the lophotrochozoan Mytilus edulis

    Science.gov (United States)

    Philipp, Eva E. R.; Kraemer, Lars; Melzner, Frank; Poustka, Albert J.; Thieme, Sebastian; Findeisen, Ulrike; Schreiber, Stefan; Rosenstiel, Philip

    2012-01-01

    The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus. PMID:22448234

  14. One Problem, Many Solutions : Simple Statistical Approaches Help Unravel the Complexity of the Immune System in an Ecological Context

    NARCIS (Netherlands)

    Buehler, Deborah M.; Versteegh, Maaike A.; Matson, Kevin D.; Tieleman, Irene

    2011-01-01

    The immune system is a complex collection of interrelated and overlapping solutions to the problem of disease. To deal with this complexity, researchers have devised multiple ways to measure immune function and to analyze the resulting data. In this way both organisms and researchers employ many

  15. Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Takahiro Tsujikawa

    2017-04-01

    Full Text Available Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.

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

    Science.gov (United States)

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

    2017-11-01

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

  17. 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...

  18. Complement-mediated solubilization of immune complexes and their interaction with complement C3 receptors

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Jepsen, H H

    1985-01-01

    Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components of the me......Some of the molecular events in the complement (C)-mediated solubilization of immune complexes (IC) have been clarified in recent years. The solubilization is primarily mediated by alternative C pathway proteins whereas factors in the classical pathway accelerate the process. Components...... of the cellular localization, expression and structure of the C3 receptors, especially the C3b (CR1) receptor, has been considerably extended in the last few years, whereas our understanding of the physiological role of these receptors is still fragmentary. However, it is becoming increasingly evident...

  19. CLINICAL CASE OF TREATMENT WITH RIBOSOMAL COMPLEX IN CHILD WITH COMPROMISED IMMUNITY

    Directory of Open Access Journals (Sweden)

    A.A. Alekseeva

    2011-01-01

    Full Text Available The leading pathology in children is acute respiratory infections (ARI according to the expert data of WHO. The incidence of prolonged and recurrent types of ARI increases during recent years. Patients with these diseases subsequently form the group of children with compromised immunity. Immunogens and immunomodulators are the drugs of nonspecific prophylaxis which are used for the prevention of ARI. The group of bacterial immunomodulators is big but most well-studied systemic drug from this group is Ribomunyl. Ribosomal complex is effective and safe in pediatric practice. The article presents the clinical case of treatment with ribosomal complex in immunocompronised child with allergic pathology.Key words: children with compromised immunity, allergy, acute respiratory infections, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 211–215

  20. Application of fluorescent monocytes for probing immune complexes on antigen microarrays.

    Directory of Open Access Journals (Sweden)

    Zoltán Szittner

    Full Text Available Microarrayed antigens are used for identifying serum antibodies with given specificities and for generating binding profiles. Antibodies bind to these arrayed antigens forming immune complexes and are conventionally identified by secondary labelled antibodies.In the body immune complexes are identified by bone marrow derived phagocytic cells, such as monocytes. In our work we were looking into the possibility of replacing secondary antibodies with monocytoid cells for the generation of antibody profiles. Using the human monocytoid cell line U937, which expresses cell surface receptors for immune complex components, we show that cell adhesion is completely dependent on the interaction of IgG heavy chains and Fcγ receptors, and this recognition is susceptible to differences between heavy chain structures and their glycosylation. We also report data on a possible application of this system in autoimmune diagnostics.Compared to secondary antibodies, fluorescent monocytesas biosensors are superior in reflecting biological functions of microarray-bound antibodies and represent an easy and robust alternative for profiling interactions between serum proteins and antigens.

  1. The alternative complement pathway control protein H binds to immune complexes and serves their detection

    International Nuclear Information System (INIS)

    Nydegger, U.E.; Corvetta, A.; Spaeth, P.J.; Spycher, M.

    1983-01-01

    During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound 125 I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of 125 I-H; when fresh serum was chelated with 10 mM EDTA, 125 I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samples from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), 125 I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while 125 I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes

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

    OpenAIRE

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

    1981-01-01

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

  3. The Value of a Comparative Approach to Understand the Complex Interplay between Microbiota and Host Immunity

    Directory of Open Access Journals (Sweden)

    Norma M. Morella

    2017-09-01

    Full Text Available The eukaryote immune system evolved and continues to evolve within a microbial world, and as such is critically shaped by—and in some cases even reliant upon—the presence of host-associated microbial species. There are clear examples of adaptations that allow the host to simultaneously tolerate and/or promote growth of symbiotic microbiota while protecting itself against pathogens, but the relationship between immunity and the microbiome reaches far beyond simple recognition and includes complex cross talk between host and microbe as well as direct microbiome-mediated protection against pathogens. Here, we present a broad but brief overview of how the microbiome is controlled by and interacts with diverse immune systems, with the goal of identifying questions that can be better addressed by taking a comparative approach across plants and animals and different types of immunity. As two key examples of such an approach, we focus on data examining the importance of early exposure on microbiome tolerance and immune system development and function, and the importance of transmission among hosts in shaping the potential coevolution between, and long-term stability of, host–microbiome associations. Then, by comparing existing evidence across short-lived plants, mouse model systems and humans, and insects, we highlight areas of microbiome research that are strong in some systems and absent in others with the hope of guiding future research that will allow for broad-scale comparisons moving forward. We argue that such an approach will not only help with identification of generalities in host–microbiome–immune interactions but also improve our understanding of the role of the microbiome in host health.

  4. Immunogenicity to Biotherapeutics – the role of Anti-drug Immune complexes

    Directory of Open Access Journals (Sweden)

    Murli eKrishna

    2016-02-01

    Full Text Available AbstractBiologic molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However by virtue of being a large protein, and having a complex structure with structural variability arising from production using recombinant gene technology in cell lines, such therapeutics run the risk of being recognized as foreign by a host immune system. Given the range of immune mediated adverse effects that have been documented to biologic drugs thus far, including infusion reactions, and the evolving therapeutic platforms in the pipeline that engineer different functional modules in a biotherapeutic, it is critical to understand the interplay of the adaptive and innate immune responses, the pathophysiology of immunogenicity to biologic drugs in instances where there have been immune mediated adverse clinical sequelae and address technical approaches for their laboratory evaluation. The current paradigm in immunogenicity evaluation has a tiered approach to the detection and characterization of anti-drug antibodies (ADAs elicited in vivo to a biotherapeutic; alongside with the structural, biophysical and molecular information of the therapeutic, these analytical assessments form the core of the immunogenicity risk assessment. However many of the immune mediated adverse effects attributed to ADAs require the formation of a drug/ADA immune complex intermediate (ICs that can have a variety of downstream effects. This review will focus on the activation of potential immunopathological pathways arising as a consequence of circulating as well as cell surface bound drug bearing-ICs, risk factors that are either intrinsic to the therapeutic molecule or to the host which might predispose to IC mediated effects, and review the recent

  5. Application of human erythrocytes to a radioimmune assay of immune complexes in serum. [Lupus erythematosus, type B hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, F; Miyakawa, Y; Mayumi, M [Tokyo Metropolitan Lab. of Public Health (Japan)

    1979-07-01

    An immune adherence receptor exists on the surface of primate erythrocytes, and has been characterized as a receptor for the activated third component of complement (C3b). Human red blood cells (RCBs, blood group O) were applied to a sensitive determination of complement-fixing, soluble immune complexes in serum. The method involved the binding of immune complexes with RBCs in the presence of complement and the detection of cell-bound IgG molecules by radiolabelled anti-human IgG antibodies. Since the binding of RBCs with monomeric IgG was minimal, cell bound IgG molecules were taken as representing immune complexes. When aggregated human gammaglobulin (AHG) was used as a model of immune complexes, as little as 5 ..mu..g dissolved in 1 ml of normal human serum were detected. The binding of RBCs with AHG was inhibited in EDTA solution where the classical complement pathway could not be activated. The RBC radioimmune assay was successfully applied to the determination of soluble immune complexes in pathological serum samples obtained from the patients with systemic lupus erythematosus and those with fulminant Type B hepatitis. False-positive results by autoantibodies against RBCs could be excluded by a Coombs test and by comparing the binding in the presence of complement with that in EDTA solution. The ubiquitous availability of RBCs coupled with a high sensitivity would allow the RBC radioimmune assay to be used as a further method of determining immune complexes in the serum.

  6. Ternary WD40 repeat-containing protein complexes: evolution, composition and roles in plant immunity

    Directory of Open Access Journals (Sweden)

    Jimi C. Miller

    2016-01-01

    Full Text Available Plants, like mammals, rely on their innate immune system to perceive and discriminate among the majority of their microbial pathogens. Unlike mammals, plants respond to this molecular dialogue by unleashing a complex chemical arsenal of defense metabolites to resist or evade pathogen infection. In basal or non-host resistance, plants utilize signal transduction pathways to detect non-self, damaged-self and altered-self-associated molecular patterns and translate these danger signals into largely inducible chemical defenses. The WD40 repeat (WDR-containing proteins Gβ and TTG1 are constituents of two independent ternary protein complexes functioning at opposite ends of a plant immune signaling pathway. Gβ and TTG1 are also encoded by single-copy genes that are ubiquitous in higher plants, implying the limited diversity and functional conservation of their respective complexes. In this review, we summarize what is currently known about the evolutionary history of these WDR-containing ternary complexes, their repertoire and combinatorial interactions, and their downstream effectors and pathways in plant defense.

  7. Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis.

    Science.gov (United States)

    Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Killingsworth, Murray; Nomura, Masaru; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

    2010-12-15

    Antibody deposition and complement activation, especially membrane attack complex (MAC) formation are considered central for immune mediated demyelination. To examine the role of MAC in immune mediated demyelination, we studied experimental allergic neuritis (EAN) in Lewis rats deficient in complement component 6 (C6) that cannot form MAC. A C6 deficient Lewis (Lewis/C6-) strain of rats was bred by backcrossing the defective C6 gene, from PVG/C6- rats, onto the Lewis background. Lewis/C6- rats had the same C6 gene deletion as PVG/C6- rats and their sera did not support immune mediated haemolysis unless C6 was added. Active EAN was induced in Lewis and Lewis/C6- rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), and Lewis/C6- rats had delayed clinical EAN compared to the Lewis rats. Peripheral nerve demyelination in Lewis/C6- was also delayed but was similar in extent at the peak of disease. Compared to Lewis, Lewis/C6- nerves had no MAC deposition, reduced macrophage infiltrate and IL-17A, but similar T cell infiltrate and Th1 cytokine mRNA expression. ICAM-1 and P-selectin mRNA expression and immunostaining on vascular endothelium were delayed in Lewis C6- compared to Lewis rats' nerves. This study found that MAC was not required for immune mediated demyelination; but that MAC enhanced early symptoms and early demyelination in EAN, either by direct lysis or by sub-lytic induction of vascular endothelial expression of ICAM-1 and P-selectin. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. FAM26F: An Enigmatic Protein Having a Complex Role in the Immune System.

    Science.gov (United States)

    Malik, Uzma; Javed, Aneela

    2016-09-19

    Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4 + , CD8 + , NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers. The complete understanding of transcriptional regulation of FAM26F is in its infancy however it is up regulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various proposed pathways including TLR3, TLR4 IFN-β and Dectin-1. These pathways can merge in STAT1 activation. The synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing therapeutic potential of FAM26F for NK sensitive tumors. Current review provides a comprehensive basis to propose that FAM26F expression level is at least a hallmark for IFN-γ-lead immune responses and thus can proficiently be regarded as an early diagnostic marker. Future investigation dissecting the role of FAM26F in activation of various immune cell populations in local amplification by cell-cell contact is crucial to provide the missing link imperative for elucidating the relevance of this protein in immune responses.

  9. Genome complexity in the coelacanth is reflected in its adaptive immune system

    Science.gov (United States)

    Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W.; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T.

    2014-01-01

    We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

  10. Scrapie affects the maturation cycle and immune complex trapping by follicular dendritic cells in mice.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    2009-12-01

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrP(d accumulations in the brain and lymphoreticular system (LRS. Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrP(d accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs and tingible body macrophages (TBMs. Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrP(d plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrP(d accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrP(d. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrP(d accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function.

  11. Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex.

    Directory of Open Access Journals (Sweden)

    Katherine Belov

    2006-03-01

    Full Text Available The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum sequence to construct the first map of a marsupial major histocompatibility complex (MHC. The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral "immune supercomplex" that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

  12. Significance of Lipid-Derived Reactive Aldehyde-Specific Immune Complexes in Systemic Lupus Erythematosus.

    Directory of Open Access Journals (Sweden)

    Gangduo Wang

    Full Text Available Even though systemic lupus erythematosus (SLE is associated with high morbidity and mortality rates among young and middle-aged women, the molecular mechanisms of disease pathogenesis are not fully understood. Previous studies from our laboratory suggested an association between oxidative stress and SLE disease activity (SLEDAI. To further assess the role of reactive oxygen species (ROS in SLE, we examined the contribution of lipid-derived reactive aldehydes (LDRAs-specific immune complexes in SLE. Sera from 60 SLE patients with varying SLEDAI and 32 age- and gender- matched healthy controls were analyzed for oxidative stress and related markers. Patients were divided into two groups based on their SLEDAI scores (<6 and ≥ 6. Both SLEDAI groups showed higher serum 4-hydroxynonenal (HNE-/malondialdehyde (MDA-protein adducts and their specific immune complexes (HNE-/MDA-specific ICs together with IL-17 than the controls, but the levels were significantly greater in the high SLEDAI (≥ 6 group. Moreover, the serum levels of anti-oxidant enzymes Cu/Zn superoxide dismutase (SOD and catalase (CAT were significantly reduced in both patient groups compared to controls. Remarkably, for the first time, our data show that increased HNE-/MDA-specific ICs are positively associated with SLEDAI and elevated circulating immune complexes (CICs, suggesting a possible causal relationship among oxidative stress, LDRA-specific ICs and the development of SLE. Our findings, apart from providing firm support to an association between oxidative stress and SLE, also suggest that these oxidative stress markers, especially the HNE-/MDA-specific ICs, may be useful in evaluating the prognosis of SLE as well as in elucidating the mechanisms of disease pathogenesis.

  13. A microplate adaptation of the solid-phase C1q immune complex assay

    International Nuclear Information System (INIS)

    Hunt, J.S.; Kennedy, M.P.; Barber, K.E.; McGiven, A.R.

    1980-01-01

    A method has been developed for the detection of C1q binding immune complexes in serum in which microculture plates are used as the solid-phase matrix for adsorption of C1q. This micromethod used only one-tenth of the amount of both C1q and [ 125 I]antihuman immunoglobulin per test and enabled 7 times as many samples to be tested in triplicate in comparison with the number performed in duplicate by the standard tube assay. (Auth.)

  14. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    IL-10 has regulatory effects in vitro on cytokine production by activated macrophages. In the IgG immune complex model of lung injury, exogenously administered IL-10 has been shown to suppress in vivo formation of TNF-alpha, up-regulation of vascular ICAM-1, neutrophil recruitment, and ensuing lung....... Blocking of IL-10 by Ab resulted in a 52% increase in lung vascular permeability, a 56% increase in TNF-alpha activity in bronchoalveolar lavage fluids, and a 47 to 48% increase in bronchoalveolar lavage neutrophils and lung myeloperoxidase content. These findings suggest that IL-10 is an important natural...

  15. Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.

    Science.gov (United States)

    Cloutier, Nathalie; Allaeys, Isabelle; Marcoux, Genevieve; Machlus, Kellie R; Mailhot, Benoit; Zufferey, Anne; Levesque, Tania; Becker, Yann; Tessandier, Nicolas; Melki, Imene; Zhi, Huiying; Poirier, Guy; Rondina, Matthew T; Italiano, Joseph E; Flamand, Louis; McKenzie, Steven E; Cote, Francine; Nieswandt, Bernhard; Khan, Waliul I; Flick, Matthew J; Newman, Peter J; Lacroix, Steve; Fortin, Paul R; Boilard, Eric

    2018-02-13

    There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood-brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.

  16. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

    Science.gov (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

    2014-01-01

    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  17. 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...

  18. CRISPR-based immune systems of the Sulfolobales: complexity and diversity

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Shah, Shiraz Ali; Vestergaard, Gisle Alberg

    2011-01-01

    CRISPR (cluster of regularly interspaced palindromic repeats)/Cas and CRISPR/Cmr systems of Sulfolobus, targeting DNA and RNA respectively of invading viruses or plasmids are complex and diverse. We address their classification and functional diversity, and the wide sequence diversity of RAMP...... (repeat-associated mysterious protein)-motif containing proteins encoded in Cmr modules. Factors influencing maintenance of partially impaired CRISPR-based systems are discussed. The capacity for whole CRISPR transcripts to be generated despite the uptake of transcription signals within spacer sequences...... is considered. Targeting of protospacer regions of invading elements by Cas protein-crRNA (CRISPR RNA) complexes exhibit relatively low sequence stringency, but the integrity of protospacer-associated motifs appears to be important. Different mechanisms for circumventing or inactivating the immune systems...

  19. Complex structure of type VI peptidoglycan muramidase effector and a cognate immunity protein

    International Nuclear Information System (INIS)

    Wang, Tianyu; Ding, Jinjing; Zhang, Ying; Wang, Da-Cheng; Liu, Wei

    2013-01-01

    The structure of the Tse3–Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed. The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1–Tsi1 has been structurally characterized. Here, the structure of the Tse3–Tsi3 complex is reported at 1.9 Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3–Tsi3 effector–immunity pair

  20. Complex structure of type VI peptidoglycan muramidase effector and a cognate immunity protein

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tianyu [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Ding, Jinjing; Zhang, Ying; Wang, Da-Cheng, E-mail: dcwang@ibp.ac.cn [Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Liu, Wei, E-mail: dcwang@ibp.ac.cn [The Third Military Medical University, Chongqing 400038 (China); Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2013-10-01

    The structure of the Tse3–Tsi3 complex associated with the bacterial type VI secretion system of P. aeruginosa has been solved and refined at 1.9 Å resolution. The structural basis of the recognition of the muramidase effector and its inactivation by its cognate immunity protein is revealed. The type VI secretion system (T6SS) is a bacterial protein-export machine that is capable of delivering virulence effectors between Gram-negative bacteria. The T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are competing for niches via amidase and muramidase activities, respectively. Two cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to inactivate the two antibacterial effectors, thereby protecting its siblings from self-intoxication. Recently, Tse1–Tsi1 has been structurally characterized. Here, the structure of the Tse3–Tsi3 complex is reported at 1.9 Å resolution. The results reveal that Tse3 contains a C-terminal catalytic domain that adopts a soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites were surprisingly observed close to the catalytic Glu residue. The electrostatic properties of the substrate-binding groove are also distinctive from those of known structures with a similar fold. All of these features imply that a unique catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3 comprises a single domain showing a β-sandwich architecture that is reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into the groove of Tse3 and completely occlude its active site, which forms the structural basis of Tse3 inactivation. This work is the first crystallographic report describing the three-dimensional structure of the Tse3–Tsi3 effector–immunity pair.

  1. Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

    Directory of Open Access Journals (Sweden)

    Carolyn Gross

    2015-09-01

    Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

  2. Spatio-temporal regulation of Hsp90-ligand complex leads to immune activation.

    Directory of Open Access Journals (Sweden)

    Yasuaki eTamura

    2016-05-01

    Full Text Available Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We found that an Hsp90-cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived dendritic cells and induced peptide-specific cytotoxic T lymphocytes. Furthermore, we observed that the internalized Hsp90-peptide complex was strictly sorted to the Rab5+, EEA1+ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through a endosome-recycling pathway. We also found that extracellular Hsp90 complexed with CpG-A or self-DNA stimulates production of a large amount of IFN-α from pDCs via static early endosome targeting. Thus, extracellular Hsp90 can target the antigen or nucleic acid to a static early endosome by spatio-temporal regulation. Moreover, we showed that Hsp90 associates with and delivers TLR7/9 from the ER to early endosomes for ligand recognition. Hsp90 inhibitor, geldanamycin derivative inhibited the Hsp90 association with TLR7/9, resulting in inhibition IFN-α production, leading to improvement of SLE symptoms. Interstingly, we observed that serum Hsp90 is clearly increased in patients with active SLE compared with that in patients with inactive disease. Serum Hsp90 detected in SLE patients binds to self-DNA and/or anti-DNA Ab, thus leading to stimulation of pDCs to produce IFN-α. Thus, Hsp90 plays a crucial role in the pathogenesis of SLE and that an Hsp90 inhibitor will therefore provide a new therapeutic approach to SLE and other nucleic acid-related autoimmune diseases. We will discuss how spatio-temporal regulation of Hsp90-ligand complexes within antigen-presenting cells affects the innate immunity and adaptive immunity.

  3. Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

    Science.gov (United States)

    Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

    2015-04-08

    Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Detection of circulating immune complexes by Raji cell assay: comparison of flow cytometric and radiometric methods

    International Nuclear Information System (INIS)

    Kingsmore, S.F.; Crockard, A.D.; Fay, A.C.; McNeill, T.A.; Roberts, S.D.; Thompson, J.M.

    1988-01-01

    Several flow cytometric methods for the measurement of circulating immune complexes (CIC) have recently become available. We report a Raji cell flow cytometric assay (FCMA) that uses aggregated human globulin (AHG) as primary calibrator. Technical advantages of the Raji cell flow cytometric assay are discussed, and its clinical usefulness is evaluated in a method comparison study with the widely used Raji cell immunoradiometric assay. FCMA is more precise and has greater analytic sensitivity for AHG. Diagnostic sensitivity by the flow cytometric method is superior in systemic lupus erythematosus (SLE), rheumatoid arthritis, and vasculitis patients: however, diagnostic specificity is similar for both assays, but the reference interval of FCMA is narrower. Significant correlations were found between CIC levels obtained with both methods in SLE, rheumatoid arthritis, and vasculitis patients and in longitudinal studies of two patients with cerebral SLE. The Raji cell FCMA is recommended for measurement of CIC levels to clinical laboratories with access to a flow cytometer

  5. Serum and plasma fibronectin binds to complement reacted immune complexes primarily via Clq

    DEFF Research Database (Denmark)

    Baatrup, G; Svehag, S E

    1986-01-01

    The binding of fibronectin to human Clq, C3b, and complement-reacted immune complexes (IC) was investigated by enzyme-linked immunosorbent assays. Microplates were coated with BSA followed by incubation with rabbit-anti-BSA IgG or F(ab')2 fragments of rabbit anti-BSA. Incubation of the solid phase...... with serum at 37 degrees C caused attachment of Clq and C3b. Addition of EDTA to the serum inhibited the binding of C3b, but not Clq, whereas substitution of the anti-BSA IgG on the solid phase with the F(ab')2 fragments abrogated the Clq, but not the C3b binding. Fibronectin binding was observed after...

  6. Ultraviolet light-denatured DNA/anti-ultraviolet light-denatured DNA immune-complex nephritis in rabbits

    International Nuclear Information System (INIS)

    Sweny, P.

    1980-01-01

    Two groups of preimmunized rabbits were studied during a 3-month course of daily intravenous injections of uv DNA in amounts sufficient to neuralize circulating antibody. One group was given high-molecular-weight uv DNA, and the other group, US uv DNA. Rabbits receiving US uv DNA formed potentially more damaging immune complexes, since this group of animals developed greater rises in blood urea and greater falls in C3. Both groups of animals developed evidence of immune complex-mediated glomerular nephritis as evidenced by heavy granular deposits of IgG and C3 in the glomeruli. The results suggest that immune complexes formed with US uv DNA may be more nephrotoxic

  7. Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

    Science.gov (United States)

    Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

    2011-11-01

    Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normalVGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

  8. Investigations of immunoglobulins, circulating immune complexes and plasma free hemoglobin in cancer patients on 60Co gamma-ray therapy

    International Nuclear Information System (INIS)

    Horvath, M.; Rode, I.L.; Fekete, B.; Kiss, B.; Ringwald, G.

    1981-01-01

    32 patients with different tumours were irradiated by 60 Co gamma-rays. During therapy lasting for several weeks, changes in the content of immunoglobulin and of some other serum proteins, circulating immune complexes and plasma free hemoglobin were determined. Immunosuppression according to immunoglobulin content in serum was not produced by this type of radiation. Decrease in immune complex levels was a good prognostic sign. Low values of plasma hemoglobin content during treatment indicated that no erythrocyte membrane damage had been effected. (orig.) [de

  9. Hepatitis B circulating immune complexes. Characterization by radioimmunoprecipitation - PEG assay (ripega)

    Energy Technology Data Exchange (ETDEWEB)

    Santoro, F; Wattre, P; Dessaint, J P; Capron, A [Institut Pasteur de Lille, 59 - Villeneuve d' Ascq (France)

    1977-04-01

    Incidence of circulating immune complexes (IC) was investigated in carriers of hepatitis B antigen (HBAg) and/or anti-HB antibodies (anti-HBAb). Three methods were used: radiolabelled C1q binding test (C1qBT), complement fixation test (CFT), and optical density (OD) measurement after dissolution of 3% polyethylene glycol (PEG) precipitate of serum. A highly significant correlation was obtained between these three techniques. The level of IC was higher in carriers of HBAg without anti-HBAb than in others. The characterization of HBAg and anti-HBAb in IC was carried out by a new procedure, the radioimmunoprecipitation-PEG assay (RIPEGA). This sensitive and reproducible test was performed by incubation of /sup 125/I-HBAg or /sup 125/I-HBAg with 3% precipitate of the carriers' sera. Separation of free from complexed /sup 125/I-HBAg or /sup 125/I-HBAb was achieved by PEG precipitation. A highly significant correlation was found between the levels of circulating IC evaluated by the C1q-BT and the quantities of HBAg or anti HBAb measured by RIPEGA. RIPEGA was used to quantify HBAg and anti-HBAb present in serum from HBAg and/or anti-HBAb carriers, confirmed by a radioimmunoassay. In preliminary results, RIGPEGA was shown to be more sensitive than classical radioimmunoassay.

  10. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A

    2010-12-01

    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  11. Structure of insoluble immune complexes as studied by spectroturbidimetry and dynamic light scattering

    Science.gov (United States)

    Khlebtsov, Boris N.; Burygin, Gennadii L.; Matora, Larisa Y.; Shchyogolev, Sergei Y.; Khlebtsov, Nikolai G.

    2004-07-01

    We describe two variants of a method for determining the average composition of insoluble immune complex particles (IICP). The first variant is based on measuring the specific turbidity (the turbidity per unit mass concentration of the dispersed substance) and the average size of IICP determined from dynamic light scattering (DLS). In the second variant, the wavelength exponent (i.e., the slope of the logarithmic turbidity spectrum) is used in combination with specific turbidity measurements. Both variants allow the average biopolymer volume fraction to be determined in terms of the average refractive index of IICP. The method is exemplified by two experimental antigen+antibody systems: (i) lipopolysaccharide-protein complex (LPPC) of Azospirillum brasilense Sp245+rabbit anti-LPPC; and (ii) human IgG (hIgG)+sheep anti-hIgG. Our measurements by the two methods for both types of systems gave, on the average, the same result: the volume fraction of the IICP biopolymers is about 30%; accordingly, the volume fraction of buffer solvent is 70%.

  12. [Autoantibody formation against the antigens of the synaptonemal complex in the syngeneic immunization of male Mus musculus].

    Science.gov (United States)

    Dadashev, S Ia; Gorach, G G; Kolomiets, O L

    1994-01-01

    Male mice were immunized with the suspension of synaptonemal complexes (SC) isolated from mouse spermatocytes nuclei. The indirect immunofluorescent analysis showed the active binding of sera obtained from immunized mice to SC of mouse spermatocyte spreads. At early and mid-pachytene, SC can be clearly identified in 19 autosome bivalents and in sex chromosome bivalent. According to the electron microscopic analysis, all structural elements of SC bind antibodies. Metaphase chromosomes were not stained with the immune sera. Specificity of interaction between SC components and antibodies was confirmed in a series of control experiments. Analysis of sera obtained from mice after their syngeneic immunization with isolated SC fraction suggested that certain mouse SC components induce the formation of autoantibodies. This, in turn, suggests that these SC components are meiosis-specific.

  13. The inhibitory receptor FcgammaRII reduces joint inflammation and destruction in experimental immune complex-mediated arthritides not only by inhibition of FcgammaRI/III but also by efficient clearance and endocytosis of immune complexes.

    NARCIS (Netherlands)

    Lent, P.L.E.M. van; Nabbe, K.C.A.M.; Boross, P.; Blom, A.B.; Roth, J.; Holthuysen, A.E.M.; Sloetjes, A.W.; Verbeek, S.; Berg, W.B. van den

    2003-01-01

    Studies of FcgammaRII-/- mice identified the inhibitory function of this receptor in joint inflammation and cartilage destruction induced with immune complexes (ICs). To extend our insight in the role of FcgammaRII in arthritis, we explored the role of FcgammaRII in the absence of activating

  14. Allergen-containing immune complexes used for immunotherapy of allergic asthma. Preparation of complexes and evaluation of their clinical performance in guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, L K; Lundberg, L; Søndergaard, I

    1989-01-01

    Guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes between antigen and specific IgG) IT were compared with placebo. The bronchial re...... groups surprisingly recovered their original sensitivity to inhalation of the antigen....

  15. Immune response of calves inoculated with proteins ofAnaplasma marginale bound to an immunostimulant complex

    Directory of Open Access Journals (Sweden)

    Marcela Ribeiro Gasparini

    Full Text Available Despite our current knowledge of the immunology, pathology, and genetics of Anaplasma marginale, prevention in cattle is currently based on old standbys, including live attenuated vaccines, antibiotic treatment, and maintaining enzootic stability in cattle herds. In the present study, we evaluated the use of an immunostimulant complex (ISCOMATRIX adjuvant, associated with a pool of recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5 to improve the humoral immune response triggered in calves mainly by IgG2. Ten calves were divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1; 2 calves were inoculated with ISCOMATRIX adjuvant (G2; and 4 calves received saline (G3. Three inoculations were administered at 21-day intervals. In G1, the calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days after the second inoculation, compared to the control group (p < 0.05, and G1 calves remained above the cut-off value 28 days after the third inoculation (p < 0.05. The post-immunized sera from calves in G1 reacted specifically for each of the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific seroconversion in calves. Therefore, additional testing to explore the protection induced by rMSPs, both alone and in conjunction with proteins previously identified as subdominant epitopes, is warranted.

  16. Innate Immune Complexity in the Purple Sea Urchin: Diversity of the Sp185/333 System

    Science.gov (United States)

    Smith, L. Courtney

    2012-01-01

    The California purple sea urchin, Strongylocentrotus purpuratus, is a long-lived echinoderm with a complex and sophisticated innate immune system. There are several large gene families that function in immunity in this species including the Sp185/333 gene family that has ∼50 (±10) members. The family shows intriguing sequence diversity and encodes a broad array of diverse yet similar proteins. The genes have two exons of which the second encodes the mature protein and has repeats and blocks of sequence called elements. Mosaics of element patterns plus single nucleotide polymorphisms-based variants of the elements result in significant sequence diversity among the genes yet maintains similar structure among the members of the family. Sequence of a bacterial artificial chromosome insert shows a cluster of six, tightly linked Sp185/333 genes that are flanked by GA microsatellites. The sequences between the GA microsatellites in which the Sp185/333 genes and flanking regions are located, are much more similar to each other than are the sequences outside the microsatellites suggesting processes such as gene conversion, recombination, or duplication. However, close linkage does not correspond with greater sequence similarity compared to randomly cloned and sequenced genes that are unlikely to be linked. There are three segmental duplications that are bounded by GAT microsatellites and include three almost identical genes plus flanking regions. RNA editing is detectible throughout the mRNAs based on comparisons to the genes, which, in combination with putative post-translational modifications to the proteins, results in broad arrays of Sp185/333 proteins that differ among individuals. The mature proteins have an N-terminal glycine-rich region, a central RGD motif, and a C-terminal histidine-rich region. The Sp185/333 proteins are localized to the cell surface and are found within vesicles in subsets of polygonal and small phagocytes. The coelomocyte proteome shows full

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

    Science.gov (United States)

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

    2014-09-01

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

  18. Detection of Immune-Complex Dissociated Nonstructural-1 (NS-1) Antigen in Patients with Acute Dengue Virus Infections

    NARCIS (Netherlands)

    P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2003-01-01

    textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

  19. B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.

    Science.gov (United States)

    Wallace, Caroline H; Wu, Bill X; Salem, Mohammad; Ansa-Addo, Ephraim A; Metelli, Alessandra; Sun, Shaoli; Gilkeson, Gary; Shlomchik, Mark J; Liu, Bei; Li, Zihai

    2018-04-05

    GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production. In contrast, B cell-specific deletion of GARP-encoding gene Lrrc32 in mice led to development of systemic autoimmune diseases spontaneously as well as worsening of pristane-induced lupus-like disease. Canonical TGF-β signaling more readily upregulates GARP in Peyer patch B cells than in splenic B cells. Furthermore, we demonstrated that B cells are required for the induction of oral tolerance of T cell-dependent antigens via GARP. Our studies reveal for the first time to our knowledge that cell surface GARP-TGF-β is an important checkpoint for regulating B cell peripheral tolerance, highlighting a mechanism of autoimmune disease pathogenesis.

  20. Formation, clearance, deposition, pathogenicity, and identification of biopharmaceutical-related immune complexes: review and case studies.

    Science.gov (United States)

    Rojko, Jennifer L; Evans, Mark G; Price, Shari A; Han, Bora; Waine, Gary; DeWitte, Mark; Haynes, Jill; Freimark, Bruce; Martin, Pauline; Raymond, James T; Evering, Winston; Rebelatto, Marlon C; Schenck, Emanuel; Horvath, Christopher

    2014-06-01

    Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans. © 2014 by The Author(s).

  1. Human erythrocytes inhibit complement-mediated solubilization of immune complexes by human serum

    International Nuclear Information System (INIS)

    Dorval, B.L.

    1987-01-01

    The aim of this study was to develop an autologus human system to evaluate the effects of human erythrocytes on solubilization of immune complex precipitates (IC) by human serum. Incubation of IC with fresh human serum or guinea pig serum resulted in solubilization of IC. When packed erythrocytes were added to human serum or guinea pig serum binding of IC to the erythrocyte occurred and IC solubilization was inhibited significantly (p <.025). Sheep erythrocytes did not bind IC or inhibit IC solubilization. To evaluate the role of human erythrocyte complement receptor (CR1) on these findings, human erythrocytes were treated with trypsin or anti-CR1 antibodies. Both treatments abrogated IC binding to human erythrocytes but did not affect the ability of the human erythrocyte to inhibit IC solubilization. Radioimmunoassay was used to measure C3, C4 and C5 activation in human serum after incubation with IC, human erythrocytes, human erythrocytes plus IC, whole blood or in whole blood plus IC

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-11-01

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

  3. Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

    Science.gov (United States)

    van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

    2001-11-01

    Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

  4. 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

  5. Platelet 3H-serotonin releasing immune complexes induced by pseudomonas aeruginosa in cystic fibrosis

    International Nuclear Information System (INIS)

    Permin, H.; Stahl Skov, P.; Norn, S.; Hoeiby, N.; Schioetz, P.O.

    1982-01-01

    In vitro formation of immune complexes was studied by 3 H-serotonin release from human platelets by P. aeruginosa antigens in the presence of serum from 22 cyctic fibrosis patients, chronically infected with mucoid P. aeruginosa (CF+P) and with a pronounced antibody response against these bacteria, and in 24 patients without P. aeruginosa (CF-P). All CF+P patients responded with 3 H-serotonin release (16-34%), whereas CF-P patients released less than 15%. In the group of CF+P patients the number of P. aeruginosa precipitins was correlated to the serotonin titer. Time courses indicated that 3 H-serotonin release was maximal between 2 and 5 min, and that no further release was observed up to 20 min. There was a gradual increase in 3 H-serotonin release with higher platelet concentrations. The response was not changed by complement inactivation, and fractionation of serum demonstrated that the serotonin release was dependent on the presence of the immunoglobulin fraction. These experiments support the suggestion of a type III reaction being involved in the lung damage in CF+P patients and also suggest a possible involvement of serotonin in the inflammatory reaction during chronic P. aeruginosa lung infection. (author)

  6. Assessment of serum copper, iron and immune complexes in potentially malignant disorders and oral cancer

    Directory of Open Access Journals (Sweden)

    Ritu TIWARI

    Full Text Available Abstract Potentially malignant disorders (PMDs of oral cavity and oral cancer remain a cause of serious concern despite intensive research and development. Diet and immunity have been identified to play a crucial role as modifying factors in these diseases. Our study intended to explore this relationship by estimating and comparing the serum levels of copper, iron and circulating immune complexes (CICs in patients diagnosed with PMDs and oral cancer and normal healthy individuals. In this study, 40 histopathologically diagnosed cases of PMDs and oral cancer were included along with 30 healthy controls and 5 ml of venous blood was drawn using venipuncture. Serum estimation of copper, iron and CIC then followed using the colorimetric and spectrophotometric methods. The data obtained was subjected to statistical analysis using one way ANOVA and Pearson’s Product-Moment Correlation Test. The mean serum copper level was measured as 138.98 ± 10.13µg/100ml in the PMD group and 141.99 ± 21.44 µg/100ml in the oral cancer as compared to 105.5 + 18.81µ/100ml in the controls. The mean serum CIC levels was highest in the oral cancer (9.65 ± 0.16OD470 followed by the PMD group (0.18 + 0.21 OD470 and least in the control group (0.048 ± 0.02OD470. Whereas, the serum levels of iron showed a significant decrease in the PMD group (110.9 ± 10.54 µg/100ml and the oral cancer group (114.29 ± 25.83 µg/100ml as compared with the control group (136.85 ± 14.48 µg/100ml. There was no positive correlation obtained between the three groups with respect to the chosen parameters indicating that the variables were independent of each other. It can be thus be ascertained that trace elements like copper and iron as well as humoral responses (CICs have a close relationship with PMDs and oral cancers.

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  8. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-08-12

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb*

    Science.gov (United States)

    Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

    2016-01-01

    Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

  10. Effect of isologous and autologous insulin antibodies on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lou/M rats

    International Nuclear Information System (INIS)

    Arquilla, E.R.; McDougall, B.R.; Stenger, D.P.

    1989-01-01

    The in vivo bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to isologous and autologous antibodies were studied in inbred Lou/M rats. There was an impaired bioavailability of the 125I-insulin bound to the isologous and autologous antibodies. Very little of the 125I-insulin in these immune complexes could bind to insulin receptors on hepatocytes or renal tubular cells and be degraded, because the amounts of 125I from degraded 125I-insulin in the blood or secreted into the stomach were markedly attenuated in both cases for at least 30 min after injection. There was a simultaneous accumulation of 125I-insulin immune complexes in the liver and the kidneys of Lou/M rats injected with 125I-insulin complexed with isologous antibodies or when insulin-immunized Lou/M rats were injected with 125I-insulin during the same interval. The impaired bioavailability of immune-complexed insulin and altered distribution of radioactivity due to the accumulation of immune complexes in the liver and kidney were also observed in previous experiments in which Lewis rats were injected with xenogenic guinea pig and homologous insulin antibodies. These observations are therefore submitted as evidence that the Lou/M rat is a valid model in which to study the bioavailability of insulin immune complexed to isologous, homologous, and xenogenic antibodies and the metabolic fate of the respective insulin-antibody immune complexes

  11. SUMO-, MAPK- and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    Burg, van den H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  12. SUMO-, MAPK-, and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    van den Burg, H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  13. Procedure for Selection of Suitable Resources in Interactions in Complex Dynamic Systems Using Artificial Immunity

    Directory of Open Access Journals (Sweden)

    Naors Y. anadalsaleem

    2017-03-01

    Full Text Available The dynamic optimization procedure for -dimensional vector function of a system, the state of which is interpreted as adaptable immune cell, is considered Using the results of the theory of artificial immune systems. The procedures for estimate of monitoring results are discussed. The procedure for assessing the entropy is recommended as a general recursive estimation algorithm. The results are focused on solving the optimization problems of cognitive selection of suitable physical resources, what expands the scope of Electromagnetic compatibility.

  14. Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.

    Science.gov (United States)

    Leopold, Philip L; Wendland, Rebecca L; Vincent, Theresa; Crystal, Ronald G

    2006-10-01

    Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum involves formation of Ad-immune complexes that prevent the virus from interacting with target cells. We hypothesized that Ad-immune complexes likely contain viable Ad vectors which, although no longer capable of gaining access to receptors on target cells, may be able to express transgenes in cells bearing Fc receptors for immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be circumvented by the Fc receptor pathway. To test this hypothesis, we expressed the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal fibroblasts and evaluated gene transfer in the presence of human neutralizing anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts of Ad, with a distinct population of internalized Ad trafficking to the nucleus. The dose-response curves for inhibition of gene transfer revealed that FcgammaR-expressing cells required a more-than-10-fold higher concentration of anti-Ad serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression compared with non-FcgammaR-expressing cells. The discrepancy between neutralization of Ad during infection of FcgammaR-expressing cells and neutralization of Ad during infection of non-FcgammaR-expressing cells occurred with either heat-inactivated or non-heat-inactivated sera, was blocked by addition of purified Fc domain protein, and did not require the cytoplasmic domain of FcgammaR, suggesting that immune complex internalization proceeded via endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune complexes did not require expression of the coxsackie virus-Ad receptor (CAR) since similar data were obtained when CAR-deficient human dermal fibroblasts were engineered to express FcgammaR. However, interaction of the Ad penton base with cell surface integrins contributed to the difference in neutralization between FcgammaR-expressing and non

  15. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed M Al Gadban

    2010-09-01

    Full Text Available Oxidized low-density lipoproteins (oxLDL and oxLDL-containing immune complexes (oxLDL-IC contribute to formation of lipid-laden macrophages (foam cells. It has been shown that oxLDL-IC are considerably more efficient than oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and cell survival promotion. Whereas oxLDL is taken up by several scavenger receptors, oxLDL-IC are predominantly internalized through the FCgamma receptor I (FCgamma RI. This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress.Fluorescently labeled lipid and protein moieties of oxLDL co-localized within endosomal and lysosomal compartments in U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was detected in the endosomal compartment, whereas its apolipoprotein moiety advanced to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL demonstrated co-localization of internalized lipid moieties from both oxLDL and oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7 macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70 (HSP70 and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the endosomal compartment. This suggests that HSP70 family members might prevent the degradation of the internalized lipid moiety of oxLDL-IC by delaying its advancement to the lysosome. The data also showed that mitochondrial membrane potential was decreased and generation of reactive oxygen and nitrogen species was increased in U937 cell treated with oxLDL compared to oxLDL-IC.Findings suggest that lipid and apolipoprotein moieties of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This mechanism could

  16. Complex multicellular functions at a unicellular eukaryote level: Learning, memory, and immunity.

    Science.gov (United States)

    Csaba, György

    2017-06-01

    According to experimental data, eukaryote unicellulars are able to learn, have immunity and memory. Learning is carried out in a very primitive form, and the memory is not neural but an epigenetic one. However, this epigenetic memory, which is well justified by the presence and manifestation of hormonal imprinting, is strong and permanent in the life of cell and also in its progenies. This memory is epigenetically executed by the alteration and fixation of methylation pattern of genes without changes in base sequences. The immunity of unicellulars is based on self/non-self discrimination, which leads to the destruction of non-self invaders and utilization of them as nourishment (by phagocytosis). The tools of learning, memory, and immunity of unicellulars are uniformly found in plasma membrane receptors, which formed under the effect of dynamic receptor pattern generation, suggested by Koch et al., and this is the basis of hormonal imprinting, by which the encounter between a chemical substance and the cell is specifically memorized. The receptors and imprinting are also used in the later steps of evolution up to mammals (including man) in each mentioned functions. This means that learning, memory, and immunity can be deduced to a unicellular eukaryote level.

  17. Diminished ability of erythrocytes from patients with systemic lupus erythematosus to limit opsonized immune complex deposition on leukocytes and activation of granulocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Rasmussen, J M; Voss, A

    1998-01-01

    OBJECTIVE: To compare the ability of normal erythrocytes and erythrocytes from systemic lupus erythematosus (SLE) patients to bind immune complexes (IC), thereby inhibiting IC deposition on polymorphonuclear leukocytes (PMN) and the consequent induction of a PMN respiratory burst (RB). METHODS...

  18. Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Wener, M.H.; Mannik, M.; Schwartz, M.M.; Lewis, E.J.

    1987-01-01

    Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc)

  19. Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses*

    OpenAIRE

    Jiang, Rui; Kim, Eun-Hye; Gong, Ji-Hee; Kwon, Hyun-Mi; Kim, Chan-Hee; Ryu, Kyoung-Hwa; Park, Ji-Won; Kurokawa, Kenji; Zhang, Jinghai; Gubb, David; Lee, Bok-Luel

    2009-01-01

    Serpins are known to be necessary for the regulation of several serine protease cascades. However, the mechanisms of how serpins regulate the innate immune responses of invertebrates are not well understood due to the uncertainty of the identity of the serine proteases targeted by the serpins. We recently reported the molecular activation mechanisms of three serine protease-mediated Toll and melanin synthesis cascades in a large beetle, Tenebrio molitor. Here, we purified three novel serpins ...

  20. Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut.

    Science.gov (United States)

    Mantis, N J; Rol, N; Corthésy, B

    2011-11-01

    Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis.

  1. Construction and comparison of gene co-expression networks shows complex plant immune responses

    Directory of Open Access Journals (Sweden)

    Luis Guillermo Leal

    2014-10-01

    Full Text Available Gene co-expression networks (GCNs are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA. Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses.

  2. Hydrodynamic delivery of plasmid DNA encoding human Fc?R-Ig dimers blocks immune-complex mediated inflammation in mice

    OpenAIRE

    Shashidharamurthy, Rangaiah; Machiah, Deepa; Bozeman, Erica N.; Srivatsan, Sanjay; Patel, Jaina; Cho, Alice; Jacob, Joshy; Selvaraj, Periasamy

    2011-01-01

    Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcgamma receptor ?Ig fusion molecules (Fc?R-Igs) in mice by administering Fc?R-Ig plasmid DNAs hydrodynamically and compared their effectiveness to purified molecules in blocking immune-complex (IC) mediated inflammation in mice. The concentration of hydrodynamically expressed Fc?R-Igs (CD16AF-Ig, CD32AR-Ig and CD32AH-Ig) reached a maximum of ...

  3. Cholesterol level in the circulating immune complexes of subjects suffering from the remote aftereffects of acute radiation sickness

    International Nuclear Information System (INIS)

    Nikitin, G.Yu.; Barabanova, A.V.; Nadezhina, N.M.; Tertov, V.V.; Orekhov, A.N.

    1994-01-01

    The potentiaoity of coronary atherosclerosis was assessed from cholesterol levels in the ciculationg immune complexes (CIC) in 53 subjects who suffered acute radiation sickness in 1986 after the Chernobyl power plant accident. CIC cholesterol levels of the subjects who suffered 3-4 years before acute radiation sickness of the first-second degrees of severity were found elevated as against an adequately matched reference group. Thus, subjects who suffered the second degree of severity acute radiation sickness after the radiation exposure, from 3-4 years later a group at high risk of coronary atherosclerosis

  4. Circulating immune complexes, immunoglobulin G, salivary proteins and salivary immunoglobulin A in patients with Sjögren's syndrome

    Directory of Open Access Journals (Sweden)

    Hadži-Mihailović Miloš

    2009-01-01

    Full Text Available Introduction. Sjögren's syndrome (SS is a chronic autoimmune disorder, with its major clinical manifestations resulting from changes in exocrine glands. Objective The aim of this study was to evaluate serum concentrations of circulating immune complexes (CIC and immunoglobulin G (IgG, and salivary proteins (SP and salivary immunoglobulin A (sIgA in 40 patients with SS, and to correlate these values among themselves, as well as with the unstimulated salivary flow rate (USFR and the duration of disease. Methods. The total of 40 patients were included in this research. CIC was determined using the solution of polyethylene glycol and IgG with the standard procedure of radial immunodiffusion. SP was investigated by the method of Lowry and sIgA was separated from the whole saliva using the method of immune chromatography. Results. The values of most of the studied parameters exceeded the normal range in a high degree: CIC 72.5%, IgG 70%, SP 80%. The concentrations of CIC were significantly higher in the patients with the duration of disease less than 10 years. With the decrease of USFR, the concentration of sIgA and IgG were increased with statistical significance. Conclusion The increased prevalence of abnormal values of CIC, IgG and SP indicate that the patients with SS have developed a higher level of immune reactivity. These results could be useful in diagnosis and disease activity monitoring.

  5. Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

    Science.gov (United States)

    Holman, David H; Wang, Danher; Raviprakash, Kanakatte; Raja, Nicholas U; Luo, Min; Zhang, Jianghui; Porter, Kevin R; Dong, John Y

    2007-02-01

    Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

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

    Science.gov (United States)

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

    2017-02-06

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

  7. Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo.

    Science.gov (United States)

    Yuan, Bangqing; Xian, Ronghua; Wu, Xianqu; Jing, Junjie; Chen, Kangning; Liu, Guojun; Zhou, Zhenhua

    2012-07-01

    Previous evidence suggested that the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors when purified from the same tumor. In addition, Pokemon can be found in almost all malignant tumor cells and is regarded to be a promising candidate for the treatment of tumors. However, the potential of the grp170-Pokemon chaperone complex has not been well described. In the present study, the natural chaperone complex between grp170 and the Pokemon was formed by heat shock, and its immunogenicity was detected by ELISPOT and (51)Cr-release assays in vitro and by tumor bearing models in vivo. Our results demonstrated that the grp170-Pokemon chaperone complex could elicit T cell responses as determined by ELISPOT and (51)Cr-release assays. In addition, immunized C57BL/6 mice were challenged with subcutaneous (s.c.) injection of Lewis cancer cells to induce primary tumors. Treatment of mice with the grp170-Pokemon chaperone complex also significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. Our results indicated that the grp170-Pokemon chaperone complex might represent a powerful approach to tumor immunotherapy and have significant potential for clinical application. Copyright © 2012 Elsevier GmbH. All rights reserved.

  8. Assessment of complex water pollution with heavy metals and Pyrethroid pesticides on transcript levels of metallothionein and immune related genes.

    Science.gov (United States)

    Ghazy, Haneen A; Abdel-Razek, Mohamed A S; El Nahas, Abeer F; Mahmoud, Shawky

    2017-09-01

    Alteration of immunological function of an aquatic organism can be used as an indicator for evaluating the direct effect of exposure to pollutants. The aim of this work is to assess the impact of complex water pollution with special reference to Pyrethroid pesticides and heavy metals on mRNA transcript levels of Metallothionine and some immune related genes of Nile tilapia (Oreochromas Niloticus). Residues of six heavy metals and six Pyrethroid were assessed in water as well as fish tissues at three different sites of Lake Burullus, located at Northern Egypt. Variations of water physicochemical properties associated with different levels of heavy metals at the three different sections were recorded. Tissue residues of Fe, Mn and Zn, Cu, Ni exceed water levels in contrast to elevated water level of Pb. All assessed Pyrethroids are detected in fish tissue samples with higher concentration (3-42 folds) than that found in water samples especially Cypermethrin. Significant down-regulation of expression levels of metallothionein (MT) at the three sections of the lake was observed. The expression of immune related genes (IgM) and inflammatory cytokines (TNF, IL.8 and IL.1) were affected. IgM and TNF were significantly down-regulated at eastern and western section of the lake; meanwhile the expression of IL8 is down regulated at the three sections of the lack. IL1 was significantly up-regulated at eastern and middle sections. We conclude that, variable gene expression of MT and immune-related genes at the three sections of the lack impose different response to complex water pollution in relation to variable aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

    Directory of Open Access Journals (Sweden)

    Matous Hrdinka

    2016-03-01

    Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

  10. 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)

  11. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  12. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen: quantitation by binding to radiolabeled Cl/sub q/

    International Nuclear Information System (INIS)

    Nydegger, U.E.; Lambert, P.H.; Gerber, H.; Miescher, P.A.

    1974-01-01

    A sensitive and reproducible procedure fr the detection of souble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled Clq is reacted with sera containing immune complexes. Separation of free from complex bound [ 125 I]Clq is achieved by selective precipitation with polyethylene glycol (PEG). The minimal amount of aggregated immunoglobulins thus detected is about 10 μg and that of soluble human IgG-anti-IgG complexes is about 3 μg of complexed antibody. Some immune complexes formed in large antigen excess (Ag 2 Ab) can still be detected by this radiolabeled Clq bining assay. In a second step, this radiolabeled Clq binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes. Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the Hepatitis B antigen (HB-Ag). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [ 125 I]Clq binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [ 125 I]Clq percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [ 125 I]Clq. The results were also used for a correlative study of [ 125 I]Clq binding to IgG levels in the sera but increased [ 125 I]Clq binding could not be attributed to high serum IgG levels which are likely to account for the evaluation of immune complex diseases in human pathology. (U.S.)

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

    Science.gov (United States)

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

    2017-01-01

    Objective The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. Methods In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Results Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. Conclusion The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls

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

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2017-08-01

    Full Text Available Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™ cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors.Results: Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response.Conclusion: The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that

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

    Science.gov (United States)

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

    2017-01-01

    The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3 + CD56 - T lymphocytes, CD3 + CD56 + NKT cells, CD3 - CD56 + NK cells, and also some cells within the CD3 - CD56 - non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls from live B. coagulans GBI-30, 6086

  16. [Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

    Science.gov (United States)

    Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

    2016-01-01

    Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

  17. Effects of Protein-Iron Complex Concentrate Supplementation on Iron Metabolism, Oxidative and Immune Status in Preweaning Calves

    Directory of Open Access Journals (Sweden)

    Robert Kupczyński

    2017-07-01

    Full Text Available The objective of this study was to determine the effects of feeding protein-iron complex (PIC on productive performance and indicators of iron metabolism, hematology parameters, antioxidant and immune status during first 35 days of a calf’s life. Preparation of the complex involved enzymatic hydrolysis of milk casein (serine protease from Yarrowia lipolytica yeast. Iron chloride was then added to the hydrolyzate and lyophilizate. Calves were divided into treated groups: LFe (low iron dose 10 g/day calf of protein-iron complex, HFe (height iron dose 20 g/day calf, and control group. Dietary supplements containing the lower dose of concentrate had a significant positive effect on iron metabolism, while the higher dose of concentrate resulted in increase of total iron binding capacity (TIBC, saturation of transferrin and decrease of and unsaturated iron binding capacity (UIBC, which suggest iron overload. Additionally, treatment with the lower dose of iron remarkably increased the antioxidant parameters, mainly total antioxidant (TAS and glutathione peroxidase activity (GPx. Higher doses of PIC were related to lower total antioxidant status. IgG, IgM, insulin, glucose, TNFα and IGF-1 concentration did not change significantly in either group after supplementation. In practice, the use of protein-iron complex concentrate requires taking into account the iron content in milk replacers and other feedstuffs.

  18. CORRECTION OF IMMUNE STATUS IN CHILDREN WITH FREQUENTLY RECURRENT INFECTIONS WITH COMPLEX PERORAL VACCINE

    Directory of Open Access Journals (Sweden)

    V.V. Chernikov

    2011-01-01

    Full Text Available The market of drugs proposes some new medicines which are labeled by manufacturers as immunomodulating agents. Most of them are not licensed and they have no any evidence of their efficacy. In opposite, non-specific ribosomal modulator (Ribomunyl is the wellstudied drug with good database on its efficacy and safety. The article presents a description of drug’s effect on the immune system of a child for increase of organism’s resistance to the most widespread causative agents of infections of ENT-organs and airways.Key words: children, respiratory infections, recurrent course, immunomodulators, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 92–96

  19. A downy mildew effector attenuates salicylic acid-triggered immunity in Arabidopsis by interacting with the host mediator complex.

    Directory of Open Access Journals (Sweden)

    Marie-Cécile Caillaud

    2013-12-01

    Full Text Available Plants are continually exposed to pathogen attack but usually remain healthy because they can activate defences upon perception of microbes. However, pathogens have evolved to overcome plant immunity by delivering effectors into the plant cell to attenuate defence, resulting in disease. Recent studies suggest that some effectors may manipulate host transcription, but the specific mechanisms by which such effectors promote susceptibility remain unclear. We study the oomycete downy mildew pathogen of Arabidopsis, Hyaloperonospora arabidopsidis (Hpa, and show here that the nuclear-localized effector HaRxL44 interacts with Mediator subunit 19a (MED19a, resulting in the degradation of MED19a in a proteasome-dependent manner. The Mediator complex of ∼25 proteins is broadly conserved in eukaryotes and mediates the interaction between transcriptional regulators and RNA polymerase II. We found MED19a to be a positive regulator of immunity against Hpa. Expression profiling experiments reveal transcriptional changes resembling jasmonic acid/ethylene (JA/ET signalling in the presence of HaRxL44, and also 3 d after infection with Hpa. Elevated JA/ET signalling is associated with a decrease in salicylic acid (SA-triggered immunity (SATI in Arabidopsis plants expressing HaRxL44 and in med19a loss-of-function mutants, whereas SATI is elevated in plants overexpressing MED19a. Using a PR1::GUS reporter, we discovered that Hpa suppresses PR1 expression specifically in cells containing haustoria, into which RxLR effectors are delivered, but not in nonhaustoriated adjacent cells, which show high PR1::GUS expression levels. Thus, HaRxL44 interferes with Mediator function by degrading MED19, shifting the balance of defence transcription from SA-responsive defence to JA/ET-signalling, and enhancing susceptibility to biotrophs by attenuating SA-dependent gene expression.

  20. Inhalable Andrographolide-β-cyclodextrin Inclusion Complexes for Treatment of Staphylococcus aureus Pneumonia by Regulating Immune Responses.

    Science.gov (United States)

    Zhang, Tongtong; Zhu, Lifei; Li, Miao; Hu, Yuzhen; Zhang, Erfeng; Jiang, Qingcheng; Han, Guang; Jin, Yiguang

    2017-05-01

    Bacterial pneumonia is a serious disease with high mortality if no appropriate and immediate therapy is available. Andrographolide (AG) is an anti-inflammatory agent extracted from a traditional Chinese herb andrographis paniculata. Oral AG tablets and pills are clinically applied for treatment of upper respiratory tract infections. However, the low solubility and bioavailability of AG lead to high doses and long-term therapy. Here we developed an andrographolide-β-cyclodextrin inclusion complex (AG-β-CD) for inhalation therapy of Staphylococcus aureus pneumonia. AG-β-CD was identified with X-ray diffraction and FT-IR. Surprisingly, both AG-β-CD and AG showed little in vitro anti-S. aureus activity. However, pulmonary delivery of AG, AG-β-CD, or penicillin had significant anti-S. aureus pneumonia effects. Leukocytes, neutrophils, white blood cells, total proteins, TNF-α, IL-6, NF-κB p65 expression, and bacterial colonies in the bronchoalveolar lavage fluids were detected. Pulmonary delivery of AG and AG-β-CD led to bacterial inhibition and inflammation alleviation by regulating immune responses, while penicillin only killed bacteria without significant immune regulation. Moreover, the antipneumonia activity of AG-β-CD was much higher than that of AG, probably resulting from locally accelerated AG dissolution due to β-CD inclusion. The aerodynamic diameter of AG-β-CD powders was 2.03 μm, suitable for pulmonary delivery. Inhalable AG-β-CD is a promising antibacterial and anti-inflammatory medicine for the treatment of S. aureus pneumonia by regulating immune responses, and the effect is enhanced by β-CD inclusion. AG and its formulations might be potent weapons against the resistant bacterial pneumonia due to their specific mechanism in the future.

  1. Bombyx mori and Aedes aegypti form multi-functional immune complexes that integrate pattern recognition, melanization, coagulants, and hemocyte recruitment.

    Science.gov (United States)

    Phillips, Dennis R; Clark, Kevin D

    2017-01-01

    The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting. Here, we used mass spectrometry to demonstrate the integration of pathogen recognition proteins, coagulants, and melanization components into stable, high-mass, multi-functional Immune Complexes (ICs) in Bombyx mori and Aedes aegypti. Essential proteins common to both include phenoloxidases, apolipophorins, serine protease homologs, and a serine protease that promotes hemocyte recruitment through cytokine activation. Pattern recognition proteins included C-type Lectins in B. mori, while A. aegypti contained a protein homologous to Plasmodium-resistant LRIM1 from Anopheles gambiae. We also found that the B. mori IC is stabilized by extensive transglutaminase-catalyzed cross-linking of multiple components. The melanization inhibitor Egf1.0, from the parasitoid wasp Microplitis demolitor, blocked inclusion of specific components into the IC and also inhibited transglutaminase activity. Our results show how coagulants, melanization components, and hemocytes can be recruited to a wound surface or pathogen, provide insight into the mechanism by which a parasitoid evades this immune response, and suggest that insects as diverse as Lepidoptera and Diptera utilize similar defensive mechanisms.

  2. Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment

    Directory of Open Access Journals (Sweden)

    Monajemi Mahdis

    2012-04-01

    Full Text Available Abstract The enzyme APOBEC3G (A3G mutates the human immunodeficiency virus (HIV genome by converting deoxycytidine (dC to deoxyuridine (dU on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G’s standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.

  3. C-reactive protein, Rheumatoid factor and circulatory immune complex as markers for monitoring treatment of infective endocarditis

    International Nuclear Information System (INIS)

    Alavi, S.M.; Ahmadi, F.; Nashibi, R.

    2010-01-01

    Objectives: To evaluate the diagnostic usefulness of serum C-reactive protein (CRP), rheumatoid factor (RF) and circulatory immune complex (CIC) determinations in monitoring the outcome of infective endocarditis (IE). Methodology: In this prospective analytic descriptive study CRP, RF and CIC were measured on admission and 4 weeks after initiation of standard antibiotic regimen in 30 hospitalized patients with IE in an educational hospital between 2006 and 2007 in Ahvaz a city south west Iran . Duke criteria were used for diagnosis of IE. CRP and RF were examined using quantitative neflometry (Binding site kit, UK) and CIC was detected by semi quantitative immune diffusion (Baharafshan SIRD kit, Iran). Data were evaluated using statistical analyses in SPSS (version 12, USA) software for windows. Results: The fall in serum C-reactive protein or RF was significant (P= 0.05). Only two of the 30 patients, who had elevated CRP, RF and CIC week four failed to response and one needed cardiac surgery. Conclusions: The C-reactive protein proved to be a good tool for monitoring the treatment of IE. Also RF proved useful in the assessment of patients with IE, but the value of CIC was negligible. (author)

  4. The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.

    2005-09-01

    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).

  5. Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

    Full Text Available The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA on the neuroendocrine-immune (NEI network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

  6. Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.

    Science.gov (United States)

    Santaguida, Stefano; Richardson, Amelia; Iyer, Divya Ramalingam; M'Saad, Ons; Zasadil, Lauren; Knouse, Kristin A; Wong, Yao Liang; Rhind, Nicholas; Desai, Arshad; Amon, Angelika

    2017-06-19

    Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways that limit the prevalence of such cells exist? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to further genomic instability that ultimately causes cell-cycle arrest. We further show that cells with complex karyotypes exhibit features of senescence and produce pro-inflammatory signals that promote their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that may serve as a means for cancer cell immunosurveillance. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis.

    Science.gov (United States)

    Zheng, Wei; Warner, Roscoe; Ruggeri, Roger; Su, Chunyan; Cortes, Christian; Skoura, Athanasia; Ward, Jessica; Ahn, Kay; Kalgutkar, Amit; Sun, Dexue; Maurer, Tristan S; Bonin, Paul D; Okerberg, Carlin; Bobrowski, Walter; Kawabe, Thomas; Zhang, Yanwei; Coskran, Timothy; Bell, Sammy; Kapoor, Bhupesh; Johnson, Kent; Buckbinder, Leonard

    2015-05-01

    Small vessel vasculitis is a life-threatening condition and patients typically present with renal and pulmonary injury. Disease pathogenesis is associated with neutrophil accumulation, activation, and oxidative damage, the latter being driven in large part by myeloperoxidase (MPO), which generates hypochlorous acid among other oxidants. MPO has been associated with vasculitis, disseminated vascular inflammation typically involving pulmonary and renal microvasculature and often resulting in critical consequences. MPO contributes to vascular injury by 1) catabolizing nitric oxide, impairing vasomotor function; 2) causing oxidative damage to lipoproteins and endothelial cells, leading to atherosclerosis; and 3) stimulating formation of neutrophil extracellular traps, resulting in vessel occlusion and thrombosis. Here we report a selective 2-thiouracil mechanism-based MPO inhibitor (PF-1355 [2-(6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide) and demonstrate that MPO is a critical mediator of vasculitis in mouse disease models. A pharmacokinetic/pharmacodynamic response model of PF-1355 exposure in relation with MPO activity was derived from mouse peritonitis. The contribution of MPO activity to vasculitis was then examined in an immune complex model of pulmonary disease. Oral administration of PF-1355 reduced plasma MPO activity, vascular edema, neutrophil recruitment, and elevated circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction were completely suppressed by PF-1355 treatment. This study shows that MPO activity is critical in driving immune complex vasculitis and provides confidence in testing the hypothesis that MPO inhibition will provide benefit in treating human vasculitic diseases. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Characterization of DNA antigens from immune complexes deposited in the skin of patients with systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    曾凡钦; 尹若菲; 谭国珍; 郭庆; 许德清

    2004-01-01

    Background Skin lesions are common manifestations in systemic lupus erythematosus (SLE). It is still unknown what the definite pathogenesis of skin involvement was and whether DNA participated in it. Our study was designed to explore the pathogenetic role and nature of nuclear antigen (DNA) deposited in the skin lesions of patients with SLE.Methods Thirty skin samples from patients with SLE and 2 normal skin samples were studied. Extracellular DNA was evaluated by indirect immunofluorescence methods. The deposited immune complexes were extracted by cryoprecipitation, and DNA was then isolated with phenol and chloroform. DNA fragment sizes were detected by agarose gel electrophoresis. Finally, 8 different probes were used to analyze the origin of these DNA molecules using Dot hybridization.Results Extracellular DNA staining was found only in skin lesions, mainly those located in the basement membrane zone, vascular wall, and hair follicle wall. Normal skin and non-lesion SLE skin showed no fluorescence at locations outside the nuclei. There were no differences in the rate and intensity of extracellular DNA staining when comparing active phase to remission phase patients. No relationship was found between extracellular DNA and circulating anti-dsDNA antibodies. Deposited DNA fragments clustered into four bands of somewhat discrete sizes: 20 000 bp, 1300 bp, 800-900 bp, 100-200 bp. Small sized fragments (100-200 bp) were positively correlated with disease activity (P<0.05, r=0.407). Dot hybridization showed significant homology of the various extracellular DNA fragments examined with human genomic DNA, but not with DNA from the microorganisms and viruses we examined. There were also homologies between DNA samples from different individuals.Conclusions DNA and its immune complexes may contribute to the pathogenesis of skin lesions in SLE. These DNA molecules range in size from 100 bp to 20 kb and may be endogenous in origin.

  9. Inferring selection in the Anopheles gambiae species complex: an example from immune-related serine protease inhibitors

    Directory of Open Access Journals (Sweden)

    Little Tom J

    2009-06-01

    Full Text Available Abstract Background Mosquitoes of the Anopheles gambiae species complex are the primary vectors of human malaria in sub-Saharan Africa. Many host genes have been shown to affect Plasmodium development in the mosquito, and so are expected to engage in an evolutionary arms race with the pathogen. However, there is little conclusive evidence that any of these mosquito genes evolve rapidly, or show other signatures of adaptive evolution. Methods Three serine protease inhibitors have previously been identified as candidate immune system genes mediating mosquito-Plasmodium interaction, and serine protease inhibitors have been identified as hot-spots of adaptive evolution in other taxa. Population-genetic tests for selection, including a recent multi-gene extension of the McDonald-Kreitman test, were applied to 16 serine protease inhibitors and 16 other genes sampled from the An. gambiae species complex in both East and West Africa. Results Serine protease inhibitors were found to show a marginally significant trend towards higher levels of amino acid diversity than other genes, and display extensive genetic structuring associated with the 2La chromosomal inversion. However, although serpins are candidate targets for strong parasite-mediated selection, no evidence was found for rapid adaptive evolution in these genes. Conclusion It is well known that phylogenetic and population history in the An. gambiae complex can present special problems for the application of standard population-genetic tests for selection, and this may explain the failure of this study to detect selection acting on serine protease inhibitors. The pitfalls of uncritically applying these tests in this species complex are highlighted, and the future prospects for detecting selection acting on the An. gambiae genome are discussed.

  10. CRISPR-Cas Adaptive Immune Systems of the Sulfolobales: Unravelling Their Complexity and Diversity

    Directory of Open Access Journals (Sweden)

    Roger A. Garrett

    2015-03-01

    Full Text Available The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive structural and functional diversity. They carry large and multiple CRISPR loci and often multiple copies of diverse Type I and Type III interference modules as well as more homogeneous adaptation modules. These acidothermophilic organisms have recently provided seminal insights into both the adaptation process, the diverse modes of interference, and their modes of regulation. The functions of the adaptation and interference modules tend to be loosely coupled and the stringency of the crRNA-DNA sequence matching during DNA interference is relatively low, in contrast to some more streamlined CRISPR-Cas systems of bacteria. Despite this, there is evidence for a complex and differential regulation of expression of the diverse functional modules in response to viral infection. Recent work also supports critical roles for non-core Cas proteins, especially during Type III-directed interference, and this is consistent with these proteins tending to coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of the Sulfolobales are considered including an alternative spacer acquisition mechanism, reversible spacer acquisition, the formation and significance of antisense CRISPR RNAs, and a novel mechanism for avoidance of CRISPR-Cas defense. Finally, questions regarding the basis for the complexity, diversity, and apparent redundancy, of the intracellular CRISPR-Cas systems are discussed.

  11. T cell immunity

    OpenAIRE

    Emel Bülbül Başkan

    2013-01-01

    Since birth, our immune system is constantly bombarded with self-antigens and foreign pathogens. To stay healthy, complex immune strategies have evolved in our immune system to maintain self-tolerance and to defend against foreign pathogens. Effector T cells are the key players in steering the immune responses to execute immune functions. While effector T cells were initially identified to be immune promoting, recent studies unraveled negative regulatory functions of effector T cells...

  12. Trial of using antibodies as carriers of alkylating agents. Pt. 2. Evaluation of ability to form /sup 32/P-cyclophosphamide + immune antibody complexes with homologous antigen

    Energy Technology Data Exchange (ETDEWEB)

    Trzeciak, J; Felus, E; Nolewajka, E; Szaflarski, J; Dudziak, Z [Slaska Akademia Medyczna, Katowice (Poland)

    1976-01-01

    /sup 32/P-cyclophosphamide was found to combine with ..gamma..-globulin fractions of immune sera. Immune sera incubated with /sup 32/P-cyclophosphamide retained ability to react specifically with homologou antigen in vitro in the system: MN antigens of human erythrocytes + rabbit anti-MN antibody, and probably reacted selectively with target antigens in vivo in the system: antigens of guinea pig kidney tissue + rabbit antibodies against these antigens. Hemagglutination, passive hemagglutination and precipitation in agar gel tests were used in the experiments. Ability to combine of the immune antibody + /sup 32/P-cyclophosphamide complex with homologous antigens was evaluated by measurements of radioactivity of studied materials (erythrocyte agglutinates and organ homogenates). The results indicate feasibility of using immune antibodies as carriers of cytostatic agents.

  13. Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

    Science.gov (United States)

    Lee, K W; Choi, B; Kim, Y M; Cho, C W; Park, H; Moon, J I; Choi, G-S; Park, J B; Kim, S J

    2017-06-01

    Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points. We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Azad A Sulaiman

    2016-11-01

    for a reduced effector response targeting juvenile parasites which we demonstrate extends to an abrogation of the ADCC response. Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors. These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection.

  15. The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses.

    Science.gov (United States)

    Takahama, Michihiro; Fukuda, Mitsunori; Ohbayashi, Norihiko; Kozaki, Tatsuya; Misawa, Takuma; Okamoto, Toru; Matsuura, Yoshiharu; Akira, Shizuo; Saitoh, Tatsuya

    2017-09-19

    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Michihiro Takahama

    2017-09-01

    Full Text Available Cyclic GMP-AMP synthase (cGAS is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5, in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING, the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis.

  17. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells

    OpenAIRE

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L.; Liao, Gongxian; Hoffman, Brad E.; Leong, Kam W.; Terhorst, Cox; Daniell, Henry; Herzog, Roland W.

    2015-01-01

    Coadministering FIX orally and systemically induces tolerance via complex immune regulation, involving tolerogenic dendritic and T-cell subsets.Induced CD4+CD25−LAP+ regulatory T cells with increased IL-10 and TGF-β expression and CD4+CD25+ regulatory T cells suppress antibody formation against FIX.

  18. Standardization and application of the solid phase C1q radioimmunoassay using soluble tetanus toxoid-antitetanus immune complexes in sera of patients with chronic polyarthritis and Lupus erythematodes

    International Nuclear Information System (INIS)

    Menzel, E.J.; Steffen, C.; Smolen, J.

    1982-01-01

    Soluble tetanus-antitetanus immune complexes were prepared with affinity-chromatography and gel chromatography. Serial dilutions of these immune complex preparations were tested in a solid phase C1q radioimmunoassay. Soluble immune complexes as well as aggregated human gamma globulin of identical protein concentrations were comparatively investigated. Soluble immune complexes rendered a more sensitive standardization of RIA. According to these observations a relation between μg/ml equivalents of defined tetanus-antitetanus complexes and ng second antibody obtained in C1q-RIA was calculated. Upper limit of mean values and two standard deviations of ng second antibody obtained in investigations of 55 normal sera was designated as 1 unit immune complexes and regarded as border line of negative results. Multiplication of μg/ml immune complex equivalents of 1 unit led to a scale of 1 to 15 units, showing the area of positive results. According to these values a standardization curve was constructed allowing a conversion of ng-second antibody obtained in serum investigations into immune complex units equivalent to defined standard immune complexes. With this curve investigation results of 56 RA sera and 21 SLE sera were expressed in the range of units, making a distinct gradation of positive results and a clear cut separation of positive and negative results possible. SLE sera of patients in acute stage showed highly positive results. (orig.) [de

  19. Standardization and application of the solid phase C1q radioimmunoassay using soluble tetanus toxoid-antitetanus immune complexes in sera of patients with chronic polyarthritis and Lupus erythematodes

    Energy Technology Data Exchange (ETDEWEB)

    Menzel, E J; Steffen, C; Smolen, J

    1982-11-22

    Soluble tetanus-antitetanus immune complexes were prepared with affinity-chromatography and gel chromatography. Serial dilutions of these immune complex preparations were tested in a solid phase C1q radioimmunoassay. Soluble immune complexes as well as aggregated human gamma globulin of identical protein concentrations were comparatively investigated. Soluble immune complexes rendered a more sensitive standardization of RIA. According to these observations a relation between ..mu..g/ml equivalents of defined tetanus-antitetanus complexes and ng second antibody obtained in C1q-RIA was calculated. Upper limit of mean values and two standard deviations of ng second antibody obtained in investigations of 55 normal sera was designated as 1 unit immune complexes and regarded as border line of negative results. Multiplication of ..mu..g/ml immune complex equivalents of 1 unit led to a scale of 1 to 15 units, showing the area of positive results. According to these values a standardization curve was constructed allowing a conversion of ng-second antibody obtained in serum investigations into immune complex units equivalent to defined standard immune complexes. With this curve investigation results of 56 RA sera and 21 SLE sera were expressed in the range of units, making a distinct gradation of positive results and a clear cut separation of positive and negative results possible. SLE sera of patients in acute stage showed highly positive results.

  20. INTEGRATED QUANTITATIVE ASSESSMENT OF CHANGES IN NEURO-ENDOCRINE-IMMUNE COMPLEX AND METABOLISM IN RATS EXPOSED TO ACUTE COLD-IMMOBILIZATION STRESS

    Directory of Open Access Journals (Sweden)

    Sydoruk O Sydoruk

    2016-09-01

        Abstracts Background. It is known that the reaction of the neuroendocrine-immune complex to acute and chronic stress are different. It is also known about sex differences in stress reactions. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress at male rats. The purpose of this study - to carry out integrated quantitative estimation of neuroendocrine, immune and metabolic responses to acute stress at male and female rats. Material and research methods. The experiment is at 58 (28 male and 30 female white rats Wistar line weighing 170-280 g (Mean=220 g; SD=28 g. The day after acute (water immersion restraint stress determined HRV, endocrine, immune and metabolic parameters as well as gastric mucosa injuries and comparing them with parameters of intact animals. Results. Acute cold-immobilization stress caused moderate injuries the stomach mucosa as erosions and ulcers. Among the metabolic parameters revealed increased activity Acid Phosphatase, Asparagine and Alanine Aminotranspherase as well as Creatinephosphokinase. It was also found to reduce plasma Testosterone as well as serum Potassium and Phosphate probably due to increased Parathyrine and Mineralocorticoid activity and Sympathotonic shift of sympatho-vagal balance. Integrated quantitative measure manifestations of Acute Stress as mean of modules of Z-Scores makes for 10 metabolic parameters 0,75±0,10 σ and for 8 neuro-endocrine parameters 0,40±0,07 σ. Among immune parameters some proved resistant to acute stress factors, while 10 significant suppressed and 12 activated. Integrated quantitative measure poststressory changes makes 0,73±0,08 σ. Found significant differences integrated status intact males and females, whereas after stress differences are insignificant. Conclusion. The approach to integrated quantitative assessment of neuroendocrine-immune complex and metabolism may be useful for testing the

  1. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Satoko Arai

    2013-04-01

    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  2. Generation of a CRISPR database for Yersinia pseudotuberculosis complex and role of CRISPR-based immunity in conjugation.

    Science.gov (United States)

    Koskela, Katja A; Mattinen, Laura; Kalin-Mänttäri, Laura; Vergnaud, Gilles; Gorgé, Olivier; Nikkari, Simo; Skurnik, Mikael

    2015-11-01

    The clustered regularly interspaced short palindromic repeat - CRISPR-associated genes (CRISPR-Cas) system is used by bacteria and archaea against invading conjugative plasmids or bacteriophages. Central to this immunity system are genomic CRISPR loci that contain fragments of invading DNA. These are maintained as spacers in the CRISPR loci between direct repeats and the spacer composition in any bacterium reflects its evolutionary history. We analysed the CRISPR locus sequences of 335 Yersinia pseudotuberculosis complex strains. Altogether 1902 different spacer sequences were identified and these were used to generate a database for the spacer sequences. Only ∼10% of the spacer sequences found matching sequences. In addition, surprisingly few spacers were shared by Yersinia pestis and Y. pseudotuberculosis strains. Interestingly, 32 different protospacers were present in the conjugative plasmid pYptb32953. The corresponding spacers were identified from 35 different Y. pseudotuberculosis strains indicating that these strains had encountered pYptb32953 earlier. In conjugation experiments, pYptb32953-specific spacers generally prevented conjugation with spacer-positive and spacer-free strains. However, some strains with one to four spacers were invaded by pYptb32953 and some spacer-free strains were fully resistant. Also some spacer-positive strains were intermediate resistant to conjugation. This suggests that one or more other defence systems are determining conjugation efficiency independent of the CRISPR-Cas system. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Allergen-containing immune complexes used for immunotherapy of allergic asthma. II. IgE and IgG immune response during and after hyposensitization of sensitized guinea pigs

    DEFF Research Database (Denmark)

    Poulsen, L K; Lundberg, L; Søndergaard, I

    1991-01-01

    In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared...... response and clinical symptoms. Thus, the strong IgG response during immunotherapy may not be causally related to the outcome of treatment....

  4. Chylous Ascites in a Patient with HIV/AIDS: A Late Complication of Mycobacterium avium Complex-Immune Reconstitution Inflammatory Syndrome

    Directory of Open Access Journals (Sweden)

    Imam H. Shaik

    2014-01-01

    Full Text Available Chylous ascites is very rare in HIV/AIDS and its association with Mycobacterium avium complex-immune reconstitution inflammatory syndrome (MAC-IRIS has been rarely reported. Here, we report a case of a young African-American male who developed chylous ascites as a late sequela to immune reconstitution inflammatory syndrome while on treatment for MAC. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV RNA level should be monitored for development of IRIS. Although the long term prognosis is poor, early diagnosis and treatment help to improve quality of life.

  5. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  6. Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test

    International Nuclear Information System (INIS)

    Casali, P.; Bossus, A.; Carpentier, N.A.; Lambert, P.H.

    1977-01-01

    Bovine conglutinin was used in a solid-phase assay for the detection of immune complexes. In a first step, the tested serum sample was incubated in polypropylene tubes coated with conglutinin to allow C3-coated immune complexes to bind to solid-phase conglutinin. In a second step, the conglutinin-bound complexes were detected using an enzyme-conjugated or radiolabelled anti-immunoglobulin antibody. The conglutinin-binding (KgB) test did not suffer from the interference of DNA, heparin or endotoxins. Its limit of sensitivity for aggregated IgG was 3 μg/ml undiluted human serum. Immune complexes prepared in vitro using tetanus toxoid, or DNA, and corresponding antibodies in human sera could be detected at various antigen/antibody ratios and at antibody concentrations lower than 8 μg/ml. The KgB test allowed for the detection of immune complexes in sera from patients with systemic lupus erythematosus, rheumatoid arthritis, idiopathic vasculitis, leprosy and leukemia. These sera were also tested using the 125 I-labelled Clq-binding activity (BA) test and the KgB test simultaneously, and a significant rank order correlation was observed. In patients with leukemia, a significant correlation was observed using three tests, KgB, 125 I-labelled Clq BA and Raji-cell radioimmunoassay (RIA). Therefore, the KgB test appears as a simple and reproducible method, utilizing a very stable reagent, with a sensitivity and specificity comparable to the other tests studied and allowing for clinical application. (author)

  7. Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10.

    Directory of Open Access Journals (Sweden)

    Carmen A Ambarus

    Full Text Available BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-γ, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs. Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MΦ(IL-4. In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2. The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10.

  8. Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection.

    Science.gov (United States)

    Hu, Ke-Qin; Cui, Wei

    2018-05-01

    Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.

  9. Evaluation of a Cordia-IC enzyme-linked immunosorbent assay kit for the detection of circulating immune complexes.

    Science.gov (United States)

    Landoy, Z; West, T E; Vladutiu, A O; Fitzpatrick, J E

    1985-01-01

    A commercial kit (Cordia-IC) from Cordis Laboratory, Miami, Fla., was compared with the Raji cell radioimmunoassay for its ability to detect circulating immune complexes (CIC) in sera from 30 control subjects and 118 patients with infectious diseases. The 118 patients were categorized into the following groups: (i) 23 patients with bacterial endocarditis, (ii) 41 patients with bacteremia from an infected intravascular catheter or access device, and (iii) 54 patients with Staphylococcus aureus bacteremia related to a deep tissue infection. The Cordia-IC was comparable to the Raji cell radioimmunoassay in intraassay variability (4.0 versus 8.0%) and interassay reproducibility (8.7 versus 20.0%). Neither assay found CIC amounts above 12.5 micrograms equivalents (eq) of aggregated human gamma globulin (AHG) per ml in any of the 30 control individuals. In group 1, Cordia-IC detected 19 of 23 positives (mean, 73.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 23 positives (mean, 54.8 micrograms eq of AHG per ml). In group 2, Cordia-IC detected 19 of 41 positives (mean, 20.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 41 positives (mean, 15.1 micrograms eq of AHG per ml). In group 3, Cordia-IC found 38 of 54 positives (mean, 28.0 micrograms eq of AHG per ml), whereas the Raji cell found 32 of 54 positives (mean, 23.9 micrograms eq of AHG per ml). Statistically, these findings were not significantly different in any of the three patient groups (P> 0.15), and there was an overall good correlation between the results obtained by the two assays (r+0.64, PCordia-IC provided a suitable assay for the detection of CIC and might find application in routine clinical laboratories. PMID:3897269

  10. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L

    1997-01-01

    chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... for these proteins, and we found cross-reactivity between polyclonal Abs raised to these chemokines. By purifying the blocking Abs using double affinity methods (with Ag-immobilized beads), this cross-reactivity was removed. Individually, anti-MIP-2 and anti-CINC Ab significantly reduced lung injury (as measured...... activity in BAL fluids collected 2 h after injury from animals undergoing immune complex deposition could be shown to be chiefly due to the combined contributions of MIP-2 (39%), CINC (28%), and C5a (21%). When either MIP-2 or CINC was blocked in vivo, up-regulation of Mac-1 expression on neutrophils...

  11. 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

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

    OpenAIRE

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

    2017-01-01

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

  13. Complex interplay of body condition, life history, and prevailing environment shapes immune defenses of garter snakes in the wild.

    Science.gov (United States)

    Palacios, Maria G; Cunnick, Joan E; Bronikowski, Anne M

    2013-01-01

    The immunocompetence "pace-of-life" hypothesis proposes that fast-living organisms should invest more in innate immune defenses and less in adaptive defenses compared to slow-living ones. We found some support for this hypothesis in two life-history ecotypes of the snake Thamnophis elegans; fast-living individuals show higher levels of innate immunity compared to slow-living ones. Here, we optimized a lymphocyte proliferation assay to assess the complementary prediction that slow-living snakes should in turn show stronger adaptive defenses. We also assessed the "environmental" hypothesis that predicts that slow-living snakes should show lower levels of immune defenses (both innate and adaptive) given the harsher environment they live in. Proliferation of B- and T-lymphocytes of free-living individuals was on average higher in fast-living than slow-living snakes, opposing the pace-of-life hypothesis and supporting the environmental hypothesis. Bactericidal capacity of plasma, an index of innate immunity, did not differ between fast-living and slow-living snakes in this study, contrasting the previously documented pattern and highlighting the importance of annual environmental conditions as determinants of immune profiles of free-living animals. Our results do not negate a link between life history and immunity, as indicated by ecotype-specific relationships between lymphocyte proliferation and body condition, but suggest more subtle nuances than those currently proposed.

  14. Down regulation of the TCR complex CD3 ζ-chain on CD3+ T cells: a potential mechanism for helminth mediated immune modulation

    Directory of Open Access Journals (Sweden)

    Laura Jane Appleby

    2015-02-01

    Full Text Available The CD3ζ forms part of the T cell receptor (TCR where it plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways leading to T cell effector functions. Down regulation of CD3ζ leads to impairment of immune responses including reduced cell proliferation and cytokine production. In experimental models helminth parasites have been shown to modulate immune responses directed against them and unrelated antigens, so called bystander antigens, but there is a lack of studies validating these observations in humans. This study focused on investigated the relationship between expression levels of the TCR CD3ζ chain with lymphocyte cell proliferation during human infection with the helminth parasite, Schistosoma haematobium which causes uro-genital schistosomiasis. Using flow cytometry, peripheral blood mononuclear cells (PBMCs from individuals naturally exposed to S. haematobium in rural Zimbabwe were phenotyped, and expression levels of CD3ζ on T cells were related to intensity of infection. In this population, parasite infection intensity was inversely related to CD3ζ expression levels (p<0.05, consistent with down-regulation of CD3ζ expression during helminth infection. Furthermore, PBMC proliferation was positively related to expression levels of CD3ζ (p<0.05 after allowing for confounding variables (host age, sex, infection level. CD3ζ expression levels had a differing relationship between immune correlates of susceptibility and immunity, measured by antibody responses, indicating a complex relationship between immune activation status and immunity. The relationships between the CD3ζ chain of the TCR and schistosome infection, PBMC proliferation and schistosome-specific antibody responses have not previously been reported, and these results may indicate a mechanism for the impaired T cell proliferative responses observed during human schistosome infection.

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

    Directory of Open Access Journals (Sweden)

    Robert J. Greenstein

    2014-09-01

    Conclusions: We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases.

  16. Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

    Science.gov (United States)

    Verma, Puja; Tapadia, Madhu G

    2015-08-01

    In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The immune strategy and stress response of the Mediterranean species of the Bemisia tabaci complex to an orally delivered bacterial pathogen.

    Directory of Open Access Journals (Sweden)

    Chang-Rong Zhang

    Full Text Available BACKGROUND: The whitefly, Bemisia tabaci, a notorious agricultural pest, has complex relationships with diverse microbes. The interactions of the whitefly with entomopathogens as well as its endosymbionts have received great attention, because of their potential importance in developing novel whitefly control technologies. To this end, a comprehensive understanding on the whitefly defense system is needed to further decipher those interactions. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a comprehensive investigation of the whitefly's defense responses to infection, via oral ingestion, of the pathogen, Pseudomonas aeruginosa, using RNA-seq technology. Compared to uninfected whiteflies, 6 and 24 hours post-infected whiteflies showed 1,348 and 1,888 differentially expressed genes, respectively. Functional analysis of the differentially expressed genes revealed that the mitogen associated protein kinase (MAPK pathway was activated after P. aeruginosa infection. Three knottin-like antimicrobial peptide genes and several components of the humoral and cellular immune responses were also activated, indicating that key immune elements recognized in other insect species are also important for the response of B. tabaci to pathogens. Our data also suggest that intestinal stem cell mediated epithelium renewal might be an important component of the whitefly's defense against oral bacterial infection. In addition, we show stress responses to be an essential component of the defense system. CONCLUSIONS/SIGNIFICANCE: We identified for the first time the key immune-response elements utilized by B. tabaci against bacterial infection. This study provides a framework for future research into the complex interactions between whiteflies and microbes.

  18. Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment

    NARCIS (Netherlands)

    Mattei, D.; Ivanov, A.; Ferrai, C.; Jordan, P.; Guneykaya, D.; Buonfiglioli, A.; Schaafsma, W.; Przanowski, P.; Deuther-Conrad, W.; Brust, P.; Hesse, S.; Patt, M.; Sabri, O.; Ross, T. L.; Eggen, B. J. L.; Boddeke, E. W. G. M.; Kaminska, B.; Beule, D.; Pombo, A.; Kettenmann, H.; Wolf, S. A.

    2017-01-01

    Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of

  19. Characterization of NF-κB Reporter U937 Cells and Their Application for the Detection of Inflammatory Immune-Complexes.

    Directory of Open Access Journals (Sweden)

    Csilla Kecse-Nagy

    Full Text Available Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases.

  20. Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus.

    Science.gov (United States)

    Moi, Meng Ling; Ami, Yasushi; Shirai, Kenji; Lim, Chang-Kweng; Suzaki, Yuriko; Saito, Yuka; Kitaura, Kazutaka; Saijo, Masayuki; Suzuki, Ryuji; Kurane, Ichiro; Takasaki, Tomohiko

    2015-02-01

    Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells. © The American Society of Tropical Medicine and Hygiene.

  1. Multiplexed screening of natural humoral immunity identifies antibodies at fine specificity for complex and dynamic viral targets.

    Science.gov (United States)

    McCutcheon, Krista M; Gray, Julia; Chen, Natalie Y; Liu, Keyi; Park, Minha; Ellsworth, Stote; Tripp, Ralph A; Tompkins, S Mark; Johnson, Scott K; Samet, Shelly; Pereira, Lenore; Kauvar, Lawrence M

    2014-01-01

    Viral entry targets with therapeutic neutralizing potential are subject to multiple escape mechanisms, including antigenic drift, immune dominance of functionally irrelevant epitopes, and subtle variations in host cell mechanisms. A surprising finding of recent years is that potent neutralizing antibodies to viral epitopes independent of strain exist, but are poorly represented across the diverse human population. Identifying these antibodies and understanding the biology mediating the specific immune response is thus difficult. An effective strategy for meeting this challenge is to incorporate multiplexed antigen screening into a high throughput survey of the memory B cell repertoire from immune individuals. We used this approach to discover suites of cross-clade antibodies directed to conformational epitopes in the stalk region of the influenza A hemagglutinin (HA) protein and to select high-affinity anti-peptide antibodies to the glycoprotein B (gB) of human cytomegalovirus. In each case, our screens revealed a restricted VH and VL germline usage, including published and previously unidentified gene families. The in vivo evolution of paratope specificity with optimal neutralizing activity was understandable after correlating biological activities with kinetic binding and epitope recognition. Iterative feedback between antigen probe design based on structure and function information with high throughput multiplexed screening demonstrated a generally applicable strategy for efficient identification of safe, native, finely tuned antibodies with the potential for high genetic barriers to viral escape.

  2. Solubilization of immune complexes in complement factor deficient sera and the influence of temperature, ionic strength and divalent cations on the solubilization reaction

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Svehag, Svend-Erik

    1984-01-01

    The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS......M. Chelation of Ca2+ in serum by Mg2+-ethylene glycol tetraacetic acid reduced the CMS capacity by up to 50% and the IKS was markedly retarded. Varying the Zn2+ or Mn2+ ion concentrations in serum influenced neither the IKS nor the CMS capacity....

  3. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

    2004-01-01

    B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto......'s thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture...

  4. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Hegedüs, Laszlo; Leslie, Robert Graham Quinton

    2004-01-01

    's thyroiditis (HT), Graves' disease (GD) and healthy controls were incubated with human thyroglobulin (Tg) before adding normal peripheral blood mononuclear cells. The deposition of immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in serum from HT patients promoted B cell capture......B cells are centrally involved as antigen-presenting cells in certain autoimmune diseases. To establish whether autoantibodies form immune complexes (IC) with self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of self-antigen, sera from patients with Hashimoto...

  5. Membrane microdomains and the cytoskeleton constrain AtHIR1 dynamics and facilitate the formation of an AtHIR1-associated immune complex.

    Science.gov (United States)

    Lv, Xueqin; Jing, Yanping; Xiao, Jianwei; Zhang, Yongdeng; Zhu, Yingfang; Julian, Russell; Lin, Jinxing

    2017-04-01

    Arabidopsis hypersensitive-induced reaction (AtHIR) proteins function in plant innate immunity. However, the underlying mechanisms by which AtHIRs participate in plant immunity remain elusive. Here, using VA-TIRFM and FLIM-FRET, we revealed that AtHIR1 is present in membrane microdomains and co-localizes with the membrane microdomain marker REM1.3. Single-particle tracking analysis revealed that membrane microdomains and the cytoskeleton, especially microtubules, restrict the lateral mobility of AtHIR1 at the plasma membrane and facilitate its oligomerization. Furthermore, protein proximity index measurements, fluorescence cross-correlation spectroscopy, and biochemical experiments demonstrated that the formation of the AtHIR1 complex upon pathogen perception requires intact microdomains and cytoskeleton. Taken together, these findings suggest that microdomains and the cytoskeleton constrain AtHIR1 dynamics, promote AtHIR1 oligomerization, and increase the efficiency of the interactions of AtHIR1 with components of the AtHIR1 complex in response to pathogens, thus providing valuable insight into the mechanisms of defense-related responses in plants. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  6. 3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

    Directory of Open Access Journals (Sweden)

    Manuel A Patarroyo

    Full Text Available T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2 and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

  7. 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.

  8. Characterizing complex polysera produced by antigen-specific immunization through the use of affinity-selected mimotopes.

    Directory of Open Access Journals (Sweden)

    Galina Denisova

    Full Text Available BACKGROUND: Antigen-based (as opposed to whole organism vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS: Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets. CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines.

  9. Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts

    International Nuclear Information System (INIS)

    Vermeer, B.J.; Santerse, B.; Van De Kerckhove, B.A.; Schothorst, A.A.; Claas, F.H.

    1988-01-01

    The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm 2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place

  10. Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats

    International Nuclear Information System (INIS)

    Arquilla, E.R.; Stenger, D.; McDougall, B.; Ulich, T.R.

    1987-01-01

    The bioavailability, distribution, and metabolic fate of 125 I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125 I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125 I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125 I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125 I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125 I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125 I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125 I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies

  11. Noise-immune complex correlation for vasculature imaging based on standard and Jones-matrix optical coherence tomography

    Science.gov (United States)

    Makita, Shuichi; Kurokawa, Kazuhiro; Hong, Young-Joo; Li, En; Miura, Masahiro; Yasuno, Yoshiaki

    2016-03-01

    A new optical coherence angiography (OCA) method, called correlation mapping OCA (cmOCA), is presented by using the SNR-corrected complex correlation. An SNR-correction theory for the complex correlation calculation is presented. The method also integrates a motion-artifact-removal method for the sample motion induced decorrelation artifact. The theory is further extended to compute more reliable correlation by using multi- channel OCT systems, such as Jones-matrix OCT. The high contrast vasculature imaging of in vivo human posterior eye has been obtained. Composite imaging of cmOCA and degree of polarization uniformity indicates abnormalities of vasculature and pigmented tissues simultaneously.

  12. Studies on the pathogenesis of Aleutian disease of mink. X. demonstration of immune complexes by the /sup 125/I-C 1 q binding test after experimental infection

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Peddinghaus, R [Kali-Chemie Pharma G.m.b.H., Hannover (Germany, F.R.). Abt. fuer Experimentelle Pathologie; Meyer zu Schwabedissen, H [Medizinische Hochschule Hannover (Germany, F.R.). Abt. fuer Klinische Immunologie und Bluttransfusionswesen; Kalden, J R [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. und Poliklinik fuer Klinische Immunologie; Trautwein, G; Ueberschaer, S [Tieraerztliche Hochschule Hannover (Germany, F.R.). Inst. fuer Pathologie

    1980-01-01

    Aleutian disease (AD) of mink most closely resembles systemic lupus erythematosus (SLE) in man; both are immune complex disease. In experimental AD serum immune complexes are determined by the /sup 125/J-C 1 q-binding test using human C 1 q. Mink (n = 12) infected intraperitoneally with Aleutian disease virus (ADV), grown in fetal mink kidney cells, developed during the course of infection a mean of /sup 125/I-C 1 q serum binding equivalent to 3.62 +- 1.68 mg./ml. aggr. HGG. (aggregated human immunoglobulin). Sera of mink (n = 8) which were infected with ADV grown in L-cells showed a less marked /sup 125/I-C 1 q binding with a mean equivalent to 2.52 +- 1.43 mg./ml. aggr. HGG. In contrast control animals (n = 8) treated with non-ADV-infected mink epidermal fibroblasts or Eagle's minimal essential medium substituted with fetal calf serum only bound /sup 125/I-C 1 q equivalent to 1.02 +- 0.99 mg./ml. aggr. HGG. In mink infected with ADV propagated in fetal mink kidney cells a constant increase in the /sup 125/I-C 1 q serum binding occurred from the 4th to the 7th and 13th week after ADV infection. Mink which were infected with ADV propagated in mouse L-cells exhibited a different pattern of the /sup 125/I-C 1 q serum binding capacity with a sharp increase from the 4th to the 7th week, followed by a decline towards the 13th week post infection. The serum /sup 125/I-C 1 q binding capacity of all experimental animal groups exhibited at different times of the experiment a significant correlation with the presence of hypergammaglobulinaemia and raised ADV-antibody titers. From the data obtained it appears that the /sup 125/I-C 1 q binding test, utilizing human C 1 q, is a suitable method for the detection of circulating serum immune complexes in mink during the course of ADV-infection.

  13. Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    Luis Fernando Cadavid Gutierrez

    2011-09-01

    Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

  14. Circadian and diurnal variation of circulating immune complexes, complement-mediated solubilization, and the complement split product C3d in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Petersen, Ivan; Baatrup, Gunnar; Brandslund, I

    1986-01-01

    Nine patients with active classical rheumatoid arthritis (ARA criteria) were studied with reference to circadian variation of immunological and clinical parameters. Complement-mediated solubilization (CMS) of immune complexes (IC) and the level of circulating IC were found to be inversely related...... with low CMS and increased IC levels in the morning, and vice versa in the afternoon. Bed rest and exercise did not influence these fluctuations. The C3d concentration in plasma was increased but showed no diurnal or circadian periodic fluctuations when the levels were corrected for fluctuations in plasma...... albumin concentration. Clinical assessment by means of pain score exhibited marked variations, with high scores in the morning, and lower in the daytime, whereas measurements of Ritchie's joint index showed no consistent pattern. The circadian variations in CMS, serum IC and clinical parameters indicate...

  15. Noise-immune complex correlation for optical coherence angiography based on standard and Jones matrix optical coherence tomography.

    Science.gov (United States)

    Makita, Shuichi; Kurokawa, Kazuhiro; Hong, Young-Joo; Miura, Masahiro; Yasuno, Yoshiaki

    2016-04-01

    This paper describes a complex correlation mapping algorithm for optical coherence angiography (cmOCA). The proposed algorithm avoids the signal-to-noise ratio dependence and exhibits low noise in vasculature imaging. The complex correlation coefficient of the signals, rather than that of the measured data are estimated, and two-step averaging is introduced. Algorithms of motion artifact removal based on non perfusing tissue detection using correlation are developed. The algorithms are implemented with Jones-matrix OCT. Simultaneous imaging of pigmented tissue and vasculature is also achieved using degree of polarization uniformity imaging with cmOCA. An application of cmOCA to in vivo posterior human eyes is presented to demonstrate that high-contrast images of patients' eyes can be obtained.

  16. Noise-immune complex correlation for optical coherence angiography based on standard and Jones matrix optical coherence tomography

    Science.gov (United States)

    Makita, Shuichi; Kurokawa, Kazuhiro; Hong, Young-Joo; Miura, Masahiro; Yasuno, Yoshiaki

    2016-01-01

    This paper describes a complex correlation mapping algorithm for optical coherence angiography (cmOCA). The proposed algorithm avoids the signal-to-noise ratio dependence and exhibits low noise in vasculature imaging. The complex correlation coefficient of the signals, rather than that of the measured data are estimated, and two-step averaging is introduced. Algorithms of motion artifact removal based on non perfusing tissue detection using correlation are developed. The algorithms are implemented with Jones-matrix OCT. Simultaneous imaging of pigmented tissue and vasculature is also achieved using degree of polarization uniformity imaging with cmOCA. An application of cmOCA to in vivo posterior human eyes is presented to demonstrate that high-contrast images of patients’ eyes can be obtained. PMID:27446673

  17. Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes.

    Science.gov (United States)

    Pestel, J; Dessaint, J P; Joseph, M; Bazin, H; Capron, A

    1984-01-01

    Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases). PMID:6088135

  18. Modulating effects of bioactive water Naftussya from layers Truskavets’ and Pomyarky on some metabolic and biophysic parameters at humans with dysfunction of neuro-endocrine-immune complex

    Directory of Open Access Journals (Sweden)

    Anatoliy I Gozhenko

    2016-12-01

    Full Text Available Background. Previously we have been carry out comparative investigation immediate effects of Bioactive Water Naftussya from layers Truskavets’, Pomyarky and Skhidnyts’a on neuro-endocrine-immune complex at men with its dysfunction. The aim of this study is the influence of the use of the course of Bioactive Water Naftussya from layers Truskavets’ and Pomyarky on some metabolic and biophysical parameters at similar patients. Materials and methods. The object of observation were 20 volunteers: ten women and ten men aged 33-76 years without clinical diagnose but with dysfunction of neuro-endocrine-immune complex and metabolism. In daily urine and venous blood we determined the content of electrolytes, nitrogenous metabolites and lipids, recorded conductivity of acupuncture points, rate of electronegative nuclei of buccal epithelium as well as parameters of gas discharge vizualisation (GDV. After examination volunteers within 7 days used bioactive water Naftussya (250 mL three times a day from Truskavets’ or Pomyarky layer, then repeated the tests listed. Results. Weekly use of Bioactive Water Naftussya increases in the normal level of plasma chloride and sodium, normalizes low level of bicarbonate and decreases within the normal levels of potassium and phosphate. Urinary excretion of sodium and chloride increases while excretion and concentration of uric acid decreases, as the urine concentration of phosphates. The index lithogenicity urine decreased from 112% to 103% norm standard. Initially reduced level of plasma triacylglycerides increases, while decreases in the normal level of cholesterol in low-density lipoprotein composition. Among the biophysical parameters detected increase in the normal conductivity acupuncture points Pg (ND at right side, which represent the nervous system, and left shift the ratio between the conductivity of acupuncture points MC (AVL, which represents the immune system. Increases electrokinetic index of

  19. Bronchial lesions of mouse model of asthma are preceded by immune complex vasculitis and induced bronchial associated lymphoid tissue (iBALT).

    Science.gov (United States)

    Guest, Ian C; Sell, Stewart

    2015-08-01

    We systematically examined by immune histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 h after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin (Ig) and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy (GCHT). After two challenges, severe eosinophilic vasculitis is present at 6 h, increases by 72 h, and then declines; B-cell proliferation and significant GCHT and hyperplasia (GCHTH) and bronchial smooth muscle hypertrophy recur more prominently. After three challenges, there is significantly increased induced bronchus-associated lymphoid tissue (iBALT) formation, GCHTH, and smooth muscle hypertrophy. Elevated levels of Th2 cytokines, IL-4, IL-5, and IL-13, are present in bronchial lavage fluids. Sensitized mice have precipitating antibody and positive Arthus skin reactions but also develop significant levels of IgE antibody to OVA but only 1 week after challenge. We conclude that the asthma like lung lesions induced in these models is preceded by immune complex-mediated eosinophilic vasculitis and iBALT formation. There are elevations of Th2 cytokines that most likely produce bronchial lesions that resemble human asthma. However, it is unlikely that mast cell-activated atopic mechanisms are responsible as we found only a few presumed mast cells by toluidine blue and metachromatic staining limited to the most proximal part of the main stem bronchus, and none in the remaining main stem bronchus or in the lung periphery.

  20. Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.

    Science.gov (United States)

    Kim, Ju Han; Ha, Il Soo; Hwang, Chang-Il; Lee, Young-Ju; Kim, Jihoon; Yang, Seung-Hee; Kim, Yon Su; Cao, Yun Anna; Choi, Sangdun; Park, Woong-Yang

    2004-11-01

    Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.

  1. Low capacity of erythrocytes to bind with immune complexes via C3b receptor in patients with systemic lupus erythematosus: correlation with pathological proteinuria

    International Nuclear Information System (INIS)

    Nojima, Y.; Terai, C.; Minota, S.; Takano, K.; Miyakawa, Y.; Takaku, F.

    1985-01-01

    Erythrocytes from 51 patients with systemic lupus erythematosus and 75 controls were tested for the capacity to bind aggregated human gamma-globulin labeled with radioiodine in the presence of complement. Both in patients and controls, a trimodal distribution of binding capacity was observed. Low (less than 9% of the added radioactivity), intermediate (9-17%), and high binding (more than 17%) were observed in 13, 58, and 29% in controls and in 49, 43 and 8% in lupus patients. The low binding capacity of erythrocytes persisted even after patients entered remission following steroid therapy. A genetic control of binding capacity was supported by familial surveys. Prevalence of pathological proteinuria was significantly higher in patients with low binding capacity than those with intermediate or high binding capacity (16/25 vs 7/26, P less than 0.01). These results indicate that an impaired physiological disposal of immune complexes via the erythrocyte C3b receptor in lupus patients may contribute to the development of renal involvement

  2. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

    Science.gov (United States)

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L; Liao, Gongxian; Hoffman, Brad E; Leong, Kam W; Terhorst, Cox; Daniell, Henry; Herzog, Roland W

    2015-04-09

    Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses. © 2015 by The American Society of Hematology.

  3. Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV Pentameric Complex Proteins GP129, 131 and 133

    Directory of Open Access Journals (Sweden)

    Josephine S. Gnanandarajah

    2014-02-01

    Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus (HCMV is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV, consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model.

  4. Membrane-localized extra-large G proteins and Gbg of the heterotrimeric G proteins form functional complexes engaged in plant immunity in Arabidopsis.

    Science.gov (United States)

    Maruta, Natsumi; Trusov, Yuri; Brenya, Eric; Parekh, Urvi; Botella, José Ramón

    2015-03-01

    In animals, heterotrimeric G proteins, comprising Ga, Gb, and Gg subunits, are molecular switches whose function tightly depends on Ga and Gbg interaction. Intriguingly, in Arabidopsis (Arabidopsis thaliana), multiple defense responses involve Gbg, but not Ga. We report here that the Gbg dimer directly partners with extra-large G proteins (XLGs) to mediate plant immunity. Arabidopsis mutants deficient in XLGs, Gb, and Gg are similarly compromised in several pathogen defense responses, including disease development and production of reactive oxygen species. Genetic analysis of double, triple, and quadruple mutants confirmed that XLGs and Gbg functionally interact in the same defense signaling pathways. In addition, mutations in XLG2 suppressed the seedling lethal and cell death phenotypes of BRASSINOSTEROID INSENSITIVE1-associated receptor kinase1-interacting receptor-like kinase1 mutants in an identical way as reported for Arabidopsis Gb-deficient mutants. Yeast (Saccharomyces cerevisiae) three-hybrid and bimolecular fluorescent complementation assays revealed that XLG2 physically interacts with all three possible Gbg dimers at the plasma membrane. Phylogenetic analysis indicated a close relationship between XLGs and plant Ga subunits, placing the divergence point at the dawn of land plant evolution. Based on these findings, we conclude that XLGs form functional complexes with Gbg dimers, although the mechanism of action of these complexes, including activation/deactivation, must be radically different form the one used by the canonical Ga subunit and are not likely to share the same receptors. Accordingly, XLGs expand the repertoire of heterotrimeric G proteins in plants and reveal a higher level of diversity in heterotrimeric G protein signaling.

  5. Use of radioimmune assay in investigating reagents to be used in the immunocytochemical localization of hepatitis B surface antigen in immune complexes in the kidney of patients with membranous nephropathy and Australia antigenaemia

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe-Coote, S [South African Medical Research Council, Tygerberg (South Africa). Inst. for Electron Microscopy

    1983-09-01

    Radioimmune assay (RIA) was used to investigate the effect of fixatives on antigenicity of the hepatitis B surface antigen (HBsAg) and the effect of pronase on the elution of antibody (Ab) from the HBsAg-Ab complex. The effect of pronase on Ab elution was also tested on sections of kidney from a patient with the immune complex disease systemic lupus erythematosus (SLE). Immunoglobulin G (IgG) was located in pronase treated and untreated sections using the indirect immunoperoxidase technique. Glutareldehyde was shown to be the fixative of choice for studies involving HBsAg. All fixatives were shown to have less effect on antigenicity at 4/sup 0/C than at room temperature. Osmium tetroxide reduced antigenicity to one-third, even at 4/sup 0/C. RIA and SLE kidney section studies showed that Ab was eluted from immune complexes by pronase. Pre-fixation of the antigen (Ag) by glutaraldehyde appears to have no effect on the final elution, although fixation after pronase treatment seemed to enhance the elution effects. The availability of an RIA kit with HBsAg- and Ab-coated beads was of great assistance in evaluating reagents to be used in immunoperoxidase studies of HBsAg in immune complexes of patients with membranous nephropathy and Australia antigenaemia.

  6. Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test. A comparative study with /sup 125/I-labelled Clq binding and Raji-cell RIA tests

    Energy Technology Data Exchange (ETDEWEB)

    Casali, P; Bossus, A; Carpentier, N A; Lambert, P H [Hopital Cantonal Geneve (Switzerland)

    1977-01-01

    Bovine conglutinin was used in a solid-phase assay for the detection of immune complexes. In a first step, the tested serum sample was incubated in polypropylene tubes coated with conglutinin to allow C3-coated immune complexes to bind to solid-phase conglutinin. In a second step, the conglutinin-bound complexes were detected using an enzyme-conjugated or radiolabelled anti-immunoglobulin antibody. The conglutinin-binding (KgB) test did not suffer from the interference of DNA, heparin or endotoxins. Its limit of sensitivity for aggregated IgG was 3 ..mu..g/ml undiluted human serum. Immune complexes prepared in vitro using tetanus toxoid, or DNA, and corresponding antibodies in human sera could be detected at various antigen/antibody ratios and at antibody concentrations lower than 8 ..mu..g/ml. The KgB test allowed for the detection of immune complexes in sera from patients with systemic lupus erythematosus, rheumatoid arthritis, idiopathic vasculitis, leprosy and leukemia. These sera were also tested using the /sup 125/I-labelled Clq-binding activity (BA) test and the KgB test simultaneously, and a significant rank order correlation was observed. In patients with leukemia, a significant correlation was observed using three tests, KgB, /sup 125/I-labelled Clq BA and Raji-cell radioimmunoassay (RIA). Therefore, the KgB test appears as a simple and reproducible method, utilizing a very stable reagent, with a sensitivity and specificity comparable to the other tests studied and allowing for clinical application.

  7. 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

  8. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  9. Analysis of complex patterns of human exposure and immunity to Schistosomiasis mansoni: the influence of age, sex, ethnicity and IgE.

    Directory of Open Access Journals (Sweden)

    Angela Pinot de Moira

    2010-09-01

    Full Text Available Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field.In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG(4 to the tegumental antigen SmTAL1 (formerly Sm22.6, which itself was significantly related to resistance to reinfection.This study highlights the benefit of taking a multidisciplinary approach in complex field settings; it allows the ecology of a

  10. FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy.

    Directory of Open Access Journals (Sweden)

    Dawn L Cooper

    Full Text Available OBJECTIVE: The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC. We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA, associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. METHODS: FcγRIIIa/CD16 expression on CD14(low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease. Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. RESULTS: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002 with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001. The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003 and was significantly increased in EULAR non-responders compared to moderate (p = 0.01 or good responders (p = 0.003. FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. CONCLUSION: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy.

  11. FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis: Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy

    Science.gov (United States)

    Cooper, Dawn L.; Martin, Stephen G.; Robinson, James I.; Mackie, Sarah L.; Charles, Christopher J.; Nam, Jackie; Consortium, YEAR; Isaacs, John D.; Emery, Paul; Morgan, Ann W.

    2012-01-01

    Objective The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. Methods FcγRIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. Results Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. Conclusion Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy. PMID:22235253

  12. Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

    Science.gov (United States)

    Shashidharamurthy, R; Machiah, D; Bozeman, E N; Srivatsan, S; Patel, J; Cho, A; Jacob, J; Selvaraj, P

    2012-09-01

    Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

  13. Immunization Coverage

    Science.gov (United States)

    ... room/fact-sheets/detail/immunization-coverage","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... Plan Global Health Observatory (GHO) data - Immunization More information on vaccines and immunization News 1 in 10 ...

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

    Directory of Open Access Journals (Sweden)

    Savel’eva NN

    2016-12-01

    Full Text Available Introduction. Due to the high prevalence of chronic generalized periodontitis there is a need for a broader analysis of the causes and development of diseases, as well as the search for effective treatments for etiopathogenetical. The aim of this work was to study the effect of newly developed therapy on local immunity in patients CGP I and II severity with enterobiasis. Material & methods. The main group consisted of 32 people with СGP I degree and 60 people with СGP II severity who were treated according to our scheme. The control group consisted of 30 people with СGP I degree and 58 people with СGP II severity, treated with conventional treatment. The control group consisted of 30 people without periodontal disease and chronic diseases of other systems. All patients were studied the main group and the comparison group conducted a basic local therapeutic treatment of periodontal disease, including professional oral hygiene, temporary splinting of teeth, selective prishlifovyvanie teeth. For medical treatment of periodontal tissues using 0.05% - 0.2% solution of chlorhexidine bigluconate. Further treatment of patients of the main group carried out in 2 stages. At the first stage the main group received: irrigation and instillation of periodontal tissue in periodontal pockets antiseptic preparation "Dekasan" application keratoplastic drug "Katomas". Systemically administered drug tonic "Sage oil" probiotic "Kvertulin" immunomodulator "Erbisol". In the second phase, patients received: applications on the gums periodontal gel "Lizomukoid" systemically complex preparation "Оil extract from pumpkin seeds." All patients of the main group used toothpaste "Lacalut flora" and rinse "grapefruit". In the comparison group, patients received applications in periodontal pockets (drug Dalatsin C application to the gums (keratoplastic drug Aekol system - a probiotic Linex, immunomodulator "Echinacea compositum С". All patients with the comparison group

  15. Artificial Immune Networks: Models and Applications

    Directory of Open Access Journals (Sweden)

    Xian Shen

    2008-06-01

    Full Text Available Artificial Immune Systems (AIS, which is inspired by the nature immune system, has been applied for solving complex computational problems in classification, pattern rec- ognition, and optimization. In this paper, the theory of the natural immune system is first briefly introduced. Next, we compare some well-known AIS and their applications. Several representative artificial immune networks models are also dis- cussed. Moreover, we demonstrate the applications of artificial immune networks in various engineering fields.

  16. Glycoproteins in circulating immune complexes are biomarkers of patients with Indian PKDL: A study from endemic districts of West Bengal, India.

    Directory of Open Access Journals (Sweden)

    Priyank Jaiswal

    Full Text Available Post Kala Azar Dermal Leishmaniasis (PKDL occurs as dermal consequence of previous Visceral Leishmaniasis (VL infection and serves as an important reservoir for transmission of VL. Diagnosis of PKDL is often challenging for its symptomatic resemblance to other co-endemic diseases like Leprosy or Vitiligo. Parasitological examination by slit-skin smear and culture are the standard methods but lack high sensitivity. Thus, for efficient control of VL, reliable diagnostic and prognostic assay of PKDL are required.Previously, glycoproteins (9-OAcSA have been reported as promising biomarkers of Indian VL patients. However, till date, the status of glycans in Indian PKDL patients remains unexplored. Accordingly, in this study, the glyco-profile of PKDL Circulating Immune Complexes (CICs as compared to other cross diseases like Vitiligo and Leprosyhas been investigated. Further, a novel Glyco CIC assay has been developed for efficient Indian PKDL patient diagnosis.In the present study, 90 PKDL patients were enrolled from 3 VL endemic districts of West Bengal during 2015-16. Glycosylation profile of isolated CICs from sera of PKDL patients were initially analyzed through gradient SDS gel electrophoresis followed by PAS silver double staining, which revealed the presence of several glycan rich PKDL specific proteins of varying molecular weights. To further characterize the glyco-profile of acid dissociated affinity purified immuno-reactive antigens present in the CICs, glycosylation was demonstrated in these purified CIC antigens by DIG glycan differentiation kit with or without glycosidase as well as neuraminidase treatment. Diagnostic evaluation of the newly developed colorimetric Glyco CIC assay through Receiver Operating Characteristic (ROC curve analysis revealed excellent (0.99 AUC value as compared to other conventional serodiagnostic assays like PEG CIC, Parasite ELISA (IgG and IgM. Additionally, longitudinal monitoring of 18 PKDL patients further

  17. Immune Aspects of Female Infertility

    Directory of Open Access Journals (Sweden)

    Andrea Brazdova

    2016-05-01

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

  18. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

    Science.gov (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

    2012-04-30

    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II.

    Science.gov (United States)

    Quinn, Laura L; Williams, Luke R; White, Claire; Forrest, Calum; Zuo, Jianmin; Rowe, Martin

    2016-01-01

    The ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8(+) cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8(+) cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8(+) cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4(+) cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8(+) and CD4(+) T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner. Immune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8(+) T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8(+) T cells specific for

  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. Mammalian Gut Immunity

    Science.gov (United States)

    Chassaing, Benoit; Kumar, Manish; Baker, Mark T.; Singh, Vishal; Vijay-Kumar, Matam

    2016-01-01

    The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells) and hemopoietic (macrophages, dendritic cells, T-cells) origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a “love–hate relationship.” Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases. PMID:25163502

  2. Immunization with the Malaria Diversity-Covering Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 DiCo in Complex with Its Natural Ligand PfRon2 Does Not Improve the In Vitro Efficacy

    Directory of Open Access Journals (Sweden)

    Holger Spiegel

    2017-06-01

    Full Text Available The blood-stage malaria vaccine candidate Plasmodium falciparum apical membrane antigen 1 (PfAMA1 can induce strong parasite growth-inhibitory antibody responses in animals but has not achieved the anticipated efficacy in clinical trials. Possible explanations in humans are the insufficient potency of the elicited antibody responses, as well as the high degree of sequence polymorphisms found in the field. Several strategies have been developed to improve the cross-strain coverage of PfAMA1-based vaccines, whereas innovative concepts to increase the potency of PfAMA1-specific IgG responses have received little attention even though this may be an essential requirement for protective efficacy. A previous study has demonstrated that immunization with a complex of PyAMA1 and PyRON2, a ligand with an essential functional role in erythrocyte invasion, leads to protection from lethal Plasmodium yoelli challenge in an animal model and suggested to extend this strategy toward improved strain coverage by using multiple PfAMA1 alleles in combination with PfRon2L. As an alternative approach along this line, we decided to use PfRon2L in combination with three PfAMA1 diversity covering variants (DiCo to investigate the potential of this complex to induce more potent parasite growth inhibitory immune response in combination with better cross-strain-specific efficacy. Within the limits of the study design, the ability of the PfAMA1 DiCo-Mix to induce cross-strain-specific antibodies was not affected in all immunization groups, but the DiCo–PfRon2L complexes did not improve the potency of PfAMA1-specific IgG responses.

  3. G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses

    Science.gov (United States)

    2013-01-01

    Background Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo. Methods We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice. Results We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation. Conclusions Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF. PMID:24279871

  4. Innate immunity

    African Journals Online (AJOL)

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

  5. Childhood immunization

    Science.gov (United States)

    Romain, Sandra; Schillaci, Michael A.

    2009-01-01

    ABSTRACT OBJECTIVE To examine childhood immunization levels relative to the number of family physicians, pediatricians, and public health nurses in Ontario. DESIGN Retrospective comparative analysis of publicly available data on immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. SETTING Ontario. PARTICIPANTS Seven-year-old children, family physicians, pediatricians, and public health nurses in Ontario. MAIN OUTCOME MEASURES The association between immunization coverage levels and the relative number of family physicians, pediatricians, and public health nurses. RESULTS We found correlations between immunization coverage levels and the relative number (ie, per 1000 Ontario residents) of family physicians (ρ = 0.60) and pediatricians (ρ = 0.70) and a lower correlation with the relative number of public health nurses (ρ = 0.40), although none of these correlations was significant. A comparison of temporal trends illustrated that variation in the relative number of family physicians and pediatricians in Ontario was associated with similar variation in immunization coverage levels. CONCLUSION Increasing the number of family physicians and pediatricians might help to boost access to immunizations and perhaps other components of cost-saving childhood preventive care. PMID:19910599

  6. Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.

    Directory of Open Access Journals (Sweden)

    Samuel O Pine

    2011-04-01

    Full Text Available The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732. Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36 or Ad5-seropositive (titer >200; n = 34. Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes. At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008, and significantly more IP-10 (p = 0.0009, IL-2 (p = 0.006 and IL-10 (p = 0.05 in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these

  7. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

  8. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  9. Immunizing Adults

    Centers for Disease Control (CDC) Podcasts

    Vaccines aren’t just for kids; adults also need to get immunized. Overall, far too many people 19 years and older aren’t getting the vaccines they need and remain unprotected. In this podcast, Dr. Walter Williams discuss the importance of adults being fully vaccinated.

  10. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...

  11. Lack of immune potentiation by complexing HBsAg in a heat-inactivated hepatitis B vaccine with antibody in hepatitis B immunoglobulin

    NARCIS (Netherlands)

    Lelie, P. N.; van Amelsfoort, P. J.; Martine de Groot, C. S.; Bakker, E.; Schaasberg, W.; Niessen, J. C.; Reesink, H. W.

    1989-01-01

    In a randomized, dose-response study among 305 health care workers, we examined whether the immunogenicity of a heat-inactivated hepatitis B vaccine could be enhanced when HBsAg was complexed by anti-HBs contained in hepatitis B immunoglobulin either at equivalent proportions or at 10-fold antigen

  12. Chicken major histocompatibility complex-encoded B-G antigens are found on many cell types that are important for the immune system

    DEFF Research Database (Denmark)

    Salomonsen, J; Dunon, D; Skjødt, K

    1991-01-01

    B-G antigens are a polymorphic multigene family of cell surface molecules encoded by the chicken major histocompatibility complex (MHC). They have previously been described only on cells of the erythroid lineage. By using flow cytometry, section staining, and immunoprecipitation with monoclonal a...

  13. Curating the innate immunity interactome.

    LENUS (Irish Health Repository)

    Lynn, David J

    2010-01-01

    The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http:\\/\\/www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.

  14. Immunization of Epidemics in Multiplex Networks

    Science.gov (United States)

    Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

    2014-01-01

    Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks. PMID:25401755

  15. Immunization of epidemics in multiplex networks.

    Science.gov (United States)

    Zhao, Dawei; Wang, Lianhai; Li, Shudong; Wang, Zhen; Wang, Lin; Gao, Bo

    2014-01-01

    Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted) immunization and layer node-based random (targeted) immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER) random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF) networks.

  16. Immunization of epidemics in multiplex networks.

    Directory of Open Access Journals (Sweden)

    Dawei Zhao

    Full Text Available Up to now, immunization of disease propagation has attracted great attention in both theoretical and experimental researches. However, vast majority of existing achievements are limited to the simple assumption of single layer networked population, which seems obviously inconsistent with recent development of complex network theory: each node could possess multiple roles in different topology connections. Inspired by this fact, we here propose the immunization strategies on multiplex networks, including multiplex node-based random (targeted immunization and layer node-based random (targeted immunization. With the theory of generating function, theoretical analysis is developed to calculate the immunization threshold, which is regarded as the most critical index for the effectiveness of addressed immunization strategies. Interestingly, both types of random immunization strategies show more efficiency in controlling disease spreading on multiplex Erdös-Rényi (ER random networks; while targeted immunization strategies provide better protection on multiplex scale-free (SF networks.

  17. The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood

    DEFF Research Database (Denmark)

    Nielsen, C H; Antonsen, S; Matthiesen, S H

    1997-01-01

    The binding of immune complexes (IC) to polymorphonuclear leukocytes (PMN) and the consequent respiratory burst (RB) were investigated in whole blood cell preparations suspended in 75% human serum, using flow cytometry. Blockade of the complement receptor (CR)1 receptor sites for C3b on whole blood...... cells using the monoclonal antibody (mAb) 3D9 resulted in a 1.9-fold increase in the IC-elicited PMN RB after 5 min of incubation, rising to 3.1-fold after 40 min. This enhancement was not due to increased IC deposition on PMN. Blockade of CR3 abrogated the mAb 3D9-induced rise in RB activity...

  18. The commensal microbiota drives immune homeostasis

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta

    2012-03-01

    Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

  19. 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.

  20. 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

  1. Cellular immune responses to ESAT-6 discriminate between patients with pulmonary disease due to Mycobacterium avium complex and those with pulmonary disease due to Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Lein, A D; von Reyn, C F; Ravn, P

    1999-01-01

    ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of the Mycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-gamma) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary...... disease due to either Mycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-gamma responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0...... (0%) of 8 controls. Significant IFN-gamma responses to M. tuberculosis purified protein derivative were detected in 23 (85%) of 27 M. tuberculosis disease patients, 2 (25%) of 8 MAC disease patients, and 5 (63%) of 8 healthy controls. M. avium sensitin was recognized in 24 (89%) of 27 M. tuberculosis...

  2. The most common friend first immunization

    International Nuclear Information System (INIS)

    Nian Fu-Zhong; Hu Cha-Sheng

    2016-01-01

    In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts–Strogatz (WS) small-world network model and the Barabsi–Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. (paper)

  3. 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 & ...

  4. 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 ...

  5. 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 & ...

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

    OpenAIRE

    Nurmasitoh, Titis

    2015-01-01

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

  7. Dynamics of immune system vulnerabilities

    Science.gov (United States)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  8. Pregnancy immunology: decidual immune cells.

    Science.gov (United States)

    Sanguansermsri, Donruedee; Pongcharoen, Sutatip

    2008-01-01

    Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.

  9. Insect Immunity: The Post-Genomic Era

    OpenAIRE

    Bangham, Jenny; Jiggins, Frank; Lemaitre, Bruno

    2006-01-01

    Insects have a complex and effective immune system, many components of which are conserved in mammals. But only in the last decade have the molecular mechanisms that regulate the insect immune response--and their relevance to general biology and human immunology--become fully appreciated. A meeting supported by the Centre National de la Récherche Scientifique (France) was held to bring together the whole spectrum of researchers working on insect immunity. The meeting addressed diverse aspects...

  10. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  11. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2013-01-01

    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  12. 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.

  13. Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire

    Science.gov (United States)

    Miracle, A. L.; Anderson, M. K.; Litman, R. T.; Walsh, C. J.; Luer, C. A.; Rothenberg, E. V.; Litman, G. W.

    2001-01-01

    Cartilaginous fish express canonical B and T cell recognition genes, but their lymphoid organs and lymphocyte development have been poorly defined. Here, the expression of Ig, TCR, recombination-activating gene (Rag)-1 and terminal deoxynucleosidase (TdT) genes has been used to identify roles of various lymphoid tissues throughout development in the cartilaginous fish, Raja eglanteria (clearnose skate). In embryogenesis, Ig and TCR genes are sharply up-regulated at 8 weeks of development. At this stage TCR and TdT expression is limited to the thymus; later, TCR gene expression appears in peripheral sites in hatchlings and adults, suggesting that the thymus is a source of T cells as in mammals. B cell gene expression indicates more complex roles for the spleen and two special organs of cartilaginous fish-the Leydig and epigonal (gonad-associated) organs. In the adult, the Leydig organ is the site of the highest IgM and IgX expression. However, the spleen is the first site of IgM expression, while IgX is expressed first in gonad, liver, Leydig and even thymus. Distinctive spatiotemporal patterns of Ig light chain gene expression also are seen. A subset of Ig genes is pre-rearranged in the germline of the cartilaginous fish, making expression possible without rearrangement. To assess whether this allows differential developmental regulation, IgM and IgX heavy chain cDNA sequences from specific tissues and developmental stages have been compared with known germline-joined genomic sequences. Both non-productively rearranged genes and germline-joined genes are transcribed in the embryo and hatchling, but not in the adult.

  14. Linear ubiquitination in immunity.

    Science.gov (United States)

    Shimizu, Yutaka; Taraborrelli, Lucia; Walczak, Henning

    2015-07-01

    Linear ubiquitination is a post-translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types. © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  15. Early nutrition and immunity - progress and perspectives

    NARCIS (Netherlands)

    Calder, Philip C.; Krauss-Etschmann, Susanne; de Jong, Esther C.; Dupont, Christophe; Frick, Julia-Stefanie; Frokiaer, Hanne; Heinrich, Joachim; Garn, Holger; Koletzko, Sibylle; Lack, Gideon; Mattelio, Gianluca; Renz, Harald; Sangild, Per T.; Schrezenmeir, Jürgen; Stulnig, Thomas M.; Thymann, Thomas; Wold, Agnes E.; Koletzko, Berthold

    2006-01-01

    The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and

  16. Immunity to gastrointestinal nematode infections

    DEFF Research Database (Denmark)

    Sorobetea, D.; Svensson Frej, M.; Grencis, R.

    2018-01-01

    Numerous species of nematodes have evolved to inhabit the gastrointestinal tract of animals and humans, with over a billion of the world's population infected with at least one species. These large multicellular pathogens present a considerable and complex challenge to the host immune system give...

  17. Immune System Quiz

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

  18. 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 ...

  19. Immunizations and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Immunizations Immunizations and African Americans African American adults are less ... 19 to 35 months had comparable rates of immunization. African American women are as likely to have ...

  20. Instant Childhood Immunization Schedule

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  1. Immunization Action Coalition

    Science.gov (United States)

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Favorites ACIP Recommendations Package Inserts Additional Immunization Resources Photos Adult Vaccination Screening Checklists Ask the ...

  2. Innate Immunity and Breast Milk.

    Science.gov (United States)

    Cacho, Nicole Theresa; Lawrence, Robert M

    2017-01-01

    Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant's intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant's gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

  3. Innate Immunity and Breast Milk

    Directory of Open Access Journals (Sweden)

    Nicole Theresa Cacho

    2017-05-01

    Full Text Available Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system

  4. Local and systemic tumor immune dynamics

    Science.gov (United States)

    Enderling, Heiko

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

  5. Innate Immune Responses in Leprosy

    Science.gov (United States)

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

    2018-01-01

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

  6. 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, ” ...

  7. The Smc5/6 Complex Restricts HBV when Localized to ND10 without Inducing an Innate Immune Response and Is Counteracted by the HBV X Protein Shortly after Infection

    Science.gov (United States)

    Daffis, Stephane; Ramakrishnan, Dhivya; Burdette, Dara; Peiser, Leanne; Salas, Eduardo; Ramos, Hilario; Yu, Mei; Cheng, Guofeng; Strubin, Michel; Delaney IV, William E.; Fletcher, Simon P.

    2017-01-01

    The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions. We determined that Smc5/6 localizes with Nuclear Domain 10 (ND10) in PHH. Co-localization has functional implications since depletion of ND10 structural components alters the nuclear distribution of Smc6 and induces HBV gene expression in the absence of HBx. We also found that HBV infection and replication does not induce a prominent global host transcriptional response in PHH, either shortly after infection when Smc5/6 is present, or at later times post-infection when Smc5/6 has been degraded. Notably, HBV and an HBx-negative virus establish high level infection in PHH without inducing expression of interferon-stimulated genes or production of interferons or other cytokines. Our study also revealed that Smc5/6 is degraded in the majority of infected PHH by the time cccDNA transcription could be detected and that HBx RNA is present in cell culture-derived virus preparations as well as HBV patient plasma. Collectively, these data indicate that Smc5/6 is an intrinsic antiviral restriction factor that suppresses HBV transcription when localized to ND10 without inducing a detectable innate immune response. Our data also suggest that HBx protein may be initially expressed by delivery of extracellular HBx RNA into HBV-infected cells. PMID:28095508

  8. CD1d-restricted IFN-γ-secreting NKT cells promote immune complex-induced acute lung injury by regulating macrophage-inflammatory protein-1α production and activation of macrophages and dendritic cells.

    Science.gov (United States)

    Kim, Ji Hyung; Chung, Doo Hyun

    2011-02-01

    Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d(-/-) and Jα18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes, whereas levels in B6 mice were greater and were increased further by α-galactosyl ceramide. IFN-γ and MIP-1α production in the lungs was greater in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-γ-, MIP-1α-, or FcγR-deficient NKT cells into CD1d(-/-) mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-γR-deficient NKT cells enhanced MIP-1α production and cell recruitment in the lungs of CD1d(-/-) or CD1d(-/-)IFN-γ(-/-) mice, but to a lesser extent than WT NKT cells. This suggests that IFN-γ-producing NKT cells enhance MIP-1α production in both an autocrine and a paracrine manner. IFN-γ-deficient NKT cells induced less IL-1β and TNF-α production by alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-γ-producing NKT cells promote IC-ALI by producing MIP-1α and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells.

  9. Immune interactions in endometriosis

    Science.gov (United States)

    Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G

    2011-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease. PMID:21895474

  10. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk

    2008-01-01

    Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

  11. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  12. The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket.

    Science.gov (United States)

    McNamara, K B; van Lieshout, E; Simmons, L W

    2014-06-01

    Trans-generational immune priming is the transmission of enhanced immunity to offspring following a parental immune challenge. Although within-generation increased investment into immunity demonstrates clear costs on reproductive investment in a number of taxa, the potential for immune priming to impact on offspring reproductive investment has not been thoroughly investigated. We explored the reproductive costs of immune priming in a field cricket, Teleogryllus oceanicus. To assess the relative importance of maternal and paternal immune status, mothers and fathers were immune-challenged with live bacteria or a control solution and assigned to one of four treatments in which one parent, neither or both parents were immune-challenged. Families of offspring were reared to adulthood under a food-restricted diet, and approximately 10 offspring in each family were assayed for two measures of immunocompetence. We additionally quantified offspring reproductive investment using sperm viability for males and ovary mass for females. We demonstrate that parental immune challenge has significant consequences for the immunocompetence and, in turn, reproductive investment of their male offspring. A complex interaction between maternal and paternal immune status increased the antibacterial immune response of male offspring. This increased immune response was associated with a reduction in son's sperm viability, implicating a trans-generational resource trade-off between investment into immunocompetence and reproduction. Our data also show that these costs are sexually dimorphic, as daughters did not demonstrate a similar increase in immunity, despite showing a reduction in ovary mass. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  13. Senescence in immune priming and attractiveness in a beetle.

    Science.gov (United States)

    Daukšte, J; Kivleniece, I; Krama, T; Rantala, M J; Krams, I

    2012-07-01

    Age-related decline in immune activity is referred to as immunosenescence and has been observed for both the adaptive immune response of vertebrates and the innate immune system of invertebrates. Because maintaining a basic level of immune defence and mounting an immune response is costly, optimal investment in immune function should vary over a wide range of individual states such as the individual's age. In this study, we tested whether the immune response and immunological priming within individuals become less efficient with age using mealworm beetles, Tenebrio molitor, as a model organism. We also tested whether ageing and immunological priming affected the odours produced by males. We found that young males of T. molitor were capable of mounting an immune response a sterile nylon monofilament implant with the potential to exhibit a simple form of immune memory through mechanisms of immune priming. Older males did not increase their immune response to a second immune challenge, which negatively affected their sexual attractiveness and remaining life span. Our results indicate that the immune system of older males in T. molitor is less effective, suggesting complex evolutionary trade-offs between ageing, immune response and sexual attractiveness. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  14. Using network properties to evaluate targeted immunization algorithms

    Directory of Open Access Journals (Sweden)

    Bita Shams

    2014-09-01

    Full Text Available Immunization of complex network with minimal or limited budget is a challenging issue for research community. In spite of much literature in network immunization, no comprehensive research has been conducted for evaluation and comparison of immunization algorithms. In this paper, we propose an evaluation framework for immunization algorithms regarding available amount of vaccination resources, goal of immunization program, and time complexity. The evaluation framework is designed based on network topological metrics which is extensible to all epidemic spreading model. Exploiting evaluation framework on well-known targeted immunization algorithms shows that in general, immunization based on PageRank centrality outperforms other targeting strategies in various types of networks, whereas, closeness and eigenvector centrality exhibit the worst case performance.

  15. 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.

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

    Science.gov (United States)

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

    2017-08-01

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

  17. Immune System (For Parents)

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario The immune system, which is made up ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  18. Immunity's ancient arms

    OpenAIRE

    Litman, Gary W.; Cannon, John P.

    2009-01-01

    Diverse receptors on two types of cell mediate adaptive immunity in jawed vertebrates. In the lamprey, a jawless vertebrate, immunity is likewise compartmentalized but the molecular mechanics are very different.

  19. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  20. Aging changes in immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. AGING CHANGES AND THEIR EFFECTS ON THE IMMUNE SYSTEM ...

  1. 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.

  2. The Commensal Microbiota Drives Immune Homeostasis

    OpenAIRE

    Arrieta, Marie-Claire; Finlay, Barton Brett

    2012-01-01

    For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use t...

  3. Immune reconstitution inflammatory syndrome due to Mycobacterium avium complex successfully followed up using 18 F-fluorodeoxyglucose positron emission tomography-computed tomography in a patient with human immunodeficiency virus infection: A case report

    International Nuclear Information System (INIS)

    Namkoong, Ho; Fujiwara, Hiroshi; Ishii, Makoto; Yagi, Kazuma; Haraguchi, Mizuha; Matsusaka, Masako; Suzuki, Shoji; Asakura, Takanori; Asami, Takahiro; Saito, Fumitake; Fukunaga, Koichi; Tasaka, Sadatomo; Betsuyaku, Tomoko; Hasegawa, Naoki

    2015-01-01

    In human immunodeficiency virus (HIV)-infected patients, immune reconstitution inflammatory syndrome (IRIS) due to nontuberculous mycobacteria (NTM) infection is one of the most difficult types of IRIS to manage. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) has been suggested as a useful tool for evaluating the inflammatory status of HIV-infected patients. We present the first case of Mycobacterium avium complex (MAC)-associated IRIS (MAC-IRIS) that was successfully followed up using 18 F-FDG PET/CT. A 44-year-old homosexual Japanese man was referred to our hospital with fever and dyspnea. He was diagnosed with Pneumocystis jiroveci pneumonia and found to be HIV positive. After the initiation of combined antiretroviral therapy (cART), the patient’s mediastinal and bilateral hilar lymphadenopathy gradually enlarged, and bilateral infiltrates appeared in the upper lung fields. 18 F-FDG PET/CT was performed five months after the initiation of cART and showed intense accumulation of fluorodeoxyglucose (FDG) corresponding to the lesions of infiltration as well as the mediastinal and bilateral hilar lymphadenopathy. A bronchial wash culture and pathology findings led to a diagnosis of MAC-IRIS. Anti-mycobacterial chemotherapy with rifampicin, ethambutol, clarithromycin, and levofloxacin was started. One year after the chemotherapy was initiated, there was a significant reduction in FDG uptake in the area of the lesions except in the mediastinal lymph node. This implied incomplete resolution of the MAC-IRIS-related inflammation. Anti-mycobacterial chemotherapy was continued because of the residual lesion. To date, the patient has not experienced a recurrence of MAC-IRIS, a period of nine months. We present a case of MAC-IRIS in an HIV-infected patient whose disease activity was successfully followed up using 18 F-FDG PET/CT. Our data suggest that 18 F-FDG PET/CT is useful for evaluating the disease activity of NTM-IRIS and

  4. Immune chromatography: a quantitative radioimmunological assay

    International Nuclear Information System (INIS)

    Davis, J.W.; Demetriades, M.; Bowen, J.M.

    1984-01-01

    Immune chromatography, a radioimmunological binding assay, employs paper chromatography to separate immune complexes from free antigen and antibodies. During chromatography free antigen and antibodies become distributed throughout the paper, while immune complexes remain near the bottoms of the strips. The chromatographic differences can be made quantitative by using either iodinated antigens or antibodies. Under these conditions nanogram quantities of antigen can be detected or antibodies in sera diluted several 1000-fold. The immune chromatography assay can also be performed as an indirect assay, since the paper strips are cut from nitrocellulose paper. In this case the immune components are absorbed by the paper during chromatography. Antigen is then detected with an iodinated second antibody. The indirect immune chromatography assay is particularly useful for identifying different sera that react with the same antigen. Reaction with the first serum before chromatography reduces the amount of antigen available to the second serum following chromatography. In addition to characterizing the immune chromatography procedure, we discuss the possible applications of chromatography assays for the quantitation of other types of molecular binding interactions. (Auth.)

  5. The Immune Epitope Database 2.0

    DEFF Research Database (Denmark)

    Hoof, Ilka; Vita, R; Zarebski, L

    2010-01-01

    The Immune Epitope Database (IEDB, www.iedb.org) provides a catalog of experimentally characterized B and T cell epitopes, as well as data on Major Histocompatibility Complex (MHC) binding and MHC ligand elution experiments. The database represents the molecular structures recognized by adaptive...... immune receptors and the experimental contexts in which these molecules were determined to be immune epitopes. Epitopes recognized in humans, nonhuman primates, rodents, pigs, cats and all other tested species are included. Both positive and negative experimental results are captured. Over the course...

  6. Adaptive Immunity to Cryptococcus neoformans Infections

    Directory of Open Access Journals (Sweden)

    Liliane Mukaremera

    2017-11-01

    Full Text Available The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the host immune system is a key determinant of the disease outcome. The species C. neoformans causes the majority of human infections, and therefore almost all immunological studies focused on C. neoformans infections. Thus, this review presents current understanding on the role of adaptive immunity during C. neoformans infections both in humans and in animal models of disease.

  7. Acquired and innate immunity to polyaromatic hydrocarbons

    International Nuclear Information System (INIS)

    Yusuf, Nabiha; Timares, Laura; Seibert, Megan D.; Xu Hui; Elmets, Craig A.

    2007-01-01

    Polyaromatic hydrocarbons are ubiquitous environmental pollutants that are potent mutagens and carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by Ah receptor genes and by genes located within the major histocompatibility complex. CD8 + T cells are effector cells in the response, whereas CD4 + T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic hydrocarbons are less likely to develop tumors when subjected to a polyaromatic hydrocarbon skin carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic hydrogen skin tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical carcinogens, play an active role in the prevention of chemical skin carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause tumors may be a productive approach to the prevention of tumors caused by these agents

  8. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  9. The Immune System Game

    Science.gov (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  10. 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 ...

  11. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  12. 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.

  13. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  14. 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.

  15. Measuring polio immunity to plan immunization activities.

    Science.gov (United States)

    Voorman, Arend; Lyons, Hil M

    2016-11-21

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

  16. Coordinate expression of activating Fc gamma receptors I and III and inhibiting Fc gamma receptor type II in the determination of joint inflammation and cartilage destruction during immune complex-mediated arthritis.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Blom, A.B.; Holthuysen, A.E.M.; Boross, P.; Roth, J.; Verbeek, S.; Lent, P.L.E.M. van; Berg, W.B. van den

    2003-01-01

    OBJECTIVE: To study the role of the activating Fc gamma receptor types I and III (Fc gamma RI and Fc gamma RIII, respectively) and the inhibiting Fc gamma receptor II (Fc gamma RII) in inflammation and in various aspects of cartilage destruction during arthritis that is solely induced by immune

  17. Regulation of TGFβ in the immune system: An emerging role for integrins and dendritic cells

    OpenAIRE

    Worthington, John J.; Fenton, Thomas M.; Czajkowska, Beata I.; Klementowicz, Joanna E.; Travis, Mark A.

    2012-01-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell?cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-? (TGF-?). TGF-? is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells ...

  18. Nutritional strategies to optimize dairy cattle immunity.

    Science.gov (United States)

    Sordillo, L M

    2016-06-01

    Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important infectious and metabolic diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system can have a reciprocal effect on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious dairy foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to compromise the immune system in transition cows will be discussed. A better understanding of the linkages between nutrition and immunity may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  20. Metabolic immune restraints: implications for anticancer vaccines.

    Science.gov (United States)

    Mocellin, Simone

    2010-01-01

    Metabolic immune restraints belong to a highly complex network of molecular mechanisms underlying the failure of naturally occurring and therapeutically induced immune responses against cancer. In the light of the disappointing results yielded so far with anticancer vaccines in the clinical setting, the dissection of the cascade of molecular events leading to tumor immune escape appears the most promising way to develop more effective immunotherapeutic strategies. Here we review the significant advances recently made in the understanding of the tumor-specific metabolic features that contribute to keep malignant cells from being recognized and destroyed by immune effectors. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits and thus to enhance the effectiveness of anticancer vaccines.

  1. Viral subversion of the immune system

    International Nuclear Information System (INIS)

    Gillet, L.; Vanderplasschen, A.

    2005-01-01

    The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines. (author)

  2. Phospholipase C-β in immune cells.

    Science.gov (United States)

    Kawakami, Toshiaki; Xiao, Wenbin

    2013-09-01

    Great progress has recently been made in structural and functional research of phospholipase C (PLC)-β. We now understand how PLC-β isoforms (β1-β4) are activated by GTP-bound Gαq downstream of G protein-coupled receptors. Numerous studies indicate that PLC-βs participate in the differentiation and activation of immune cells that control both the innate and adaptive immune systems. The PLC-β3 isoform also interplays with tyrosine kinase-based signaling pathways, to inhibit Stat5 activation by recruiting the protein-tyrosine phosphatase SHP-1, with which PLC-β3 and Stat5 form a multi-molecular signaling platform, named SPS complex. The SPS complex has important regulatory roles in tumorigenesis and immune cell activation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. CMV immune evasion and manipulation of the immune system with aging.

    Science.gov (United States)

    Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

    2017-06-01

    Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

  4. Reinfection immunity in schistosomiasis

    International Nuclear Information System (INIS)

    Kamiya, Haruo

    1987-01-01

    Schistosomiasis is one of the most important parasitic diseases in the world, especially in endemic areas of developing countries. This situation has prompted parasitologist to attempt intensive researches on immune mechanisms, especially those of reinfection immunity associated with eliminating challenge infection. The current knowledge of reinfection immunity against Schistosoma spp. infection was therefore reviewed briefly and discussed with special reference to our data on protective immune responses induced by radiation-attenuated cercarial infection. A recently developed technique of compressed organ autoradiography (COA) has contributed to assessing parasite attrition in immune animals following challenge infection. Our study using COA has demonstrated that major attrition of schistosomula from challenge infection occurs in the skin of CBA/Ca mice vaccinated with 20 Krad gamma radiation-attenuated cercariae of S. mansoni, while in both lungs and liver of similarly vaccinated guinea pig model. Furthermore, gamma-irradiation to cercariae affected their migration potential and surface-antigen profiles. The immunizing stimuli of gamma radiation-attenuated cercariae profoundly affected the expression of responsiveness in vaccinated animals. The change in antigenic profiles and migration potential of those vaccinating population was discussed in relation to the kinetics of reinfection immunity induced in vaccinated amimal models. These works might provide a base line data to develop a practical vaccine for schistosomiasis using defined antigens. It must be emphasized that these vaccines could serve as a practical prophylactic measure for schistosomiasis in the endemic areas, even if the vaccines fail to induce sterilizing immunity. (author). 141 refs

  5. Ethics of Immunization

    NARCIS (Netherlands)

    Verweij, M.F.; Quah, S.R.; Cockerham, W.C.

    2017-01-01

    Collective immunization can be highly effective in protecting societies against infectious diseases, but policy decisions about both the character and the content of immunization policies require ethical justification. This article offers an overview of ethical aspects that should be taken into

  6. Immunity and skin cancer

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  7. Immunizations. Position Statement. Revised

    Science.gov (United States)

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  8. Disparity in childhood immunizations

    NARCIS (Netherlands)

    Lemstra, Mark; Neudorf, Cory; Opondo, Johnmark; Toye, Jennifer; Kurji, Ayisha; Kunst, Anton; Tournier, Ceal

    2007-01-01

    BACKGROUND: Incomplete immunization coverage is common in low-income families and Aboriginal children in Canada. OBJECTIVE: To determine whether child immunization coverage rates at two years of age were lower in low-income neighbourhoods of Saskatoon, Saskatchewan. METHODS: Parents who were and

  9. Neural circuitry and immunity

    Science.gov (United States)

    Pavlov, Valentin A.; Tracey, Kevin J.

    2015-01-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine. PMID:26512000

  10. Honeybee immunity and colony losses

    Directory of Open Access Journals (Sweden)

    F. Nazzi

    2014-10-01

    Full Text Available The decline of honeybee colonies and their eventual collapse is a widespread phenomenon in the Northern hemisphere of the globe, which severely limits the beekeeping industry. This dramatic event is associated with an enhanced impact of parasites and pathogens on honeybees, which is indicative of reduced immunocompetence. The parasitic mite Varroa destructor and the vectored viral pathogens appear to play a key-role in the induction of this complex syndrome. In particular, the Deformed Wing Virus (DWV is widespread and is now considered, along with Varroa, one of the major causes of bee colony losses. Several lines of evidence indicate that this mite/DWV association severely affects the immune system of honeybees and makes them more sensitive to the action of other stress factors. The molecular mechanisms underpinning these complex interactions are currently being investigated and the emerging information has allowed the development of a new functional model, describing how different stress factors may synergistically concur in the induction of bee immune alteration and health decline. This provides a new logical framework in which to interpret the proposed multifactorial origin of bee colony losses and sets the stage for a more comprehensive and integrated analysis of the effect that multiple stress agents may have on honeybees.

  11. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

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

  14. National Network for Immunization Information

    Science.gov (United States)

    ... American College of Obstetricians and Gynecologists . © Copyright National Network for Immunization Information. The information contained in the National Network for Immunization Information Web site should not be ...

  15. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Trauma equals danger—damage control by the immune system

    Science.gov (United States)

    Stoecklein, Veit M.; Osuka, Akinori; Lederer, James A.

    2012-01-01

    Traumatic injuries induce a complex host response that disrupts immune system homeostasis and predisposes patients to opportunistic infections and inflammatory complications. The response to injuries varies considerably by type and severity, as well as by individual variables, such as age, sex, and genetics. These variables make studying the impact of trauma on the immune system challenging. Nevertheless, advances have been made in understanding how injuries influence immune system function as well as the immune cells and pathways involved in regulating the response to injuries. This review provides an overview of current knowledge about how traumatic injuries affect immune system phenotype and function. We discuss the current ideas that traumatic injuries induce a unique type of a response that may be triggered by a combination of endogenous danger signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally, we review and propose strategies for redirecting injury responses to help restore immune system homeostasis. PMID:22654121

  17. Nutrition, immune function and health of dairy cattle

    DEFF Research Database (Denmark)

    Ingvartsen, Klaus Lønne; Moyes, Kasey

    2013-01-01

    not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our......) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where...... the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response...

  18. Immunity: Insect Immune Memory Goes Viral.

    Science.gov (United States)

    Ligoxygakis, Petros

    2017-11-20

    Adaptive memory in insect immunity has been controversial. In this issue, Andino and co-workers propose that acquisition of viral sequences in the host genome gives rise to anti-sense, anti-viral piRNAs. Such sequences can be regarded as both a genomic archive of past infections and as an armour of potential heritable memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota

    OpenAIRE

    Feng, Ting; Elson, Charles O.; Cong, Yingzi

    2010-01-01

    The intestine is the home to a vast diversity of microbiota and a complex of mucosal immune system. Multiple regulatory mechanisms control host immune responses to microbiota and maintain intestinal immune homeostasis. This mini review will provide evidence indicating a Treg cell-IgA axis and such axis playing a major role in maintenance of intestinal homeostasis.

  20. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  1. Immunity to parasitic infection

    National Research Council Canada - National Science Library

    Lamb, Tracey J

    2012-01-01

    .... Often endemic in developing countries many parasitic diseases are neglected in terms of research funding and much remains to be understood about parasites and the interactions they have with the immune system...

  2. Exercise and immunity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007165.htm Exercise and immunity To use the sharing features on ... take a daily walk or follow a simple exercise routine a few times a week. Exercise helps ...

  3. 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.

  4. [Exosomes and Immune Cells].

    Science.gov (United States)

    Seo, Naohiro

    2017-05-01

    In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.

  5. Immune responses to metastases

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  6. Immunity of international organizations

    CERN Document Server

    Schrijver, Nico

    2015-01-01

    Immunity rules are part and parcel of the law of international organizations. It has long been accepted that international organizations and their staff need to enjoy immunity from the jurisdiction of national courts. However, it is the application of these rules in practice that increasingly causes controversy. Claims against international organizations are brought before national courts by those who allegedly suffer from their activities. These can be both natural and legal persons such as companies. National courts, in particular lower courts, have often been less willing to recognize the immunity of the organization concerned than the organization s founding fathers. Likewise, public opinion and legal writings frequently criticize international organizations for invoking their immunity and for the lack of adequate means of redress for claimants. It is against this background that an international conference was organized at Leiden University in June 2013. A number of highly qualified academics and practit...

  7. Vaccines and immunization

    African Journals Online (AJOL)

    Prof Ezechukwu

    vaccines for malaria and HIV infection. Despite the ... decades, effective vaccines against the major causes of ... challenge antibodies, specific helper and effector T lymphocytes ... materials to produced immunity to a disease. It was originally ...

  8. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  9. Immunization in pregnancy.

    Science.gov (United States)

    Gruslin, Andrée; Steben, Marc; Halperin, Scott; Money, Deborah M; Yudin, Mark H

    2009-11-01

    To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization, risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to June 2008 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). (1) All women of childbearing age should be evaluated for the possibility of pregnancy before immunization. (III-A). (2) Health care providers should obtain a relevant immunization history from all women accessing prenatal care. (III-A). (3) In general, live and/or live-attenuated virus vaccines should not be administered during pregnancy, as there is a, largely theoretical, risk to the fetus. (II-3B). (4) Women who have inadvertently received immunization with live or live-attenuated vaccines during pregnancy should not be counselled to terminate the pregnancy because of a teratogenic risk. (II-2A). (5) Non-pregnant women immunized with a live or live-attenuated vaccine should be counselled to delay pregnancy for at least four weeks. (III-B). (6) Inactivated viral vaccines, bacterial vaccines, and toxoids can be used safely in pregnancy. (II-1A). (7) Women who are breastfeeding can still be immunized (passive-active immunization, live or killed

  10. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  11. Adults Need Immunizations, Too!

    Centers for Disease Control (CDC) Podcasts

    2012-03-19

    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.  Created: 3/19/2012 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 3/19/2012.

  12. Immune dysfunction in cirrhosis

    Science.gov (United States)

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  13. Immunity to Fish Rhabdoviruses

    OpenAIRE

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabd...

  14. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  15. Centrality measures for immunization of weighted networks

    Directory of Open Access Journals (Sweden)

    Mohammad Khansari

    2016-03-01

    Full Text Available Effective immunization of individual communities with minimal cost in vaccination has made great discussion surrounding the realm of complex networks. Meanwhile, proper realization of relationship among people in society and applying it to social networks brings about substantial improvements in immunization. Accordingly, weighted graph in which link weights represent the intensity and intimacy of relationships is an acceptable approach. In this work we employ weighted graphs and a wide variety of weighted centrality measures to distinguish important individuals in contagion of diseases. Furthermore, we propose new centrality measures for weighted networks. Our experimental results show that Radiality-Degree centrality is satisfying for weighted BA networks. Additionally, PageRank-Degree and Radiality-Degree centralities showmoreacceptable performance in targeted immunization of weighted networks.

  16. Vitamin D and neonatal immune function.

    LENUS (Irish Health Repository)

    Clancy, N

    2013-05-01

    Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

  17. [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.

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Role of Osmolytes in Regulating Immune System.

    Science.gov (United States)

    Kumar, Tarun; Yadav, Manisha; Singh, Laishram Rajendrakumar

    2016-01-01

    The immune system has evolved to protect the host organism from diverse range of pathogenic microbes that are themselves constantly evolving. It is a complex network of cells, humoral factors, chemokines and cytokines. Dysregulation of immune system results in various kinds of immunological disorders. There are several external agents which govern the regulation of immune system. Recent studies have indicated the role of osmolytes in regulation of various immunological processes such as Ag-Ab interaction, Ig assembly, Ag presentation etc. In this present review, we have systematically discussed the role of osmolytes involved in regulation of several key immunological processes. Osmolytes are involved in the regulation of several key immunological processes such as immunoglobulin assembly and folding, immune cells proliferation, regulation of immune cells function, Ag-Ab interaction, antigen presentation, inflammatory response and protection against photo-immunosuppression. Hence, osmolytes and their transporters might be used as potential drug and drug targets respectively. This review is therefore designed to help clinicians in development of osmolyte based therapeutic strategies in the treatment of various immunological disorders. Appropriate future perspectives have also been included.

  20. Altered Immune Regulation in Type 1 Diabetes

    Science.gov (United States)

    Zóka, András; Műzes, Györgyi; Somogyi, Anikó; Varga, Tímea; Szémán, Barbara; Al-Aissa, Zahra; Hadarits, Orsolya; Firneisz, Gábor

    2013-01-01

    Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development. PMID:24285974

  1. Altered Immune Regulation in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    András Zóka

    2013-01-01

    Full Text Available Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.

  2. CD4 T cells mediate both positive and negative regulation of the immune response to HIV infection: complex role of T follicular helper cells and Regulatory T cells in pathogenesis

    Directory of Open Access Journals (Sweden)

    Chansavath ePhetsouphanh

    2015-01-01

    Full Text Available HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B cells and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely regulatory T cells (Tregs and T follicular helper cells (Tfh. These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B cell hyperplasia and increased germinal centre activity. Antiretroviral therapy (ART may reduce the lymphocyte activation, but not completely, and therefore there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B cell or Treg dysfunction.

  3. Filoviral Immune Evasion Mechanisms

    Directory of Open Access Journals (Sweden)

    Christopher F. Basler

    2011-09-01

    Full Text Available The Filoviridae family of viruses, which includes the genera Ebolavirus (EBOV and Marburgvirus (MARV, causes severe and often times lethal hemorrhagic fever in humans. Filoviral infections are associated with ineffective innate antiviral responses as a result of virally encoded immune antagonists, which render the host incapable of mounting effective innate or adaptive immune responses. The Type I interferon (IFN response is critical for establishing an antiviral state in the host cell and subsequent activation of the adaptive immune responses. Several filoviral encoded components target Type I IFN responses, and this innate immune suppression is important for viral replication and pathogenesis. For example, EBOV VP35 inhibits the phosphorylation of IRF-3/7 by the TBK-1/IKKε kinases in addition to sequestering viral RNA from detection by RIG-I like receptors. MARV VP40 inhibits STAT1/2 phosphorylation by inhibiting the JAK family kinases. EBOV VP24 inhibits nuclear translocation of activated STAT1 by karyopherin-α. The examples also represent distinct mechanisms utilized by filoviral proteins in order to counter immune responses, which results in limited IFN-α/β production and downstream signaling.

  4. Immune memory in invertebrates.

    Science.gov (United States)

    Milutinović, Barbara; Kurtz, Joachim

    2016-08-01

    Evidence for innate immune memory (or 'priming') in invertebrates has been accumulating over the last years. We here provide an in-depth review of the current state of evidence for immune memory in invertebrates, and in particular take a phylogenetic viewpoint. Invertebrates are a very heterogeneous group of animals and accordingly, evidence for the phenomenon of immune memory as well as the hypothesized molecular underpinnings differ largely for the diverse invertebrate taxa. The majority of research currently focuses on Arthropods, while evidence from many other groups of invertebrates is fragmentary or even lacking. We here concentrate on immune memory that is induced by pathogenic challenges, but also extent our view to a non-pathogenic context, i.e. allograft rejection, which can also show forms of memory and can inform us about general principles of specific self-nonself recognition. We discuss definitions of immune memory and a number of relevant aspects such as the type of antigens used, the route of exposure, and the kinetics of reactions following priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Immunity to fish rhabdoviruses

    Science.gov (United States)

    Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non-virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  6. Immunity to fish rhabdoviruses.

    Science.gov (United States)

    Purcell, Maureen K; Laing, Kerry J; Winton, James R

    2012-01-01

    Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  7. Immunity to Fish Rhabdoviruses

    Directory of Open Access Journals (Sweden)

    Maureen K. Purcell

    2012-01-01

    Full Text Available Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M protein to mediate host-cell shutoff and the non‑virion (NV protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

  8. Friends and foes of tuberculosis: modulation of protective immunity.

    Science.gov (United States)

    Brighenti, Susanna; Joosten, Simone A

    2018-05-27

    Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN-γ producing CD4 + T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T cell subsets, including classical and non-classical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights in effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common co-morbidities such as HIV, helminthes and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Trichomoniasis immunity and the involvement of the purinergic signaling

    Directory of Open Access Journals (Sweden)

    Camila Braz Menezes

    2016-08-01

    Full Text Available Innate and adaptive immunity play a significant role in trichomoniasis, the most common non-viral sexually transmitted disease worldwide. In the urogenital tract, innate immunity is accomplished by a defense physical barrier constituted by epithelial cells, mucus, and acidic pH. During infection, immune cells, antimicrobial peptides, cytokines, chemokines, and adaptive immunity evolve in the reproductive tract, and a proinflammatory response is generated to eliminate the invading extracellular pathogen Trichomonas vaginalis. However, the parasite has developed complex evolutionary mechanisms to evade the host immune response through cysteine proteases, phenotypic variation, and molecular mimicry. The purinergic system constitutes a signaling cellular net where nucleotides and nucleosides, enzymes, purinoceptors and transporters are involved in almost all cells and tissues signaling pathways, especially in central and autonomic nervous systems, endocrine, respiratory, cardiac, reproductive, and immune systems, during physiological as well as pathological processes. The involvement of the purinergic system in T. vaginalis biology and infection has been demonstrated and this review highlights the participation of this signaling pathway in the parasite immune evasion strategies. Keywords: Trichomoniasis, Innate immune response, Adaptive immune response, Evasion mechanisms, Purinergic signaling

  10. Quercetin, Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Yao Li

    2016-03-01

    Full Text Available In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

  11. Pentraxins and immunity

    Directory of Open Access Journals (Sweden)

    Priya Nagar

    2014-01-01

    Full Text Available Pentraxin-3 (PTX3 is a multifactorial protein involved in immunity and inflammation, which is rapidly produced and released by several cell types in response to inflammatory signals. It may be suggested that PTX3 is related to periodontal tissue inflammation. Its salivary concentrations may have a diagnostic potential. Pentraxin-3 (PTX3 is an ancient family of multifactorial proteins involved in immunity and inflammation. They are rapidly produced and released by various types of cells when there are indications of inflammation. PTX3 is related to inflammation in the periodontal tissue and it can be suggested that salivary concentrations may be used for diagnosing the same.

  12. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  13. Training and natural immunity

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund; Helge, Jørn Wulff; Richter, Erik

    2000-01-01

    these subjects were used to eliminate day-to-day variation in the immunological tests. Independently of diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK) cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell activity, either unstimulated or stimulated...... influence natural immunity, and suggest that ingestion of a fat-rich diet during training is detrimental to the immune system compared to the effect of a carbohydrate-rich diet....

  14. Vaccines and Immunization Practice.

    Science.gov (United States)

    Hogue, Michael D; Meador, Anna E

    2016-03-01

    Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Oana Marcu

    2011-01-01

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

  17. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

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

    2000-01-01

    to specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes...

  18. Immune System and Kidney Transplantation.

    Science.gov (United States)

    Shrestha, Badri Man

    2017-01-01

    The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

  19. Immune mechanisms and immuno therapy of thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

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

  20. Cheetahs have a stronger constitutive innate immunity than leopards.

    Science.gov (United States)

    Heinrich, Sonja K; Hofer, Heribert; Courtiol, Alexandre; Melzheimer, Jörg; Dehnhard, Martin; Czirják, Gábor Á; Wachter, Bettina

    2017-03-23

    As a textbook case for the importance of genetics in conservation, absence of genetic variability at the major histocompatibility complex (MHC) is thought to endanger species viability, since it is considered crucial for pathogen resistance. An alternative view of the immune system inspired by life history theory posits that a strong response should evolve in other components of the immune system if there is little variation in the MHC. In contrast to the leopard (Panthera pardus), the cheetah (Acinonyx jubatus) has a relatively low genetic variability at the MHC, yet free-ranging cheetahs are healthy. By comparing the functional competence of the humoral immune system of both species in sympatric populations in Namibia, we demonstrate that cheetahs have a higher constitutive innate but lower induced innate and adaptive immunity than leopards. We conclude (1) immunocompetence of cheetahs is higher than previously thought; (2) studying both innate and adaptive components of immune systems will enrich conservation science.

  1. Circumvention of MHC class II restriction by genetic immunization.

    Science.gov (United States)

    Schuler, K; Lu, C; Chang, H D; Croft, M; Zanetti, M; Gerloni, M

    2001-11-12

    The fate of T cell responses to peptide-based vaccination is subject to constraints by the major histocompatibility complex (MHC), MHC restriction. Using as a model system of T and B cell epitopes from the circumsporozoite protein of Plasmodium falciparum malaria parasite, we show that vaccination by somatic transgene immunization readily primes Balb/c mice (H-2(d)) a strain previously reported to be non-responder to immunization with a synthetic peptide vaccine encompassing these epitopes. Following genetic vaccination Balb/c mice developed a primary T cell response comparable to that of the responder strain C57Bl/6 (H-2(b)). Following booster immunization on day 45 Balb/c mice responded with a typical T cell memory response. Priming induced the formation of specific antibodies, which rose sharply after booster immunization. These findings suggests that genetic immunization can circumvent MHC class II restriction.

  2. Cannabinoids and Innate Immunity: Taking a Toll on Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Eric J. Downer

    2011-01-01

    Full Text Available The biologically active components of cannabis have therapeutic potential in neuroinflammatory disorders due to their anti-inflammatory propensity. Cannabinoids influence immune function in both the peripheral and the central nervous system (CNS, and the components of the cannabinoid system, the cannabinoid receptors and their endogenous ligands (endocannabinoids, have been detected on immune cells as well as in brain glia. Neuroinflammation is the complex innate immune response of neural tissue to control infection and eliminate pathogens, and Toll-like receptors (TLRs, a major family of pattern recognition receptors (PRRs that mediate innate immunity, have emerged as players in the neuroinflammatory processes underpinning various CNS diseases. This review will highlight evidence that cannabinoids interact with the immune system by impacting TLR-mediated signaling events, which may provide cues for devising novel therapeutic approaches for cannabinoid ligands.

  3. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2017-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  4. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  6. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  7. Fully immunized child

    DEFF Research Database (Denmark)

    Mutua, Martin Kavao; Kimani-Murage, Elizabeth; Ngomi, Nicholas

    2016-01-01

    Background: More efforts have been put in place to increase full immunization coverage rates in the last decade. Little is known about the levels and consequences of delaying or vaccinating children in different schedules. Vaccine effectiveness depends on the timing of its administration, and it ...

  8. Tick Innate Immunity.

    Czech Academy of Sciences Publication Activity Database

    Kopáček, Petr; Hajdušek, Ondřej; Burešová, Veronika; Daffre, S.

    2010-01-01

    Roč. 708, - (2010), 137-162 ISSN 0065-2598 R&D Projects: GA ČR GAP506/10/2136; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : tick * pathogen transmission * innate immunity Subject RIV: EC - Immunology Impact factor: 1.379, year: 2010

  9. Comparative Prevalence of Immune Evasion Complex Genes Associated with β-Hemolysin Converting Bacteriophages in MRSA ST5 Isolates from Swine, Swine Facilities, Humans with Swine Contact, and Humans with No Swine Contact.

    Directory of Open Access Journals (Sweden)

    Samantha J Hau

    Full Text Available Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genetically diverse than the first reported sequence type ST398. In the US, a diverse population of LA-MRSA is found including organisms of the ST398, ST9, and ST5 lineages. Occurrence of ST5 MRSA in swine is of particular concern since ST5 is among the most prevalent lineages causing clinical infections in humans. The prominence of ST5 in clinical disease is believed to result from acquisition of bacteriophages containing virulence or host-adapted genes including the immune-evasion cluster (IEC genes carried by β-hemolysin converting bacteriophages, whose absence in LA-MRSA ST398 is thought to contribute to reduced rates of human infection and transmission associated with this lineage. The goal of this study was to investigate the prevalence of IEC genes associated with β-hemolysin converting bacteriophages in MRSA ST5 isolates obtained from agricultural sources, including swine, swine facilities, and humans with short- or long-term swine exposure. To gain a broader perspective, the prevalence of these genes in LA-MRSA ST5 strains was compared to the prevalence in clinical MRSA ST5 strains from humans with no known exposure to swine. IEC genes were not present in any of the tested MRSA ST5 strains from agricultural sources and the β-hemolysin gene was intact in these strains, indicating the bacteriophage's absence. In contrast, the prevalence of the β-hemolysin converting bacteriophage in MRSA ST5 strains from humans with no exposure to swine was 90.4%. The absence of β-hemolysin converting bacteriophage in LA-MRSA ST5 isolates is consistent with previous reports evaluating ST398 strains and provides genetic evidence indicating LA-MRSA ST5 isolates

  10. Comparative Prevalence of Immune Evasion Complex Genes Associated with β-Hemolysin Converting Bacteriophages in MRSA ST5 Isolates from Swine, Swine Facilities, Humans with Swine Contact, and Humans with No Swine Contact

    Science.gov (United States)

    Hau, Samantha J.; Sun, Jisun; Davies, Peter R.; Frana, Timothy S.; Nicholson, Tracy L.

    2015-01-01

    Livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) draws concern from the public health community because in some countries these organisms may represent the largest reservoir of MRSA outside hospital settings. Recent studies indicate LA-MRSA strains from swine are more genetically diverse than the first reported sequence type ST398. In the US, a diverse population of LA-MRSA is found including organisms of the ST398, ST9, and ST5 lineages. Occurrence of ST5 MRSA in swine is of particular concern since ST5 is among the most prevalent lineages causing clinical infections in humans. The prominence of ST5 in clinical disease is believed to result from acquisition of bacteriophages containing virulence or host-adapted genes including the immune-evasion cluster (IEC) genes carried by β-hemolysin converting bacteriophages, whose absence in LA-MRSA ST398 is thought to contribute to reduced rates of human infection and transmission associated with this lineage. The goal of this study was to investigate the prevalence of IEC genes associated with β-hemolysin converting bacteriophages in MRSA ST5 isolates obtained from agricultural sources, including swine, swine facilities, and humans with short- or long-term swine exposure. To gain a broader perspective, the prevalence of these genes in LA-MRSA ST5 strains was compared to the prevalence in clinical MRSA ST5 strains from humans with no known exposure to swine. IEC genes were not present in any of the tested MRSA ST5 strains from agricultural sources and the β-hemolysin gene was intact in these strains, indicating the bacteriophage’s absence. In contrast, the prevalence of the β-hemolysin converting bacteriophage in MRSA ST5 strains from humans with no exposure to swine was 90.4%. The absence of β-hemolysin converting bacteriophage in LA-MRSA ST5 isolates is consistent with previous reports evaluating ST398 strains and provides genetic evidence indicating LA-MRSA ST5 isolates may harbor a

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Frequently Asked Questions about Immunizations

    Science.gov (United States)

    ... will be too late for the vaccine to work. The best time to immunize kids is when they're healthy. Can immunizations cause a bad reaction in my child? The most common reactions to vaccines are minor ...

  13. Technique Selectively Represses Immune System

    Science.gov (United States)

    ... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

  14. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

    Science.gov (United States)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-06-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

  15. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

    International Nuclear Information System (INIS)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-01-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

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

    International Nuclear Information System (INIS)

    Norval, M.

    2000-01-01

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

  17. Signaling Mechanisms in Pattern-Triggered Immunity (PTI)

    KAUST Repository

    Bigeard, Jean; Colcombet, Jean; Hirt, Heribert

    2015-01-01

    In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases. © 2015 The Author.

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

    Science.gov (United States)

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

    2015-06-23

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

  19. Vitamin E, immunity, and infection

    Science.gov (United States)

    A normally functioning immune system is critical for the body to fight and eliminate invading pathogens from the environment. On the other hand, the immune system also protects the body from internal risks such as neoplasia growing within and autoimmune responses that attack self. The immune system ...

  20. Regulatory T cells and immunity to pathogens.

    Science.gov (United States)

    Rouse, Barry T; Suvas, Susmit

    2007-09-01

    Immune responses to pathogens are modulated by one or more types of cells that perform a regulatory function. Some cells with this function, such as CD4+ Foxp3+ natural regulatory T cells (nTreg), pre-exist prior to infections whereas others may be induced as a consequence of infection (adaptive Treg). With pathogens that have a complex pathogenesis, multiple types of regulatory cells could influence the outcome. One major property of Treg is to help minimize collateral tissue damage that can occur during immune reactions to a chronic infection. The consequence is less damage to the host but in such situations the pathogen is likely to establish persistence. In some cases, a fine balance is established between Treg responses, effector components of immunity and the pathogen. Treg responses to pathogens may also act to hamper the efficacy of immune control. This review discusses these issues as well as the likely mechanisms by which various pathogens can signal the participation of Treg during infection.

  1. Gut Mesenchymal Stromal Cells in Immunity

    Directory of Open Access Journals (Sweden)

    Valeria Messina

    2017-01-01

    Full Text Available Mesenchymal stromal cells (MSCs, first found in bone marrow (BM, are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal or interspersed within intestinal submucosa (intercryptal. In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC. The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFNγ is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer.

  2. Hyperthyroidism caused by acquired immune deficiency syndrome.

    Science.gov (United States)

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  3. Modulation of immune response by bacterial lipopolysaccharides

    Directory of Open Access Journals (Sweden)

    Gustavo Aldapa-Vega

    2016-08-01

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

  4. mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

    Science.gov (United States)

    Guri, Yakir; Nordmann, Thierry M; Roszik, Jason

    2018-01-01

    Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

  5. mTOR at the Transmitting and Receiving Ends in Tumor Immunity

    Directory of Open Access Journals (Sweden)

    Yakir Guri

    2018-03-01

    Full Text Available Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

  6. COMPARATIVE STUDY OF TUMORIGENESIS AND TUMOR IMMUNITY IN INVERTEBRATES AND NONMAMMALIAN VERTEBRATES

    Science.gov (United States)

    Robert, Jacques

    2010-01-01

    Despite intense study in mammals, the different roles played by the immune system in detecting (immunosurveillance), controlling and remodeling (immunoediting) neoplasia, and perhaps in metastasis are not fully understood. In this review, I will present evidence of neoplasia and invasive malignancy, as well as tumor immunity in invertebrates and nonmammalian vertebrates. I will also present a comparative and evolutionary view of the complex interactions between neoplasia and the host immune system. Overall, I wish to go beyond the too simplistic dichotomy between invertebrates with innate immunity that are only affected with benign neoplasia and vertebrates with adaptive immunity that are affected by metastatic malignancies or cancer. PMID:20553753

  7. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  8. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  9. The Basic Immune Simulator: An agent-based model to study the interactions between innate and adaptive immunity

    Directory of Open Access Journals (Sweden)

    Orosz Charles G

    2007-09-01

    Full Text Available Abstract Background We introduce the Basic Immune Simulator (BIS, an agent-based model created to study the interactions between the cells of the innate and adaptive immune system. Innate immunity, the initial host response to a pathogen, generally precedes adaptive immunity, which generates immune memory for an antigen. The BIS simulates basic cell types, mediators and antibodies, and consists of three virtual spaces representing parenchymal tissue, secondary lymphoid tissue and the lymphatic/humoral circulation. The BIS includes a Graphical User Interface (GUI to facilitate its use as an educational and research tool. Results The BIS was used to qualitatively examine the innate and adaptive interactions of the immune response to a viral infection. Calibration was accomplished via a parameter sweep of initial agent population size, and comparison of simulation patterns to those reported in the basic science literature. The BIS demonstrated that the degree of the initial innate response was a crucial determinant for an appropriate adaptive response. Deficiency or excess in innate immunity resulted in excessive proliferation of adaptive immune cells. Deficiency in any of the immune system components increased the probability of failure to clear the simulated viral infection. Conclusion The behavior of the BIS matches both normal and pathological behavior patterns in a generic viral infection scenario. Thus, the BIS effectively translates mechanistic cellular and molecular knowledge regarding the innate and adaptive immune response and reproduces the immune system's complex behavioral patterns. The BIS can be used both as an educational tool to demonstrate the emergence of these patterns and as a research tool to systematically identify potential targets for more effective treatment strategies for diseases processes including hypersensitivity reactions (allergies, asthma, autoimmunity and cancer. We believe that the BIS can be a useful addition to

  10. Agency privileges and immunities

    International Nuclear Information System (INIS)

    1969-01-01

    Switzerland has become the thirty-fifth Member State to be a party to the Agreement on the Privileges and Immunities of the International Atomic Energy Agency. Its Resident Representative, Ambassador Alfred Eschler, deposited his Government's instrument of acceptance on 16 September. This is the fourth such instrument to be deposited with the Agency since the beginning of this year, the others being Ecuador on 16 April, Niger on 17 June and Vietnam on 31 July. (author)

  11. Immune disorders in anorexia

    OpenAIRE

    SŁOTWIŃSKA, SYLWIA MAŁGORZATA; SŁOTWIŃSKI, ROBERT

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters pla...

  12. Ebola and Immune System

    OpenAIRE

    KOMENAN, Alexis

    2016-01-01

    Ebola hemorrhagic fever is a formidable disease whose surges always result in a high number of victims in sub-Saharan Africa. There is no official treatment against the virus, which makes the task of containment extremely delicate. However, the existence of survivors to the virus demonstrates curable nature of the disease and suggests the existence of favorable factors of immunity. The author examines these factors and their challenges and perspectives in the cure of the disease.

  13. Immune disorders in anorexia

    Directory of Open Access Journals (Sweden)

    Sylwia Małgorzata Słotwińska

    2017-10-01

    Full Text Available Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  14. Immune disorders in anorexia.

    Science.gov (United States)

    Słotwińska, Sylwia Małgorzata; Słotwiński, Robert

    2017-01-01

    Anorexia nervosa is a disease involving eating disorders. It mainly affects young people, especially teenage women. The disease is often latent and occurs in many sub-clinical and partial forms. Approximately from 0.3% to 1% of the population suffers from anorexia. It has been shown that patients with anorexia develop neurotransmitter-related disorders, leading to uncontrolled changes in the immune and endocrine systems. Interactions between cytokines, neuropeptides, and neurotransmitters play an important role in disease development. Significant malnutrition induces disorders and alterations in T-cell populations. The cellular response in patients with anorexia nervosa has been shown to be normal, although opinions on this issue are controversial. Laboratory studies on neutrophils in anorexia patients showed decreased adhesion and reduced bactericidal and cell activities. Despite such unfavourable results, patients with anorexia are resistant to infections, which are very rare in this group. Glutamine improves the performance of the human immune system. The administration of glutamine to anorexia patients, as a supplement to parenteral nutrition, has resulted in significant improvements in immune system parameters. The results of previous studies on the causes and risk factors in the development of anorexia nervosa are still ambiguous. One can hope that the differences and similarities between patients with anorexia nervosa and those with other forms of protein-calorie malnutrition may be helpful in determining the relationship between nutritional status and body defences and susceptibility to infection, and can help to broaden the knowledge about the aetiopathogenesis of anorexia nervosa.

  15. Hyperthermia, immunity and metastases

    International Nuclear Information System (INIS)

    Lopatin, V.F.

    1983-01-01

    The analysis of literature data concerning local hyperthermia effects shows that temperatures over 41-42 deg C (in the whole tumor volume), causing tumor growth inhibition and cell injury, can change antigenic nature of a malignant tissue. The tumor injured by thermal effect is able probably the full length of time of injured tissue resorption to maintain at a sufficiently high level antitumoral immunity and lay obstacles to emergence of metastases or even cause regression of those tumoral foci which have not been exposed to direct effect of the injuring agent. The facts of tumoral foci regression take place also upon radiation effect which is associated as well with participation of immune mechanisms. In.experiments with animals an essential increase of immunogenic character of malignant cells exposed to ionizing radiation effect has been observed. It follows that radiation injury of tumoral tissue as well as thermal one is able to stimulate antitumoral immunity and reduce the probability of emergence of metastases. But in case of radiotherapy immunosuppression effect of ionizing radiation (at the expense of inhibition of proliferation and death of immunocompetent cells) can essentially overlap immunostimulating effect related to the changes in antigenic character of tumoral cells

  16. Stress proteins and the immune response.

    Science.gov (United States)

    Moseley, P

    2000-07-25

    , 243-282.]. This importance in immune regulation is best addressed using Matzinger's model of the immune response - The Danger Theory of Immunity [Matzinger, P., Fuchs, E.J., 1996. Beyond self and non-self: immunity is a conversation, not a war. J. NIH Res. 8, 35-39.]. Matzinger suggests that an immune system model based on the differentiation between "self and non-self" does not easily account for the changes that occur in the organism with growth and development. Why, for example does an organism not self-destruct when the immune system encounters the myriad of new peptides generated at puberty? Instead, she proposes a model of immune function based on the ability to detect and address dangers. This model states that the basic function of all cells of the organism is appropriately timed death "from natural causes". This type of cell death, or apoptosis, generates no stress signals. If, on the other hand, a cell is "murdered" by an infectious agent or dies an untimely death due to necrosis or ischemia, the cell undergoes a stress response with the liberation of stress protein-peptide complexes into the extracellular environment upon cell lysis. Not only do they serve as a "danger signal" to alert the immune system to the death of a cell under stress, but their role as protein carriers allows the immune effector cells to survey the peptides released by this stressed cell and to activate against new or unrecognized peptides carried by the stress protein. Matzinger bases the Danger Theory of Immunity on three "Laws of Lymphotics". These laws state that: (1) resting T lymphocytes require both antigen stimulation by an antigen-presenting cell (APC) and co-stimulation with a danger signal to become activated; (2) the co-stimulatory signal must be received through the APC; and (3) T cells receiving only antigen stimulation without the co-stimulatory signal undergo apoptosis. The Danger Theory gives a simple model for both tolerance and activation. (ABSTRACT TRUNCATED)

  17. Adaptation in the innate immune system and heterologous innate immunity.

    Science.gov (United States)

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  18. Impact of pharmacists providing immunizations on adolescent influenza immunization.

    Science.gov (United States)

    Robison, Steve G

    2016-01-01

    To determine if the Oregon law change in 2011 to allow pharmacists to immunize adolescents 11 to 17 years of age increased influenza immunizations or changed existing immunization venues. With the use of Oregon's ALERT Immunization Information System (IIS), 2 measures of impact were developed. First, the change in adolescent age 11-17 influenza immunizations before (2007-2010) and after (2011-2014) the pharmacy law change was evaluated against a reference cohort (aged 7-10) not affected by the law. Community pharmacies were also compared with other types of influenza immunization sites within one of the study influenza seasons (2013-2014). From 2007 to 2014, adolescent influenza immunizations at community pharmacies increased from 36 to 6372 per year. After the 2011 pharmacy law change, adolescents aged 11 to 17 were more likely to receive an influenza immunization compared with the reference population (odds ratio, 1.21; 95% CI, 1.19-1.22). Analysis of the 2013-2014 influenza season suggests that community pharmacies immunized a different population of adolescents than other providers. The 2011 change in Oregon law allowed pharmacists to increase the total of influenza immunizations given to adolescents. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Captive and free-living red knots Calidris canutus exhibit differences in non-induced immunity that suggest different immune strategies in different environments

    NARCIS (Netherlands)

    Buehler, Deborah M.; Piersma, Theunis; Tieleman, B. Irene

    Experiments on captive animals, in which conditions can be controlled, are useful for examining complex biological phenomena such as immune function. Such experiments have increased our understanding of immune responses in the context of trade-offs and pathogen pressure. However, few studies have

  20. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Immunity and immunosuppression in experimental visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Goto H.

    2004-01-01

    Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

  2. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  3. Pseudoachondroplasia with immune deficiency

    International Nuclear Information System (INIS)

    Kultursay, N.; Taneli, B.; Cavusoglu, A.

    1988-01-01

    A 5-year old boy was admitted to the hospital with failure to thrive since he was 2 years old, with weakness in his legs and a waddling gait. He has normal mental development. His parents are normal phenotypically and are unrelated. In analysing his pedigree only a grandfather is described to have waddling gait. He has a normal craniofacial appearance but a disproportionate body with normal trunk and short extremities with height below the 3rd percentile. The diagnosis of pseudoachondroplasia was made on clinical, radiological and laboratory findings. He also had immune deficiency characterised by low T-lymphocyte populations and a low level of serum immunoglobulin A. (orig.)

  4. Escaping deleterious immune response in their hosts: lessons from trypanosomatids

    Directory of Open Access Journals (Sweden)

    Anne eGeiger

    2016-05-01

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

  5. Modeling evolution and immune system by cellular automata

    International Nuclear Information System (INIS)

    Bezzi, M.

    2001-01-01

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

  6. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    Science.gov (United States)

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

    2016-01-01

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

  7. Peptide pool immunization and CD8+ T cell reactivity

    DEFF Research Database (Denmark)

    Rasmussen, Susanne B; Harndahl, Mikkel N; Buus, Anette Stryhn

    2013-01-01

    Mice were immunized twice with a pool of five peptides selected among twenty 8-9-mer peptides for their ability to form stable complexes at 37°C with recombinant H-2K(b) (half-lives 10-15h). Vaccine-induced immunity of splenic CD8(+) T cells was studied in a 24h IFNγ Elispot assay. Surprisingly...... peptides induced normal peptide immunity i.e. the specific T cell reactivity in the Elispot culture was strictly dependent on exposure to the immunizing peptide ex vivo. However, immunization with two of the peptides, a VSV- and a Mycobacterium-derived peptide, resulted in IFNγ spot formation without...... peptide in the Elispot culture. Immunization with a mixture of the VSV-peptide and a "normal" peptide also resulted in IFNγ spot formation without addition of peptide to the assay culture. Peptide-tetramer staining of CD8(+) T cells from mice immunized with a mixture of VSV-peptide and "normal" peptide...

  8. Impact of aging immune system on neurodegeneration and potential immunotherapies.

    Science.gov (United States)

    Liang, Zhanfeng; Zhao, Yang; Ruan, Linhui; Zhu, Linnan; Jin, Kunlin; Zhuge, Qichuan; Su, Dong-Ming; Zhao, Yong

    2017-10-01

    The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Complex chemistry

    International Nuclear Information System (INIS)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-01

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  10. Mathematical and Computational Modeling for Tumor Virotherapy with Mediated Immunity.

    Science.gov (United States)

    Timalsina, Asim; Tian, Jianjun Paul; Wang, Jin

    2017-08-01

    We propose a new mathematical modeling framework based on partial differential equations to study tumor virotherapy with mediated immunity. The model incorporates both innate and adaptive immune responses and represents the complex interaction among tumor cells, oncolytic viruses, and immune systems on a domain with a moving boundary. Using carefully designed computational methods, we conduct extensive numerical simulation to the model. The results allow us to examine tumor development under a wide range of settings and provide insight into several important aspects of the virotherapy, including the dependence of the efficacy on a few key parameters and the delay in the adaptive immunity. Our findings also suggest possible ways to improve the virotherapy for tumor treatment.

  11. Stromal infrastructure of the lymph node and coordination of immunity.

    Science.gov (United States)

    Chang, Jonathan E; Turley, Shannon J

    2015-01-01

    The initiation of adaptive immune responses depends upon the careful maneuvering of lymphocytes and antigen into and within strategically placed lymph nodes (LNs). Non-hematopoietic stromal cells form the cellular infrastructure that directs this process. Once regarded as merely structural features of lymphoid tissues, these cells are now appreciated as essential regulators of immune cell trafficking, fluid flow, and LN homeostasis. Recent advances in the identification and in vivo targeting of specific stromal populations have resulted in striking new insights to the function of stromal cells and reveal a level of complexity previously unrealized. We discuss here recent discoveries that highlight the pivotal role that stromal cells play in orchestrating immune cell homeostasis and adaptive immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. The interplay between the gut microbiota and the immune system.

    Science.gov (United States)

    Geuking, Markus B; Köller, Yasmin; Rupp, Sandra; McCoy, Kathy D

    2014-01-01

    The impact of the gut microbiota on immune homeostasis within the gut and, importantly, also at systemic sites has gained tremendous research interest over the last few years. The intestinal microbiota is an integral component of a fascinating ecosystem that interacts with and benefits its host on several complex levels to achieve a mutualistic relationship. Host-microbial homeostasis involves appropriate immune regulation within the gut mucosa to maintain a healthy gut while preventing uncontrolled immune responses against the beneficial commensal microbiota potentially leading to chronic inflammatory bowel diseases (IBD). Furthermore, recent studies suggest that the microbiota composition might impact on the susceptibility to immune-mediated disorders such as autoimmunity and allergy. Understanding how the microbiota modulates susceptibility to these diseases is an important step toward better prevention or treatment options for such diseases.

  13. Crosstalk between cancer and the neuro-immune system.

    Science.gov (United States)

    Kuol, Nyanbol; Stojanovska, Lily; Apostolopoulos, Vasso; Nurgali, Kulmira

    2018-02-15

    In the last decade, understanding of cancer initiation and progression has been given much attention with studies mainly focusing on genetic abnormalities. Importantly, cancer cells can influence their microenvironment and bi-directionally communicate with other systems such as the immune system. The nervous system plays a fundamental role in regulating immune responses to a range of disease states including cancer. Its dysfunction influences the progression of cancer. The role of the immune system in tumor progression is of relevance to the nervous system since they can bi-directionally communicate via neurotransmitters and neuropeptides, common receptors, and, cytokines. However, cross-talk between these cells is highly complex in nature, and numerous variations are possible according to the type of cancer involved. The neuro-immune interaction is essential in influencing cancer development and progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    Directory of Open Access Journals (Sweden)

    Rhonda M. Brand

    2015-11-01

    Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

  15. Immune Evasion, Immunopathology and the Regulation of the Immune System

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

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

  16. Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms

    OpenAIRE

    de la Cruz-Merino, Luis; Henao Carrasco, Fernando; Vicente Baz, David; Nogales Fernández, Esteban; Reina Zoilo, Juan José; Codes Manuel de Villena, Manuel; Pulido, Enrique Grande

    2011-01-01

    Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cance...

  17. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  18. 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.

  19. Archaeal CRISPR-based immune systems

    DEFF Research Database (Denmark)

    Garrett, Roger A; Vestergaard, Gisle Alberg; Shah, Shiraz Ali

    2011-01-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-based immune systems are essentially modular with three primary functions: the excision and integration of new spacers, the processing of CRISPR transcripts to yield mature CRISPR RNAs (crRNAs), and the targeting and cleavage...... of foreign nucleic acid. The primary target appears to be the DNA of foreign genetic elements, but the CRISPR/Cmr system that is widespread amongst archaea also specifically targets and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and complex. Here we examine evidence...... of CRISPR loci and the evidence for intergenomic exchange of CRISPR systems....

  20. Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

    Science.gov (United States)

    Muscoplat, Miriam Halstead; Rajamani, Sripriya

    2017-01-01

    The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

  1. The Major Players in Adaptive Immunity-Cell-mediated Immunity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 6. The Major Players in Adaptive Immunity - Cell-mediated Immunity. Asma Ahmed Banishree Saha Anand Patwardhan Shwetha Shivaprasad Dipankar Nandi. General Article Volume 14 Issue 6 June 2009 pp 610-621 ...

  2. Partial immunity in murine by immunization with a toxoplasmic DNA ...

    African Journals Online (AJOL)

    arsenal

    2012-06-12

    Jun 12, 2012 ... vaccine can be effective in partial protection against this parasite. In this study ... that mice immunized by pcROP1 with or without alum produced high Th1 immune response compared .... antigen-specific antibodies, 96-well costar plates were coated .... vaccines against some protozoa, for example, malaria,.

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

    African Journals Online (AJOL)

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

  4. Immune reactivities against gums.

    Science.gov (United States)

    Vojdani, Aristo; Vojdani, Charlene

    2015-01-01

    Different kinds of gums from various sources enjoy an extremely broad range of commercial and industrial use, from food and pharmaceuticals to printing and adhesives. Although generally recognized as safe by the US Food and Drug Administration (FDA), gums have a history of association with sensitive or allergic reactions. In addition, studies have shown that gums have a structural, molecular similarity to a number of common foods. A possibility exists for cross-reactivity. Due to the widespread use of gums in almost every aspect of modern life, the overall goal of the current investigation was to determine the degree of immune reactivity to various gum antigens in the sera of individuals representing the general population. The study was a randomized, controlled trial. 288 sera purchased from a commercial source. The sera was screened for immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies against extracts of mastic gum, carrageenan, xantham gum, guar gum, gum tragacanth, locust bean gum, and β-glucan, using indirect enzyme-linked immunosorbent assay (ELISA) testing. For each gum antigen, inhibition testing was performed on the 4 sera that showed the highest IgG and IgE immune reactivity against the different gums used in the study. Inhibition testing on these same sera for sesame albumin, lentil, corn, rice, pineapple, peanut, pea protein, shrimp, or kidney bean was used to determine the cross-reactivity of these foods with the gum. Of the 288 samples, 4.2%-27% of the specimens showed a significant elevation in IgG antibodies against various gums. Only 4 of 288, or 1.4%, showed a simultaneous elevation of the IgG antibody against all 7 gum extracts. For the IgE antibody, 15.6%-29.1% of the specimens showed an elevation against the various gums. A significant percentage of the specimens, 12.8%, simultaneously produced IgE antibodies against all 7 tested extracts. Overall, the percentage of elevation in IgE antibodies against different gum extracts, with

  5. Complex Regional Pain Syndrome: An inflammatory disease

    NARCIS (Netherlands)

    M. Dirckx (Maaike)

    2015-01-01

    markdownabstractThe pathophysiology of Complex Regional Pain Syndrome (CRPS) is complex and still not completely understood. In addition to a convincing role of inflammation, there are a number of arguments why an involvement of the immune system has been suggested in the pathophysiology of CRPS.

  6. Persistent viral infections and immune aging.

    Science.gov (United States)

    Brunner, Stefan; Herndler-Brandstetter, Dietmar; Weinberger, Birgit; Grubeck-Loebenstein, Beatrix

    2011-07-01

    Immunosenescence comprises a set of dynamic changes occurring to both, the innate as well as the adaptive immune system that accompany human aging and result in complex manifestations of still poorly defined deficiencies in the elderly population. One of the most prominent alterations during aging is the continuous involution of the thymus gland which is almost complete by the age of 50. Consequently, the output of naïve T cells is greatly diminished in elderly individuals which puts pressure on homeostatic forces to maintain a steady T cell pool for most of adulthood. In a great proportion of the human population, this fragile balance is challenged by persistent viral infections, especially Cytomegalovirus (CMV), that oblige certain T cell clones to monoclonally expand repeatedly over a lifetime which then occupy space within the T cell pool. Eventually, these inflated memory T cell clones become exhausted and their extensive accumulation accelerates the age-dependent decline of the diversity of the T cell pool. As a consequence, infectious diseases are more frequent and severe in elderly persons and immunological protection following vaccination is reduced. This review therefore aims to shed light on how various types of persistent viral infections, especially CMV, influence the aging of the immune system and highlight potential measures to prevent the age-related decline in immune function. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Quantitating cellular immune responses to cancer vaccines.

    Science.gov (United States)

    Lyerly, H Kim

    2003-06-01

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

  8. Microbial Induction of Immunity, Inflammation And Cancer

    Directory of Open Access Journals (Sweden)

    Stephen John O'Keefe

    2011-01-01

    Full Text Available The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a ‘clean’ environment, termed the ‘hygiene hypothesis’, has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, which comprises the largest immune organ within the body. The elevated risk of colon cancer is associated with the suppression of microbial fermentation and butyrate production, as butyrate provides fuel for the mucosa and is anti-inflammatory and anti-proliferative. This article will summarize the work to date highlighting the complicated and dynamic relationship between the gut microbiota and immunity, inflammation and carcinogenesis.

  9. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  10. Microscale Immune Studies Laboratory.

    Energy Technology Data Exchange (ETDEWEB)

    Poschet, Jens Fredrich; Carroll-Portillo, Amanda; Wu, Meiye; Manginell, Ronald Paul; Herr, Amy Elizabeth; Martino, Anthony A.; Perroud, Thomas D.; Branda, Catherine; Srivastava, Nimisha; Sinclair, Michael B.; Moorman, Matthew Wallace; Apblett, Christopher Alan; Sale, Kenneth L.; James, Conrad D.; Carles, Elizabeth L.; Lidke, Diane S. (University of New Mexico, Albuquerque, NM); Van Benthem, Mark Hilary; Rebeil, Roberto; Kaiser, Julie; Seaman, William (University of California, San Francisco, CA); Rempe, Susan; Brozik, Susan Marie; Jones, Howland D. T.; Gemperline, Paul (East Carolina University, Greenville, NC); Throckmorton, Daniel J.; Misra, Milind; Murton, Jaclyn K.; Carson, Bryan D.; Zhang, Zhaoduo; Plimpton, Steven James; Renzi, Ronald F.; Lane, Todd W.; Ndiaye-Dulac, Elsa; Singh, Anup K.; Haaland, David Michael; Faulon, Jean-Loup Michel; Davis, Ryan W.; Ricken, James Bryce; Branda, Steven S.; Patel, Kamlesh D.; Joo, Jaewook; Kubiak, Glenn D.; Brennan, James S.; Martin, Shawn Bryan; Brasier, Allan (University of Texas Mecial Branch, Galveston, TX)

    2009-01-01

    The overarching goal is to develop novel technologies to elucidate molecular mechanisms of the innate immune response in host cells to pathogens such as bacteria and viruses including the mechanisms used by pathogens to subvert/suppress/obfuscate the immune response to cause their harmful effects. Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like receptor (TLR) pathways is the key to deciphering mechanisms of pathogenesis and can lead to improvements in early diagnosis or developing improved therapeutics. Current methods for studying signaling focus on measurements of a limited number of components in a pathway and hence, fail to provide a systems-level understanding. We have developed a systems biology approach to decipher TLR4 pathways in macrophage cell lines in response to exposure to pathogenic bacteria and their lipopolysaccharide (LPS). Our approach integrates biological reagents, a microfluidic cell handling and analysis platform, high-resolution imaging and computational modeling to provide spatially- and temporally-resolved measurement of TLR-network components. The Integrated microfluidic platform is capable of imaging single cells to obtain dynamic translocation data as well as high-throughput acquisition of quantitative protein expression and phosphorylation information of selected cell populations. The platform consists of multiple modules such as single-cell array, cell sorter, and phosphoflow chip to provide confocal imaging, cell sorting, flow cytomtery and phosphorylation assays. The single-cell array module contains fluidic constrictions designed to trap and hold single host cells. Up to 100 single cells can be trapped and monitored for hours, enabling detailed statistically-significant measurements. The module was used to analyze translocation behavior of transcription factor NF-kB in macrophages upon activation

  11. Post-translational regulation of Foxp3 : identification of novel molecular targets for immune modulation

    NARCIS (Netherlands)

    van Loosdregt, J.

    2011-01-01

    Maintenance of immune homeostasis is a complex process allowing the immune system to be both aggressive enough to eradicate cells that express foreign antigens, and yet provide sensitivity to tolerate cells expressing self antigens. Key modulators allowing tolerance of host antigens, thereby

  12. Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

    NARCIS (Netherlands)

    Aguirre-Gamboa, Raul; Joosten, Irma; Urbano, Paulo C. M.; van der Molen, Renate G.; van Rijssen, Esther; van Cranenbroek, Bram; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Zorro, Maria; Withoff, Sebo; van Herwaarden, Antonius E.; Sweep, Fred C. G. J.; Netea, Romana T.; Swertz, Morris A.; Franke, Lude; Xavier, Ramnik J.; Joosten, Leo A. B.; Netea, Mihai G.; Wijmenga, Cisca; Kumar, Vinod; Li, Yang; Koenen, Hans J. P. M.

    2016-01-01

    Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell

  13. The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin

    NARCIS (Netherlands)

    Bos, J. D.; Zonneveld, I.; Das, P. K.; Krieg, S. R.; van der Loos, C. M.; Kapsenberg, M. L.

    1987-01-01

    The complexity of immune response-associated cells present in normal human skin was recently redefined as the skin immune system (SIS). In the present study, the exact immunophenotypes of lymphocyte subpopulations with their localizations in normal human skin were determined quantitatively. B cells

  14. TLR4 links podocytes with the innate immune system to mediate glomerular injury

    DEFF Research Database (Denmark)

    Banas, Miriam C; Banas, Bernhard; Hudkins, Kelly L

    2008-01-01

    profile of chemokines. In conclusion, it was demonstrated that TLR4 is constitutively expressed by podocytes and is upregulated in MPGN, where it may mediate glomerular injury by modulating expression of chemokines; therefore, TLR4 may link podocytes with the innate immune system to mediate MPGN triggered...... by the deposition of immune complexes....

  15. Influence of the gastrointestinal microbiota on development of the immune system in young animals

    NARCIS (Netherlands)

    Bauer, E.; Williams, B.A.; Smidt, H.; Verstegen, M.W.A.; Mosenthin, R.

    2006-01-01

    The gastrointestinal tract (GIT) of adult mammals is colonized by a complex and dynamic community of microorganisms. Most protection against potential pathogens occurs via a mucosal immune system involving mechanisms of innate immunity as well as a secondary lymphoid organ, the gut-associated

  16. Immune systems in animals involve complex combi- nations of ...

    African Journals Online (AJOL)

    spamer

    nations of humoral and cellular components, as well as external ... repair, coagulation, phagocytosis, encapsulation, nodule ... The haemolymph, haemocytes and certain tissues from E. cirrhosa exhibit lysozyme and antiprotease activity.

  17. Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana

    OpenAIRE

    Bhoo, Seong Hee; Lai, Huafang; Ma, Julian; Arntzen, Charles J.; Chen, Qiang; Mason, Hugh S.

    2011-01-01

    Filoviruses (Ebola and Marburg viruses) cause severe and often fatal hemorrhagic fever in humans and non-human primates. The US Centers for Disease Control identify Ebola and Marburg viruses as “category A” pathogens (defined as posing a risk to national security as bioterrorism agents), which has lead to a search for vaccines that could prevent the disease. Because the use of such vaccines would be in the service of public health, the cost of production is an important component of their dev...

  18. Modeling rejection immunity

    Directory of Open Access Journals (Sweden)

    Gaetano Andrea De

    2012-05-01

    Full Text Available Abstract Background Transplantation is often the only way to treat a number of diseases leading to organ failure. To overcome rejection towards the transplanted organ (graft, immunosuppression therapies are used, which have considerable side-effects and expose patients to opportunistic infections. The development of a model to complement the physician’s experience in specifying therapeutic regimens is therefore desirable. The present work proposes an Ordinary Differential Equations model accounting for immune cell proliferation in response to the sudden entry of graft antigens, through different activation mechanisms. The model considers the effect of a single immunosuppressive medication (e.g. cyclosporine, subject to first-order linear kinetics and acting by modifying, in a saturable concentration-dependent fashion, the proliferation coefficient. The latter has been determined experimentally. All other model parameter values have been set so as to reproduce reported state variable time-courses, and to maintain consistency with one another and with the experimentally derived proliferation coefficient. Results The proposed model substantially simplifies the chain of events potentially leading to organ rejection. It is however able to simulate quantitatively the time course of graft-related antigen and competent immunoreactive cell populations, showing the long-term alternative outcomes of rejection, tolerance or tolerance at a reduced functional tissue mass. In particular, the model shows that it may be difficult to attain tolerance at full tissue mass with acceptably low doses of a single immunosuppressant, in accord with clinical experience. Conclusions The introduced model is mathematically consistent with known physiology and can reproduce variations in immune status and allograft survival after transplantation. The model can be adapted to represent different therapeutic schemes and may offer useful indications for the optimization of

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

    Science.gov (United States)

    Webb, Lauren M; Tait Wojno, Elia D

    2017-09-01

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

  20. The Major Histocompatibility Complex in Transplantation

    Directory of Open Access Journals (Sweden)

    Marco Antonio Ayala García

    2012-01-01

    Full Text Available The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

  1. MECHANISMS OF IMMUNE RESPONSES IN CNIDARIANS

    Directory of Open Access Journals (Sweden)

    Iván Darío Ocampo

    2015-05-01

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

  2. 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

  3. Cholinergic signalling in gut immunity

    NARCIS (Netherlands)

    Dhawan, Shobhit; Cailotto, Cathy; Harthoorn, Lucien F.; de Jonge, Wouter J.

    2012-01-01

    The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an

  4. Alcohol, aging, and innate immunity.

    Science.gov (United States)

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  5. VACCINES AND IMMUNIZATION: WORLD SITUATION

    Directory of Open Access Journals (Sweden)

    G.H. Brundtland

    2007-01-01

    Full Text Available The last issue of the report «vaccines and immunization: world situation» stresses considerable success in immunization at the global level since the mid 90 s — completely total eradication of poliomyelitis across the world, as well as the drastic reduction of the new measles and tetanus cases among mothers and newborns in some poor countries. The report also briefly describes the progress in the development and implementation of the new life saving vaccines, which may save millions of lives annually. The authors have explained some of the reasons, why the global community should invest in immunization, as well as the perspectives for the use of vaccines and immunization in future.Key words: vaccine, immunization, children.

  6. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  7. [Stress and auto-immunity].

    Science.gov (United States)

    Delévaux, I; Chamoux, A; Aumaître, O

    2013-08-01

    The etiology of auto-immune disorders is multifactorial. Stress is probably a participating factor. Indeed, a high proportion of patients with auto-immune diseases report uncommon stress before disease onset or disease flare. The biological consequences of stress are increasingly well understood. Glucocorticoids and catecholamines released by hypothalamic-pituitary-adrenal axis during stress will alter the balance Th1/Th2 and the balance Th17/Treg. Stress impairs cellular immunity, decreases immune tolerance and stimulates humoral immunity exposing individuals to autoimmune disease among others. The treatment for autoimmune disease should include stress management. Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

    2016-01-01

    diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

  9. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

  10. Melatonin: Buffering the Immune System

    Science.gov (United States)

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  11. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  12. Student pharmacists' perceptions of immunizations.

    Science.gov (United States)

    Kubli, Kara; McBane, Sarah; Hirsch, Jan D; Lorentz, Sarah

    2017-05-01

    The primary aim of this study was to explore changes in knowledge level, perceived importance and apprehension of immunizations by first year pharmacy students pre- vs. post-immunization education and training. First year pharmacy students at the University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences (UC San Diego SSPPS) completed a pre- and post-immunization training course questionnaire. Knowledge base and perceived importance level of immunizations including hepatitis B, influenza, measles, mumps, rubella (MMR), varicella, tetanus, diphtheria, pertussis (Tdap), meningococcal and human papilloma virus (HPV) were assessed. In addition, apprehension of needle administration and fears regarding safety and efficacy were evaluated. Of 120 students, 85 (71%) completed pre- and post-course questionnaires for this study. Mean knowledge test scores increased from 56% pre-course to 83% post-course. Pre-course, 73% of participants considered immunizations as very important in preventing future disease outbreaks. Post-course, this percentage climbed to 94%. Prior to taking the course, 52% of students were apprehensive about administering injections; however, after completing the course this percentage declined to 33%. The majority of students who had been fearful prior to the course retained their fears of receiving needle injections. The proportion of students believing immunizations should be a personal choice, not mandatory, did not significantly change from pre-course (49%) to post-course (44%). The UC San Diego SSPPS immunization course increased student knowledge of immunization facts and the perceived importance of immunizations. However, a substantial portion of students retained apprehension about administering and receiving needle injections and the proportion believing immunizations should be a personal choice, almost half, did not change appreciably. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Immune oncology, immune responsiveness and the theory of everything.

    Science.gov (United States)

    Turan, Tolga; Kannan, Deepti; Patel, Maulik; Matthew Barnes, J; Tanlimco, Sonia G; Lu, Rongze; Halliwill, Kyle; Kongpachith, Sarah; Kline, Douglas E; Hendrickx, Wouter; Cesano, Alessandra; Butterfield, Lisa H; Kaufman, Howard L; Hudson, Thomas J; Bedognetti, Davide; Marincola, Francesco; Samayoa, Josue

    2018-06-05

    Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.

  14. PATHOGENETIC MECHANISMS IN EXPERIMENTAL IMMUNE FEVER

    Science.gov (United States)

    Root, Richard K.; Wolff, Sheldon M.

    1968-01-01

    When rabbits sensitized to human serum albumin (HSA) are challenged intravenously with specific antigen, fever develops and two transferable pyrogens can be demonstrated in the circulation. The first appears prior to the development of fever and has properties consistent with soluble antigen-antibody complexes. These have been shown to be pyrogenic when prepared in vitro and to produce a state of febrile tolerance when repeatedly administered. The second pyrogen, demonstrable during fever in donor rabbits, appears to be similar to endogenous pyrogen described in other experimental fevers. It is postulated that the formation of antigen-antibody complexes constitutes an important initial phase of the febrile reaction in this type of immune fever. PMID:4873023

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

    Science.gov (United States)

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

    2016-01-01

    The purple sea urchin (Strongylocentrotus purpuratus) genome sequence contains a complex repertoire of genes encoding innate immune recognition proteins and homologs of important vertebrate immune regulatory factors. To characterize how this immune system is deployed within an experimentally tractable, intact animal, we investigate the immune capability of the larval stage. Sea urchin embryos and larvae are morphologically simple and transparent, providing an organism-wide model to view immune response at cellular resolution. Here we present evidence for immune function in five mesenchymal cell types based on morphology, behavior and gene expression. Two cell types are phagocytic; the others interact at sites of microbial detection or injury. We characterize immune-associated gene markers for three cell types, including a perforin-like molecule, a scavenger receptor, a complement-like thioester-containing protein and the echinoderm-specific immune response factor 185/333. We elicit larval immune responses by (1) bacterial injection into the blastocoel and (2) seawater exposure to the marine bacterium Vibrio diazotrophicus to perturb immune state in the gut. Exposure at the epithelium induces a strong response in which pigment cells (one type of immune cell) migrate from the ectoderm to interact with the gut epithelium. Bacteria that accumulate in the gut later invade the blastocoel, where they are cleared by phagocytic and granular immune cells. The complexity of this coordinated, dynamic inflammatory program within the simple larval morphology provides a system in which to characterize processes that direct both aspects of the echinoderm-specific immune response as well as those that are shared with other deuterostomes, including vertebrates. PMID:27192936

  16. Preparation of antisera specific for human B cells by immunization of rabbits with immune complexes

    International Nuclear Information System (INIS)

    Welsh, K.I.; Turner, M.J.

    1976-01-01

    Three rabbit antisera are described which are specific without absorption (titer 1:100) for separated human B cells, as measured by complement and non-complement fixing assays. The method of production of these sera involved injections of rabbits with precipitin lines formed between 10μ1 of three separate detergent solubilized membrane preparations and 4μ1 aliquots of rabbit antisera to human B cells. In addition to being B cell specific, the three sera block the MLC reaction, inhibit aggregated IgG binding to B cells, and show differential degrees of B cell lysis when tested on a panel of separated B and T cells. These and other properties suggest that the target specificities of the antibodies are the human equivalent of the murine Ia antigens. (author)

  17. Complement System Part II: Role in Immunity

    Science.gov (United States)

    Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

  18. Dynamic complexity: plant receptor complexes at the plasma membrane.

    Science.gov (United States)

    Burkart, Rebecca C; Stahl, Yvonne

    2017-12-01

    Plant receptor complexes at the cell surface perceive many different external and internal signalling molecules and relay these signals into the cell to regulate development, growth and immunity. Recent progress in the analyses of receptor complexes using different live cell imaging approaches have shown that receptor complex formation and composition are dynamic and take place at specific microdomains at the plasma membrane. In this review we focus on three prominent examples of Arabidopsis thaliana receptor complexes and how their dynamic spatio-temporal distribution at the PM has been studied recently. We will elaborate on the newly emerging concept of plasma membrane microdomains as potential hubs for specific receptor complex assembly and signalling outputs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Late effects of radiation on immune system; a review

    International Nuclear Information System (INIS)

    Sado, T.

    1979-01-01

    Lymphocytes are divided into 2 major classes: T and B lymphocytes (or cells). T cells are responsible for cell-mediated immune response, and B cells for humoral immune response or antibody formation. The possible immunological complications that might develop as the late manifestation of radiation effects include: lymphoid neoplasms, immune complex diseases, auto-aggressive immune reactions, and other degenerative diseases of immunological nature. The development of lymphoid neoplasma following the exposure to radiation was extensively studied with mice. Radiation-induced immunological compications would not contribute significantly to the life-shortening of exposed individuals. The extensive health survey of adult A-bomb survivors revealed little evidence of immunological complications such as rheumatoid arthritis, kidney diseases, paraproteinemia, etc. The young healthy adults who had received thymic irradiation during infancy for the treatment of enlarged thymus manifested higher incidence of illness with abnormal immunological features. Immune complex diseases, particularly the inter-capillary glomerulosclerosis of kidneys, develop as a result of earlier exposure to high dose of radiation. (Yamashita, S.)

  20. The Role of Innate Immune System Receptors in Epilepsy Research.

    Science.gov (United States)

    Cordero-Arreola, Jessica; West, Rachel M; Mendoza-Torreblanca, Julieta; Mendez-Hernandez, Edna; Salas-Pacheco, Jose; Menendez-Gonzalez, Manuel; Freire, Rafael C; Machado, Sergio; Murillo-Rodriguez, Eric; Nardi, Antonio E; Arias-Carrion, Oscar

    2017-01-01

    Epilepsy is one of the most complex neurological disorders and its study requires a broad knowledge of neurology and neuroscience. It comprises a diverse group of neurological disorders that share the central feature of spontaneous recurrent seizures, and are often accompanied by cognitive deficits and mood disorder. This condition is one of the most common neurological disorders. Until recently, alterations of neuronal activities had been the focus of epilepsy research. This neurocentric emphasis did not address issues that arise in more complex models of epileptogenesis. An important factor in epilepsy that is not regulated directly by neurons is inflammation and the immune response of the brain. Recent evidence obtained in rodent epilepsy models supports the role of immune responses in the initiation and maintenance of epilepsy. Recognition of exogenous pathogens by the innate immune system is mediated by some pattern recognition receptors such as Toll-like receptors leading to cell activation and cytokine production. Currently, these receptors have been the focus of epilepsy studies looking to determine whether the innate immune activation is neuroprotective or neurotoxic for the brain. Here, we present the evidence in the literature of the involvement of key innate immune receptors in the development of epilepsy. We address some of the contradictory findings in these studies and also mention possible avenues for research into epilepsy treatments that target these receptors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Immunization Schedules for Infants and Children

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Infants and Children (Birth through 6 ... any questions please talk to your doctor. 2018 Immunization Schedule Recommended Vaccinations for Infants and Children Schedule ...

  2. Immunizations and Asians and Pacific Islanders

    Science.gov (United States)

    ... and Data > Minority Population Profiles > Asian American > Immunizations Immunizations and Asians and Pacific Islanders Asian/Pacific Islander ... 35 months reached the Healthy People goal for immunizations for hepatitis B, MMR (measles-mumps-rubella), polio ...

  3. Play the Immune System Defender Game

    Science.gov (United States)

    ... Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic cells are immune cells ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  4. Molecular mechanisms of aging and immune system regulation in Drosophila.

    Science.gov (United States)

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

    Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

  5. Suppressive influences in the immune response to cancer.

    Science.gov (United States)

    Bronte, Vincenzo; Mocellin, Simone

    2009-01-01

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

  6. Immune Reconstitution Inflammatory Syndrome (IRIS): What pathologists should know.

    Science.gov (United States)

    Nelson, Ann Marie; Manabe, Yukari C; Lucas, Sebastian B

    2017-07-01

    Antiretroviral therapy has significantly improved the quality and length of life for those patients able to access effective and sustained treatment. The resulting restoration of the immune response is associated with a change in the clinical presentation of opportunistic infections, and the histologic reaction to pathogens. A complex combination of alterations in host response across the stages of HIV infection has been documented over the past 3 decades. The defects are seen in both acute and chronic phases of inflammation and involve innate and adaptive immunity. In advanced stages of HIV infection, the marked disruption of lymphoid tissue and loss of follicular dendritic cells limits the host's ability to process antigen and mount specific responses to pathogens. There are qualitative and quantitative defects in CD4 T cells due to HIV infection. The resulting indirect effects include loss of cytokine production, dysregulation of B-cell function, loss of cellular mediated immunity and "holes" in the immunologic repertoire that may not be restored with the use of antiretroviral therapy. Immune reconstitution allows the host to respond to and control infection, but a significant number of patients will have atypical inflammatory syndromes during the recovery period. We briefly discuss the impact of HIV infection on the immune system and give an overview of the spectrum of conditions attributed to the Immune Reconstitution Inflammatory syndrome (IRIS). Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Modulation of immune responses in stress by Yoga

    Directory of Open Access Journals (Sweden)

    Arora Sarika

    2008-01-01

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

  8. Graphene and the immune system: Challenges and potentiality.

    Science.gov (United States)

    Orecchioni, Marco; Ménard-Moyon, Cécilia; Delogu, Lucia Gemma; Bianco, Alberto

    2016-10-01

    In the growing area of nanomedicine, graphene-based materials (GBMs) are some of the most recent explored nanomaterials. For the majority of GBM applications in nanomedicine, the immune system plays a fundamental role. It is necessary to well understand the complexity of the interactions between GBMs, the immune cells, and the immune components and how they could be of advantage for novel effective diagnostic and therapeutic approaches. In this review, we aimed at painting the current picture of GBMs in the background of the immune system. The picture we have drawn looks like a cubist image, a sort of Picasso-like portrait looking at the topic from all perspectives: the challenges (due to the potential toxicity) and the potentiality like the conjugation of GBMs to biomolecules to develop advanced nanomedicine tools. In this context, we have described and discussed i) the impact of graphene on immune cells, ii) graphene as immunobiosensor, and iii) antibodies conjugated to graphene for tumor targeting. Thanks to the huge advances on graphene research, it seems realistic to hypothesize in the near future that some graphene immunoconjugates, endowed of defined immune properties, can go through preclinical test and be successfully used in nanomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Deciphering dendritic cell heterogenity in immunity

    Directory of Open Access Journals (Sweden)

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  10. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  11. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  12. Pregnancy: an immune challenge

    Directory of Open Access Journals (Sweden)

    Maria Angelica Ehara Watanabe

    2014-12-01

    Full Text Available Several studies demonstrate the importance of immunological aspects of pregnancy. During pregnancy, the embryo is implanted in the womb, where it will develop until the end of pregnancy. Amongst the immune aspects, the importance of the modulation of T lymphocytes, natural killers (NK cells and many cytokines in maternal organism can be mentioned. The maternal tolerance to the fetus appears to be mediated by specific maternal hormones and by the expression of human leukocyte antigen G (HLA-G - characteristic in pregnancy. Other studies suggest that fetal rejection and complications during pregnancy may occur because of the presence of minor histocompatibility antigens (mHAg, acquired by blood sharing of the mother with the fetus, and because of the presence of maternal antibodies against the sperm and against the fetus. The purpose of this review is to describe the immunological aspects that allow maternal tolerance to the fetus during pregnancy, as well as possible causes for rejection of the embryo and complications during pregnancy.

  13. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  14. Immunity's fourth dimension: approaching the circadian-immune connection.

    Science.gov (United States)

    Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

    2012-12-01

    The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. immune response can measuring immunity to hiv during ...

    African Journals Online (AJOL)

    2005-11-01

    Nov 1, 2005 ... inhibitors (PIs), have resulted in significant suppression of viral replication. ... thymus, with the potential for immune reconstitution when ..... HIV-exposed but uninfected Gambian women [published erratum appears in. Nat Med ...

  17. Spirochetal Lipoproteins and Immune Evasion

    Science.gov (United States)

    Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

    2017-01-01

    Spirochetes are a major threat to public health. However, the exact pathogenesis of spirochetal diseases remains unclear. Spirochetes express lipoproteins that often determine the cross talk between the host and spirochetes. Lipoproteins are pro-inflammatory, modulatory of immune responses, and enable the spirochetes to evade the immune system. In this article, we review the modulatory effects of spirochetal lipoproteins related to immune evasion. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate pathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and treatment. PMID:28424696

  18. Immunizations challenge healthcare personnel and affects immunization rates.

    Science.gov (United States)

    Strohfus, Pamela K; Kim, Susan C; Palma, Sara; Duke, Russell A; Remington, Richard; Roberts, Caleb

    2017-02-01

    This study measured 1. medical office immunization rates and 2. health care personnel competency in managing vaccine practices before and after evidence-based immunization education was provided. This descriptive study compared 32 family medicine and pediatric offices and 178 medical assistants, licensed practical nurses, registered nurses, nurse practitioners, and physicians in knowledge-based testing pre-education, post-education, and 12-months post-education. Immunization rates were assessed before and 18-months post-education. Immunization rates increased 10.3% - 18months post-education; knowledge increased 7.8% - 12months post-education. Family medicine offices, licensed practical nurses, and medical assistants showed significant knowledge deficits before and 12-months post-education. All demographic groups scored less in storage/handling 12-months post-education. This study is one of the first studies to identify competency challenges in effective immunization delivery among medical assistants, licensed practical nurses, and family medicine offices. Formal and continuous education in immunization administration and storage/handling is recommended among these select groups. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  20. 2012 National Immunization Survey Data

    Science.gov (United States)

    ... Tweet Share Compartir This website is archived for historical purposes and is no longer being maintained or ... 12, 2013: Content on this page kept for historical reasons. National Immunization Survey (NIS) – Children (19-35 ...

  1. Pauci-immune necrotizing glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Sanders, Jan S F; Stegeman, Coen A; Kallenberg, Cees G M

    Pauci-immune necrotizing glomerulonephritis is the most frequent cause of rapidly progressive glomerulonephritis and, in most cases, is associated with antineutrophil cytoplasmic antibodies (ANCA). It is either the renal manifestation of Wegener's granulomatosis, microscopic polyangiitis of

  2. Arkansas community pharmacists' opinions on providing immunizations.

    Science.gov (United States)

    Pace, Anne C; Flowers, Schwanda K; Hastings, Jan K

    2010-10-01

    To determine community pharmacists' attitudes and knowledge on providing immunizations including perceived barriers to immunizing. The study also examined the percentage of Arkansas pharmacists providing immunizations and the utilization of student pharmacists. Survey. Arkansas community pharmacies from February to March 2009. Community pharmacists. Mailed survey. Perceived barriers to providing immunizations, pharmacists' attitudes regarding immunizations, number of immunization-certified pharmacists, immunization administration rates within the last year, and senior student pharmacists utilization. A total of 350 surveys were mailed, and 129 were returned. In all, 79% of the respondents believed administering immunizations has advanced or significantly advanced the profession. Being certified and attitude toward providing immunizations were correlated; 37% of the respondents held certification to immunize, of which 77% reported immunizing within the last year. Commonly reported barriers included time (76%) followed by reimbursement and legal liability. Only half the respondents realized fourth year student pharmacists could immunize and only 33% of certified pharmacists utilized student pharmacists to immunize. Pharmacists perceive many barriers to providing immunizations. Training student pharmacists to give immunizations may not result in them providing immunizations upon graduation. Additional education on overcoming potential barriers and using senior student pharmacists to administer immunizations is needed.

  3. The identification of immune genes in the milk transcriptome of the Tasmanian devil (Sarcophilus harrisii

    Directory of Open Access Journals (Sweden)

    Rehana V. Hewavisenti

    2016-01-01

    Full Text Available Tasmanian devil (Sarcophilus harrisii pouch young, like other marsupials, are born underdeveloped and immunologically naïve, and are unable to mount an adaptive immune response. The mother’s milk provides nutrients for growth and development as well as providing passive immunity. To better understand immune response in this endangered species, we set out to characterise the genes involved in passive immunity by sequencing and annotating the transcriptome of a devil milk sample collected during mid-lactation. At mid-lactation we expect the young to have heightened immune responses, as they have emerged from the pouch, encountering new pathogens. A total of 233,660 transcripts were identified, including approximately 17,827 unique protein-coding genes and 846 immune genes. The most highly expressed transcripts were dominated by milk protein genes such as those encoding early lactation protein, late lactation proteins, α-lactalbumin, α-casein and β-casein. There were numerous highly expressed immune genes including lysozyme, whey acidic protein, ferritin and major histocompatibility complex I and II. Genes encoding immunoglobulins, antimicrobial peptides, chemokines and immune cell receptors were also identified. The array of immune genes identified in this study reflects the importance of the milk in providing immune protection to Tasmanian devil young and provides the first insight into Tasmanian devil milk.

  4. The optimal dynamic immunization under a controlled heterogeneous node-based SIRS model

    Science.gov (United States)

    Yang, Lu-Xing; Draief, Moez; Yang, Xiaofan

    2016-05-01

    Dynamic immunizations, under which the state of the propagation network of electronic viruses can be changed by adjusting the control measures, are regarded as an alternative to static immunizations. This paper addresses the optimal dynamical immunization under the widely accepted SIRS assumption. First, based on a controlled heterogeneous node-based SIRS model, an optimal control problem capturing the optimal dynamical immunization is formulated. Second, the existence of an optimal dynamical immunization scheme is shown, and the corresponding optimality system is derived. Next, some numerical examples are given to show that an optimal immunization strategy can be worked out by numerically solving the optimality system, from which it is found that the network topology has a complex impact on the optimal immunization strategy. Finally, the difference between a payoff and the minimum payoff is estimated in terms of the deviation of the corresponding immunization strategy from the optimal immunization strategy. The proposed optimal immunization scheme is justified, because it can achieve a low level of infections at a low cost.

  5. Mediated Plastid RNA Editing in Plant Immunity

    Science.gov (United States)

    García-Andrade, Javier; Ramírez, Vicente; López, Ana; Vera, Pablo

    2013-01-01

    Plant regulatory circuits coordinating nuclear and plastid gene expression have evolved in response to external stimuli. RNA editing is one of such control mechanisms. We determined the Arabidopsis nuclear-encoded homeodomain-containing protein OCP3 is incorporated into the chloroplast, and contributes to control over the extent of ndhB transcript editing. ndhB encodes the B subunit of the chloroplast NADH dehydrogenase-like complex (NDH) involved in cyclic electron flow (CEF) around photosystem I. In ocp3 mutant strains, ndhB editing efficiency decays, CEF is impaired and disease resistance to fungal pathogens substantially enhanced, a process recapitulated in plants defective in editing plastid RNAs encoding NDH complex subunits due to mutations in previously described nuclear-encoded pentatricopeptide-related proteins (i.e. CRR21, CRR2). Furthermore, we observed that following a pathogenic challenge, wild type plants respond with editing inhibition of ndhB transcript. In parallel, rapid destabilization of the plastidial NDH complex is also observed in the plant following perception of a pathogenic cue. Therefore, NDH complex activity and plant immunity appear as interlinked processes. PMID:24204264

  6. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  7. Gut immunity in Lepidopteran insects.

    Science.gov (United States)

    Wu, Kai; Yang, Bing; Huang, Wuren; Dobens, Leonard; Song, Hongsheng; Ling, Erjun

    2016-11-01

    Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Universal immunity to influenza must outwit immune evasion

    Directory of Open Access Journals (Sweden)

    Sergio Manuel Quinones-Parra

    2014-06-01

    Full Text Available Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody responses to the surface haemagglutinin (HA and neuraminidase (NA proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a need for cross-protective or universal influenza vaccines to overcome the necessity for annual immunisation against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1 and H7N9. The key to generating universal influenza immunity via vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive antibody responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and antibodies, the mechanisms of immune evasion in influenza, and how to counteract commonly occurring

  9. Immunization coverage among Hispanic ancestry, 2003 National Immunization Survey.

    Science.gov (United States)

    Darling, Natalie J; Barker, Lawrence E; Shefer, Abigail M; Chu, Susan Y

    2005-12-01

    The Hispanic population is increasing and heterogeneous (Hispanic refers to persons of Spanish, Hispanic, or Latino descent). The objective was to examine immunization rates among Hispanic ancestry for the 4:3:1:3:3 series (> or = 4 doses diphtheria, tetanus toxoids, and pertussis vaccine; > or = 3 doses poliovirus vaccine; > or = 1 doses measles-containing vaccine; > or = 3 doses Haemophilus influenzae type b vaccine; and > or = 3 doses hepatitis B vaccine). The National Immunization Survey measures immunization coverage among 19- to 35-month-old U.S. children. Coverage was compared from combined 2001-2003 data among Hispanics and non-Hispanic whites using t-tests, and among Hispanic ancestry using a chi-square test. Hispanics were categorized as Mexican, Mexican American, Central American, South American, Puerto Rican, Cuban, Spanish Caribbean (primarily Dominican Republic), other, and multiple ancestry. Children of Hispanic ancestry increased from 21% in 1999 to 25% in 2003. These Hispanic children were less well immunized than non-Hispanic whites (77.0%, +/-2.1% [95% confidence interval] compared to 82.5%, +/-1.1% (95% CI) > in 2003). Immunization coverage did not vary significantly among Hispanics of varying ancestries (p=0.26); however, there was substantial geographic variability. In some areas, immunization coverage among Hispanics was significantly higher than non-Hispanic whites. Hispanic children were less well immunized than non-Hispanic whites; however, coverage varied notably by geographic area. Although a chi-square test found no significant differences in coverage among Hispanic ancestries, the range of coverage, 79.2%, +/-5.1% for Cuban Americans to 72.1%, +/-2.4% for Mexican descent, may suggest a need for improved and more localized monitoring among Hispanic communities.

  10. Report 10. Cooperative immune responses of different generations of mice

    International Nuclear Information System (INIS)

    Savtsova, Z.D.; Kovbasyuk, S.A.; Yudina, O.Yu.; Zaritskaya, M.Yu.; Voejkova, I.M.; Orlovskij, A.A.; Indyk, V.M.; Serkiz, Ya.I.

    1991-01-01

    The immune status of mice has been assessed by the whole complex of data. The permanent action of low-level radiation has been shown to suppress considerably the rate of reactions of the delayed-type hypersensitivity and graft-versus host disease, as well as NK and specific cytolytic T-lymphocyte activity. The dynamics of accumulation and the levels of antibodies in the serum, lung and trachea extracts are virtually invariable. The resistance of experimental animals to influenza is lower than that of non-irradiated mice of the same line and age. The data obtained indicate that the immune disturbances revealed are connected not only with the alteration of lymphoid cell populations, but also with the alteration of the immune regulation mechanisms

  11. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

    2013-01-01

    Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  12. Soft tissue abscess and lymphadenitis due to Mycobacterium avium Complex as an expression of immune reconstitution inflammatory syndrome after a second scheme of highly active antiretroviral therapy Linfadenitis y absceso subcutáneo por Complejo Mycobacterium avium como manifestación de síndrome inflamatorio de reconstitución inmune luego de un segundo esquema de terapia antirretroviral de gran actividad

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2007-08-01

    Full Text Available Immune reconstitution inflammatory syndrome (IRIS is an atypical and unexpected reaction related to highly active antiretroviral therapy (HAART in human immunodeficiency virus (HIV infected patients. IRIS includes an atypical response to an opportunistic pathogen (generally Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus and herpes varicella-zoster, in patients responding to HAART with a reduction of plasma viral load and evidence of immune restoration based on increase of CD4+ T-cell count. We reported a case of a patient with AIDS which, after a first failure of HAART, developed a subcutaneous abscess and supraclavicular lymphadenitis as an expression of IRIS due to Mycobacterium avium complex after starting a second scheme of HAART.El síndrome inflamatorio de reconstitución inmune (SIRI es una reacción atípica e inesperada relacionada con el tratamiento antirretroviral de gran actividad (TARGA en pacientes infectados por el virus de la inmunodeficiencia humana (VIH. El SIRI representa una respuesta inflamatoria frente a un patógeno oportunista (generalmente Mycobacterium tuberculosis, Complejo Mycobacterium avium, citomegalovirus y herpes varicela-zóster en pacientes que responden a la TARGA con una marcada reducción de la carga viral en plasma y evidencia de una recuperación inmunológica expresada por el incremento de los niveles de linfocitos T CD4+. Presentamos el caso de un paciente con síndrome de inmunodeficiencia adquirida que desarrolló un absceso subcutáneo en muslo derecho y una adenitis supraclavicular izquierda como manifestación de SIRI por Complejo Mycobacterium avium luego del inicio de un segundo esquema de TARGA.

  13. Nutrition, immune function and health of dairy cattle.

    Science.gov (United States)

    Ingvartsen, K L; Moyes, K

    2013-03-01

    The large increase in milk yield and the structural changes in the dairy industry have caused major changes in the housing, feeding and management of the dairy cow. However, while large improvements have occurred in production and efficiency, the disease incidence, based on veterinary records, does not seem to be improved. Earlier reviews have covered critical periods such as the transition period in the cow and its influence on health and immune function, the interplay between the endocrine system and the immune system and nutrition and immune function. Knowledge on these topics is crucial for our understanding of disease risk and our effort to develop health and welfare improving strategies, including proactive management for preventing diseases and reducing the severity of diseases. To build onto this the main purpose of this review will therefore be on the effect of physiological imbalance (PI) on immune function, and to give perspectives for prevention of diseases in the dairy cow through nutrition. To a large extent, the health problems during the periparturient period relate to cows having difficulty in adapting to the nutrient needs for lactation. This may result in PI, a situation where the regulatory mechanisms are insufficient for the animals to function optimally leading to a high risk of a complex of digestive, metabolic and infectious problems. The risk of infectious diseases will be increased if the immune competence is reduced. Nutrition plays a pivotal role in the immune response and the effect of nutrition may be directly through nutrients or indirectly by metabolites, for example, in situations with PI. This review discusses the complex relationships between metabolic status and immune function and how these complex interactions increase the risk of disease during early lactation. A special focus will be placed on the major energetic fuels currently known to be used by immune cells (i.e. glucose, non-esterified fatty acids, beta

  14. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

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

    Science.gov (United States)

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

    2001-06-14

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

  16. 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.

  17. SOME ISSUES OF DIAGNOSTICS IN IMMUNE PATHOLOGY

    Directory of Open Access Journals (Sweden)

    I. A. Tousankina

    2010-01-01

    Full Text Available Present lecture contains an author's opinion concerning diagnostic issues in immunopathology, including primary and secondary immune deficiencies, immune-dependent states that are based on immunopathological syndromes. Original formulations are suggested for some key categories of clinical immunology, physical, instrumental and laboratory diagnostics of immune deficiencies and immune-dependent diseases. The results of original long-term observations, as well as data on Sverdlovsk Regional Register of primary immune deficiencies are presented in the work.

  18. Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System

    DEFF Research Database (Denmark)

    Rapin, N.; Lund, Ole; Bernaschi, M.

    2010-01-01

    potential measurements, for assessing molecular binding in the context of immune complexes. We benchmark the resulting model by simulating a classical immunization experiment that reproduces the development of immune memory. We also investigate the role of major histocompatibility complex (MHC) haplotype...... proliferate more than any other. These results show that the simulator produces dynamics that are stable and consistent with basic immunological knowledge. We believe that the combination of genomic information and simulation of the dynamics of the immune system, in one single tool, can offer new perspectives......We present a new approach to the study of the immune system that combines techniques of systems biology with information provided by data-driven prediction methods. To this end, we have extended an agent-based simulator of the immune response, C-IMMSIM, such that it represents pathogens, as well...

  19. Indispensable Role of Proteases in Plant Innate Immunity.

    Science.gov (United States)

    Balakireva, Anastasia V; Zamyatnin, Andrey A

    2018-02-23

    Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered.

  20. Viral degradasome hijacks mitochondria to suppress innate immunity

    Science.gov (United States)

    Goswami, Ramansu; Majumdar, Tanmay; Dhar, Jayeeta; Chattopadhyay, Saurabh; Bandyopadhyay, Sudip K; Verbovetskaya, Valentina; Sen, Ganes C; Barik, Sailen

    2013-01-01

    The balance between the innate immunity of the host and the ability of a pathogen to evade it strongly influences pathogenesis and virulence. The two nonstructural (NS) proteins, NS1 and NS2, of respiratory syncytial virus (RSV) are critically required for RSV virulence. Together, they strongly suppress the type I interferon (IFN)-mediated innate immunity of the host cells by degrading or inhibiting multiple cellular factors required for either IFN induction or response pathways, including RIG-I, IRF3, IRF7, TBK1 and STAT2. Here, we provide evidence for the existence of a large and heterogeneous degradative complex assembled by the NS proteins, which we named “NS-degradasome” (NSD). The NSD is roughly ∼300-750 kD in size, and its degradative activity was enhanced by the addition of purified mitochondria in vitro. Inside the cell, the majority of the NS proteins and the substrates of the NSD translocated to the mitochondria upon RSV infection. Genetic and pharmacological evidence shows that optimal suppression of innate immunity requires mitochondrial MAVS and mitochondrial motility. Together, we propose a novel paradigm in which the mitochondria, known to be important for the innate immune activation of the host, are also important for viral suppression of the innate immunity. PMID:23877405