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Sample records for th1-type antigens recognized

  1. Induction of antigen-specific Th1-type immune responses by gamma-irradiated recombinant Brucella abortus RB51.

    Science.gov (United States)

    Sanakkayala, Neelima; Sokolovska, Anna; Gulani, Jatinder; Hogenesch, Harm; Sriranganathan, Nammalwar; Boyle, Stephen M; Schurig, Gerhardt G; Vemulapalli, Ramesh

    2005-12-01

    Brucella abortus strain RB51 is an attenuated rough mutant used as the live vaccine against bovine brucellosis in the United States and other countries. We previously reported the development of strain RB51 as a bacterial vaccine vector for inducing Th1-type immune responses against heterologous proteins. Because safety concerns may preclude the use of strain RB51-based recombinant live vaccines, we explored the ability of a gamma-irradiated recombinant RB51 strain to induce heterologous antigen-specific immune responses in BALB/c mice. Exposure of strain RB51G/LacZ expressing Escherichia coli beta-galactosidase to a minimum of 300 kilorads of gamma radiation resulted in complete loss of replicative ability. These bacteria, however, remained metabolically active and continued to synthesize beta-galactosidase. A single intraperitoneal inoculation of mice with 10(9) CFU equivalents of gamma-irradiated, but not heat-killed, RB51G/LacZ induced a beta-galactosidase-specific Th1-type immune response. Though no obvious differences were detected in immune responses to B. abortus-specific antigens, mice vaccinated with gamma-irradiated, but not heat-killed, RB51G/LacZ developed significant protection against challenge with virulent B. abortus. In vitro experiments indicated that gamma-irradiated and heat-killed RB51G/LacZ induced maturation of dendritic cells; however, stimulation with gamma-irradiated bacteria resulted in more interleukin-12 secretion. These results suggest that recombinant RB51 strains exposed to an appropriate minimum dose of gamma radiation are unable to replicate but retain their ability to stimulate Th1 immune responses against the heterologous antigens and confer protection against B. abortus challenge in mice.

  2. Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response.

    Science.gov (United States)

    Handman, E; Symons, F M; Baldwin, T M; Curtis, J M; Scheerlinck, J P

    1995-11-01

    Leishmania major promastigote surface antigen-2 complex (PSA-2) comprises a family of three similar but distinct polypeptides. The three PSA-2 polypeptides were purified from cultured promastigotes by a combination of detergent phase separation and monoclonal antibody affinity chromatography. Intraperitoneal vaccination of C3H/He mice with PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent L. major. Significant protection was also obtained in the genetically susceptible BALB/cH-2k and BALB/c mice. One of the PSA-2 genes was cloned and expressed in both Escherichia coli and Leishmania mexicana promastigotes. Vaccination with the recombinant PSA-2 purified from E. coli did not confer protection, in contrast to the L. mexicana-derived recombinant PSA-2, which provided excellent protection. CD4+ T cells isolated from the spleens of vaccinated mice produced large amounts of gamma interferon but no detectable interleukin 4 upon stimulation with PSA-2 in vitro. Limiting dilution analysis showed a marked increase in the precursor frequency of PSA-2-specific gamma interferon-secreting CD4+ T cells. No substantial change in precursor frequency was observed for interleukin 4-secreting T cells in the vaccinated mice. A CD4+ PSA-2 specific T-cell line generated from splenocytes of a vaccinated mouse produces a cytokine pattern consistent with a TH1 phenotype. Intravenous injection of this line into naive mice reduced significantly the parasite burden upon challenge infection. Taken together, the data suggest that vaccination with PSA-2 induces a TH1 type of immune response which protects mice from L. major infection. Moreover, a single recombinant PSA-2 polypeptide derived from a genomic clone can also vaccinate, provided that the structural form of the antigen is near native.

  3. Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response.

    OpenAIRE

    Handman, E; Symons, F M; Baldwin, T M; Curtis, J M; Scheerlinck, J P

    1995-01-01

    Leishmania major promastigote surface antigen-2 complex (PSA-2) comprises a family of three similar but distinct polypeptides. The three PSA-2 polypeptides were purified from cultured promastigotes by a combination of detergent phase separation and monoclonal antibody affinity chromatography. Intraperitoneal vaccination of C3H/He mice with PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent L. major. ...

  4. Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies

    International Nuclear Information System (INIS)

    Holers, V.M.; Kotzin, B.L.

    1985-01-01

    The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases

  5. T Cell Receptors that Recognize the Tyrosinase Tumor Antigen | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute, Surgery Branch, Tumor Immunology Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize T Cells Attacking Cancer: T Cell Receptors that Recognize the Tyrosinase Tumor Antigen

  6. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes.

    Science.gov (United States)

    Boël, P; Wildmann, C; Sensi, M L; Brasseur, R; Renauld, J C; Coulie, P; Boon, T; van der Bruggen, P

    1995-02-01

    Several tumor antigens are recognized by autologous cytolytic T lymphocytes (CTL) on human melanoma MZ2-MEL. Some of them are encoded by genes MAGE-1 and MAGE-3, which are not expressed in normal tissues except in testis. Here, we report the identification of a new gene that codes for another of these antigens. This gene, named BAGE, codes for a putative protein of 43 aa and seems to belong to a family of several genes. The antigen recognized by the autologous CTL consists of BAGE-encoded peptide AARAVFLAL bound to an HLA-Cw 1601 molecule. Gene BAGE is expressed in 22% of melanomas, 30% of infiltrating bladder carcinomas, 10% of mammary carcinomas, 8% of head and neck squamous cell carcinomas, and 6% of non-small cell lung carcinomas. Like the MAGE genes, it is silent in normal tissues with the exception of testis. Because of its tumor-specific expression, the BAGE-encoded antigen may prove useful for cancer immunotherapy.

  7. Excretory-secretory antigenic components of Paragonimus heterotremus recognized by infected human sera.

    Science.gov (United States)

    Maleewong, W; Wongkham, C; Intapan, P; Pariyanonda, S; Morakote, N

    1992-01-01

    Antigenic components of Paragonimus heterotremus metabolic products were revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis of sera from patients with P. heterotremus infection, from patients with other illnesses, and from healthy adults. By SDS-PAGE, it was found that the metabolic products comprised more than eight major polypeptides. Immunoblot analysis revealed 11 components which were strongly recognized by paragonimiasis antisera. These antigenic components had molecular masses ranging from less than 12.3 kDa to 144 kDa. One antigenic band of 31.5 kDa was found to give a consistent reaction with paragonimiasis antisera (97% sensitivity). Of the other patient sera, only sera from patients with Fasciola sp. infection reacted with antigenic bands of 56, 38, and 18.5 kDa. The present findings suggest that the 31.5-kDa component is sensitive and specific for the diagnosis of human P. heterotremus paragonimiasis. Images PMID:1500515

  8. Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice

    International Nuclear Information System (INIS)

    Jin Huali; Xiao Chong; Chen Ze; Kang Youmin; Ma Yijie; Zhu Kaichun; Xie Qifa; Tu Yixian; Yu Yang; Wang Bin

    2005-01-01

    Vaccination against the SARS-CoV infection is an attractive means to control the spread of viruses in public. In this study, we employed a DNA vaccine technology with the levamisole, our newly discovered chemical adjuvant, to generate Th1 type of response. To avoid the enhancement antibody issue, genes encoding the nucleocapsid, membrane, and envelope protein of SARS-CoV were cloned and their expressions in mammalian cells were determined. After the intramuscular introduction into animals, we observed that the constructs of the E, M, and N genes could induce high levels of specific antibodies, T cell proliferations, IFN-γ, DTH responses, and in vivo cytotoxic T cells activities specifically against SARS-CoV antigens. The highest immune responses were generated by the construct encoding the nucleocapsid protein. The results suggest that the N, M, and E genes could be used as the targets to prevent SARS-CoV infection in the DNA vaccine development

  9. Th1 type lymphocyte reactivity to metals in patients with total hip arthroplasty

    Directory of Open Access Journals (Sweden)

    Finnegan Alison

    2008-02-01

    releasing IFN-gamma and IL-4, respectively between those total hip arthroplasty subjects which demonstrated metal-reactivity and those that did not, indicated a Th1 type (IFN-gamma pro-inflammatory response. Conclusion Elevated proliferation and production of IFN-gamma to metals in hip arthroplasty subjects' lymphocytes indicates that a Th1 (vs. Th2 type response is likely associated with any metal induced reactivity. The involvement of an elevated and specific lymphocyte response suggests an adaptive (macrophage recruiting immunity response to metallic implant debris rather than an innate (nonspecific immune response.

  10. Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs.

    Science.gov (United States)

    Pollak, Cora N; Wanke, María Magdalena; Estein, Silvia M; Delpino, M Victoria; Monachesi, Norma E; Comercio, Elida A; Fossati, Carlos A; Baldi, Pablo C

    2015-03-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Alternative variants of human HYDIN are novel cancer-associated antigens recognized by adaptive immunity.

    Science.gov (United States)

    Laske, Karoline; Shebzukhov, Yuriy V; Grosse-Hovest, Ludger; Kuprash, Dmitry V; Khlgatian, Svetlana V; Koroleva, Ekaterina P; Sazykin, Alexey Y; Penkov, Dmitry N; Belousov, Pavel V; Stevanovic, Stefan; Vass, Verona; Walter, Steffen; Eisel, David; Schmid-Horch, Barbara D; Nedospasov, Sergei A; Rammensee, Hans-Georg; Gouttefangeas, Cécile

    2013-09-01

    A mutation in the hydin gene has been recently described as one possible mechanism leading to lethal congenital hydrocephalus in mice, and a similar defect is proposed to be involved in an autosomal recessive form of hydrocephalus in human. Here, we report for the first time on the cancer association and immunogenicity of two HYDIN variants in humans. One is a previously described sequence derived from the chromosome 1 gene copy, that is, KIAA1864. The second is encoded by a novel alternative transcript originating from the chromosome 16, which we identified by immunoscreening of a testis-derived cDNA expression library with sera of patients with colorectal cancer, and called MO-TES391. Both variants are targeted by immunoglobulin G antibodies in a significant subset of cancer patients but only rarely in healthy donors. Moreover, we identify HLA-A*0201-restricted sequences derived from MO-TES391 and KIAA1864, which are specifically recognized by human cytotoxic CD8(+) T cells. Taken together, these results suggest frequent and coordinated adaptive immune responses against HYDIN variants in patients with cancer and propose HYDIN as a novel cancer-associated antigen. ©2013 AACR.

  12. Gamma delta T cells recognize a microbial encoded B Cell antigen to initiate a rapid antigen-specific Interleukin-17 response

    Science.gov (United States)

    Gamma delta T cells contribute uniquely to host immune defense, but the way in which they do so remains an enigma. Here we show that an algae protein, phycoerythrin (PE) is recognized by gamma delta T cells from mice, bovine and humans and binds directly to specific gamma delta T cell antigen recept...

  13. Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

    Science.gov (United States)

    Radhakrishnan, Ammu Kutty; Mahalingam, Dashayini; Selvaduray, Kanga Rani; Nesaretnam, Kalanithi

    2013-01-01

    This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P < 0.05) in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P < 0.05) higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response. PMID:23936847

  14. Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

    Directory of Open Access Journals (Sweden)

    Ammu Kutty Radhakrishnan

    2013-01-01

    Full Text Available This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF, alpha-tocopherol (α-T, and delta-tocotrienol (δ-T3] to enhance immune response to tetanus toxoid (TT immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.. Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56 to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P<0.05 in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P<0.05 higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1 immune response.

  15. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria

    2014-12-04

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  16. Brucella abortus strain RB51 as a vector for heterologous protein expression and induction of specific Th1 type immune responses.

    Science.gov (United States)

    Vemulapalli, R; He, Y; Boyle, S M; Sriranganathan, N; Schurig, G G

    2000-06-01

    Brucella abortus strain RB51 is a stable, rough, attenuated mutant widely used as a live vaccine for bovine brucellosis. Our ultimate goal is to develop strain RB51 as a preferential vector for the delivery of protective antigens of other intracellular pathogens to which the induction of a strong Th1 type of immune response is needed for effective protection. As a first step in that direction, we studied the expression of a foreign reporter protein, beta-galactosidase of Escherichia coli, and the 65-kDa heat shock protein (HSP65) of Mycobacterium bovis in strain RB51. We cloned the promoter sequences of Brucella sodC and groE genes in pBBR1MCS to generate plasmids pBBSODpro and pBBgroE, respectively. The genes for beta-galactosidase (lacZ) and HSP65 were cloned in these plasmids and used to transform strain RB51. An enzyme assay in the recombinant RB51 strains indicated that the level of beta-galactosidase expression is higher under the groE promoter than under the sodC promoter. In strain RB51 containing pBBgroE/lacZ, but not pBBSODpro/lacZ, increased levels of beta-galactosidase expression were observed after subjecting the bacteria to heat shock or following internalization into macrophage-like J774A.1 cells. Mice vaccinated with either of the beta-galactosidase-expressing recombinant RB51 strains developed specific antibodies of predominantly the immunoglobulin G2a (IgG2a) isotype, and in vitro stimulation of their splenocytes with beta-galactosidase induced the secretion of gamma interferon (IFN-gamma), but not interleukin-4 (IL-4). A Th1 type of immune response to HSP65, as indicated by the presence of specific serum IgG2a, but not IgG1, antibodies, and IFN-gamma, but not IL-4, secretion by the specific-antigen-stimulated splenocytes, was also detected in mice vaccinated with strain RB51 containing pBBgroE/hsp65. Studies with mice indicated that expression of beta-galactosidase or HSP65 did not alter either the attenuation characteristics of strain RB51 or

  17. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.

    Directory of Open Access Journals (Sweden)

    Yukiko Kiniwa

    Full Text Available Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8(+ T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4(+ T helper (Th cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4(+ T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1 as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+ Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4(+ T cell-mediated immunotherapy in melanoma.

  18. Identification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells.

    Science.gov (United States)

    Goh, Shan; Ngugi, Daniel; Lizundia, Regina; Hostettler, Isabel; Woods, Kerry; Ballingall, Keith; MacHugh, Niall D; Morrison, W Ivan; Weir, Willie; Shiels, Brian; Werling, Dirk

    2016-01-01

    As part of an international effort to develop vaccines for Theileria lestoquardi, we undertook a limited screen to test T. lestoquardi orthologues of antigens recognised by CD8+ T lymphocyte responses against T. annulata and T. parva in cattle. Five MHC defined sheep were immunized by live T. lestoquardi infection and their CD8+ T lymphocyte responses determined. Thirteen T. lestoquardi orthologues of T. parva and T. annulata genes, previously shown to be targets of CD8+ T lymphocyte responses of immune cattle, were expressed in autologous fibroblasts and screened for T cell recognition using an IFNγ assay. Genes encoding T. lestoquardi antigens Tl8 (putative cysteine proteinase, 349 aa) or Tl9 (hypothetical secreted protein, 293 aa) were recognise by T cells from one animal that displayed a unique MHC class I genotype. Antigenic 9-mer peptide epitopes of Tl8 and Tl9 were identified through peptide scans using CD8+ T cells from the responding animal. These experiments identify the first T. lestoquardi antigens recognised by CD8+ T cell responses linked to specific MHC class I alleles.

  19. Identification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells.

    Directory of Open Access Journals (Sweden)

    Shan Goh

    Full Text Available As part of an international effort to develop vaccines for Theileria lestoquardi, we undertook a limited screen to test T. lestoquardi orthologues of antigens recognised by CD8+ T lymphocyte responses against T. annulata and T. parva in cattle. Five MHC defined sheep were immunized by live T. lestoquardi infection and their CD8+ T lymphocyte responses determined. Thirteen T. lestoquardi orthologues of T. parva and T. annulata genes, previously shown to be targets of CD8+ T lymphocyte responses of immune cattle, were expressed in autologous fibroblasts and screened for T cell recognition using an IFNγ assay. Genes encoding T. lestoquardi antigens Tl8 (putative cysteine proteinase, 349 aa or Tl9 (hypothetical secreted protein, 293 aa were recognise by T cells from one animal that displayed a unique MHC class I genotype. Antigenic 9-mer peptide epitopes of Tl8 and Tl9 were identified through peptide scans using CD8+ T cells from the responding animal. These experiments identify the first T. lestoquardi antigens recognised by CD8+ T cell responses linked to specific MHC class I alleles.

  20. Decreased Th1-type inflammatory cytokine expression in the skin is associated with persisting symptoms after treatment of erythema migrans.

    Science.gov (United States)

    Sjöwall, Johanna; Fryland, Linda; Nordberg, Marika; Sjögren, Florence; Garpmo, Ulf; Jansson, Christian; Carlsson, Sten-Anders; Bergström, Sven; Ernerudh, Jan; Nyman, Dag; Forsberg, Pia; Ekerfelt, Christina

    2011-03-31

    Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e.g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. A prospective follow-up study of 109 patients with EM was conducted at the Åland Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-γ, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-γ in the EM biopsies (p=0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal

  1. Clostridium perfringens Antigens Recognized by Broiler Chickens Immune to Necrotic Enteritis▿

    OpenAIRE

    Kulkarni, R. R.; Parreira, V. R.; Sharif, S.; Prescott, J. F.

    2006-01-01

    Little is known about immunity to necrotic enteritis (NE) in chickens. A recent study of broiler chickens showed that protection against NE was associated with infection-immunization with virulent but not with avirulent Clostridium perfringens.In the current study, six secreted antigenic proteins unique to virulent C. perfringens that reacted to serum antibodies from immune birds were identified by mass spectrophotometry; three of these proteins are part of the VirR-VirS regulon.

  2. NY-ESO-1-specific circulating CD4+ T cells in ovarian cancer patients are prevalently T(H)1 type cells undetectable in the CD25+ FOXP3+ Treg compartment.

    Science.gov (United States)

    Redjimi, Nassima; Duperrier-Amouriaux, Karine; Raimbaud, Isabelle; Luescher, Immanuel; Dojcinovic, Danijel; Classe, Jean-Marc; Berton-Rigaud, Dominique; Frenel, Jean-Sébastien; Bourbouloux, Emmanuelle; Valmori, Danila; Ayyoub, Maha

    2011-01-01

    Spontaneous CD4(+) T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4(+) T cells in EOC patients with spontaneous immune responses to the antigen are prevalently T(H)1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer(+) cells ex vivo, at an average frequency of 1:25,000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer(+) cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25(+)FOXP3(+)Treg. Thus, spontaneous CD4(+) T-cell responses to ESO in cancer patients are prevalently of T(H)1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines.

  3. NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment

    Science.gov (United States)

    Redjimi, Nassima; Duperrier-Amouriaux, Karine; Raimbaud, Isabelle; Luescher, Immanuel; Dojcinovic, Danijel; Classe, Jean-Marc; Berton-Rigaud, Dominique; Frenel, Jean-Sébastien; Bourbouloux, Emmanuelle

    2011-01-01

    Spontaneous CD4+ T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4+ T cells in EOC patients with spontaneous immune responses to the antigen are prevalently TH1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer+ cells ex vivo, at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer+ cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25+FOXP3+Treg. Thus, spontaneous CD4+ T-cell responses to ESO in cancer patients are prevalently of TH1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines. PMID:21829534

  4. Carbohydrate-rich high-molecular-mass antigens are strongly recognized during experimental Histoplasma capsulatum infection

    Directory of Open Access Journals (Sweden)

    Fabrine Sales Massafera Tristão

    2012-04-01

    Full Text Available INTRODUCTION: During histoplasmosis, Histoplasma capsulatum soluble antigens (CFAg can be naturally released by yeast cells. Because CFAg can be specifically targeted during infection, in the present study we investigated CFAg release in experimental murine histoplasmosis, and evaluated the host humoral immune response against high-molecular-mass antigens (hMMAg. >150 kDa, the more immunogenic CFAg fraction. METHODS: Mice were infected with 2.2x10(4 H. capsulatum IMT/HC128 yeast cells. The soluble CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg circulating immune complexes (CIC levels were determined by enzymelinked immunosorbent assay, at days 0, 7, 14, and 28 post-infection. RESULTS: We observed a progressive increase in circulating levels of CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg CIC after H. capsulatum infection. The hMMAg showed a high percentage of carbohydrates and at least two main immunogenic components. CONCLUSIONS: We verified for the first time that hMMAg from H. capsulatum IMT/HC128 strain induce humoral immune response and lead to CIC formation during experimental histoplasmosis.

  5. Biological characterization and clinical applications of a monoclonal antibody recognizing an antigen restricted to neuroectodermal tissues.

    Science.gov (United States)

    Allan, P M; Garson, J A; Harper, E I; Asser, U; Coakham, H B; Brownell, B; Kemshead, J T

    1983-05-15

    The monoclonal antibody UJ13A was raised following immunization of mice with human foetal brain and subsequent somatic cell hyridization of spleen cells with the mouse myeloma cell line P3-X63-AG8-653. The antibody is of the IgG1 subclass and has been shown by indirect immunofluorescence studies on normal foetal, paediatric and adult tissues to selectively bind to most tissues of neuroectodermal origin. Many tumours of neural origin also express the UJ13A antigen and the reagent can be used to distinguish primary intracranial neural tumours from secondary carcinomas and lymphomas. UJ13A is also useful as one of a panel of reagents employed for the identification of metastatic spread of neuroblastoma cells to bone marrow and cerebrospinal fluid. Knowledge of the full spectrum of normal and malignant tissues binding UJ13A suggests that the antibody may have a role in the radioimmunolocalization of neuronal tumours such as neuroblastoma.

  6. Decreased Th1-type inflammatory cytokine expression in the skin is associated with persisting symptoms after treatment of erythema migrans.

    Directory of Open Access Journals (Sweden)

    Johanna Sjöwall

    Full Text Available BACKGROUND: Despite the good prognosis of erythema migrans (EM, some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e.g. the early interaction between Borrelia (B. burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. METHODS: A prospective follow-up study of 109 patients with EM was conducted at the Åland Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL-4, IL-10, IL-12p70 and interferon (IFN-γ, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. FINDINGS: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-γ in the EM biopsies (p=0.003. B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. CONCLUSION: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the

  7. CryJ-LAMP DNA Vaccines for Japanese Red Cedar Allergy Induce Robust Th1-Type Immune Responses in Murine Model

    Directory of Open Access Journals (Sweden)

    Yan Su

    2016-01-01

    Full Text Available Allergies caused by Japanese Red Cedar (JRC pollen affect up to a third of Japanese people, necessitating development of an effective therapeutic. We utilized the lysosomal targeting property of lysosomal-associated membrane protein-1 (LAMP-1 to make DNA vaccines that encode LAMP-1 and the sequences of immunodominant allergen CryJ1 or CryJ2 from the JRC pollen. This novel strategy is designed to skew the CD4 T cell responses to the target allergens towards a nonallergenic Th1 response. CryJ1-LAMP and CryJ2-LAMP were administrated to BALB/c mice and antigen-specific Th1-type IgG2a and Th2-type IgG1 antibodies, as well as IgE antibodies, were assayed longitudinally. We also isolated different T cell populations from immunized mice and adoptively transferred them into naïve mice followed by CryJ1/CryJ2 protein boosts. We demonstrated that CryJ-LAMP immunized mice produce high levels of IFN-γ and anti-CryJ1 or anti-CryJ2 IgG2a antibodies and low levels of IgE antibodies, suggesting that a Th1 response was induced. In addition, we found that CD4+ T cells are the immunological effectors of DNA vaccination in this allergy model. Together, our results suggest the CryJ-LAMP Vaccine has a potential as an effective therapeutic for JRC induced allergy by skewing Th1/Th2 responses.

  8. CryJ-LAMP DNA Vaccines for Japanese Red Cedar Allergy Induce Robust Th1-Type Immune Responses in Murine Model.

    Science.gov (United States)

    Su, Yan; Connolly, Michael; Marketon, Anthony; Heiland, Teri

    2016-01-01

    Allergies caused by Japanese Red Cedar (JRC) pollen affect up to a third of Japanese people, necessitating development of an effective therapeutic. We utilized the lysosomal targeting property of lysosomal-associated membrane protein-1 (LAMP-1) to make DNA vaccines that encode LAMP-1 and the sequences of immunodominant allergen CryJ1 or CryJ2 from the JRC pollen. This novel strategy is designed to skew the CD4 T cell responses to the target allergens towards a nonallergenic Th1 response. CryJ1-LAMP and CryJ2-LAMP were administrated to BALB/c mice and antigen-specific Th1-type IgG2a and Th2-type IgG1 antibodies, as well as IgE antibodies, were assayed longitudinally. We also isolated different T cell populations from immunized mice and adoptively transferred them into naïve mice followed by CryJ1/CryJ2 protein boosts. We demonstrated that CryJ-LAMP immunized mice produce high levels of IFN-γ and anti-CryJ1 or anti-CryJ2 IgG2a antibodies and low levels of IgE antibodies, suggesting that a Th1 response was induced. In addition, we found that CD4(+) T cells are the immunological effectors of DNA vaccination in this allergy model. Together, our results suggest the CryJ-LAMP Vaccine has a potential as an effective therapeutic for JRC induced allergy by skewing Th1/Th2 responses.

  9. Commercial bacterins did not induce detectable levels of antibodies in mice against Mycoplasma hyopneumoniae antigens strongly recognized by swine immune system

    Directory of Open Access Journals (Sweden)

    Andressa Fisch

    2016-01-01

    Full Text Available Enzootic Pneumonia (EP caused by Mycoplasma hyopneumoniae results in major economic losses to the swine industry. Hence, the identification of factors that provide protection against EP could help to develop effective vaccines. One such factor that provides partial protection are bacterins. Therefore, the aim of this study was to verify the induction of antibodies against fifteen M. hyopneumoniae antigens, strongly recognized by the swine immune system during natural infection, in mice vaccinated with six commercial bacterins. Each group of mice was inoculated with one bacterin, and seroconversion was assessed by indirect ELISA using recombinant antigens and M. hyopneumoniae 7448 whole cell extract. Sera from one inoculated group recognized antigen MHP_0067, and sera from four inoculated groups recognized antigens MHP_0513 and MHP_0580. None of the bacterins was able to induce seroconversion against the twelve remaining antigens. This absence of a serological response could be attributed to the lack of antigen expression in M. hyopneumoniae strains used in bacterin production. Additionally the partial protection provided by these vaccines could be due to low expression or misfolding of antigens during vaccine preparation. Therefore, the supplementation of bacterins with these recombinant antigens could be a potential alternative in the development of more effective vaccines.

  10. Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro.

    Science.gov (United States)

    Prasanna, Vaddi K; Venkatesh, Yeldur P

    2015-06-01

    Onion (Allium cepa), a bulb crop of economic importance, is known to have many health benefits. The major objective of the present study is to address the immunomodulatory properties of onion lectin (A. cepa agglutinin; ACA). ACA was purified from onion extract by D-mannose-agarose chromatography (yield: ~1 mg/kg). ACA is non-glycosylated and showed a molecular mass of ~12 kDa under reducing/non-reducing SDS-PAGE; glutaraldehyde cross-linking indicated that ACA is a non-covalent tetramer of ~12 kDa subunits. Its N-terminal sequence (RNVLLNNEGL; UniProt KB Accn. C0HJM8) showed 70-90% homology to mannose-specific Allium agglutinins. ACA showed specific hemagglutination activity of 8200 units/mg and is stable in the pH range 6-10 and up to 45° C. The immunomodulatory activity of ACA was assessed using the macrophage cell line, RAW264.7 and rat peritoneal macrophages; at 0.1 μg/well, it showed a significant increase (6-8-fold vs. control) in the production of nitric oxide at 24h, and significantly stimulated (2-4-fold vs. control) the production of pro-inflammatory cytokines (TNF-α and IL-12) at 24h. ACA (0.1 μg/well) enhanced the proliferation of murine thymocytes by ~4 fold (vs. control) at 24h; however, ACA does not proliferate B cell-enriched rat splenocytes. Further, it significantly elevated the expression levels of cytokines (IFN-γ and IL-2) over the control in murine thymocytes. Taken together, purified ACA induces a Th1-type immune response in vitro. Though present in low amounts, ACA may contribute to the immune-boosting potential of the popular spice onion since considerable amounts are consumed on a daily basis universally. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Kiichiro Kaji

    Full Text Available Squamous cell carcinoma antigen recognized by T cells 3 (SART3, a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC.The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315 were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ enzyme-linked immunospot and cytotoxic T lymphocyte (CTL assays using peripheral blood mononuclear cells (PBMCs in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677.The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.UMIN000005677.

  12. Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway.

    Science.gov (United States)

    Mariotti, Jacopo; Foley, Jason; Ryan, Kaitlyn; Buxhoeveden, Nicole; Kapoor, Veena; Amarnath, Shoba; Fowler, Daniel H

    2008-12-01

    Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted posttransplantation, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells.

  13. GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

    Science.gov (United States)

    Judkowski, Valeria; Bunying, Alcinette; Ge, Feng; Appel, Jon R.; Law, Kingyee; Sharma, Atima; Raja- Gabaglia, Claudia; Norori, Patricia; Santos, Radleigh G.; Giulianotti, Marc A.; Slifka, Mark K.; Douek, Daniel C.; Graham, Barney S.; Pinilla, Clemencia

    2011-01-01

    The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a “T cell–driven” methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens. PMID:21931646

  14. GM-CSF production allows the identification of immunoprevalent antigens recognized by human CD4+ T cells following smallpox vaccination.

    Directory of Open Access Journals (Sweden)

    Valeria Judkowski

    Full Text Available The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a "T cell-driven" methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.

  15. Western blot analysis of antigens specifically recognized by natural immune responses of patients with Japanese encephalitis infections.

    Science.gov (United States)

    Patarapotikul, J; Pothipunya, S; Wanotayan, R; Hongyantarachai, A; Tharavanij, S

    1993-06-01

    Specific recognition of antigenic proteins of Japanese encephalitis virus (JEV) by JE patients was investigated by using non-reducing and reducing Western immunoblot analysis. Under non-reducing conditions, the profile of JEV proteins recognized comprised E (52 kDa), NS1 (45 and 41 kDa), NS3 (66.2 kDa) and NS5 (103 and 97.4 kDa). When recognition patterns of sera from JE and dengue patients were compared, only slight differences between JE and dengue sera were found (under non-reducing conditions), involving only the 66.2 kDa protein: to this protein, JE sera exhibited greater reactivity, but not in greater frequency, than did dengue sera. In contrast, cerebrospinal fluid (CSF) from JE patients showed more differences from JE sera: CSF antibody lacked recognition of the 41 kDa protein and had lower frequencies, as well as less reactivities to several other proteins. These results suggested that restricted populations of lymphocytes were localized in the central nervous system of JE patients. The effect of reducing agent (2 beta-mercaptoethanol) on the recognition patterns of those groups of sera was also analysed: the reducing agent affected all the proteins mentioned above, however, the effects were not uniform. It is proposed that JE and dengue sera may recognize different epitopes on some or all of these proteins. Such differences cannot be detected by Western immunoblot analysis, but it would be feasible to test this hypothesis using epitope mapping with synthetic peptides in a multi-pin ELISA. Analysis in this fine detail is essential for designing improved JE vaccines.

  16. Cloning of a cDNA encoding a surface antigen of Schistosoma mansoni schistosomula recognized by sera of vassinated mice

    International Nuclear Information System (INIS)

    Dalton, J.P.; Tom, T.D.; Strand, M.

    1987-01-01

    Spleen cells of mice vaccinated with radiation-attenuated Schistosoma mansoni cercariae were used to produce monoclonal antibodies directed against newly transformed schistosomular surface antigens. One of these monoclonal antibodies recognized a polypeptide of 18 kDa. Binding was measured by radioimmunoassay. This glycoprotein was purified by monoclonal antibody immunoaffinity chromatography and a polyclonal antiserum was prepared against it. Immunofluorescence assays showed that the polyclonal antiserum bound to the surface of newly transformed schistosomula and lung-stage organisms but not to the surface of liver-stage and adult worms. Using this polyclonal antiserum we isolated recombinant clones from an adult worm cDNA expression library constructed in λgt11. Clone 654.2 contained an insert of 0.52 kilobase and hybridized to a 1.2-kilobase mRNA species from adult worms. Most importantly, clone 654.2 produced a fusion protein of 125 kDa that was reactive with sera of vaccinated mice that are capable of transferring resistance. This result encourages future vaccination trials with the fusion protein

  17. Major role for carbohydrate epitopes preferentially recognized by chronically infected mice in the determination of Schistosoma mansoni schistosomulum surface antigenicity

    International Nuclear Information System (INIS)

    Omer-ali, P.; Magee, A.I.; Kelly, C.; Simpson, A.J.G.

    1986-01-01

    A radioimmunoassay that makes use of whole Schistosomula and 125 I-labeled protein A has been used to characterize and to quantify the binding of antisera to the surface of 3 hr mechanically transformed schistosomula of Schistosoma mansoni. This technique facilitates the determination of epitopes on the schistosomula in addition to those detected by surface labeling and immunoprecipitation. By using this technique, it has been demonstrated that there is a much greater binding to the parasite surface of antibodies from chronically infected mice (CMS) than of antibodies from mice infected with highly irradiated cercariae (VMS), and CMS recognizes epitopes that VMS does not. Treatment of the surface of the schistosomula with trifluoromethanesulphonic acid and sodium metaperiodate has suggested that the discrepancy of the binding between the two sera is due to the recognition of a large number of additional epitopes by CMS, which are carbohydrate in nature. Some of the carbohydrate epitopes are expressed on the previously described surface glycoprotein antigens of M/sub r/ 200,000, 38,000, and 17,000

  18. Interferon-¿ and interleukin-4 production by human T cells recognizing Leishmania donovani antigens separated by SDS-PAGE

    DEFF Research Database (Denmark)

    Bahrenscheer, J; Kemp, M; Kurtzhals, J A

    1995-01-01

    of proliferation and interferon-gamma (IFN-gamma) production in cultures of peripheral blood mononuclear cells (PBMC) from individuals who had recovered from visceral leishmaniasis caused by L. donovani. The release of interleukin-4 (IL-4) by PBMC stimulated with the isolated L. donovani antigen fractions...... was infrequently observed. The results show that T cells from individuals who have been cured of visceral leishmaniasis recognize and respond to a wide range of leishmanial antigens. There was no evidence of particular fractions constantly giving either IFN-gamma or IL-4-producing responses....

  19. A Promising Listeria-Vectored Vaccine Induces Th1-Type Immune Responses and Confers Protection Against Tuberculosis

    Directory of Open Access Journals (Sweden)

    Yuelan Yin

    2017-09-01

    Full Text Available Deaths associated with tuberculosis (TB is rising and accounted for 1.4 million deaths in 2015 many of which were due to drug-resistant bacteria. Vaccines represent an important medical intervention, but the current Bacilli Calmette-Guerin (BCG vaccine is not ideal for the protection of teenagers and adults. Therefore, a safe and effective vaccine is urgently needed. In this study, we designed a novel vaccine using an attenuated Listeria monocytogenes strain carrying fusion antigen FbpB-ESAT-6 (rLM and characterized its safety and protective efficacy against Mycobacterium tuberculosis (M.tb infection in mice. Compared to the wild type strain yzuLM4 and parental strain LMΔactA/plcB (LM1-2, the virulence of rLM was significantly reduced as judged by its infectious kinetics and LD50 dose. Further characterization of intravenous immunization showed that prime-boost vaccination significantly increased the levels of Th1 cytokines (IFN-γ, IL-17, and IL-6, and enhanced cytotoxic T lymphocyte (CTL CTLs activity, suggesting that rLM could elicit potent Th1/Th17 responses. More importantly, rLM significantly conferred the protection against M.tb H37Rv challenge. Collectively, our findings indicated that rLM is a novel and useful tool to prevent M.tb infection, and can be potentially be used to boost BCG-primed immunity.

  20. Insights into the biological features of the antigenic determinants recognized by four monoclonal antibodies in redia and adult stages of the liver fluke Fasciola hepatica.

    Science.gov (United States)

    Alba, Annia; Sánchez, Jorge; Hernández, Hilda; Mosqueda, Maryani; Rodríguez, Suanel Y; Capó, Virginia; Otero, Oscar; Alfonso, Carlos; Marcet, Ricardo; Sarracent, Jorge

    2016-09-01

    Fasciola hepatica is a digenean trematode which infects a wide variety of domestic animals and also humans. Previous studies have demonstrated that four monoclonal antibodies (Mabs) against the total extract of F. hepatica redia (named as 1E4, 6G11, 4E5 and 4G11) also recognized the excretion - secretion antigens (ES Ag) of adult parasites, which is a biologically-relevant mixture of molecules with functional roles during infection and immune evasion on definitive hosts. In the present report we describe the partial characterization of the epitopes recognized by these Mabs by heat treatment, mercaptoethanol reduction, pronase proteolysis and sodium peryodate oxidation, which suggested their predominant protein and conformational nature. Also, a comparative study using immunodetection assays on crude extracts and on histological sections of both rediae and adults of F. hepatica were performed to explore the expression pattern of the antigenic determinants in these developmental stages. From these experiments it was found that the Mabs reacted most likely with the same proteins of approximately 64 and 105 kDa present on both rediae and adult's extracts. However, the 1E4, 6G11 and 4E5 Mabs also recognized other molecules of the total extract of F. hepatica adults, a fact that constitutes an evidence of the antigenic variation between both stages and points at a certain biological relevance of the recognized antigenic determinants. Immunolocalization studies on histological sections revealed that all Mabs reacted with the tegument of F. hepatica in both rediae and adults stages, while the epitopes recognized by 1E4, 6G11 and 4E5 antibodies were also preferentially localized in the intestinal caeca and in different organs of the reproductive system of adult specimens. The immunogenicity of these antigenic determinants, their conserved status among different stages of the life cycle of F. hepatica and their presence in both tegument and ES Ag of adult parasites

  1. Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Nissen, Thomas Nørrelykke; Fredslund, Sine

    2016-01-01

    No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well...

  2. Identification and characterization of new Leishmania promastigote surface antigens, LaPSA-38S and LiPSA-50S, as major immunodominant excreted/secreted components of L. amazonensis and L. infantum

    OpenAIRE

    Bras Goncalves, Rachel; Petitdidier, Elodie; Pagniez, Julie; Veyrier, Renaud; Cibrelus, P.; Cavaleyra, Mireille; Maquaire, S.; Moreaux, J.; Lemesre, Jean-Loup

    2014-01-01

    We have previously demonstrated that sera from dogs vaccinated with excreted/secreted antigens (ESA) of Leishmania infantum promastigotes (LiESAp) mainly recognized an immunodominant antigen of 54 kDa. An anti-LiESAp-specific IgG2 humoral response was observed and associated to Th1-type response in vaccinated dogs. This response was highly correlated with a long-lasting and strong LiES-Ap-vaccine protection toward L. infantum experimental infection. In addition, it was also shown that dogs fr...

  3. Phytomonas serpens, a tomato parasite, shares antigens with Trypanosoma cruzi that are recognized by human sera and induce protective immunity in mice.

    Science.gov (United States)

    Breganó, José Wander; Picão, Renata Cristina; Graça, Viviane Krominski; Menolli, Rafael Andrade; Itow Jankevicius, Shiduca; Pinge Filho, P; Jankevicius, José Vítor

    2003-12-05

    The immune cross-reactivity between Trypanosoma cruzi, the protozoan that causes Chagas' disease, and Phytomonas serpens, a trypanosomatid that infects tomatoes, was studied. Sera from patients with Chagas' disease presented a strong reactivity with P. serpens antigens by conventional serological assays such as indirect immunofluorescence (IIF) and direct agglutination test (DAT), confirmed after cross-absorption experiments. The results show that this protozoan is highly immunogenic and that rabbit and mouse hyperimmune serum raised against T. cruzi or P. serpens was able to recognize both T. cruzi and P. serpens antigens in immunofluorescence and agglutination assays. The antigenic cross-reactivity between T. cruzi and P. serpens was also demonstrated in vivo. BALB/c mice immunized by the intraperitoneal or oral route with P. serpens and later challenged with a lethal inoculum of T. cruzi blood forms showed a significant decrease in parasitemia and increase in survival compared to controls. A practical implication of these findings is that the ingestion by humans or animals of living plant trypanosomatids present in naturally infected edible fruits could potentially prime the immune response to T. cruzi antigens and interfere with the development of T. cruzi infection.

  4. The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells.

    Science.gov (United States)

    Holtappels, R; Thomas, D; Podlech, J; Geginat, G; Steffens, H P; Reddehase, M J

    2000-02-01

    Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the "missing self." The retention, however, is counteracted by the m04 early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 might serve to silence NK cells and thereby complete the immune evasion of MCMV. In light of these current views, we provide here results demonstrating an in vivo role for gp34 in protective antiviral immunity. We have identified an antigenic nonapeptide derived from gp34 and presented by the MHC-I molecule D(d). Besides the immunodominant immediate-early nonapeptide consisting of IE1 amino acids 168-176 (IE1(168-176)), the early nonapeptide m04(243-251) is the second antigenic peptide described for MCMV. The primary immune response to MCMV generates significant m04-specific CD8 T-cell memory. Upon adoptive transfer into immunodeficient recipients, an m04-specific CTL line controls MCMV infection with an efficacy comparable to that of an IE1-specific CTL line. Thus, gp34 is the first noted early protein of MCMV that escapes viral immune evasion mechanisms. These data document that MCMV is held in check by a redundance of protective CD8 T cells recognizing antigenic peptides in different phases of viral gene expression.

  5. Identification of Eps15 as antigen recognized by the monoclonal antibodies aa2 and ab52 of the Wuerzburg Hybridoma Library against Drosophila brain.

    Directory of Open Access Journals (Sweden)

    Partho Halder

    Full Text Available The Wuerzburg Hybridoma Library against the Drosophila brain represents a collection of around 200 monoclonal antibodies that bind to specific structures in the Drosophila brain. Here we describe the immunohistochemical staining patterns, the Western blot signals of one- and two-dimensional electrophoretic separation, and the mass spectrometric characterization of the target protein candidates recognized by the monoclonal antibodies aa2 and ab52 from the library. Analysis of a mutant of a candidate gene identified the Drosophila homolog of the Epidermal growth factor receptor Pathway Substrate clone 15 (Eps15 as the antigen for these two antibodies.

  6. The Putative Natural Killer Decoy Early Gene m04 (gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T Cells

    OpenAIRE

    Holtappels, Rafaela; Thomas, Doris; Podlech, Jürgen; Geginat, Gernot; Steffens, Hans-Peter; Reddehase, Matthias J.

    2000-01-01

    Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the “missing self.” The re...

  7. Identification of special AT-rich sequence binding protein 1 as a novel tumor antigen recognized by CD8+ T cells: implication for cancer immunotherapy.

    Directory of Open Access Journals (Sweden)

    Mingjun Wang

    Full Text Available BACKGROUND: A large number of human tumor-associated antigens that are recognized by CD8(+ T cells in a human leukocyte antigen class I (HLA-I-restricted fashion have been identified. Special AT-rich sequence binding protein 1 (SATB1 is highly expressed in many types of human cancers as part of their neoplastic phenotype, and up-regulation of SATB1 expression is essential for tumor survival and metastasis, thus this protein may serve as a rational target for cancer vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Twelve SATB1-derived peptides were predicted by an immuno-informatics approach based on the HLA-A*02 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs obtained from HLA-A*02(+ healthy donors and/or HLA-A*02(+ cancer patients. The recognition of HLA-A*02(+ SATB1-expressing cancer cells was also tested. Among the twelve SATB1-derived peptides, SATB1(565-574 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and cancer patients. Importantly, SATB1(565-574-specific T cells recognized and killed HLA-A*02(+ SATB1(+ cancer cells in an HLA-I-restricted manner. CONCLUSIONS/SIGNIFICANCE: We have identified a novel HLA-A*02-restricted SATB1-derived peptide epitope recognized by CD8(+ T cells, which, in turn, recognizes and kills HLA-A*02(+ SATB1(+ tumor cells. The SATB1-derived epitope identified may be used as a diagnostic marker as well as an immune target for development of cancer vaccines.

  8. Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+ T cells for cancer immunotherapy.

    Directory of Open Access Journals (Sweden)

    Satoko Matsueda

    Full Text Available Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8(+ T cells in an HLA-A2 dependent manner.Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs obtained from either HLA-A2(+ healthy donors or HLA-A2(+ prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner.We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8(+ T cells, which, in turn, recognize HLA-A2(+ and PSGR(+ tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.

  9. The protease inhibitor alpha-2-macroglobulin-like-1 is the p170 antigen recognized by paraneoplastic pemphigus autoantibodies in human.

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    Isabelle Schepens

    Full Text Available BACKGROUND: Paraneoplastic pemphigus (PNP is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170, thought to be critical in PNP pathogenesis, has remained unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using an immunoprecipitation and mass spectrometry based approach, we identified p170 as alpha-2-macroglobuline-like-1, a broad range protease inhibitor expressed in stratified epithelia and other tissues damaged in the PNP disease course. We demonstrate that 10 PNP sera recognize alpha-2-macroglobuline-like-1 (A2ML1, while none of the control sera obtained from patients with bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus and normal subjects does. CONCLUSIONS/SIGNIFICANCE: Our study unravels a broad range protease inhibitor as a new class of target antigens in a paraneoplastic autoimmune multiorgan syndrome and opens a new challenging investigation avenue for a better understanding of PNP pathogenesis.

  10. Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro

    International Nuclear Information System (INIS)

    Shiba, Takahiro; Kawakami, Koji; Sasaki, Takashi; Makino, Ikuyo; Kato, Ikuo; Kobayashi, Toshihide; Uchida, Kazumi; Kaneko, Kimiyuki

    2014-01-01

    Protein fermentation by intestinal bacteria generates various compounds that are not synthesized by their hosts. An example is p-cresol, which is produced from tyrosine. Patients with chronic kidney disease (CKD) accumulate high concentrations of intestinal bacteria-derived p-cresyl sulfate (pCS), which is the major metabolite of p-cresol, in their blood, and this accumulation contributes to certain CKD-associated disorders. Immune dysfunction is a CKD-associated disorder that frequently contributes to infectious diseases among CKD patients. Although some studies imply pCS as an etiological factor, the relation between pCS and immune systems is poorly understood. In the present study, we investigated the immunological effects of pCS derived from intestinal bacteria in mice. For this purpose, we fed mice a tyrosine-rich diet that causes the accumulation of pCS in their blood. The mice were shown to exhibit decreased Th1-driven 2, 4-dinitrofluorobenzene-induced contact hypersensitivity response. The concentration of pCS in blood was negatively correlated with the degree of the contact hypersensitivity response. In contrast, the T cell-dependent antibody response was not influenced by the accumulated pCS. We also examined the in vitro cytokine responses by T cells in the presence of pCS. The production of IFN-γ was suppressed by pCS. Further, pCS decreased the percentage of IFN-γ-producing Th1 cells. Our results suggest that intestinal bacteria-derived pCS suppressesTh1-type cellular immune responses. - Highlights: • Mice fed a tyrosine-rich diet accumulated p-cresyl sulfate in their blood. • p-Cresyl sulfate negatively correlated with contact hypersensitivity response. • The in vitro production of IFN-γ was suppressed by p-cresyl sulfate. • p-Cresyl sulfate decreased the percentage of IFN-γ-producing Th1 cells in vitro

  11. Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Takahiro, E-mail: takahiro-shiba@yakult.co.jp; Kawakami, Koji; Sasaki, Takashi; Makino, Ikuyo; Kato, Ikuo; Kobayashi, Toshihide; Uchida, Kazumi; Kaneko, Kimiyuki

    2014-01-15

    Protein fermentation by intestinal bacteria generates various compounds that are not synthesized by their hosts. An example is p-cresol, which is produced from tyrosine. Patients with chronic kidney disease (CKD) accumulate high concentrations of intestinal bacteria-derived p-cresyl sulfate (pCS), which is the major metabolite of p-cresol, in their blood, and this accumulation contributes to certain CKD-associated disorders. Immune dysfunction is a CKD-associated disorder that frequently contributes to infectious diseases among CKD patients. Although some studies imply pCS as an etiological factor, the relation between pCS and immune systems is poorly understood. In the present study, we investigated the immunological effects of pCS derived from intestinal bacteria in mice. For this purpose, we fed mice a tyrosine-rich diet that causes the accumulation of pCS in their blood. The mice were shown to exhibit decreased Th1-driven 2, 4-dinitrofluorobenzene-induced contact hypersensitivity response. The concentration of pCS in blood was negatively correlated with the degree of the contact hypersensitivity response. In contrast, the T cell-dependent antibody response was not influenced by the accumulated pCS. We also examined the in vitro cytokine responses by T cells in the presence of pCS. The production of IFN-γ was suppressed by pCS. Further, pCS decreased the percentage of IFN-γ-producing Th1 cells. Our results suggest that intestinal bacteria-derived pCS suppressesTh1-type cellular immune responses. - Highlights: • Mice fed a tyrosine-rich diet accumulated p-cresyl sulfate in their blood. • p-Cresyl sulfate negatively correlated with contact hypersensitivity response. • The in vitro production of IFN-γ was suppressed by p-cresyl sulfate. • p-Cresyl sulfate decreased the percentage of IFN-γ-producing Th1 cells in vitro.

  12. Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

    OpenAIRE

    Cardoso, Fernanda C.; Macedo, Gilson C.; Gava, Elisandra; Kitten, Gregory T.; Mati, Vitor L.; de Melo, Alan L.; Caliari, Marcelo V.; Almeida, Giulliana T.; Venancio, Thiago M.; Verjovski-Almeida, Sergio; Oliveira, Sergio C.

    2008-01-01

    BACKGROUND: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present a...

  13. Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection.

    Directory of Open Access Journals (Sweden)

    Fernanda C Cardoso

    Full Text Available BACKGROUND: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r Sm29 and tested this protein as a vaccine candidate. METHODS AND FINDINGS: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05. Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01 down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. CONCLUSION: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

  14. Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection.

    Science.gov (United States)

    Cardoso, Fernanda C; Macedo, Gilson C; Gava, Elisandra; Kitten, Gregory T; Mati, Vitor L; de Melo, Alan L; Caliari, Marcelo V; Almeida, Giulliana T; Venancio, Thiago M; Verjovski-Almeida, Sergio; Oliveira, Sergio C

    2008-10-01

    Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate. We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

  15. Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device

    Directory of Open Access Journals (Sweden)

    Susanne Johansson

    2007-01-01

    Full Text Available The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector. CEA was expressed either in a membrane-bound form (wild-type CEA or in two truncated forms (CEA6 and CEA66 with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.

  16. Expanded cells in monoclonal TCR-{alpha}{beta}+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis recognize hCMV antigens

    NARCIS (Netherlands)

    A. Rodríguez-Caballero (Arancha); A.C. García-Montero (Andrés); P. Bárcena (Paloma); J.M.M. Almeida (Julia); F. Ruiz-Cabello (Francisco); M.D. Tabernero; P. Garrido (Pilar); S. Muñoz-Criado (Santiago); Y. Sandberg (Yorick); A.W. Langerak (Anton); M. González (Marcos); A. Balanzategui (Ana); A. Orfao (Alberto)

    2008-01-01

    textabstractRecent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal T-cell receptor (TCR)- αβ+/CD4+/NKa+/CD8-/+dimT-large granular lymphocyte (LGL) lymphocytosis. Because healthy persons show (oligo)clonal expansions of human cytomegalovirus

  17. Recognizing Symptoms

    Science.gov (United States)

    ... for IBS Signs and Symptoms Overview Recognizing Symptoms Diagnosis of IBS Pain in IBS IBS with Constipation Constipated Diarrhea IBS ... for IBS Signs and Symptoms Overview Recognizing Symptoms Diagnosis of IBS Pain in IBS IBS with Constipation Constipated Diarrhea IBS ...

  18. In silico and cell-based analyses reveal strong divergence between prediction and observation of T-cell-recognized tumor antigen T-cell epitopes.

    Science.gov (United States)

    Schmidt, Julien; Guillaume, Philippe; Dojcinovic, Danijel; Karbach, Julia; Coukos, George; Luescher, Immanuel

    2017-07-14

    Tumor exomes provide comprehensive information on mutated, overexpressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T-cell epitopes, because neoepitope-specific T cells often are tumoricidal. However, identifying tumor-specific T-cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen-binding peptides by in silico algorithms, but the predictive power of this approach is unclear. Here, we used the human tumor antigen NY-ESO-1 (ESO) and the human leukocyte antigen variant HLA-A*0201 (A2) as a model and predicted in silico the 41 highest-affinity, A2-binding 8-11-mer peptides and assessed their binding, kinetic complex stability, and immunogenicity in A2-transgenic mice and on peripheral blood mononuclear cells from ESO-vaccinated melanoma patients. We found that 19 of the peptides strongly bound to A2, 10 of which formed stable A2-peptide complexes and induced CD8 + T cells in A2-transgenic mice. However, only 5 of the peptides induced cognate T cells in humans; these peptides exhibited strong binding and complex stability and contained multiple large hydrophobic and aromatic amino acids. These results were not predicted by in silico algorithms and provide new clues to improving T-cell epitope identification. In conclusion, our findings indicate that only a small fraction of in silico -predicted A2-binding ESO peptides are immunogenic in humans, namely those that have high peptide-binding strength and complex stability. This observation highlights the need for improving in silico predictions of peptide immunogenicity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

    DEFF Research Database (Denmark)

    Hart, Jane; MacHugh, Niall D.; Sheldrake, Tara

    2017-01-01

    candidate viral gene products with CD8 T-cell lines from 3 BHV-1-immune cattle of defined MHC genotypes identified 4 antigens, including 3 immediate early (IE) gene products (ICP4, ICP22 and Circ) and a tegument protein (UL49). Identification of the MHC restriction specificities revealed that the antigens...... were presented by two or three class I MHC alleles in each animal. Six CD8 T-cell epitopes were identified in the three IE proteins by screening of synthetic peptides. Use of an algorithm (NetMHCpan) that predicts the peptide-binding characteristics of restricting MHC alleles confirmed and, in some......In common with other herpes viruses, bovine herpes virus 1 (BHV-1) induces strong virus-specific CD8 T-cell responses. However, there is a paucity of information on the antigenic specificity of the responding T-cells. The development of a system to generate virus-specific CD8 T-cell lines from BHV...

  20. Diversity of Francisella tularensis Schu4 antigens recognized by T lymphocytes after natural infections in humans: identification of candidate epitopes for inclusion in a rationally designed tularemia vaccine

    DEFF Research Database (Denmark)

    McMurry, Julie A; Gregory, Stephen H; Moise, Leonard

    2007-01-01

    The T lymphocyte antigens, which may have a role in protection against tularemia, were predicted by immunoinformatics analysis of Francisella tularensis Schu4. Twenty-seven class II putative promiscuous epitopes and 125 putative class I supertype epitopes were chosen for synthesis; peptides were...... tested in vitro for their ability to bind HLA and to induce immune responses from PBMCs of 23 previously infected subjects. While the immune responses of individual subjects showed heterogeneity, 95% of the subjects responded strongly to a pool of 27 promiscuous peptides; 25%, 33%, and 44% of subjects...

  1. Monoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of Mouse and Human Stem Cell Antigen Prominin-1 (CD133.

    Directory of Open Access Journals (Sweden)

    Kristina Thamm

    Full Text Available The pentaspan membrane glycoprotein prominin-1 (CD133 is widely used in medicine as a cell surface marker of stem and cancer stem cells. It has opened new avenues in stem cell-based regenerative therapy and oncology. This molecule is largely used with human samples or the mouse model, and consequently most biological tools including antibodies are directed against human and murine prominin-1. Although the general structure of prominin-1 including its membrane topology is conserved throughout the animal kingdom, its primary sequence is poorly conserved. Thus, it is unclear if anti-human and -mouse prominin-1 antibodies cross-react with their orthologs in other species, especially dog. Answering this issue is imperative in light of the growing number of studies using canine prominin-1 as an antigenic marker. Here, we address this issue by cloning the canine prominin-1 and use its overexpression as a green fluorescent protein fusion protein in Madin-Darby canine kidney cells to determine its immunoreactivity with antibodies against human or mouse prominin-1. We used immunocytochemistry, flow cytometry and immunoblotting techniques and surprisingly found no cross-species immunoreactivity. These results raise some caution in data interpretation when anti-prominin-1 antibodies are used in interspecies studies.

  2. Chemical Characterization of N-Linked Oligosaccharide As the Antigen Epitope Recognized by an Anti-Sperm Auto-Monoclonal Antibody, Ts4.

    Directory of Open Access Journals (Sweden)

    Hiroshi Yoshitake

    Full Text Available Ts4, an anti-sperm auto-monoclonal antibody, possesses immunoreactivity to the acrosomal region of mouse epididymal spermatozoa. In addition, the mAb shows specific immunoreactivity to reproduction-related regions such as testicular germ cells and early embryo. Our qualitative study previously showed that the antigen epitope for Ts4 contained a N-linked common oligosaccharide (OS chain on testicular glycoproteins as determined by Western blotting for testicular glycoproteins after treatment with several glycohydrolases. Since the distribution of the Ts4-epitope is unique, the OS chain in Ts4-epitope may have role(s in the reproductive process. The aim of this study was to clarify the molecular structure of the Ts4-epitope, particularly its OS moiety. Using Ts4 immunoprecipitation combined with liquid chromatography and multiple-stage mass spectrometry, the candidate carbohydrate structure in the Ts4-epitope is proposed to be N-linked fucosylated agalacto-biantennary with bisecting N-acetylglucosamine (GlcNAc or with N-acetylgalactosamine-GlcNAc motif. Further binding analyses using various lectins against the mouse testicular Ts4-immunoprecipitants revealed that Phaseolus vulgaris erythroagglutinin and Pisum sativum agglutinin showed positive staining of the bands corresponding to Ts4 reactive proteins. Moreover, the immunoreactivity of Ts4 against the testicular extract was completely abrogated after digestion with β-N-acetylglucosaminidase. These results show that the Ts4-epitope contains agalacto-biantennary N-glycan with bisecting GlcNAc carrying fucose residues.

  3. Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera.

    Science.gov (United States)

    Ravindranath, M H; Terasaki, P I; Maehara, C Y; Jucaud, V; Kawakita, S; Pham, T; Yamashita, W

    2015-02-01

    Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti-HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA-I/-II alleles, indicating that anti-HLA IgG may be masked in normal sera - either by peptides derived from soluble HLA or by those from antibodies. A HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti-HLA IgG purified from normal sera - and serum IgG from a few donors - indeed recognized the HLA types of the corresponding donors, confirming the presence of auto-HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto-HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto-HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg. © 2014 British Society for Immunology.

  4. 6-Phosphogluconate dehydrogenase is a 45-kDa antigen recognized by S4D5, a monoclonal antibody specific to vanadocytes in the vanadium-rich ascidian Ascidia sydneiensis samea.

    Science.gov (United States)

    Uyama, T; Kinoshita, T; Takahashi, H; Satoh, N; Kanamori, K; Michibata, H

    1998-08-01

    We previously prepared a monoclonal antibody, S4D5, specific to vanadocytes, vanadium-containing blood cells, in the vanadium-rich ascidian Ascidia sydneiensis samea. Here, we demonstrate that a 45-kDa antigen recognized by S4D5 is 6-phosphogluconate dehydrogenase (6-PGDH), an enzyme of the pentose phosphate pathway, based on cDNA isolation of RNA samples from blood cells of the ascidian. Western blot analysis confirmed an abundance of 6-PGDH protein in the vanadocytes and localization of 6-PGDH in the soluble extract of the blood cells. Soluble protein exhibited a correspondingly high level of 6-PGDH enzymatic activity. Ascidians are known to selectively accumulate high levels of vanadium in vanadocytes, and the highest recorded concentration of accumulated vanadium is 350 mM, which is 10(7) times the concentration in sea water. Almost all vanadium ions are reduced to the +3 oxidation state via the +4 oxidation state in vanadocytes, indicating that reducing agents must participate in the accumulation. On the other hand, vanadium ions in the +5 oxidation state are reduced to the +4 oxidation state by the presence of NADPH in vitro. Together, these observations suggest that NADPH produced in the pentose phosphate pathway may conjugate the reduction of vanadium from the +5 oxidation state through the +4 oxidation state in vanadocytes of ascidians.

  5. Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on em>Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A

    DEFF Research Database (Denmark)

    Ricke, C H; Staalsoe, T; Koram, K

    2000-01-01

    Abs from malaria-exposed multiparous women are able to interfere with binding of P. falciparum parasites to CSA in vitro, and acquisition of Abs interfering with CSA-specific parasite sequestration thus appears to be a critical element in acquired protection against PAM. Here we show that adults from...... an area of hyperendemic P. falciparum transmission generally possessed low levels of Abs specifically recognizing surface Ags expressed by a CSA-adhering parasite isolate, while unselected isolates were well recognized. In marked contrast, most third-trimester pregnant women from that area had very high...

  6. Antigenicity and protective efficacy of a Leishmania amastigote-specific protein, member of the super-oxygenase family, against visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Vivian T Martins

    Full Text Available The present study aimed to evaluate a hypothetical Leishmania amastigote-specific protein (LiHyp1, previously identified by an immunoproteomic approach performed in Leishmania infantum, which showed homology to the super-oxygenase gene family, attempting to select a new candidate antigen for specific serodiagnosis, as well as to compose a vaccine against VL.The LiHyp1 DNA sequence was cloned; the recombinant protein (rLiHyp1 was purified and evaluated for its antigenicity and immunogenicity. The rLiHyp1 protein was recognized by antibodies from sera of asymptomatic and symptomatic animals with canine visceral leishmaniasis (CVL, but presented no cross-reactivity with sera of dogs vaccinated with Leish-Tec, a Brazilian commercial vaccine; with Chagas' disease or healthy animals. In addition, the immunogenicity and protective efficacy of rLiHyp1 plus saponin was evaluated in BALB/c mice challenged subcutaneously with virulent L. infantum promastigotes. rLiHyp1 plus saponin vaccinated mice showed a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with the recombinant protein. Immunized and infected mice, as compared to the control groups (saline and saponin, showed significant reductions in the number of parasites found in the liver, spleen, bone marrow, and in the paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, produced mainly by CD4 T cells. In these mice, a decrease in the parasite-mediated IL-4 and IL-10 response could also be observed.The present study showed that this Leishmania oxygenase amastigote-specific protein can be used for a more sensitive and specific serodiagnosis of asymptomatic and symptomatic CVL and, when combined with a Th1-type adjuvant, can also be employ as a candidate antigen to develop vaccines against VL.

  7. Identification and characterization of new Leishmania promastigote surface antigens, LaPSA-38S and LiPSA-50S, as major immunodominant excreted/secreted components of L. amazonensis and L. infantum.

    Science.gov (United States)

    Bras-Gonçalves, Rachel; Petitdidier, Elodie; Pagniez, Julie; Veyrier, Renaud; Cibrelus, Prisca; Cavaleyra, Mireille; Maquaire, Sarah; Moreaux, Jérôme; Lemesre, Jean-Loup

    2014-06-01

    We have previously demonstrated that sera from dogs vaccinated with excreted/secreted antigens (ESA) of Leishmania infantum promastigotes (LiESAp) mainly recognized an immunodominant antigen of 54 kDa. An anti-LiESAp-specific IgG2 humoral response was observed and associated to Th1-type response in vaccinated dogs. This response was highly correlated with a long-lasting and strong LiESAp-vaccine protection toward L. infantum experimental infection. In addition, it was also shown that dogs from the vaccinated group developed a selective IgG2 response against an immunodominant antigen of 45 kDa of Leishmania amazonensis ESA promastigotes (LaESAp). In order to identify and characterize these immunodominant antigens, a mouse monoclonal antibody (mAb F5) was produced by immunization against LaESAp. It was found to recognize the major antigenic targets of both LaESAp and LiESAp. Analysis with mAb F5 of L. amazonensis amastigote and promastigote cDNA expression libraries enabled the identification of clones encoding proteins with significant structural homology to the promastigote surface antigens named PSA-2/gp-46. Among them, one clone presented a full-length cDNA and encoded a novel L. amazonensis protein of 38.6 kDa calculated molecular mass (LaPSA-38S) sharing an amino acid sequence consistent with that of the PSA polymorphic family and a N-terminal signal peptide, characteristic of a secreted protein. We then screened a L. infantum promastigote DNA cosmid library using a cDNA probe derived from the LaPSA-38S gene and identified a full-length clone of a novel excreted/secreted protein of L. infantum with a calculated molecular mass of 49.2 kDa and named LiPSA-50S. The fact that a significant immunological reactivity was observed against PSA, suggests that these newly identified proteins could have an important immunoregulatory influence on the immune response. This hypothesis is supported by the fact that (i) these proteins were naturally excreted/secreted by viable

  8. Accumulation of 111In-neutrophils in rabbit skin in allergic and non-allergic inflammatory reactions in vivo. Inhibition by neutrophil pretreatment in vitro with a monoclonal antibody recognizing the CD18 antigen

    International Nuclear Information System (INIS)

    Nourshargh, S.; Rampart, M.; Hellewell, P.G.; Jose, P.J.; Harlan, J.M.; Edwards, A.J.; Williams, T.J.

    1989-01-01

    The mAb 60.3 recognizes the neutrophil CD18 Ag. We have investigated the effect of in vitro pretreatment of radiolabeled neutrophils with mAb 60.3 on their accumulation in vivo. Further, we have compared the in vivo effects of mAb 60.3 with its effects on neutrophil adherence in vitro. Neutrophil accumulation in vivo was measured in response to: (1) exogenous mediators FMLP, C5a des Arg, LTB4 and IL-1; (2) endogenous mediators generated in a non-allergic inflammatory reaction induced by zymosan; and (3) endogenous mediators generated in two allergic inflammatory reactions, a passive cutaneous anaphylactic reaction and a reversed passive Arthus reaction in rabbit skin. Pretreatment of neutrophils with mAb 60.3 inhibited their accumulation in all the responses. The results demonstrate that there is a common mechanism mediating neutrophil accumulation in these inflammatory reactions. Neutrophils pretreated with mAb 60.3 were also unresponsive to chemoattractants in in vitro adherence assays. However, the antibody-treated neutrophils responded normally to FMLP and C5a with respect to granular enzyme release. These results suggest that the basal expression of CD18 Ag is important for the adherence of neutrophils to microvascular endothelial cells stimulated by the local generation, or administration, of chemical mediators in vivo. Despite the fact that mediators such as FMLP can increase CD18 expression in vitro, it appears more likely that such mediators act in vivo by inducing a conformational change in the basally expressed neutrophil adhesive molecules

  9. Recognizing teen depression

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000648.htm Recognizing teen depression To use the sharing features on this ... teen's life. Be Aware of the Risk for Teen Depression Your teen is more at risk for ...

  10. FDA Recognized Consensus Standards

    Data.gov (United States)

    U.S. Department of Health & Human Services — This database consists of those national and international standards recognized by FDA which manufacturers can declare conformity to and is part of the information...

  11. Recognizing genetic hemochromatosis.

    Science.gov (United States)

    Welch, F J

    1994-12-01

    This article reviews the disease process hemochromatosis, which is now recognized as one of the most common genetic disorders. Hemochromatosis is transmitted as autosomal recessive, and occurs in 3% of persons of Anglo-Saxon descent. It is caused by an inappropriate increase in intestinal iron absorption resulting in deposition of excess iron in tissues. Hemochromatosis usually presents in males in their 40s, and females much later. The most frequent initial symptoms are weakness, lassitude, weight loss, and symptoms related to the onset of diabetes mellitus. The classical triad of cirrhosis, diabetes mellitus, and skin pigmentation occurs late in the disease. There is debate over the value of mass screening for the disorder; however, it is recommended that once a case has been identified family members at risk should be screened. Therapy is directed at removing excess iron by phlebotomy. By instituting early therapy, many of the long-term complications, including cirrhosis and hepatoma, can be prevented. It is imperative that physicians learn to recognize early signs and symptoms of hemochromatosis so that treated patients can expect a normal life span with minimal medical intervention.

  12. Do monoclonal antibodies recognize linear sequential determinants?

    Science.gov (United States)

    Camera, M; Muratti, E; Trinca, M L; Chersi, A

    1988-01-01

    A group of 19 anti-class II monoclonal antibodies produced in different laboratories were tested in ELISA for their ability to bind to a panel of synthetic peptides selected from HLA-DQ alpha and beta chains. No one of the antibodies tested was found to react with the synthetic fragments, thus confirming the common finding that MoAbs generally fail to recognize fragments of the native antigen. The possibility that this result might be partly due to the procedure used for screening hybridoma supernatants is discussed.

  13. Studies on cocktails of 31-kDa, 36-kDa and 51-kDa antigens of Leishmania donovani along with saponin against murine visceral leishmaniasis.

    Science.gov (United States)

    Kaur, H; Thakur, A; Kaur, S

    2015-04-01

    A substantial number of antigens of Leishmania donovani have been described in the past. However, identifying candidate antigens is not enough. Appropriate antigen delivery to induce the right type of immune response against leishmaniasis (i.e. induction of a strong antigen-specific Th1 type of immune response) is another crucial component of an effective vaccine. Therefore, 'cocktail' vaccines are proposed based on the assumption that such cocktails will show enhanced efficacy. Studies have been carried out on LD31 and LD51 polypeptides from L. donovani promastigotes, which have proven to be potential vaccine candidates. This study was designed to check the protective efficacy of various cocktails of low molecular weight antigens alone and along with saponin as adjuvant. Mice were sacrificed on different post-challenge days for evaluation of parasite load and other immunological parameters. Protective efficacy of different vaccine formulations was revealed by significant decline in parasite burden and increased DTH Delayed Type Hypersenstivity responses. The antibody response was of IgG type with elevated IgG2a and decreased production of IgG1, whereas cytokine levels pointed towards the generation of protective Th1 type of immune response. Among all vaccine formulations, cocktail of 31+51+saponin was found to be highly immunogenic and imparted maximum protection. © 2015 John Wiley & Sons Ltd.

  14. How legumes recognize rhizobia.

    Science.gov (United States)

    Via, Virginia Dalla; Zanetti, María Eugenia; Blanco, Flavio

    2016-01-01

    Legume plants have developed the capacity to establish symbiotic interactions with soil bacteria (known as rhizobia) that can convert N2 to molecular forms that are incorporated into the plant metabolism. The first step of this relationship is the recognition of bacteria by the plant, which allows to distinguish potentially harmful species from symbiotic partners. The main molecular determinant of this symbiotic interaction is the Nod Factor, a diffusible lipochitooligosaccharide molecule produced by rhizobia and perceived by LysM receptor kinases; however, other important molecules involved in the specific recognition have emerged over the years. Secreted exopolysaccharides and the lipopolysaccharides present in the bacterial cell wall have been proposed to act as signaling molecules, triggering the expression of specific genes related to the symbiotic process. In this review we will briefly discuss how transcriptomic analysis are helping to understand how multiple signaling pathways, triggered by the perception of different molecules produced by rhizobia, control the genetic programs of root nodule organogenesis and bacterial infection. This knowledge can help to understand how legumes have evolved to recognize and establish complex ecological relationships with particular species and strains of rhizobia, adjusting gene expression in response to identity determinants of bacteria.

  15. Recognize and classify pneumoconiosis

    International Nuclear Information System (INIS)

    Hering, K.G.; Hofmann-Preiss, K.

    2014-01-01

    In the year 2012, out of the 10 most frequently recognized occupational diseases 6 were forms of pneumoconiosis. With respect to healthcare and economic aspects, silicosis and asbestos-associated diseases are of foremost importance. The latter are to be found everywhere and are not restricted to large industrial areas. Radiology has a central role in the diagnosis and evaluation of occupational lung disorders. In cases of known exposure mainly to asbestos and quartz, the diagnosis of pneumoconiosis, with few exceptions will be established primarily by the radiological findings. As these disorders are asymptomatic for a long time they are quite often detected as incidental findings in examinations for other reasons. Therefore, radiologists have to be familiar with the pattern of findings of the most frequent forms of pneumoconiosis and the differential diagnoses. For reasons of equal treatment of the insured a quality-based, standardized performance, documentation and evaluation of radiological examinations is required in preventive procedures and evaluations. Above all, a standardized low-dose protocol has to be used in computed tomography (CT) examinations, although individualized concerning the dose, in order to keep radiation exposure as low as possible for the patient. The International Labour Office (ILO) classification for the coding of chest X-rays and the international classification of occupational and environmental respiratory diseases (ICOERD) classification used since 2004 for CT examinations meet the requirements of the insured and the occupational insurance associations as a means of reproducible and comparable data for decision-making. (orig.) [de

  16. Human platelet antigens - 2013.

    Science.gov (United States)

    Curtis, B R; McFarland, J G

    2014-02-01

    To date, 33 human platelet alloantigens (HPAs) have been identified on six functionally important platelet glycoprotein (GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and multitransfusion platelet refractoriness (MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA-1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic 'systems' where the -a form designates the higher frequency allele and the -b form, the lower. Twenty-one other HPAs are low-frequency or rare antigens for which postulated higher frequency -a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen (HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR. © 2013 International Society of Blood Transfusion.

  17. The Duty to Recognize Culture

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2012-01-01

    On Taylor and Honneth's theories of recognition and whether one can derive a "duty to recognize Culture" from these......On Taylor and Honneth's theories of recognition and whether one can derive a "duty to recognize Culture" from these...

  18. Radioimmunoassay for detecting antibodies against murine malarial parasite antigens: monoclonal antibodies recognizing Plasmodium yoelii antigens

    International Nuclear Information System (INIS)

    Kim, K.J.; Taylor, D.W.; Evans, C.B.; Asofsky, R.

    1980-01-01

    A solid-phase radioimmunoassay (SPRIA) in microtiter wells was established for detecting antibodies against Plasmodium yoelii Ag. The SPRIA was found (1) to require as little as 5 μg of crude parasite Ag per well, (2) to be able to detect 0.5 ng of monoclonal Ab, and (3) to be 10 4 times more sensitive than the indirect fluorescent Ab staining technique. In a modification of the above assay using intact RBC as an Ag, hyperimmune serum showed significant binding to the surface of erythrocytes of mice infected with P. yoelii parasites but not to RBC of normal mice. Hybridomas were prepared by fusing infected mouse spleen cells with myeloma cells. Using the SPRIA, hybrids secreting Ab against P. yoelii 17XL Ag were detected

  19. Assessment of vaccine-induced CD4 T cell responses to the 119-143 immunodominant region of the tumor-specific antigen NY-ESO-1 using DRB1*0101 tetramers.

    Science.gov (United States)

    Ayyoub, Maha; Pignon, Pascale; Dojcinovic, Danijel; Raimbaud, Isabelle; Old, Lloyd J; Luescher, Immanuel; Valmori, Danila

    2010-09-15

    NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO(119-143) region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO(119-143) tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1). We generated tetramers of DRB1*0101 incorporating peptide ESO(119-143) using a previously described strategy. We assessed ESO(119-143)-specific CD4 T cells in peptide-stimulated postvaccine cultures using the tetramers. We isolated DR1/ESO(119-143) tetramer(+) cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4(+) DR1/ESO(119-143) tetramer(+) T cells ex vivo and characterized them phenotypically. Staining of cultures from vaccinated patients with DR1/ESO(119-143) tetramers identified vaccine-induced CD4 T cells. Tetramer(+) cells isolated by cell sorting were of T(H)1 type and efficiently recognized full-length ESO. We identified ESO(123-137) as the minimal optimal epitope recognized by DR1-restricted ESO-specific CD4 T cells. By assessing DR1/ESO(119-143) tetramer(+) cells using T cell receptor (TCR) β chain variable region (Vβ)-specific antibodies, we identified several frequently used Vβ. Finally, direct ex vivo staining of patients' CD4 T cells with tetramers allowed the direct quantification and phenotyping of vaccine-induced ESO-specific CD4 T cells. The development of DR1/ESO(119-143) tetramers, allowing the direct visualization, isolation, and characterization of ESO-specific CD4 T cells, will be instrumental for the evaluation of spontaneous and vaccine-induced immune responses to this important tumor antigen in DR1-expressing patients. ©2010 AACR.

  20. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  1. Flow Cytometric Determination of Cellular Sources and Frequencies of Key Cytokine-Producing Lymphocytes Directed against Recombinant LACK and Soluble Leishmania Antigen in Human Cutaneous Leishmaniasis

    Science.gov (United States)

    Bottrel, R. L. A.; Dutra, W. O.; Martins, F. A.; Gontijo, B.; Carvalho, E.; Barral-Netto, M.; Barral, A.; Almeida, R. P.; Mayrink, W.; Locksley, R.; Gollob, K. J.

    2001-01-01

    Leishmaniasis, caused by infection with the protozoan parasite Leishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-γ) production by several different sources, listed in order of contribution: CD4+ T lymphocytes, CD4−, CD8− lymphocytes, and CD8+ T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-γ and tumor necrosis factor alpha (TNF-α) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4+ T lymphocytes (IFN-γ+ and IL-10−/IL-4−), Tc1 CD8+ T cells (IFN-γ+, and IL-10−/IL-4−), and a high frequency of TNF-α-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA. PMID:11292745

  2. Carcinoma-associated antigens

    International Nuclear Information System (INIS)

    Bartorelli, A.; Accinni, R.

    1981-01-01

    This invention relates to novel antigens associated with breast carcinoma, anti-sera specific to said antigens, 125 I-labeled forms of said antigens and methods of detecting said antigens in serum or plasma. The invention also relates to a diagnostic kit containing standardised antigens or antisera or marked forms thereof for the detection of said antigens in human blood, serum or plasma. (author)

  3. Peripheral blood lymphocytes from low-grade squamous intraepithelial lesions patients recognize vaccine antigens in the presence of activated dendritic cells, and produced high levels of CD8 + IFNγ + T cells and low levels of IL-2 when induced to proliferate

    Directory of Open Access Journals (Sweden)

    Hernández-Montes Jorge

    2012-05-01

    Full Text Available Abstract Background Most infections with human papillomavirus (HPV are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL from low-grade squamous intraepithelial lesions (LSIL patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when

  4. Recognizing Prefixes in Scientific Quantities

    Science.gov (United States)

    Sokolowski, Andrzej

    2015-01-01

    Although recognizing prefixes in physical quantities is inherent for practitioners, it might not be inherent for students, who do not use prefixes in their everyday life experiences. This deficiency surfaces in AP Physics exams. For example, readers of an AP Physics exam reported "a common mistake of incorrectly converting nanometers to…

  5. ANTIGENIC PROMOTION

    Science.gov (United States)

    Wu, Chin-Yu; Cinader, Bernard

    1971-01-01

    Rabbits were immunized with p-azobenzene arsonic acid derivatives of human serum albumin (HA-As) or of dissociated keyhole limpet hemocyanin. The IgM response to the hapten was evaluated in terms of the number of hapten-specific plaque-forming cells in the lymph node draining the injection site. In some experiments, antibody was measured by agglutination of tanned and sensitized erythrocytes. The hapten response of animals immunized with HA-As was increased (promoting effect) when the animals were injected with one of several structurally unrelated macromolecules: keyhole limpet hemocyanin (KLH), horse spleen ferritin (HSF), lysozyme (Lys), alum-precipitated human gamma globulin (alum-precipitated HGG). Different macromolecules differed in the magnitude of the promoting effect they induced, e.g., promotion by the associated form of KLH was greater than that by the dissociated form; alum-precipitated HGG was a better promoter than was soluble HGG. The relative magnitude of promotion by different macromolecules (associated vs. dissociated KLH, alum-precipitated vs. soluble HGG) correlated with the relative magnitude of the carrier effect, as judged by the hapten response induced by p-azobenzene arsonic acid conjugated to various proteins. Promotion was detected by agglutination assay of circulating antibody, by plaque assay of cells from the popliteal lymph node draining the site of preinjection, but not by plaque assay of cells from the contralateral lymph node. Promotion was dependent on the dose of the promoting macromolecule and on the dose of the hapten-protein conjugate. It was not observed in animals tolerant to the promoting macromolecule. Inhibition (i.e. antigenic competition), rather than promotion, was observed upon a secondary response to the preinjected macromolecule or when the hapten-protein conjugate was incorporated in Freund's adjuvant. PMID:15776570

  6. Recognizing Body Dysmorphic Disorder (Dysmorphophobia).

    Science.gov (United States)

    Varma, Anukriti; Rastogi, Rajesh

    2015-01-01

    Dysmorphophobia is a psychiatric condition which frequently presents in the clinics of dermatologists and plastic surgeons. This disorder (also called body dysmorphic disorder) is troublesome to the patient whilst being confusing for the doctor. This commonly undiagnosed condition can be detected by a few simple steps. Timely referral to a psychiatrist benefits most patients suffering from it. This article describes with a case vignette, how to recognize body dysmorphic disorder presenting in the dermatological or aesthetic surgery set up. Diagnostic criteria, eitiology, approach to patient, management strategy and when to refer are important learning points. The importance of recognizing this disorder timely and referring the patient to the psychiatrist for appropriate treatment is crucial. This article covers all aspects of body dysmorphic disorder relevant to dermatologists and plastic surgeons and hopes to be useful in a better understanding of this disorder.

  7. Recognizing body dysmorphic disorder (dysmorphophobia

    Directory of Open Access Journals (Sweden)

    Anukriti Varma

    2015-01-01

    Full Text Available Dysmorphophobia is a psychiatric condition which frequently presents in the clinics of dermatologists and plastic surgeons. This disorder (also called body dysmorphic disorder is troublesome to the patient whilst being confusing for the doctor. This commonly undiagnosed condition can be detected by a few simple steps. Timely referral to a psychiatrist benefits most patients suffering from it. This article describes with a case vignette, how to recognize body dysmorphic disorder presenting in the dermatological or aesthetic surgery set up. Diagnostic criteria, eitiology, approach to patient, management strategy and when to refer are important learning points. The importance of recognizing this disorder timely and referring the patient to the psychiatrist for appropriate treatment is crucial.This article covers all aspects of body dysmorphic disorder relevant to dermatologists and plastic surgeons and hopes to be useful in a better understanding of this disorder.

  8. Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

    Science.gov (United States)

    Hasanzadeh, Leila; Ghaznavi-Rad, Ehsanollah; Soufian, Safieh; Farjadi, Vahideh; Abtahi, Hamid

    2013-01-01

    Objective(s) : Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA) is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity. Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3) pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis . PMID:23997913

  9. Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

    Directory of Open Access Journals (Sweden)

    Leila Hasanzadeh

    2013-07-01

    Full Text Available Objective(s: Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity.   Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3 pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis .

  10. Antibodies against HLA-DP recognize broadly expressed epitopes.

    Science.gov (United States)

    Simmons, Daimon P; Kafetzi, Maria L; Wood, Isabelle; Macaskill, Peter C; Milford, Edgar L; Guleria, Indira

    2016-12-01

    HLA matching and avoidance of pre-transplant donor-specific antibodies are important in selection of donors for solid organ transplant. Solid phase testing with single antigen beads allows resolution of antibody reactivity to the level of the allele. Single antigen bead testing results at a large transplant center were reviewed to identify selective reactivity patterns of anti-HLA antibodies. Many HLA-DP antibodies were identified in the context of other HLA antibodies, but some sera had antibodies against only HLA-DP. B cell flow crossmatch testing was positive for 2 out of 9 sera with HLA-DP antibodies. Many patterns of reactivity corresponded to epitopes in hypervariable regions C and F of DPB1, but some matched epitopes in other regions or DPA1. Through analysis of single antigen bead testing from a large number of patients, we report that anti-HLA-DP antibodies predominantly recognize broadly cross-reactive epitopes. The United Network for Organ Sharing has mandated HLA-DP typing on all deceased kidney donors, and HLA-DP epitopes should be considered as the major antigens for avoidance of pre-transplant donor-specific antibodies. Published by Elsevier Inc.

  11. Antarctic skuas recognize individual humans.

    Science.gov (United States)

    Lee, Won Young; Han, Yeong-Deok; Lee, Sang-Im; Jablonski, Piotr G; Jung, Jin-Woo; Kim, Jeong-Hoon

    2016-07-01

    Recent findings report that wild animals can recognize individual humans. To explain how the animals distinguish humans, two hypotheses are proposed. The high cognitive abilities hypothesis implies that pre-existing high intelligence enabled animals to acquire such abilities. The pre-exposure to stimuli hypothesis suggests that frequent encounters with humans promote the acquisition of discriminatory abilities in these species. Here, we examine individual human recognition abilities in a wild Antarctic species, the brown skua (Stercorarius antarcticus), which lives away from typical human settlements and was only recently exposed to humans due to activities at Antarctic stations. We found that, as nest visits were repeated, the skua parents responded at further distances and were more likely to attack the nest intruder. Also, we demonstrated that seven out of seven breeding pairs of skuas selectively responded to a human nest intruder with aggression and ignored a neutral human who had not previously approached the nest. The results indicate that Antarctic skuas, a species that typically inhabited in human-free areas, are able to recognize individual humans who disturbed their nests. Our findings generally support the high cognitive abilities hypothesis, but this ability can be acquired during a relatively short period in the life of an individual as a result of interactions between individual birds and humans.

  12. CD8(+) T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products

    NARCIS (Netherlands)

    Platteel, Anouk C M; Mishto, Michele; Textoris-Taube, Kathrin; Keller, Christin; Liepe, Juliane; Busch, Dirk H; Kloetzel, Peter M; Sijts, Alice J A M

    CD8(+) T cells responding to infection recognize pathogen-derived epitopes presented by MHC class-I molecules. While most of such epitopes are generated by proteasome-mediated antigen cleavage, analysis of tumor antigen processing has revealed that epitopes may also derive from proteasome-catalyzed

  13. Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

    OpenAIRE

    Long Zheng; Peisheng Hu; Brandon Wolfe; Caryn Gonsalves; Luqing Ren; Leslie A. Khawli; Harvey R. Kaslow; Alan L. Epstein

    2017-01-01

    T cells expressing chimeric antigen receptors (CARs) recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR) on the surface of human B-cell lymphomas...

  14. The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn

    Tumor antigens are a group of proteins recognized by the cells of immune system. Specifically, they are recognized in tumor cells where they are present in larger than usual amounts, or are physiochemically altered to a degree at which they no longer resemble native human proteins. Their presence...

  15. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker

    2012-01-01

    Large numbers of tumor associated antigens has been characterized, but only a minor fraction of these are recognized by tumor infiltrating lymphocytes of melanoma, although these have shown the ability to recognize tumor and provide tumor regression upon adoptive transfer. Thus the peptide...

  16. Enhancement of Th1 type cytokine production and primary T cell activation by PBI-1393.

    Science.gov (United States)

    Allam, Mustapha; Julien, Nathalie; Zacharie, Boulos; Penney, Christopher; Gagnon, Lyne

    2007-12-01

    In previous reports, we have shown that PBI-1393 (formerly BCH-1393), N,N-Dimethylaminopurine pentoxycarbonyl D-arginine, stimulates cytotoxic T-lymphocyte (CTL) responses both in vitro and in vivo in normal immune status and immunosuppressed mice. Additionally, PBI-1393 was tested for anticancer activity in syngeneic mouse experimental tumor models and it displayed significant inhibition of tumor outgrowths when given in combination with sub-therapeutic doses of cytotoxic drugs (cyclophosphamide, 5-fluorouracil, doxorubicin and cis-platinum). However, the mechanism of action of PBI-1393 was still unknown. Here, we report that PBI-1393 enhances IL-2 and IFN-gamma production in human activated T cells by 51% and 46% respectively. PBI-1393 increases also IL-2 and IFN-gamma mRNA expression as shown by RT-PCR. The physiological relevance of IL-2 and IFN-gamma gene modulation by PBI-1393 is illustrated by the advantageous increase of T cell proliferation (39+/-0.3% above control) and human CTL response against prostate (PC-3) cancer cells (42+/-0.03%). The enhancement of human T cell proliferation and CTL activation by PBI-1393 demonstrates that this compound potentiates the immune response and in this regard, it could be used as an alternative approach to IL-2 and/or IFN-gamma therapy against cancer.

  17. Recognizing child maltreatment in Bangladesh.

    Science.gov (United States)

    Khan, N Z; Lynch, M A

    1997-08-01

    Concern is increasing in Bangladesh over child abuse, neglect, and exploitation. Children from all walks of life are being treated at the Child Development Center (CDC) Dhaka Shishu Hospital for neurodevelopmental problems resulting from abuse and neglect. Efforts to protect children from sexual harassment result in girls being isolated at home or married at an early age. Some young brides are eventually abandoned and forced into prostitution. Early marriage reflects the lack of acknowledgement of a period of adolescence and the belief that puberty is a marker of adulthood. Many girls aged 8-16 are employed as live-in domestic servants, and many suffer sexual as well as emotional abuse. Garment factories, on the other hand, offer girls an escape from extreme poverty, domestic service, and early marriage but are threatened by forces that condemn child labor. Rather than ending such opportunities, employers should be encouraged to provide employees with educational and welfare facilities. The CDC seeks to explore the extent and depth of the problem of child abuse while recognizing the special circumstances at work in Bangladesh. It is also necessary to raise awareness of these issues and of the discrepancies between the law and cultural practices. For example, the legal marriage age of 18 years for a woman and 21 years for a man is often ignored. Additional forms of abuse receiving the attention of women's organizations and human rights groups include the trafficking of children. A network of concerned organizations should be created to work against the child abuse, neglect, and exploitation that Bangladesh has pledged to overcome by signing the UN Convention on the Rights of the Child.

  18. Producing and Recognizing Analogical Relations

    Science.gov (United States)

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  19. AntigenMap 3D: an online antigenic cartography resource.

    Science.gov (United States)

    Barnett, J Lamar; Yang, Jialiang; Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2012-05-01

    Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. http://sysbio.cvm.msstate.edu/AntigenMap3D

  20. Antigens of Streptococcus sanguis

    Science.gov (United States)

    Rosan, Burton

    1973-01-01

    An antigenic analysis of the alpha-hemolytic streptococci isolated from dental plaque was performed by use of antisera against a strain of Streptococcus sanguis (M-5) which was isolated from dental plaque. Immunoelectrophoretic and Ouchterlony tests of Rantz and Randall extracts of 45 strains gave positive reactions with the M-5 antisera. These strains represented 60% of the strains tested. The number of antigens which could be identified in these extracts varied from one to five and were designated a to e. The a antigen was found in 36 of the strains tested, including reference strains of S. sanguis and the group H streptococci. The strains reacting with the M-5 antisera were divided into two majors types: type I consisted of 23 strains in which the a antigen was found alone or with one or more of the c, d, and e antigens; type II consisted of 13 strains in which both the a and b antigens were found with or without one or more of the c, d, and e antigens. The remaining strains contained, either singly or in combination, the b, c, d, and e antigens but not the a antigen. Biochemical tests of representatives of each serotype and reference strains indicated that strains reacting with M-5 antisera were S. sanguis. These findings suggest that S. sanguis strains share common physiological and serological properties. Images PMID:4633291

  1. The potential for induction of autoimmune disease by a randomly-mutated self-antigen

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm

    2007-01-01

    -antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto......-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead......The pathology of most autoimmune diseases is well described. However, the exact event that triggers the onset of the inflammatory cascade leading to disease is less certain and most autoimmune diseases are complex idiopathic diseases with no single gene known to be causative. In many cases...

  2. Eosinofil Sel Penyaji Antigen

    Directory of Open Access Journals (Sweden)

    Safari Wahyu Jatmiko

    2015-04-01

    Full Text Available Sel eosinofil merupakan jenis sel lekosit yang terlibat dalam berbagai patogenesis penyakit. Sel eosinofil pada awalnya dikenal sebagai sel efektor  dari sistem imunitas alamiah. Akan tetapi, kemampuan sel eosinofil dalam memfagositosis patogen menimbulkan dugaan bahwa sel eosinofil ikut berperan sebagai sel penyaji antigen. Hal ini dianalogikan dengan sel makrofag dan sel dendritik yang bisa memfagositosis dan menyajikan antigen sebagai hasil dari degradasi patogen yang difagositosis. Untuk menjawab permasalahan ini, penulis melakukan penelusuran artikel tentang eosinofil sebagai sel penyaji antigen melalui US National Library of Medicine National Institute of Healthdengan kata kunci eoshinophil dan antigen presenting cell. Hasil penelusuran adalah ditemukannya 10 artikel yang relevan dengan topik. Hasil dari sintesis kesepuluh jurnal tersebut adalah sel eosinofil mampu berperan sebagai sel penyaji antigen yang profesional (professionalantigenpresentng cell

  3. Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

    Science.gov (United States)

    Pinto, Eduardo Fonseca; Pinheiro, Roberta Olmo; Rayol, Alice; Larraga, Vicente; Rossi-Bergmann, Bartira

    2004-01-01

    We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA. PMID:15271911

  4. Assessing the Prognostic Value of Preoperative Carcinoembryonic Antigen-Specific T-Cell Responses in Colorectal Cancer

    Science.gov (United States)

    Scurr, Martin J.; Brown, Clare M.; Costa Bento, Diana F.; Betts, Gareth J.; Rees, Brian I.; Hills, Robert K.; Gallimore, Awen; Godkin, Andrew

    2015-01-01

    Current dogma suggests that tumor-reactive IFN-γ–producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, we compared the utility of preoperative, peripheral blood–derived IFN-γ+ T-cell responses specific to carcinoembryonic antigen (CEA), 5T4, or control antigens (n = 64) with tumor staging and clinical details (n = 87) in predicting five-year outcome of CRC patients who underwent resection with curative intent. Although disease recurrence was more likely in patients with stage III tumors, the presence of preoperative, CEA-specific IFN-γ–producing T-cells identified patients at a statistically significantly greater risk of tumor recurrence following surgical resection, irrespective of tumor stage (odds ratio = 5.00, 95% confidence interval = 1.96 to 12.77, two-sided P antigens, including 5T4, did not reflect outcome. Whilst these results initially appear surprising, they could improve prognostication and help redirect adjuvant treatments. PMID:25669203

  5. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  6. TRAFFIC SIGN RECOGNATION WITH VIDEO PROCESSING TECHNIQUE

    Directory of Open Access Journals (Sweden)

    Musa AYDIN

    2013-01-01

    Full Text Available In this study, traffic signs are aimed to be recognized and identified from a video image which is taken through a video camera. To accomplish our aim, a traffic sign recognition program has been developed in MATLAB/Simulink environment. The target traffic sign are recognized in the video image with the developed program.

  7. Carcinoembryonic antigen (CEA)

    International Nuclear Information System (INIS)

    Ephraim, K.H.; Cox, P.H.; Hamer, C.J.A. v.d.; Berends, W.; Delhez, H.

    1977-01-01

    The carcinoembryonic antigen (CEA) is a complex of antigen determinants and also the carrier of these determinants. Chemically it is a glycoprotein. Its occurrence in blood serum or urine is correlated with malignant disease. Several radioimmunoassays (RIA) have been developed, one by Hoffmann-Laroche and one by the Rotterdam Radiotherapeutic Institute. Both methods and the Hoffmann assay kit are tested. Specifications are given for isolation of the antigen, preparation of the antiserum, and the execution of the RIA. Biochemical and clinical aspects are discussed

  8. Dendritic Cells as Danger-Recognizing Biosensors

    Directory of Open Access Journals (Sweden)

    Seokmann Hong

    2009-08-01

    Full Text Available Dendritic cells (DCs are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. DCs comprise several subsets with distinct phenotypes. After sensing any danger(s to the host via their innate immune receptors such as Toll-like receptors, DCs become mature and subsequently present antigens to CD4+ T cells. Since DCs possess the intrinsic capacity to polarize CD4+ helper cells, it is critical to understand the immunological roles of DCs for clinical applications. Here, we review the different DC subsets, their danger-sensing receptors and immunological functions. Furthermore, the cytokine reporter mouse model for studying DC activation is introduced.

  9. Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA).

    Science.gov (United States)

    Firouzmand, Hengameh; Badiee, Ali; Khamesipour, Ali; Heravi Shargh, Vahid; Alavizadeh, Seyedeh Hoda; Abbasi, Azam; Jaafari, Mahmoud Reza

    2013-12-01

    A suitable adjuvant and delivery system are needed to develop an effective vaccine against leishmaniasis. To induce a Th1 type of response and protection in BALB/c mice against Leishmania major infection, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) nanoliposomes bearing an intrinsic adjuvanticity, were used as an antigen delivery system and immunoadjuvant for soluble Leishmania antigens (SLA). DOTAP liposomes containing different concentrations of SLA were prepared by using lipid film method followed by sonication. The prepared vesicles showed a diameter of about 100nm, a positive zeta potential and approximately 70% encapsulation efficiency of SLA. BALB/c mice were immunized subcutaneously (SC), three times in a 3-week interval with different concentrations of liposomal SLA (12.5, 25, and 50μg of SLA/50μl/mice), free SLA and as well as free liposome. The group of mice received 50μg of SLA in DOTAP-nanoliposomes showed a significantly (p<0.001) smaller footpad swelling and the lowest spleen and footpad parasite burden after the challenge. This group also showed the highest IFN-γ production compared to the other groups, lower IL-4 level and higher IgG2a antibody titer. Taken together, the results indicated that simple DOTAP nanoliposome containing 1μg/μl SLA are appropriate delivery systems to induce a Th1 type of immune response and protection against L. major infection in BALB/c mice. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Self-Amplified Optical Pattern Recognizer

    Science.gov (United States)

    Liu, Hua-Kuang

    1993-01-01

    Self-amplified optical pattern recognizers developed for use in recognition of patterns, in optical computing, and in optoelectronic neural networks. In recognizer, photorefractive crystal serves as medium in which one holographically records diffraction-grating filter representing pattern with which recognition sought. Apparatus "self-amplified" because signal amplified within filter to many orders of magnitude greater than in prior optical pattern recognizers. Basic principle of operation applicable to many types of correlation filters, including (but not limited to) Vander Lugt matched filters, joint-transform filters, and phase-only filters.

  11. Structure-function analysis of the self-recognizing Antigen 43 autotransporter protein from Escherichia coli

    DEFF Research Database (Denmark)

    Klemm, Per; Hjerrild, L.; Gjermansen, Morten

    2004-01-01

    -clumping variants, we have pinpointed the region of the protein responsible for autoaggregation to be located within the N-terminal one-third of the passenger domain. Our data suggest that ionic interactions between charged residues residing in interacting pairs of Ag43(alpha) domains may be important for the self...

  12. Apoptosis and necrosis increase antigenicity of proteins recognized by antinuclear antibodies

    Directory of Open Access Journals (Sweden)

    J.J. Bollain-y-Goitia

    2011-09-01

    Full Text Available Obiettivo. Lo scopo di questo studio è quello di indagare se l’apoptosis e la necrosi aumentano l’antigenicità delle proteine riconosciute da anticorpi antinucleo. Materiale e metodi. Cellule HEp-2 sono state coltivate in condizioni standard; l’apoptosis è stata indotta con camptecina e la necrosi con cloruro di mercurio. L’antigenicità delle proteine estratte dalle cellule è stato testata su membrane di nitrocellulosa e sondata con sieri positivi o negativi per anticorpi antinucleo utilizzando un sistema ELISA a luminescenza (luminescent. Risultati. Le alterazioni apoptotiche nelle cellule HEp-2 sono apparse entro 24 ore dall’esposizione alla camptoicina, mentre i segni di necrosi si sono evidenziati più precocemente. La luminescenza si è dimostrata significativamente superiore nei sieri ANA positivi che nei controlli ANA negativi. Gli antcorpi antinucleari sieirici riconoscono meglio gli antigeni da cellule apoptotiche e necrotiche rispetto ai controlli che non hanno subito trattamenti chimici. Conclusioni. L’apoptosi e la necrosi incrementano la capacità legante degli ANA attraverso una migliore disponibilità di antigeni intracellulari o svelando epitopi criptici.

  13. Novel Monoclonal Antibodies Recognizing Human Prostate-Specific Membrane Antigen (PSMA) as Research and Theranostic Tools

    Czech Academy of Sciences Publication Activity Database

    Nováková, Zora; Foss, C. A.; Copeland, B. T.; Morath, V.; Baranová, Petra; Havlínová, Barbora; Skerra, A.; Pomper, M.G.; Bařinka, Cyril

    2017-01-01

    Roč. 77, č. 7 (2017), s. 749-764 ISSN 0270-4137 R&D Projects: GA ČR GAP301/12/1513; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : monoclonal antibody * glutamate carboxypeptidase II * NAALADase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 3.820, year: 2016

  14. Label-free chronopotentiometric glycoprofiling of prostate specific antigen using sialic acid recognizing lectins

    Czech Academy of Sciences Publication Activity Database

    Belicky, S.; Černocká, Hana; Bertok, T.; Holazova, A.; Réblová, K.; Paleček, Emil; Tkáč, J.; Ostatná, Veronika

    2017-01-01

    Roč. 117, OCT2017 (2017), s. 89-94 ISSN 1567-5394 R&D Projects: GA ČR(CZ) GA15-15479S Institutional support: RVO:68081707 Keywords : amalgam electrodes * cancer * glycosylation * interface Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.346, year: 2016

  15. How plants recognize pathogens and defend themselves

    NARCIS (Netherlands)

    Wit, de P.J.G.M.

    2007-01-01

    Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize microbe-associated molecular patterns (MAMPs) of potential pathogens through pattern recognition receptors (PRRs) that mediate a basal defense response. Plant pathogens

  16. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  17. Structural Elements Recognized by Abacavir-Induced T Cells

    Directory of Open Access Journals (Sweden)

    Daniel Yerly

    2017-07-01

    Full Text Available Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976–984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230–238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.

  18. Yeast proteins that recognize nuclear localization sequences

    OpenAIRE

    1989-01-01

    A variety of peptides can mediate the localization of proteins to the nucleus. We have identified yeast proteins of 70 and 59 kD that bind to nuclear localization peptides of SV-40 T antigen, Xenopus nucleoplasmin, and the yeast proteins Ga14 and histone H2B. These proteins are assayed by the binding of peptide-albumin conjugates to proteins immobilized on nitrocellulose filters. These binding proteins fractionate with nuclei and are extractable with salt but not detergent. Radiolabeled pepti...

  19. Characterization of a cDNA encoding a 34-kDa Purkinje neuron protein recognized by sera from patients with paraneoplastic cerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Furneaux, H.M.; Dropcho, E.J.; Barbut, D.; Chen, Yaotseng; Rosenblum, M.K.; Old, L.J.; Posner, J.B. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

    1989-04-01

    Paraneoplastic cerebellar degeneration is a neurological disorder of unknown cause occurring in patients with an identified or occult cancer. An autoimmune etiology is likely since autoantibodies directed against the Purkinje cells of the cerebellum have been found in the serum and cerebrospinal fluid of some patients. Two Purkinje cell-specific antigens are recognized by these autoantibodies, a major antigen of 62 kDa (CDR 62, cerebellar degeneration-related 62-kDa protein) and a minor antigen of 34 kDa (CDR 34). Previous studies have described the isolation and characterization of a human cerebellar cDNA that encodes an epitope recognized by sera from patients with paraneoplastic cerebellar degeneration. The authors have now established by two independent methods that this gene is uniquely expressed in Purkinje cells of the cerebellum and corresponds to the minor antigen CDR 34. This antigen is also expressed in tumor tissue from a patient with paraneoplastic cerebellar degeneration.

  20. Equipping African American Clergy to Recognize Depression.

    Science.gov (United States)

    Anthony, Jean Spann; Morris, Edith; Collins, Charles W; Watson, Albert; Williams, Jennifer E; Ferguson, Bʼnai; Ruhlman, Deborah L

    2016-01-01

    Many African Americans (AAs) use clergy as their primary source of help for depression, with few being referred to mental health providers. This study used face-to-face workshops to train AA clergy to recognize the symptoms and levels of severity of depression. A pretest/posttest format was used to test knowledge (N = 42) about depression symptoms. Results showed that the participation improved the clergy's ability to recognize depression symptoms. Faith community nurses can develop workshops for clergy to improve recognition and treatment of depression.

  1. Recognizing textual entailment models and applications

    CERN Document Server

    Dagan, Ido; Sammons, Mark

    2013-01-01

    In the last few years, a number of NLP researchers have developed and participated in the task of Recognizing Textual Entailment (RTE). This task encapsulates Natural Language Understanding capabilities within a very simple interface: recognizing when the meaning of a text snippet is contained in the meaning of a second piece of text. This simple abstraction of an exceedingly complex problem has broad appeal partly because it can be conceived also as a component in other NLP applications, from Machine Translation to Semantic Search to Information Extraction. It also avoids commitment to any sp

  2. A monkey antigen crossreacting with carcinoembryonic antigen, CEA.

    Science.gov (United States)

    Engvall, E.; Vuento, M.; Ruoslahti, E.

    1976-01-01

    Normal monkey tissues were found to contain an antigen which crossreacts immunologically with the carcinoembryonic antigen (CEA) of the human digestive tract. The monkey antigen reacted with complete or partial identity to the normal crossreacting antigen (NCA) in humans when tested in immunodiffusion against anti-CEA or anti-NCA. Extracts of monkey tissues inhibited in radioimmunoassays measuring human NCA. It is possible that monkey foetuses and colonic tumours contain CEA. Images Fig. 1 PMID:823952

  3. Antigen smuggling in tuberculosis.

    Science.gov (United States)

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 58, č. 6 (2001), s. 425-430 ISSN 0001-2815. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 2.864, year: 2001

  5. CD antigens 2002

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2002-01-01

    Roč. 99, č. 10 (2002), s. 3877-3880 ISSN 0006-4971. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 9.631, year: 2002

  6. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2002-01-01

    Roč. 168, č. 5 (2002), s. 2083-2086 ISSN 0022-1767. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 7.014, year: 2002

  7. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 103, č. 4 (2001), s. 401-406 ISSN 0019-2805 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : antigen * CD * leukocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.656, year: 2001

  8. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 19, č. 6 (2001), s. 556-562 ISSN 1066-5099 R&D Projects: GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD * leukocyte antigens Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.689, year: 2001

  9. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 31, č. 10 (2001), s. 2841-2847 ISSN 0014-2980 R&D Projects: GA AV ČR IAA7052904 Keywords : CD * leukocyte antigens Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.990, year: 2001

  10. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 211, č. 2 (2001), s. 81-85 ISSN 0008-8749 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : antigen * CD * leukocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.604, year: 2001

  11. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2002-01-01

    Roč. 15, č. 1 (2002), s. 71-76 ISSN 0893-3952. [Conference on Human leucocyte differentiation antigens /7./. Harrogate, 20.06.2000-25.06.2000] Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules, HLDA Subject RIV: EC - Immunology Impact factor: 3.821, year: 2002

  12. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 70, č. 5 (2001), s. 685-690 ISSN 0741-5400 R&D Projects: GA AV ČR IAA7052904 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD * leukocyte antigens Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.516, year: 2001

  13. CD antigens 2001

    Czech Academy of Sciences Publication Activity Database

    Mason, D.; Andre, P.; Bensussan, A.; Buckley, C.; Civin, C.; Clark, E.; de Haas, M.; Goyert, S.; Hadam, M.; Hart, D.; Hořejší, Václav; Meuer, S.; Morrissey, J.; Schwartz-Albiez, R.; Shaw, S.; Simmons, D.; Uguccioni, M.; van der Schoot, E.; Vivier, E.; Zola, H.

    2001-01-01

    Roč. 13, č. 9 (2001), s. 1095-1098 ISSN 0953-8178 R&D Projects: GA ČR GA310/99/0349 Institutional research plan: CEZ:AV0Z5052915 Keywords : antigen * CD * leukocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.611, year: 2001

  14. β-endorphin antigen

    International Nuclear Information System (INIS)

    1981-01-01

    This invention relates to the production of antigens comprising β-endorphin, βsub(h)-endorphin, or βsub(c)-endorphin, in covalent conjugation with human gammaglobulin as immunogenic carrier material, and an antibody having the property of specifically binding β-endorphin or fragments thereof, containing the (6-15) residue sequence. (U.K.)

  15. Great Apes' Capacities to Recognize Relational Similarity

    Science.gov (United States)

    Haun, Daniel B. M.; Call, Josep

    2009-01-01

    Recognizing relational similarity relies on the ability to understand that defining object properties might not lie in the objects individually, but in the relations of the properties of various object to each other. This aptitude is highly relevant for many important human skills such as language, reasoning, categorization and understanding…

  16. Fast Feature-Recognizing Optoelectronic System

    Science.gov (United States)

    Thakoor, S.; Thakoor, A. P.

    1990-01-01

    Proposed optoelectronic system recognizes features or classifies images by processing outputs of photosensors rapidly, in parallel, through circuits developed in research on neural networks. Array of photoconductive elements serve as photomodulated connections in electronic neural network, which provides high speed data compression to generate feature vector. System able to "learn" new patterns for subsequent recognition. Potential applications in robotic vision systems and pattern recognition.

  17. Pooling Objects for Recognizing Scenes without Examples

    NARCIS (Netherlands)

    Kordumova, S.; Mensink, T.; Snoek, C.G.M.

    2016-01-01

    In this paper we aim to recognize scenes in images without using any scene images as training data. Different from attribute based approaches, we do not carefully select the training classes to match the unseen scene classes. Instead, we propose a pooling over ten thousand of off-the-shelf object

  18. Discoverers of the Neutrino and Tau Recognized

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 2. Discoverers of the Neutrino and Tau Recognized. K V L Sarma. Research News Volume 1 Issue 2 February 1996 pp ... Author Affiliations. K V L Sarma1. Tata Institute of Fundamental Research, Homi Bhabha Road, Bombay 400005, India.

  19. Analysis of Tn antigenicity with a panel of new IgM and IgG1 monoclonal antibodies raised against leukemic cells

    DEFF Research Database (Denmark)

    Blixt, Klas Ola; Lavrova, Olga I; Mazurov, Dmitriy V

    2012-01-01

    NAc residue of the Tn antigen irrespective of the peptide context or with low selectivity to the glycoproteins. In contrast, IgG mAbs recognized the Tn antigen in the context of a specific peptide motif. Particularly, JA3 mAb reacted to the GSPP or GSPAPP, and JA5 mAb recognized specifically the GSP motif...

  20. Invariant NKT cells recognize glycolipids from pathogenic Gram-positive bacteria

    Science.gov (United States)

    Kinjo, Yuki; Illarionov, Petr; Vela, José Luis; Pei, Bo; Girardi, Enrico; Li, Xiangming; Li, Yali; Imamura, Masakazu; Kaneko, Yukihiro; Okawara, Akiko; Miyazaki, Yoshitsugu; Gómez-Velasco, Anaximandro; Rogers, Paul; Dahesh, Samira; Uchiyama, Satoshi; Khurana, Archana; Kawahara, Kazuyoshi; Yesilkaya, Hasan; Andrew, Peter W.; Wong, Chi-Huey; Kawakami, Kazuyoshi; Nizet, Victor; Besra, Gurdyal S.; Tsuji, Moriya; Zajonc, Dirk M.; Kronenberg, Mitchell

    2011-01-01

    Natural killer T (NKT) cells recognize glycolipid antigens presented by CD1d. These cells express an evolutionarily conserved, invariant T cell receptor (TCR), but the forces driving TCR conservation have remained uncertain. Here we show that NKT cells recognize diacylglycerol-containing glycolipids from Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, and group B Streptococcus, which causes neonatal sepsis and meningitis. Furthermore, CD1d-dependent responses by NKT cells are required for activation and host protection. The glycolipid response was dependent on vaccenic acid, which is found at a low level in mammalian cells. Our results show how microbial lipids position the sugar for recognition by the invariant TCR, and most important, they extend the range of microbes recognized by this conserved TCR to several clinically important bacteria. PMID:21892173

  1. Identification and characterization of a 29-kilodalton protein from Mycobacterium tuberculosis culture filtrate recognized by mouse memory effector cells

    DEFF Research Database (Denmark)

    Rosenkrands, I; Rasmussen, P.B.; Carnio, M

    1998-01-01

    Culture filtrate proteins from Mycobacterium tuberculosis induce protective immunity in various animal models of tuberculosis. Two molecular mass regions (6 to 10 kDa and 24 to 36 kDa) of short-term culture filtrate are preferentially recognized by Th1 cells in animal models as well as by patients...... the antigen 85 complex was selected. The 29-kDa antigen (CFP29) was purified from M. tuberculosis short-term culture filtrate by thiophilic adsorption chromatography, anion-exchange chromatography, and gel filtration, In its native form, CFP29 forms a polymer with a high molecular mass. CFP29 was mapped...... in two-dimensional electrophoresis gels as three distinct spots just below the antigen 85 complex component MPT59, CFP29 is present in both culture filtrate and the membrane fraction from M. tuberculosis, suggesting that this antigen is released from the envelope to culture filtrate during growth...

  2. Recognizing Cuneiform Signs Using Graph Based Methods

    OpenAIRE

    Kriege, Nils M.; Fey, Matthias; Fisseler, Denis; Mutzel, Petra; Weichert, Frank

    2018-01-01

    The cuneiform script constitutes one of the earliest systems of writing and is realized by wedge-shaped marks on clay tablets. A tremendous number of cuneiform tablets have already been discovered and are incrementally digitalized and made available to automated processing. As reading cuneiform script is still a manual task, we address the real-world application of recognizing cuneiform signs by two graph based methods with complementary runtime characteristics. We present a graph model for c...

  3. Proteomic Analysis of Trichinella spiralis Adult Worm Excretory-Secretory Proteins Recognized by Sera of Patients with Early Trichinellosis

    Directory of Open Access Journals (Sweden)

    Zhong Q. Wang

    2017-05-01

    Full Text Available The most commonly used serodiagnostic antigens for trichinellosis are the excretory-secretory (ES antigens from T. spiralis muscle larvae (ML, but the specific antibodies against the ML ES antigens are usually negative during early stage of Trichinella infection. The recent studies demonstrated that T. spiralis adult worm (AW antigens were recognized by mouse or swine infection sera on Western blot as early as 7–15 days post-infection (dpi, the AW antigens might contain the early diagnostic markers for trichinellosis. The purpose of this study was to screen early diagnostic antigens in T. spiralis AW ES proteins recognized by sera of early patients with trichinellosis. T. spiralis AW were collected at 72 h post-infection (hpi, and their ES antigens were analyzed by SDS-PAGE and Western blot. Our results showed that 5 protein bands (55, 48–50, 45, 44, and 36 kDa were recognized by sera of early patients with trichinellosis collected at 19 dpi, and were subjected to shotgun LC–MS/MS and bioinformatics analyses. A total of 185 proteins were identified from T. spiralis protein database, of which 116 (67.2% proteins had molecular weights of 30∼60 kDa, and 125 (67.6% proteins with pI 4–7. Bioinformatic analyses showed that the identified proteins have a wide diversity of biological functions (binding of nucleotides, proteins, ions, carbohydrates, and lipids; hydrolase, transferase, and oxidoreductase, etc.. Several enzymes (e.g., adult-specific DNase II, serine protease and serine protease inhibitor could be the invasion-related proteins and early diagnostic markers for trichinellosis. Moreover, recombinant T. spiralis serine protease (rTsSP-ZH68 was expressed in E. coli and its antigenicity was analyzed by Western blot with the early infection sera. The rTsSP-ZH68 was recognized by sera of infected mice at 8–10 dpi and sera of early patients with trichinellosis at 19 dpi. T. spiralis AW proteins identified in this study, especially serine

  4. The ability of IgY to recognize surface proteins of Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Basri A. Gani

    2009-12-01

    Full Text Available Background: Streptococcus mutans are gram positive bacteria classified into viridians group, and have a role in pathogenesis of dental caries. It’s adhesion to the tooth surface is mediated by cell surface proteins, which interact with specific receptor located in tooth pellicle. Glucan binding protein, Glukosyltransferase, and antigen I/II are basic proteins of S. mutans, which have a role in initiating the interaction. A previous study showed that chicken’s IgY can interfere the interaction. Purpose: The objective of this study was to assess the ability of IgY in recognizing the surface molecule of Streptococcus mutans expressed by various serotypes (c, d, e, f and a strain derived from IPB, Bogor. Method: Western blot was used as a method to determine such capability. Result: The result showed that IgY has a potency to recognize antigen I/II, but not the other proteins on the cell surface of all bacteria tested. Conclusion: The ability of IgY to bind the surface protein, antigen I/II, indicates that this avian antibody could be used as a candidate for anti-adhesion in preventing dental caries.

  5. Therapeutic Antibodies against Intracellular Tumor Antigens

    Directory of Open Access Journals (Sweden)

    Iva Trenevska

    2017-08-01

    Full Text Available Monoclonal antibodies are among the most clinically effective drugs used to treat cancer. However, their target repertoire is limited as there are relatively few tumor-specific or tumor-associated cell surface or soluble antigens. Intracellular molecules represent nearly half of the human proteome and provide an untapped reservoir of potential therapeutic targets. Antibodies have been developed to target externalized antigens, have also been engineered to enter into cells or may be expressed intracellularly with the aim of binding intracellular antigens. Furthermore, intracellular proteins can be degraded by the proteasome into short, commonly 8–10 amino acid long, peptides that are presented on the cell surface in the context of major histocompatibility complex class I (MHC-I molecules. These tumor-associated peptide–MHC-I complexes can then be targeted by antibodies known as T-cell receptor mimic (TCRm or T-cell receptor (TCR-like antibodies, which recognize epitopes comprising both the peptide and the MHC-I molecule, similar to the recognition of such complexes by the TCR on T cells. Advances in the production of TCRm antibodies have enabled the generation of multiple TCRm antibodies, which have been tested in vitro and in vivo, expanding our understanding of their mechanisms of action and the importance of target epitope selection and expression. This review will summarize multiple approaches to targeting intracellular antigens with therapeutic antibodies, in particular describing the production and characterization of TCRm antibodies, the factors influencing their target identification, their advantages and disadvantages in the context of TCR therapies, and the potential to advance TCRm-based therapies into the clinic.

  6. A strategy for identifying serodiagnostically relevant antigens of Leishmania or other pathogens in genetic libraries.

    Science.gov (United States)

    Teixeira, Márcia C A; Oliveira, Geraldo G S; Silvany, Marco A; Alcântara-Neves, Neuza M; Soares, Milena B P; Ribeiro-Dos-Santos, Ricardo; Jerônimo, Selma M B; Costa, Carlos H; dos-Santos, Washington L C; Eichinger, Daniel; Pontes-de-Carvalho, Lain

    2007-03-01

    Different individuals, when infected with the same parasite, rarely produce antibodies against the same set of antigens. Indeed, unless a particular antigen happens to be recognized by antibodies in all individuals, the use of a single antigen in the serodiagnosis of parasitic diseases leads, invariably, to false-negative results. A straightforward method for pin-pointing, in genetic libraries, the precise antigens that would increase serodiagnostic assay sensitivities is presented. The method is based on the utilization of sera that produced false-negative results against previously available antigens. Employing this false-negative serum-selection methodology for the identification of new Leishmania infantum recombinant antigens (rAgs), the sensitivity of a dipstick assay for anti-Leishmania antibodies in a panel of sera from patients with visceral leishmaniasis was increased from 83.3% to 98.1%, without affecting its specificity, by the inclusion of a fifth and a sixth L. infantum rAg.

  7. Determination of Diagnostic Antigens in Cattle Amphistomiasis Using Western Blotting

    Directory of Open Access Journals (Sweden)

    A Halajian

    2009-05-01

    Full Text Available "nBackground: Mixed infection with amphistomes seems common in native cattle of Iran. The aim of this study was to determine diagnostic antigens in cattle mixed amphistomiasis."nMethods: Specific antigens of Cotylophoron cotylophorum, Gastrothylax crumenifer and Paramphisto­mum cervi (mixed infection, the most common species, were collected from cattle was deter­mined. Adult trematodes were collected from the rumen of naturally infected cattle at meat inspec­tion. After their homogenization and centrifugation, somatic antigens were prepared and ana­lyzed by SDS-PAGE. Specific antigens were determinated by western blot with homologous and heterolo­gous sera. SDS-PAGE of whole worms extract was performed at different concentrations and subse­quent gels staining. Immunoblotting analysis using sera from cattle naturally infected with am­phistomes, Dicrocoelium dendriticum, Fasciola spp. and hydatid cyst was performed."nResults: Electrophorese analysis of somatic antigens revealed the presence of 10 and 21 protein bands at 4 µgr/ml and 8 µgr/ml with molecular weights ranging from 25-120 and 25-150 kDa, respectively. The best result was taken at 8 mg/ml concentration. Although western blot of these proteins demon­strate 5 major antigenic polypeptides ranging from 50 to 100 kDa which were recognized by serum of cat­tle naturally infected with mixed amphistomes.

  8. Interpretation of sequential measurements of cancer antigen 125 (CA 125), Carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer

    DEFF Research Database (Denmark)

    Tuxen, M.K.; Söletormos, G.; Petersen, P.H.

    2001-01-01

    The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer......, the standard deviations, and the coefficients of variation differed among subjects, and iii) the steady state variability differed among the markers. In conclusion, our data indicate that the assessment of sequential CA 125, CEA, and TPA concentrations is more complex than hitherto recognized. We suggest...

  9. Ants recognize foes and not friends

    Science.gov (United States)

    Guerrieri, Fernando J.; Nehring, Volker; Jørgensen, Charlotte G.; Nielsen, John; Galizia, C. Giovanni; d'Ettorre, Patrizia

    2009-01-01

    Discriminating among individuals and rejecting non-group members is essential for the evolution and stability of animal societies. Ants are good models for studying recognition mechanisms, because they are typically very efficient in discriminating ‘friends’ (nest-mates) from ‘foes’ (non-nest-mates). Recognition in ants involves multicomponent cues encoded in cuticular hydrocarbon profiles. Here, we tested whether workers of the carpenter ant Camponotus herculeanus use the presence and/or absence of cuticular hydrocarbons to discriminate between nest-mates and non-nest-mates. We supplemented the cuticular profile with synthetic hydrocarbons mixed to liquid food and then assessed behavioural responses using two different bioassays. Our results show that (i) the presence, but not the absence, of an additional hydrocarbon elicited aggression and that (ii) among the three classes of hydrocarbons tested (unbranched, mono-methylated and dimethylated alkanes; for mono-methylated alkanes, we present a new synthetic pathway), only the dimethylated alkane was effective in eliciting aggression. Our results suggest that carpenter ants use a fundamentally different mechanism for nest-mate recognition than previously thought. They do not specifically recognize nest-mates, but rather recognize and reject non-nest-mates bearing odour cues that are novel to their own colony cuticular hydrocarbon profile. This begs for a reappraisal of the mechanisms underlying recognition systems in social insects. PMID:19364750

  10. How do infants recognize joint attention?

    Science.gov (United States)

    Gustafsson, Erik; Brisson, Julie; Beaulieu, Christelle; Mainville, Marc; Mailloux, Dominique; Sirois, Sylvain

    2015-08-01

    The emergence of joint attention is still a matter of vigorous debate. It involves diverse hypotheses ranging from innate modules dedicated to intention reading to more neuro-constructivist approaches. The aim of this study was to assess whether 12-month-old infants are able to recognize a "joint attention" situation when observing such a social interaction. Using a violation-of-expectation paradigm, we habituated infants to a "joint attention" video and then compared their looking time durations between "divergent attention" videos and "joint attention" ones using a 2 (familiar or novel perceptual component)×2 (familiar or novel conceptual component) factorial design. These results were enriched with measures of pupil dilation, which are considered to be reliable measures of cognitive load. Infants looked longer at test events that involved novel speaker and divergent attention but no changes in infants' pupil dilation were observed in any conditions. Although looking time data suggest that infants may appreciate discrepancies from expectations related to joint attention behavior, in the absence of clear evidence from pupillometry, the results show no demonstration of understanding of joint attention, even at a tacit level. Our results suggest that infants may be sensitive to relevant perceptual variables in joint attention situations, which would help scaffold social cognitive development. This study supports a gradual, learning interpretation of how infants come to recognize, understand, and participate in joint attention. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  12. Genetic and antigenic characterization of Bungowannah virus, a novel pestivirus.

    Science.gov (United States)

    Kirkland, P D; Frost, M J; King, K R; Finlaison, D S; Hornitzky, C L; Gu, X; Richter, M; Reimann, I; Dauber, M; Schirrmeier, H; Beer, M; Ridpath, J F

    2015-08-05

    Bungowannah virus, a possible new species within the genus Pestivirus, has been associated with a disease syndrome in pigs characterized by myocarditis with a high incidence of stillbirths. The current analysis of the whole-genome and antigenic properties of this virus confirms its unique identity, and further suggests that this virus is both genetically and antigenically remote from previously recognized pestiviruses. There was no evidence of reactivity with monoclonal antibodies (mAbs) that are generally considered to be pan-reactive with other viruses in the genus, and there was little cross reactivity with polyclonal sera. Subsequently, a set of novel mAbs has been generated which allow detection of Bungowannah virus. The combined data provide convincing evidence that Bungowannah virus is a member of the genus Pestivirus and should be officially recognized as a novel virus species. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  13. Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

    Directory of Open Access Journals (Sweden)

    Pelliccia Angela

    2007-10-01

    Full Text Available Abstract Background There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients. Methods The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells. Results Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells. Conclusion Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens

  14. Recognizing limitations in eddy current testing

    International Nuclear Information System (INIS)

    Van Drunen, G.; Cecco, V.S.

    1981-11-01

    This paper addresses known limitations and constraints in eddy current nondestructive testing. Incomplete appreciation for eddy current limitations is believed to have contributed to both under-utilization and misapplication of the technique. Neither situation need arise if known limitations are recognized. Some, such as the skin depth effect, are inherent to electromagnetic test methods and define the role of eddy current testing. Others can be overcome with available technology such as surface probes to find circumferential cracks in tubes and magnetic saturation of ferromagnetic alloys to eliminate permeability effects. The variables responsible for limitations in eddy current testing are discussed and where alternative approaches exist, these are presented. Areas with potential for further research and development are also identified

  15. Neural nets for radio Morse code recognizing

    Science.gov (United States)

    Fu, Hsin-Chia; Lin, Y. Y.; Pao, Hsiao-Tien

    1993-09-01

    This paper proposes a neural network recognition system for hand keying Radio Morse codes. The system has been trained and tested on real world data recorded from amateur radio Morse codes. The overall recognizing process can be partitioned into 3 major parts, the preprocessing, the feature extracting, and the character decoding. The whole operation is able to be performed in real-time on a PC/486 system. Self-Organizing Maps are used intensively in the recognition system to adaptively learn the variation of the Morse code signal. The average performance of the recognition system has been achieved about 96.4% with a rejection rate of 6.5%. It is hoped that many of the techniques would be applicable to a wide range of DSP and recognition tasks.

  16. How can we recognize continuous quality improvement?

    Science.gov (United States)

    Rubenstein, Lisa; Khodyakov, Dmitry; Hempel, Susanne; Danz, Margie; Salem-Schatz, Susanne; Foy, Robbie; O'Neill, Sean; Dalal, Siddhartha; Shekelle, Paul

    2014-02-01

    Continuous quality improvement (CQI) methods are foundational approaches to improving healthcare delivery. Publications using the term CQI, however, are methodologically heterogeneous, and labels other than CQI are used to signify relevant approaches. Standards for identifying the use of CQI based on its key methodological features could enable more effective learning across quality improvement (QI) efforts. The objective was to identify essential methodological features for recognizing CQI. Previous work with a 12-member international expert panel identified reliably abstracted CQI methodological features. We tested which features met rigorous a priori standards as essential features of CQI using a three-phase online modified-Delphi process. Primarily United States and Canada. 119 QI experts randomly assigned into four on-line panels. Participants rated CQI features and discussed their answers using online, anonymous and asynchronous discussion boards. We analyzed ratings quantitatively and discussion threads qualitatively. Main outcome measure(s) Panel consensus on definitional CQI features. /st> Seventy-nine (66%) panelists completed the process. Thirty-three completers self-identified as QI researchers, 18 as QI practitioners and 28 as both equally. The features 'systematic data guided activities,' 'designing with local conditions in mind' and 'iterative development and testing' met a priori standards as essential CQI features. Qualitative analyses showed cross-cutting themes focused on differences between QI and CQI. We found consensus among a broad group of CQI researchers and practitioners on three features as essential for identifying QI work more specifically as 'CQI.' All three features are needed as a minimum standard for recognizing CQI methods.

  17. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

    Directory of Open Access Journals (Sweden)

    Marcela V Maus

    2016-01-01

    Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

  18. Differential expression of the Escherichia coli autoaggregation factor antigen 43

    DEFF Research Database (Denmark)

    Schembri, Mark; Hjerrild, Louise; Gjermansen, Morten

    2003-01-01

    Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Due to its excellent cell-to-cell aggregation characteristics, Ag43 expression confers clumping and fluffing of cells and promotes biofilm formation. Ag43 expression is repressed by the cellular redox......-forming potential of E. coli. Finally, we demonstrated that Ag43-mediated cell aggregation confers significant protection against hydrogen peroxide killing....

  19. Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens.

    Science.gov (United States)

    Brännström, Johan; Hässler, Signe; Peltonen, Leena; Herrmann, Björn; Winqvist, Ola

    2006-12-01

    Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.

  20. A mucin-like peptide from Fasciola hepatica induces parasite-specific Th1-type cell immunity.

    Science.gov (United States)

    Noya, Verónica; Brossard, Natalie; Berasaín, Patricia; Rodríguez, Ernesto; Chiale, Carolina; Mazal, Daniel; Carmona, Carlos; Freire, Teresa

    2016-03-01

    Fasciolosis, caused by the liver fluke Fasciola hepatica, is a major parasitic disease of livestock that causes significant economic losses worldwide. Although drugs are effective against liver flukes, they do not prevent reinfection, and continuous treatment is costly. Moreover, resistant fluke strains are emerging. In this context, vaccination is a good alternative since it provides a cost-effective long-term prevention strategy to control fasciolosis. In this paper, we evaluate the Fhmuc peptide as a potential vaccine against fasciolosis. This peptide derives from a mucin-like protein highly expressed in the infective stage of Fasciola hepatica. Mucin-like molecules expressed by parasites can contribute to several infection processes by protecting the parasite from host proteases and recognition by the immune system. We show that the Fhmuc peptide induces Th1-like immune responses specific for F. hepatica excretion-secretion products (FhESP) with a high production of IFNγ. We also investigated whether this peptide could protect animals from infection, and present preliminary data indicating that animals treated with Fhmuc exhibited reduced liver damage compared to non-immunised animals and that this protection was associated with a recruitment of B and T lymphocytes in the peritoneum, as well as eosinophils and mature dendritic cells. These results suggest that the mucin-like peptide Fhmuc could constitute a potential vaccine candidate against fasciolosis and pave the way towards the development of vaccines against parasites.

  1. Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway.

    Science.gov (United States)

    Mao, Mao; Qian, Yanning; Sun, Jie

    2016-04-01

    To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-θ) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner. However, Th2 cell percentage kept stable after morphine treatment. The phosphorylation of PI3K and AKT decreased, but the phosphorylation of PKC-θ did not change in the presence of morphine. The decreased percentage of Th1 cells and ratio of Th1/Th2 was recovered by naloxone concentration-dependently. Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT. The effect can be inhibited by naloxone.

  2. Comparison of innate and Th1-type host immune responses inOesophagostomum dentatumandTrichuris suisinfections in pigs

    DEFF Research Database (Denmark)

    Andreasen, Annette; Skovgaard, Kerstin; Klaver, Elsenoor J.

    2016-01-01

    The present study investigated details of the innate and Th1/Treg type associated host immune responses in Trichuris suis and Oesophagostomum dentatum mono- and co-infected pigs and in vitro in stimulated porcine dendritic cell cultures. Forty-eight pigs were allocated into a 2-factorial design...... with two groups trickle inoculated with 10 T. suis eggs/kg/day (Group T) or 20 O. dentatum L3/kg/day (O). Another group (OT) was infected with both parasites. Group C remained uninfected. Expression of innate and Th1/Treg cell associated genes in gut mucosa and associated lymph nodes was determined by q......PCR at necropsy day 35 and 71. Gene expression showed suppressed/inhibited Th1 and Treg type immune reactions, in accordance with previous findings of a predominant Th2 type immune response to both nematodes. The in vitro part examined production of TNF-α in porcine dendritic cells (DC) exposed to T. suis and...

  3. 46 CFR 160.049-8 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.049-8 Section 160.049-8... Recognized laboratory. (a) A manufacturer seeking Coast Guard approval of a product under this subpart shall... to a recognized independent laboratory. The following laboratories are recognized under § 159.010-7...

  4. 46 CFR 162.039-5 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 162.039-5 Section 162.039-5... Recognized laboratory. (a) A recognized laboratory is one which is regularly engaged in the examination... motorboats. The following laboratories are recognized, and the semiportable fire extinguishers bearing their...

  5. 46 CFR 160.077-9 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.077-9 Section 160.077-9... Recognized laboratory. (a) A manufacturer seeking Coast Guard approval of a product under this subpart shall... to a recognized independent laboratory. The following laboratories are recognized under § 159.010-7...

  6. 46 CFR 160.048-8 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.048-8 Section 160.048-8... Recognized laboratory. (a) A manufacturer seeking Coast Guard approval of a product under this subpart shall... to a recognized independent laboratory. The following laboratories are recognized under § 159.010-7...

  7. Expression of antigen tf and galectin-3 in fibroadenoma.

    Science.gov (United States)

    Gallegos, Itandehui Belem; Pérez-Campos, Eduardo; Martinez, Margarito; Mayoral, Miguel Ángel; Pérez, Laura; Aguilar, Sergio; Zenteno, Edgar; Pina, Maria del Socorro; Hernández, Pedro

    2012-12-24

    Fibroadenomas are benign human breast tumors, characterized by proliferation of epithelial and stromal components of the terminal ductal unit. They may grow, regress or remain unchanged, as the hormonal environment of the patient changes. Expression of antigen TF in mucin or mucin-type glycoproteins and of galectin-3 seems to contribute to proliferation and transformations events; their expression has been reported in ductal breast cancer and in aggressive tumors. Lectin histochemistry, immunohistochemistry, and immunofluorescence were used to examine the expression and distribution of antigen TF and galectin-3. We used lectins from Arachis hypogaea, Artocarpus integrifolia, and Amaranthus lecuocarpus to evaluate TF expression and a monoclonal antibody to evaluate galectin-3 expression. We used paraffin-embedded blocks from 10 breast tissues diagnosed with fibroadenoma and as control 10 healthy tissue samples. Histochemical and immunofluorescence analysis showed positive expression of galectin-3 in fibroadenoma tissue, mainly in stroma, weak interaction in ducts was observed; whereas, in healthy tissue samples the staining was also weak in ducts. Lectins from A. leucocarpus and A. integrifolia specificaly recognized ducts in healthy breast samples, whereas the lectin from A. hypogaea recognized ducts and stroma. In fibroadenoma tissue, the lectins from A. integrifolia, A. Hypogaea, and A. leucocarpus recognized mainly ducts. Our results suggest that expression of antigen TF and galectin-3 seems to participate in fibroadenoma development.

  8. Expression of antigen tf and galectin-3 in fibroadenoma

    Directory of Open Access Journals (Sweden)

    Gallegos Itandehui Belem

    2012-12-01

    Full Text Available Abstract Background Fibroadenomas are benign human breast tumors, characterized by proliferation of epithelial and stromal components of the terminal ductal unit. They may grow, regress or remain unchanged, as the hormonal environment of the patient changes. Expression of antigen TF in mucin or mucin-type glycoproteins and of galectin-3 seems to contribute to proliferation and transformations events; their expression has been reported in ductal breast cancer and in aggressive tumors. Findings Lectin histochemistry, immunohistochemistry, and immunofluorescence were used to examine the expression and distribution of antigen TF and galectin-3. We used lectins from Arachis hypogaea, Artocarpus integrifolia, and Amaranthus lecuocarpus to evaluate TF expression and a monoclonal antibody to evaluate galectin-3 expression. We used paraffin-embedded blocks from 10 breast tissues diagnosed with fibroadenoma and as control 10 healthy tissue samples. Histochemical and immunofluorescence analysis showed positive expression of galectin-3 in fibroadenoma tissue, mainly in stroma, weak interaction in ducts was observed; whereas, in healthy tissue samples the staining was also weak in ducts. Lectins from A. leucocarpus and A. integrifolia specificaly recognized ducts in healthy breast samples, whereas the lectin from A. hypogaea recognized ducts and stroma. In fibroadenoma tissue, the lectins from A. integrifolia, A. Hypogaea, and A. leucocarpus recognized mainly ducts. Conclusions Our results suggest that expression of antigen TF and galectin-3 seems to participate in fibroadenoma development.

  9. Expression of antigen tf and galectin-3 in fibroadenoma

    Science.gov (United States)

    2012-01-01

    Background Fibroadenomas are benign human breast tumors, characterized by proliferation of epithelial and stromal components of the terminal ductal unit. They may grow, regress or remain unchanged, as the hormonal environment of the patient changes. Expression of antigen TF in mucin or mucin-type glycoproteins and of galectin-3 seems to contribute to proliferation and transformations events; their expression has been reported in ductal breast cancer and in aggressive tumors. Findings Lectin histochemistry, immunohistochemistry, and immunofluorescence were used to examine the expression and distribution of antigen TF and galectin-3. We used lectins from Arachis hypogaea, Artocarpus integrifolia, and Amaranthus lecuocarpus to evaluate TF expression and a monoclonal antibody to evaluate galectin-3 expression. We used paraffin-embedded blocks from 10 breast tissues diagnosed with fibroadenoma and as control 10 healthy tissue samples. Histochemical and immunofluorescence analysis showed positive expression of galectin-3 in fibroadenoma tissue, mainly in stroma, weak interaction in ducts was observed; whereas, in healthy tissue samples the staining was also weak in ducts. Lectins from A. leucocarpus and A. integrifolia specificaly recognized ducts in healthy breast samples, whereas the lectin from A. hypogaea recognized ducts and stroma. In fibroadenoma tissue, the lectins from A. integrifolia, A. Hypogaea, and A. leucocarpus recognized mainly ducts. Conclusions Our results suggest that expression of antigen TF and galectin-3 seems to participate in fibroadenoma development. PMID:23265237

  10. Cationic liposomes containing soluble Leishmania antigens (SLA) plus CpG ODNs induce protection against murine model of leishmaniasis.

    Science.gov (United States)

    Heravi Shargh, Vahid; Jaafari, Mahmoud Reza; Khamesipour, Ali; Jalali, Seyed Amir; Firouzmand, Hengameh; Abbasi, Azam; Badiee, Ali

    2012-07-01

    Development of an effective vaccine against leishmaniasis is possible due to the fact that individuals cured from cutaneous leishmaniasis (CL) are protected from further infection. First generation Leishmania vaccines consisting of whole killed parasites reached to phase 3 clinical trials but failed to show enough efficacies mainly due to the lack of an appropriate adjuvant. In this study, an efficient liposomal protein-based vaccine against Leishmania major infection was developed using soluble Leishmania antigens (SLA) as a first generation vaccine and cytidine phosphate guanosine oligodeoxynucleotides (CpG ODNs) as an immunostimulatory adjuvant. 1, 2-Dioleoyl-3-trimethylammonium-propane was used as a cationic lipid to prepare the liposomes due to its intrinsic adjuvanticity. BALB/c mice were immunized subcutaneously (SC), three times in 2-week intervals, with Lip-SLA-CpG, Lip-SLA, SLA + CpG, SLA, or HEPES buffer. As criteria for protection, footpad swelling at the site of challenge and spleen parasite loads were assessed, and the immune responses were evaluated by determination of IFN-γ and IL-4 levels of cultured splenocytes, and IgG subtypes. The group of mice that received Lip-SLA-CpG showed a significantly smaller footpad swelling, lower spleen parasite burden, higher IgG2a antibody, and lower IL-4 level compared to the control groups. It is concluded that cationic liposomes containing SLA and CpG ODNs are appropriate to induce Th1 type of immune response and protection against leishmaniasis.

  11. Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

    Science.gov (United States)

    Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

    2015-01-01

    Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

  12. Cancer antigen 125 and prognosis

    DEFF Research Database (Denmark)

    Høgdall, Estrid Vilma Solyom

    2008-01-01

    cancer antigen 125 determination may be implemented into clinical practice, cut-off levels must be evaluated and internationally defined. Studies examining serum cancer antigen 125 levels after surgery but before, during, or after treatment confirmed that changes in serum levels are of prognostic value...

  13. Dogs recognize dog and human emotions.

    Science.gov (United States)

    Albuquerque, Natalia; Guo, Kun; Wilkinson, Anna; Savalli, Carine; Otta, Emma; Mills, Daniel

    2016-01-01

    The perception of emotional expressions allows animals to evaluate the social intentions and motivations of each other. This usually takes place within species; however, in the case of domestic dogs, it might be advantageous to recognize the emotions of humans as well as other dogs. In this sense, the combination of visual and auditory cues to categorize others' emotions facilitates the information processing and indicates high-level cognitive representations. Using a cross-modal preferential looking paradigm, we presented dogs with either human or dog faces with different emotional valences (happy/playful versus angry/aggressive) paired with a single vocalization from the same individual with either a positive or negative valence or Brownian noise. Dogs looked significantly longer at the face whose expression was congruent to the valence of vocalization, for both conspecifics and heterospecifics, an ability previously known only in humans. These results demonstrate that dogs can extract and integrate bimodal sensory emotional information, and discriminate between positive and negative emotions from both humans and dogs. © 2016 The Author(s).

  14. Perspective: Recognizing and rewarding clinical scholarship.

    Science.gov (United States)

    Grigsby, R Kevin; Thorndyke, Luanne

    2011-01-01

    Faculty members in medical schools and academic medical centers are in a constant process of generating new knowledge. The cornerstone of academia--and academic medicine--is scholarship. Traditionally, tenure and/or academic promotion in the professorial ranks is awarded to those who meet institutional criteria in the missions of research, teaching, and service, including patient care. In the academic review process, priority is often placed on a record of demonstrated, consistent success in traditional laboratory research, also known as the scholarship of discovery. More recently, there has been greater recognition of other forms of scholarship: education, application, and integration. These forms of scholarship, although less recognized, also result in the generation of new knowledge. In an attempt to understand the breadth and scope of clinical scholarship, the authors searched the extant literature in academic medicine for a definition of clinical scholarship and expanded the search to disciplines outside of medicine. They found that succinct, discrete definitions of clinical scholarship have been published in other disciplines, but not in academic medicine. After reviewing definitions of clinical scholarship from other disciplines, adapting definitions of educational scholarship in academic medicine, and including qualities unique to clinical scholarship, the authors developed a framework for understanding clinical scholarship in academic medicine as a means for opening a dialogue within the academic medical community. This dialogue hopefully will lead to formulating a succinct, discrete definition of clinical scholarship that will allow greater recognition and reward for clinical scholars in the promotion and tenure process.

  15. Overview: recognizing the problem of magnesium deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Seelig, M.S.

    1988-01-01

    The magnesium content of the usual American diet is less than the recommended dietary allowance. Excesses of some macro- and micro-nutrients interact with Mg, increasing its requirements. Marginal deficiency of Mg is not associated with hypomagnesemia, is not characterized by typical manifestations, as is thus difficult to diagnose. Serum or plasma Mg levels are held within narrow limits unless tissue levels are very low, or renal function is poor. Vulnerability to Mg deficiency increases during growth and development, pregnancy, when under physical or psychological stress, and during illness or its treatment that interferes with absorption or causes loss of Mg. Evidence of biochemical changes of early Mg deficiency is rarely sought, although the roles of Mg in many enzyme systems are recognized. The effects of Mg deficiency on metabolism, even in disorders caused by vitamin dependencies in which Mg is a co-factor, are largely unexplored. Deficiency of Mg is diagnosed confidently when the laboratory reports hypomagnesemia in patients with convulsions or arrhythmias. Without these signs, Mg levels are not often ordered, even in the presence of neuromuscular irritability such as respond to Mg repletion. Because Mg supplementation or Mg-sparing drugs protect against premature or ectopic heart beats and sudden death, to which diuretic-treated hypertensive patients are at risk, it is increasingly being advised that their Mg status be determined.

  16. Recognizing disguised faces: human and machine evaluation.

    Directory of Open Access Journals (Sweden)

    Tejas Indulal Dhamecha

    Full Text Available Face verification, though an easy task for humans, is a long-standing open research area. This is largely due to the challenging covariates, such as disguise and aging, which make it very hard to accurately verify the identity of a person. This paper investigates human and machine performance for recognizing/verifying disguised faces. Performance is also evaluated under familiarity and match/mismatch with the ethnicity of observers. The findings of this study are used to develop an automated algorithm to verify the faces presented under disguise variations. We use automatically localized feature descriptors which can identify disguised face patches and account for this information to achieve improved matching accuracy. The performance of the proposed algorithm is evaluated on the IIIT-Delhi Disguise database that contains images pertaining to 75 subjects with different kinds of disguise variations. The experiments suggest that the proposed algorithm can outperform a popular commercial system and evaluates them against humans in matching disguised face images.

  17. Radioimmunoassays of hidden viral antigens

    International Nuclear Information System (INIS)

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure

  18. Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

    Science.gov (United States)

    Moguche, Albanus O; Musvosvi, Munyaradzi; Penn-Nicholson, Adam; Plumlee, Courtney R; Mearns, Helen; Geldenhuys, Hennie; Smit, Erica; Abrahams, Deborah; Rozot, Virginie; Dintwe, One; Hoff, Søren T; Kromann, Ingrid; Ruhwald, Morten; Bang, Peter; Larson, Ryan P; Shafiani, Shahin; Ma, Shuyi; Sherman, David R; Sette, Alessandro; Lindestam Arlehamn, Cecilia S; McKinney, Denise M; Maecker, Holden; Hanekom, Willem A; Hatherill, Mark; Andersen, Peter; Scriba, Thomas J; Urdahl, Kevin B

    2017-06-14

    CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. The ability of each T cell population to control Mtb in the lungs of mice was restricted for opposite reasons: Ag85B-specific T cells were limited by reduced antigen expression during persistent infection, whereas ESAT-6-specific T cells became functionally exhausted due to chronic antigenic stimulation. Our findings suggest that different vaccination strategies will be required to optimize protection mediated by T cells recognizing antigens expressed at distinct stages of Mtb infection. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Reeves, Emma; James, Edward

    2017-01-01

    The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8 + cytotoxic and CD4 + helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8 + cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4 + T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8 + cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets. © 2016 John Wiley & Sons Ltd.

  20. Identification and characterization of HLA-A24-specific XBP1, CD138 (Syndecan-1) and CS1 (SLAMF7) peptides inducing antigens-specific memory cytotoxic T lymphocytes targeting multiple myeloma.

    Science.gov (United States)

    Bae, J; Hideshima, T; Zhang, G L; Zhou, J; Keskin, D B; Munshi, N C; Anderson, K C

    2018-03-01

    X-box binding protein 1 (XBP1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens in cancers including multiple myeloma (MM). Here, we identify and characterize immunogenic HLA-A24 peptides derived from these antigens for potential vaccination therapy of HLA-A24+ patients with MM. The identified immunogenic HLA-A24-specific XBP1 unspliced (UN) 185-193 (I S P W I L A V L), XBP1 spliced (SP) 223-231 (V Y P E G P S S L), CD138 265-273 (I F A V C L V G F) and CS1 240-248 (L F V L G L F L W) peptides induced antigen-specific CTL with anti-MM activity in an HLA-A24 restricted manner. Furthermore, a cocktail containing the four HLA-A24 peptides evoked MM-specific CTL with distinct phenotypic profiles (CD28, CD40L, 41BB, CD38, CD69) and anti-tumor activities, evidenced by perforin upregulation, CD107a degranulation (cytotoxicity) and Th1-type cytokines (IFN-γ/IL-2/TNF-α) production in response to HLA-A24 + MM cells. The multipeptide-specific CTL included antigen-specific memory CD8 + T cells expressing both T-cell activation (CD38, CD69) and immune checkpoints antigens (CTLA, PD-1, LAG-3, TIM-3). These results provide the framework for a multipeptide vaccination therapy to induce tumor-specific CTL in HLA-A24-positive patients with myeloma and other cancers expressing these antigens.

  1. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    DEFF Research Database (Denmark)

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... self-healing cutaneous leishmaniasis. The T-cell clones expressed CD4, and the alpha chain of the T-cell antigen receptor. GP63 reactive T-cell clones activated by antigen or by immobilized anti-CD3 antibody released relative large amounts of interferon-gamma and no or little interleukin-4, thereby...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...

  2. Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1.

    Directory of Open Access Journals (Sweden)

    Kimberley D Seed

    2012-09-01

    Full Text Available The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage.

  3. Phase Variable O Antigen Biosynthetic Genes Control Expression of the Major Protective Antigen and Bacteriophage Receptor in Vibrio cholerae O1

    Science.gov (United States)

    Seed, Kimberley D.; Faruque, Shah M.; Mekalanos, John J.; Calderwood, Stephen B.; Qadri, Firdausi; Camilli, Andrew

    2012-01-01

    The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage. PMID:23028317

  4. Glycoconjugates as target antigens in peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Ljubica Suturkova

    2014-12-01

    Full Text Available Identification and characterization of antigens present at the human peripheral nerve is a great challenge in the field of neuroimmunology. The latest investigations are focused on the understanding of the biology of glycoconjugates present at the peripheral nerve, and their immunological reactivity. Increased titers of antibodies that recognize carbohydrate determinants of glycoconjugates (glycolipids and glycoproteins are associated with distinct neuropathic syndromes. There is considerable cross-reactivity among anti-ganglioside antibodies, resulting from shared oligosaccharide epitopes, possibly explaining the overlap in syndromes observed in many affected patients. Sera from patients with neuropathies (GBS, chronic inflammatory demielynating polyneuropathy - CIDP, multifocal motor neuropathy - MMN, cross-react with glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni O:19. The frequency of occurrence of antibodies against these glycoproteins is different, depending of the type of neuropathy. Identification of the cross-reactive glycoproteins and possible additional auto antigens could be useful in laboratory evaluation of peripheral neuropathies and help to develop a more effective therapeutic approach.

  5. Can a CNN recognize Catalan diet?

    Science.gov (United States)

    Herruzo, P.; Bolaños, M.; Radeva, P.

    2016-10-01

    Nowadays, we can find several diseases related to the unhealthy diet habits of the population, such as diabetes, obesity, anemia, bulimia and anorexia. In many cases, these diseases are related to the food consumption of people. Mediterranean diet is scientifically known as a healthy diet that helps to prevent many metabolic diseases. In particular, our work focuses on the recognition of Mediterranean food and dishes. The development of this methodology would allow to analise the daily habits of users with wearable cameras, within the topic of lifelogging. By using automatic mechanisms we could build an objective tool for the analysis of the patient's behavior, allowing specialists to discover unhealthy food patterns and understand the user's lifestyle. With the aim to automatically recognize a complete diet, we introduce a challenging multi-labeled dataset related to Mediter-ranean diet called FoodCAT. The first type of label provided consists of 115 food classes with an average of 400 images per dish, and the second one consists of 12 food categories with an average of 3800 pictures per class. This dataset will serve as a basis for the development of automatic diet recognition. In this context, deep learning and more specifically, Convolutional Neural Networks (CNNs), currently are state-of-the-art methods for automatic food recognition. In our work, we compare several architectures for image classification, with the purpose of diet recognition. Applying the best model for recognising food categories, we achieve a top-1 accuracy of 72.29%, and top-5 of 97.07%. In a complete diet recognition of dishes from Mediterranean diet, enlarged with the Food-101 dataset for international dishes recognition, we achieve a top-1 accuracy of 68.07%, and top-5 of 89.53%, for a total of 115+101 food classes.

  6. Recognizing flu-like symptoms from videos.

    Science.gov (United States)

    Thi, Tuan Hue; Wang, Li; Ye, Ning; Zhang, Jian; Maurer-Stroh, Sebastian; Cheng, Li

    2014-09-12

    Vision-based surveillance and monitoring is a potential alternative for early detection of respiratory disease outbreaks in urban areas complementing molecular diagnostics and hospital and doctor visit-based alert systems. Visible actions representing typical flu-like symptoms include sneeze and cough that are associated with changing patterns of hand to head distances, among others. The technical difficulties lie in the high complexity and large variation of those actions as well as numerous similar background actions such as scratching head, cell phone use, eating, drinking and so on. In this paper, we make a first attempt at the challenging problem of recognizing flu-like symptoms from videos. Since there was no related dataset available, we created a new public health dataset for action recognition that includes two major flu-like symptom related actions (sneeze and cough) and a number of background actions. We also developed a suitable novel algorithm by introducing two types of Action Matching Kernels, where both types aim to integrate two aspects of local features, namely the space-time layout and the Bag-of-Words representations. In particular, we show that the Pyramid Match Kernel and Spatial Pyramid Matching are both special cases of our proposed kernels. Besides experimenting on standard testbed, the proposed algorithm is evaluated also on the new sneeze and cough set. Empirically, we observe that our approach achieves competitive performance compared to the state-of-the-arts, while recognition on the new public health dataset is shown to be a non-trivial task even with simple single person unobstructed view. Our sneeze and cough video dataset and newly developed action recognition algorithm is the first of its kind and aims to kick-start the field of action recognition of flu-like symptoms from videos. It will be challenging but necessary in future developments to consider more complex real-life scenario of detecting these actions simultaneously from

  7. The antibody response to well-defined malaria antigens after acute malaria in individuals living under continuous malaria transmission

    DEFF Research Database (Denmark)

    Petersen, E; Høgh, B; Dziegiel, Morten Hanefeld

    1992-01-01

    , and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing...... elicited by natural malaria infection in previously primed donors....

  8. Toxocara canis glycans influence antigen recognition by mouse IgG1 and IgM antibodies.

    Science.gov (United States)

    Długosz, Ewa; Wiśniewski, Marcin

    2016-01-01

    The impact of sugar moieties of Toxocara canis glycoprotein antigens on their recognition by infected mouse antibodies was investigated in this study. Native TES and recombinant Toxocara mucins generated in Pichia pastoris yeast as well as their deglycosylated forms were used in ELISA. TES and recombinant mucins were equally recognized by T. canis infected mouse IgG1 antibodies. IgM immunoglobulins predominantly recognized TES antigens. Among mucins recognition of Tc-MUC-4 was the most significant. Deglycosylation of antigens resulted in significant loss of IgM and IgG1 reactivity to TES, mucins, Tc-MUC-3 and Tc-MUC-4. The presence of sugar moieties had no influence on IgE binding to native or recombinant T. canis antigens. Our results suggest that glycans are involved in epitope formation what should be taken into consideration in production of recombinant helminth antigens for diagnostic purposes.

  9. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

    Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  10. Colonoscopy and carcinoembryonic antigen variations.

    Science.gov (United States)

    Sousa, Rita G; Nunes, Ana; Meira, Tânia; Carreira, Olga; Pires, Ana M; Freitas, João

    2014-01-01

    Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1) before bowel cleaning, (2) before colonoscopy and (3) immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by "Sandwich" immunoassay. The statistical methods used were the paired t-test and ANOVA. Thirty-seven patients (22M/15F) were included; age range 28-84 (mean 56 years). Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1), (2) and (3), respectively. An increase in value (2) compared with (1) was observed in 20/37 patients (P = 0.018), mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2) to (3) (P = 1.3x10-7). A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  11. INNOVATIVE STRATEGIES TO IDENTIFY M. TUBERCULOSIS ANTIGENS AND EPITOPES USING GENOME-WIDE ANALYSES

    Directory of Open Access Journals (Sweden)

    Annemieke eGeluk

    2014-06-01

    Full Text Available In view of the fact that only a small part of the Mtb expressome has been explored for identification of antigens capable of activating human T-cell responses, which is critically required for the design of better TB vaccination strategies, more emphasis should be placed on innovative ways to discover new Mtb antigens and explore their function at the several stages of infection. Better protective antigens for TB vaccines are urgently needed, also in view of the disappointing results of the MVA85 vaccine which failed to induce additional protection in BCG vaccinated infants [54]. Moreover, immune responses to relevant antigens may be useful to identify TB-specific biomarker signatures. Here we describe the potency of novel tools and strategies to reveal such Mtb antigens. Using proteins specific for different Mtb infection phases, many new antigens of the latency-associated Mtb DosR regulon as well as Rpf proteins, associated with resuscitating TB, were discovered that were recognized by CD4+ and CD8+ T-cells. Furthermore, by employing MHC binding algorithms and bioinformatics combined with high throughput human T-cell screens and tetramers, HLA-class Ia restricted poly-functional CD8+ T-cells were identified in TB patients. Comparable methods, led to the identification of HLA-E-restricted Mtb epitopes recognized by CD8+ T-cells. A genome-wide unbiased antigen discovery approach was applied to analyse the in vivo Mtb gene expression profiles in the lungs of mice, resulting in the identification of IVE-TB antigens, which are expressed during infection in the lung, the main target organ of Mtb. IVE-TB antigens induce strong T cell responses in long-term latently Mtb infected individuals, and represent an interesting new group of TB antigens for vaccination. In summary, new tools have helped expand our view on the Mtb antigenome involved in human cellular immunity and provided new candidates for TB vaccination.

  12. Acanthocheilonema viteae: Vaccination of jirds with irradiation-attenuated stage-3 larvae and with exported larval antigens

    International Nuclear Information System (INIS)

    Lucius, R.; Textor, G.; Kern, A.; Kirsten, C.

    1991-01-01

    Jirds (Meriones unguiculatus) were immunized with irradiated (35 krad) stage-3 larvae (L3) of Acanthocheilonema viteae. The induced resistance against homologous challenge infection and the antibody response of the animals were studied. Immunization with 3, 2, or 1 dose of 50 irradiated L3 induced approximately 90% resistance. Immunization with a single dose of only 5 irradiated L3 resulted in 60.8% protection while immunization with a single dose of 25 L3 induced 94.1% protection. The protection induced with 3 doses of 50 irradiated L3 did not decrease significantly during a period of 6 months. Sera of a proportion, but not all resistant jirds, contained antibodies against the surface of vector derived L3 as defined by IFAT. No surface antigens of microfilariae or adult worms were recognized by the sera. Vaccinated animals had antibody responses against antigens in the inner organs of L3 and in the cuticle and reproductive organs of adult worms as shown by IFAT. Immunoblotting with SDS-PAGE-separated L3 antigens and L3-CSN revealed that all sera contained antibodies against two exported antigens of 205 and 68 kDa, and against a nonexported antigen of 18 kDa. The 205-kDa antigen easily degraded into fragments of 165, 140, 125, and 105 kDa which were recognized by resistant jird sera. Various antigens of adult worms, but relatively few antigens of microfilariae, were also recognized. To test the relevance of exported antigens of L3 to resistance, jirds were immunized with L3-CSN together with a mild adjuvant. This immunization induced 67.7% resistance against challenge infection and sera of the immunized animals recognized the 205- and 68-kDa antigens of L3

  13. Antigenic relationships among four herpesviruses.

    Science.gov (United States)

    Blue, W T; Plummer, G

    1973-06-01

    Common viral antigens were detected, by fluorescent-antibody studies, in cells infected with herpes simplex virus 1, squirrel monkey herpesvirus 1, bovine rhinotracheitis, and equine abortion viruses. The two primate viruses showed slight cross-neutralization.

  14. HLA-B27 antigen

    Science.gov (United States)

    Human leukocyte antigen B27; Ankylosing spondylitis-HLA; Psoriatic arthritis-HLA; Reactive arthritis-HLA ... Erythrocyte sedimentation rate ( ESR ) Rheumatoid factor X-rays HLA testing is also used to match donated tissue ...

  15. 46 CFR 160.064-7 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.064-7 Section 160.064-7...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Marine Buoyant Devices § 160.064-7 Recognized laboratory. (a) A... laboratory. The following laboratories are recognized under § 159.010-7 of this part, to perform testing and...

  16. 46 CFR 160.052-9 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.052-9 Section 160.052-9..., Adult and Child § 160.052-9 Recognized laboratory. (a) A manufacturer seeking Coast Guard approval of a... shall apply for approval directly to a recognized independent laboratory. The following laboratories are...

  17. 46 CFR 164.019-17 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 164.019-17 Section 164.019-17...: SPECIFICATIONS AND APPROVAL MATERIALS Personal Flotation Device Components § 164.019-17 Recognized laboratory. (a) General. A laboratory may be designated as a recognized laboratory under this subpart if it is— (1...

  18. 46 CFR 160.047-7 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.047-7 Section 160.047-7... and Child § 160.047-7 Recognized laboratory. (a) A manufacturer seeking Coast Guard approval of a... shall apply for approval directly to a recognized independent laboratory. The following laboratories are...

  19. 46 CFR 160.060-9 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 160.060-9 Section 160.060-9..., Adult and Child § 160.060-9 Recognized laboratory. (a) A manufacturer seeking Coast Guard approval of a... shall apply for approval directly to a recognized independent laboratory. The following laboratories are...

  20. 46 CFR 164.012-12 - Recognized laboratory.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Recognized laboratory. 164.012-12 Section 164.012-12...: SPECIFICATIONS AND APPROVAL MATERIALS Interior Finishes for Merchant Vessels § 164.012-12 Recognized laboratory. A recognized laboratory is one which is operated as a nonprofit public service and is regularly...

  1. Natural selection promotes antigenic evolvability.

    Science.gov (United States)

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  2. Epicutaneous sensitization with protein antigen

    Directory of Open Access Journals (Sweden)

    I-Lin Liu

    2012-12-01

    Full Text Available In the past few decades there has been a progressive understanding that epicutaneous sensitization with protein antigen is an important sensitization route in patients with atopic dermatitis. A murine protein-patch model has been established, and an abundance of data has been obtained from experiments using this model. This review discusses the characteristics of epicutaneous sensitization with protein antigen, the induced immune responses, the underlying mechanisms, and the therapeutic potential.

  3. Proteomic analysis of Trichinella spiralis adult worm excretory-secretory proteins recognized by early infection sera.

    Science.gov (United States)

    Liu, Ruo Dan; Qi, Xin; Sun, Ge Ge; Jiang, Peng; Zhang, Xi; Wang, Li Ang; Liu, Xiao Lin; Wang, Zhong Quan; Cui, Jing

    2016-11-15

    At the intestinal stage of a Trichinella spiralis (T. spiralis) infection, the excretory-secretory (ES) antigens produced by adult worms (AWs) result in an early exposure to the host's immune system and elicit the production of specific antibodies; the AW ES proteins might provide early diagnostic markers of trichinellosis. The aim of this study was to identify early serodiagnostic markers from T. spiralis AW ES antigens. T. spiralis AWs were collected at 72h post infection, and their ES antigens were analysed by SDS-PAGE and Western blot. Then, the immunoreactive bands were subjected to shotgun LC-MS/MS and bioinformatics analyses. Our results showed that only one protein band (33kDa) was recognized by the sera of mice infected with T. spiralis at 8 days after infection. The shotgun LC-MS/MS analysis identified 23 proteins that were then clustered into 10 types; these proteins had molecular weights of 28.13-71.62kDa and pI 5.05-9.20. Certain enzymes (e.g., serine protease, adult-specific deoxyribonuclease [DNase] II, peptidase S1A subfamily, and multi cystatin-like domain protein) were found to be highly represented. The functions of the 10 proteins were further analysed: of the 6 annotated proteins, 3 had serine hydrolase activity and 2 had DNase II activity. These results provide a valuable basis for identifying early diagnostic antigens and vaccine candidates for trichinellosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment. Project 2 - Identification of Autologous Antigens in Early Stage Serous Carcinoma

    National Research Council Canada - National Science Library

    Kurman, Robert

    2003-01-01

    Our goal is to develop an early detection screening test for serous carcinoma. Specific aim 1: Obtain cDNAs of autologous tumor antigens recognized by sera of patients with early stage serous carcinoma, but not controls...

  5. Three novel NY-ESO-1 epitopes bound to DRB1*0803, DQB1*0401 and DRB1*0901 recognized by CD4 T cells from CHP-NY-ESO-1-vaccinated patients.

    Science.gov (United States)

    Mizote, Yu; Taniguchi, Taku; Tanaka, Kei; Isobe, Midori; Wada, Hisashi; Saika, Takashi; Kita, Shoichi; Koide, Yukari; Uenaka, Akiko; Nakayama, Eiichi

    2010-07-19

    Three novel NY-ESO-1 CD4 T cell epitopes were identified using PBMC obtained from patients who were vaccinated with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1). The restriction molecules were determined by antibody blocking and using various EBV-B cells with different HLA alleles as APC to present peptides to CD4 T cells. The minimal epitope peptides were determined using various N- and C-termini truncated peptides deduced from 18-mer overlapping peptides originally identified for recognition. Those epitopes were DRB1*0901-restricted NY-ESO-1 87-100, DQB1*0401-restricted NY-ESO-1 95-107 and DRB1*0803-restricted NY-ESO-1 124-134. CD4 T cells used to determine those epitope peptides recognized EBV-B cells or DC that were treated with recombinant NY-ESO-1 protein or NY-ESO-1-expressing tumor cell lysate, suggesting that the epitope peptides are naturally processed. These CD4 T cells showed a cytokine profile with Th1 characteristics. Furthermore, NY-ESO-1 87-100 peptide/HLA-DRB1*0901 tetramer staining was observed. Multiple Th1-type CD4 T cell responses are beneficial for inducing effective anti-tumor responses after NY-ESO-1 protein vaccination. (c) 2010 Elsevier Ltd. All rights reserved.

  6. Identification of a Highly Antigenic Linear B Cell Epitope within Plasmodium vivax Apical Membrane Antigen 1 (AMA-1)

    Science.gov (United States)

    Bueno, Lilian Lacerda; Lobo, Francisco Pereira; Morais, Cristiane Guimarães; Mourão, Luíza Carvalho; de Ávila, Ricardo Andrez Machado; Soares, Irene Silva; Fontes, Cor Jesus; Lacerda, Marcus Vinícius; Olórtegui, Carlos Chavez; Bartholomeu, Daniella Castanheira; Fujiwara, Ricardo Toshio; Braga, Érika Martins

    2011-01-01

    Apical membrane antigen 1 (AMA-1) is considered to be a major candidate antigen for a malaria vaccine. Previous immunoepidemiological studies of naturally acquired immunity to Plasmodium vivax AMA-1 (PvAMA-1) have shown a higher prevalence of specific antibodies to domain II (DII) of AMA-1. In the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length AMA-1 and DII. Also, we demonstrated a strong association between AMA-1 and DII IgG and IgG subclass responses. We analyzed the primary sequence of PvAMA-1 for B cell linear epitopes co-occurring with intrinsically unstructured/disordered regions (IURs). The B cell epitope comprising the amino acid sequence 290–307 of PvAMA-1 (SASDQPTQYEEEMTDYQK), with the highest prediction scores, was identified in domain II and further selected for chemical synthesis and immunological testing. The antigenicity of the synthetic peptide was identified by serological analysis using sera from P. vivax-infected individuals who were knowingly reactive to the PvAMA-1 ectodomain only, domain II only, or reactive to both antigens. Although the synthetic peptide was recognized by all serum samples specific to domain II, serum with reactivity only to the full-length protein presented 58.3% positivity. Moreover, IgG reactivity against PvAMA-1 and domain II after depletion of specific synthetic peptide antibodies was reduced by 18% and 33% (P = 0.0001 for both), respectively. These results suggest that the linear epitope SASDQPTQYEEEMTDYQK is highly antigenic during natural human infections and is an important antigenic region of the domain II of PvAMA-1, suggesting its possible future use in pre-clinical studies. PMID:21713006

  7. Identification and characterization of Neospora caninum tachyzoite antigens useful for diagnosis of neosporosis.

    Science.gov (United States)

    Bjerkas, I; Jenkins, M C; Dubey, J P

    1994-01-01

    The purpose of the present study was to identify antigens of the protozoan Neospora caninum that could be useful for the diagnosis of neosporosis in domestic animals. As revealed by immunoblotting, immune sera from a wide range of animal species exhibited a similar recognition pattern of four major and several minor N. caninum antigens. In contrast to preinoculation sera, all tested immune sera recognized nonreduced immunodominant 17-, 29-, 30-, and 27-kDa antigens. A 46-kDa protein which showed faint recognition by preimmune sera also exhibited a strong response by immune sera. Immunolocalization of the four immunodominant N. caninum antigens was investigated by immunogold electron microscopy using monospecific polyclonal antisera. The 17-kDa antigen appears to be associated with the body part of the rhoptries, while the 29- and 30-kDa antigens were associated with the dense granules, network, and limiting membrane of the parasitophorous vacuole. Studies were also conducted to compare antibody responses to N. caninum and the related protozoan Toxoplasma gondii. Although N. caninum and T. gondii (RH strain) tachyzoites shared a few cross-reacting antigens, the immunodominant antigens of both parasites were not recognized by heterologous sera. Also, immunogold staining with rabbit anti-Neospora hyperimmune serum exhibited almost no labeling of external membranes of Neospora tachyzoites compared with the very marked labeling seen when Toxoplasma tachyzoites (RH strain) were incubated with rabbit anti-Toxoplasma hyperimmune serum. These unique antigenic differences should be useful in developing a diagnostic assay for N. caninum. Images PMID:7496948

  8. Males without apparent alloimmunization could have HLA antibodies that recognize target HLA specificities expressed on cells.

    Science.gov (United States)

    Nakamura, J; Nakajima, F; Kamada, H; Tadokoro, K; Nagai, T; Satake, M

    2017-05-01

    Human leukocyte antigen (HLA) antibodies, which are involved in the development of transfusion-related side effects such as transfusion-related lung injury, are sometimes found in males without a history of alloimmunization (eg, transplantation and transfusion). Whether HLA antibodies in male donors can interact with their target HLA specificities expressed on cells have not been completely investigated. The HLA antibodies detected in 7 male donors were characterized. Flow cytometry and immunocomplex capture fluorescence analysis were performed to evaluate the ability of these antibodies to bind with target HLA specificities expressed on cells. The association of these antibodies with complement was examined using anti-C1q antibody. Sustainability of HLA antibodies over time was compared in 26 male vs 57 female donors. The antibodies from all 7 donors recognized intact HLA molecules coated onto microbeads. The antibodies in 2 of 7 donors also recognized their target HLA specificities expressed on cells. Furthermore, the antibodies in one of these 2 donors showed HLA specificities that involved complement binding. Twenty-one of 26 initially positive male donors had turned negative for HLA antibody at least 1 year after their initial positive screening, whereas HLA antibody positivity was maintained for a long time in most female donors. Males without apparent alloimmunization could have HLA antibodies that recognize their target HLA specificities on cells and that could potentially modify molecular events in affected cells. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Modulation of associated ovarian carcinoma antigens by 5 cytokines used as single agents or in combination.

    Science.gov (United States)

    Imbert-Marcille, B M; Thédrez, P; Saï-Maurel, C; François, C; Auget, J L; Benard, J; Jacques, Y; Imai, S; Chatal, J F

    1994-05-01

    Optimization of intraperitoneal radioimmunotherapy of ovarian cancer depends on increasing the antigenic expression of tumor cells. For this purpose, we studied the effect of 5 cytokines (IFN-alpha, IFN-beta, IFN-gamma, TNF-alpha and TGF-beta), used as single agents or in combination, on 4 ovarian cancer cell lines which present different antigenic profiles with the monoclonal antibodies (MAbs) tested (OC125, OVTL-3, MOv 18 and MOv 19). Analyses were performed by flow cytometry and the Scatchard technique in order to study antigenic modulation. The effect on proliferation was determined by cell counting. Expression of O3 antigen, recognized by the OVTL3 MAb, was increased up to 2.5 times after IFNs and TNF-alpha (used as single agent) on the 2 lines presenting low basal expression (SHIN-3 and IGROVI). The expression of CA125 antigen and the antigens recognized by MOv 18 and MOv 19 MAbs was not increased by any of the cytokines tested. The combination IFN-gamma+TNF-alpha was synergistic on cytotoxicity and enhanced O3 expression, providing 10 times as many sites per cell on the SHIN-3 line. For 3 other associations (IFN-alpha+IFN-gamma, IFN-beta+IFN-gamma and IFN-alpha+TNF-alpha), there was an additive effect on O3 expression and on cell cytotoxicity.

  10. Preservation of surface-dependent properties of viral antigens following immobilization on particulate ceramic delivery vehicles.

    Science.gov (United States)

    Kossovsky, N; Gelman, A; Sponsler, E; Rajguru, S; Torres, M; Mena, E; Ly, K; Festekjian, A

    1995-05-01

    B-cell stimulation for the purpose of evoking an effective neutralizing humoral immune response is a surface phenomenon that is exquisitely specific to antigen conformation. Consequently, successful delivery of antigen, such as would be desired in a vaccine, entails preservation of an antigen's apparent native surface (conformational) properties. Prior to testing the actual vaccinating efficacy of delivered antigens, the surface properties could be assessed through a variety of in vitro and in vivo assays in which the measurement standard would be the properties of the antigens in their native state (whole virus). Using surface modified nanocrystalline carbon and calcium-phosphate ceramic particulates (carbon ceramics and brushite), we evaluated the surface activity of immobilized non-nuclear material extracted from HIV-1. Physical characterization showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole (live) HIV. In vitro testing showed that the HIV decoys were recognized by both conformationally nonspecific and specific monoclonal antibodies, were recognized by human IgG from HIV antibody-positive patients, and could promote surface agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing in three vaccinated animal species showed that the HIV decoys elicited humoral and cellular immune responses similar to that evoked by whole (live) HIV.

  11. Studies on antigenic and genomic properties of Brazilian rabies virus isolates

    NARCIS (Netherlands)

    Schaefer, R.; Batista, H.B.; Franco, A.C.; Rijsewijk, F.A.M.; Roehe, P.M.

    2005-01-01

    Despite the recognized stability of rabies virus, differences among isolates from different species have been found. This work was carried out with the aim to identify antigenic and genomic differences in Brazilian rabies virus isolates and to verify whether such alterations would bear any

  12. Human sensitization to Ganoderma antigen.

    Science.gov (United States)

    Tarlo, S M; Bell, B; Srinivasan, J; Dolovich, J; Hargreave, F E

    1979-07-01

    Continuous air sampling with a Hirst volumetric spore trap over 3 yr has identified basidiospores of Ganoderma applanatum, a bracket fungus, as the most numerous fungal spores in two southern Ontario locations. The particle size is small and the calculated total spore mass approximates that of the spores of Cladosporium and Alternaria. Extracts of Ganoderma applanatum bracket fungus and spores in w/v, 1:10 concentration were prepared after collection of samples of the fungus from local woods. Skin prick tests with the extracts were performed in 294 consecutive children and adults attending two chest/allergy clinics. Of these patients, 182 (61.9%) reacted to 1 or more of the common inhalant allergen extracts and 24 (8.2%) reacted to Ganoderma antigen. There was no consistent relationship between reactivity to Ganoderma antigen and any of the common inhaled allergens. IgE-dependent sensitization to Ganoderma was confirmed by the radioallergosorbent test (RAST). Rabbit antisera to Ganoderma antigen preparations did not appear to cross-react with preparations of the various clinically important allergens. The findings indicate that Ganoderma antigen is commonly encountered, can induce human sensitization, and has unique antigenicity among common allergens of clinical importance.

  13. Structural requirements for the interaction between class II MHC molecules and peptide antigens

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Appella, E

    1990-01-01

    IA(d) and IE(d) molecules and their peptide ligands, we found that some structural characteristics apply to both antigen-MHC interactions. In particular, we found: 1) each MHC molecule is capable of binding many unrelated peptides through the same peptide-binding site; 2) despite this permissiveness......Previous work from our and other laboratories indicates that T cells recognize a complex between the MHC restriction element and peptide antigen fragments. This paper reviews the structural characteristics of the formation of such a complex. By analyzing in detail the interactions between purified...... of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity (IA(d) or IE(d)); 3) IA(d) and IE(d) molecules recognize different and independent structures on the antigen molecule; 4) only about 10% of the single...

  14. Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis.

    Science.gov (United States)

    Costa, Lourena Emanuele; Goulart, Luiz Ricardo; Pereira, Nathália Cristina de Jesus; Lima, Mayara Ingrid Sousa; Duarte, Mariana Costa; Martins, Vivian Tamietti; Lage, Paula Sousa; Menezes-Souza, Daniel; Ribeiro, Tatiana Gomes; Melo, Maria Norma; Fernandes, Ana Paula; Soto, Manuel; Tavares, Carlos Alberto Pereira; Chávez-Fumagalli, Miguel Angel; Coelho, Eduardo Antonio Ferraz

    2014-01-01

    The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL). Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin), showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the parasite burden. This is the first study that describes phage-displayed peptides as

  15. Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Lourena Emanuele Costa

    Full Text Available BACKGROUND: The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL. Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. METHODOLOGY/MAIN FINDINGS: Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin, showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. CONCLUSIONS/SIGNIFICANCE: This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the

  16. Recognizing Bedside Events Using Thermal and Ultrasonic Readings

    Directory of Open Access Journals (Sweden)

    Danielsen Asbjørn

    2017-06-01

    Full Text Available Falls in homes of the elderly, in residential care facilities and in hospitals commonly occur in close proximity to the bed. Most approaches for recognizing falls use cameras, which challenge privacy, or sensor devices attached to the bed or the body to recognize bedside events and bedside falls. We use data collected from a ceiling mounted 80 × 60 thermal array combined with an ultrasonic sensor device. This approach makes it possible to monitor activity while preserving privacy in a non-intrusive manner. We evaluate three different approaches towards recognizing location and posture of an individual. Bedside events are recognized using a 10-second floating image rule/filter-based approach, recognizing bedside falls with 98.62% accuracy. Bed-entry and exit events are recognized with 98.66% and 96.73% accuracy, respectively.

  17. Characterisation of Sarcoptes scabiei antigens.

    Science.gov (United States)

    Hejduk, Gloria; Hofstätter, Katja; Löwenstein, Michael; Peschke, Roman; Miller, Ingrid; Joachim, Anja

    2011-02-01

    In pig herds, the status of Sarcoptes scabiei infections is routinely monitored by serodiagnosis. Crude antigen for ELISA is usually prepared from S. scabiei var. canis or other variations and may lead to variations in the outcome of different tests, making assay standardisation difficult. This study was performed to investigate the antigen profiles of S. scabiei, including differences between hydrophilic and more hydrophobic protein fractions, by Western blotting with sera from pigs with defined infection status. Potential cross-reactivity among S. scabiei (var. canis, suis and bovis), Dermatophagoides farinae and Tyrophagus putrescentiae was also analysed. Hydrophobic S. scabiei antigens were detectable in the range of 40-50 kDa, whilst the hydrophilic fraction showed no specific antigenicity. In the hydrophobic fractions of D. farinae and T. putrescentiae, two major protein fractions in a similar size range could be identified, but no cross-reactivity with Sarcoptes-positive sera was detectable. However, examination of the hydrophilic fractions revealed cross-reactivity between Sarcoptes-positive sera and both the house dust mite and the storage mite in the range of 115 and 28/38 kDa. Specific bands in the same range (42 and 48 kDa) could be detected in blots from hydrophobic fractions of all three tested variations of S. scabiei (var. canis, bovis and suis). These results show that there are considerable differences in mange antibody reactivity, including reactions with proteins from free-living mites, which may interfere with tests based on hydrophilic antigens. Further refinement of antigen and the use of specific hydrophobic proteins could improve ELISA performance and standardisation.

  18. Recombinant proteinase 3 (Wregener's antigen) expressed in Pichia pastoris is functionally active and is recognized by patient sera

    NARCIS (Netherlands)

    Harmsen, MC; Heeringa, P; VanderGeld, YM; Huitema, MG; Klimp, A; Tiran, A; Kallenberg, CGM

    1997-01-01

    The open reading frame of human proteinase 3 (PR3) without the prepro-peptide was cloned and expressed in Escherichia coli (rcPR3) and in Pichia pastoris (rpPR3). The 6-histidine tagged rpPR3 was efficiently secreted into culture supernatant from which it could be purified by immobilized metal

  19. Interferon-¿ and interleukin-4 production by human T cells recognizing Leishmania donovani antigens separated by SDS-PAGE

    DEFF Research Database (Denmark)

    Bahrenscheer, J; Kemp, M; Kurtzhals, J A

    1995-01-01

    Crude preparations of Leishmania donovani proteins were separated by preparative SDS-polyacrylamide gel electrophoresis. Fractions of separated proteins were recovered by electroelution directly from the gel into separate chambers. The isolated protein fractions were tested for induction of proli......Crude preparations of Leishmania donovani proteins were separated by preparative SDS-polyacrylamide gel electrophoresis. Fractions of separated proteins were recovered by electroelution directly from the gel into separate chambers. The isolated protein fractions were tested for induction...

  20. T lymphocytes from human chimeras do recognize antigen in the context of allogeneic determinants of the major histocompatibility complex

    NARCIS (Netherlands)

    Touraine, J. L.; Roncarolo, M. G.; Plotnicky, H.; Bachetta, R.; Spits, H.

    1993-01-01

    Human stem cells from the fetal liver can be transplanted to immunodeficient patients and reconstitute their immunity by giving rise to immunocompetent T lymphocytes of donor origin. Despite full HLA mismatch between donor and host, the helper T cells and the cytotoxic T cells which develop in these

  1. [Farmer's lung antigens in Germany].

    Science.gov (United States)

    Sennekamp, J; Joest, M; Sander, I; Engelhart, S; Raulf-Heimsoth, M

    2012-05-01

    Recent studies suggest that besides the long-known farmer's lung antigen sources Saccharopolyspora rectivirgula (Micropolyspora faeni), Thermoactinomyces vulgaris, and Aspergillus fumigatus, additionally the mold Absidia (Lichtheimia) corymbifera as well as the bacteria Erwinia herbicola (Pantoea agglomerans) and Streptomyces albus may cause farmer's lung in Germany. In this study the sera of 64 farmers with a suspicion of farmer's lung were examined for the following further antigens: Wallemia sebi, Cladosporium herbarum, Aspergillus versicolor, and Eurotium amstelodami. Our results indicate that these molds are not frequent causes of farmer's lung in Germany. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Effects of radiation on the expression of antigens on the membranes of human adenocarcinoma cells

    International Nuclear Information System (INIS)

    Hareyama, Masato; Imai, Kozo; Oouchi, Atsushi; Shidou, Mitsuo; Takahashi, Hiroki; Koshiba, Hirohumi; Yachi, Akira; Morita, Kazuo

    1992-01-01

    We have investigated the effects of irradiation on the membranes of tumor cells. X-ray irradiation caused remarkable increases in the expression of tumor-associated antigens (YH206, CEA) and c-erbB-2 protein by flow cytometry, whereas IFN had no obvious effect on the expression of tumor-associated antigens and c-erbB-2 protein. On the other hand, the expression of MHC Class I and ICAM-1 antigen on the membrane by flow cytometry was enhanced by both irradiation and IFN. In addition, the irradiated cells, when analyzed using a CEA specific probe, showed remarkable increases in the CEA mRNA compared to IFN-treated cells. It is possible that enhancement of the expression of tumor-associated antigens and c-erbB-2 protein, together with the enhancement of that of MHC-Class I and ICAM-1, would help cytotoxic killer cells recognize the tumor cells. (author)

  3. Chimeric Antigen Receptor-Engineered T Cells in Tumor Immunotherapy: From Bench to Beside

    Directory of Open Access Journals (Sweden)

    Peng WANG

    2017-06-01

    Full Text Available Chimeric antigen receptor-engineered T cells (CAR-T cells, a classification of cultured T cells after modification of gene engineering technology, can recognize specific tumor antigens in a major histocompatibility complex (MHC-independent manner, consequently leading to the activation of antitumor function. The recent studies have confirmed that a variety of tumor-associated antigens (TAAs can act as target antigens for CAR-T cells. Nowadays, CAR T-cell therapy, one of the most potential tumor immunotherapies, has made great breakthroughs in hematological malignancies and promising outcomes in solid tumors. In this article, the biological characteristics and antitumor mechanism of CAR-T cells, and their application in tumor treatment were mainly reviewed.

  4. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  5. HIV immune evasion disruption of antigen presentation by the HIV Nef protein.

    Science.gov (United States)

    Wonderlich, Elizabeth R; Leonard, Jolie A; Collins, Kathleen L

    2011-01-01

    The Human Immunodeficiency Virus (HIV) Nef protein is necessary for high viral loads and for timely progression to AIDS. Nef plays a number of roles, but its effect on antigen presentation and immune evasion are among the best characterized. Cytotoxic T lymphocytes (CTLs) recognize and lyse virally infected cells by detecting viral antigens in complex with host major histocompatibility complex class I (MHC-I) molecules on the infected cell surface. The HIV Nef protein disrupts antigen presentation at the cell surface by interfering with the normal trafficking pathway of MHC-I and thus reduces CTL recognition and lysis of infected cells. The molecular mechanism by which Nef causes MHC-I downmodulation is becoming more clear, but some questions remain. A better understanding of how Nef disrupts antigen presentation may lead to the development of drugs that enhance the ability of the anti-HIV CTLs to control HIV disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Subash Babu

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.To elucidate the role of CD4(+ T cell subsets in the development of lymphatic pathology, we examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA and compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like receptors (TLR1-10 and Nod-like receptors (Nod1, Nod2, and NALP3 in response to BmA. BmA induced significantly higher production of Th1-type cytokines-IFN-gamma and TNF-alpha-in patients with lymphedema compared with asymptomatic individuals. Notably, expression of the Th17 family of cytokines-IL-17A, IL-17F, IL-21, and IL-23-was also significantly upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFbeta, and CTLA-4, known to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with asymptomatic controls.Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of Toll- and Nod-like receptors in pathogenesis of filarial lymphedema.

  7. Glycan bioengineering in immunogen design for tumor T antigen immunotargeting

    DEFF Research Database (Denmark)

    Sendra, Victor G; Zlocowski, Natacha; Ditamo, Yanina

    2009-01-01

    . Antibodies produced by glycan bioengineering recognize HT29, T47D, MCF7, and CT26 epithelial tumor cells. Epithelial tumor cell adhesion to T antigen-binding lectins and endothelial cells was lower in the presence of antibodies raised against the engineered immunogen. The immune response directed...... to the bioengineered glycoconjugate inhibited CT26 tumor cell proliferation and reduced tumor growth in an in vivo mouse model. These results show that TFD bioengineering is a useful immunogenic strategy with potential application in cancer therapy. The same approach can be extended to other glycan immunogens...

  8. Determining the binding affinity of therapeutic monoclonal antibodies towards their native unpurified antigens in human serum.

    Science.gov (United States)

    Bee, Christine; Abdiche, Yasmina N; Pons, Jaume; Rajpal, Arvind

    2013-01-01

    Monoclonal antibodies (mAbs) are a growing segment of therapeutics, yet their in vitro characterization remains challenging. While it is essential that a therapeutic mAb recognizes the native, physiologically occurring epitope, the generation and selection of mAbs often rely on the use of purified recombinant versions of the antigen that may display non-native epitopes. Here, we present a method to measure both, the binding affinity of a therapeutic mAb towards its native unpurified antigen in human serum, and the antigen's endogenous concentration, by combining the kinetic exclusion assay and Biacore's calibration free concentration analysis. To illustrate the broad utility of our method, we studied a panel of mAbs raised against three disparate soluble antigens that are abundant in the serum of healthy donors: proprotein convertase subtilisin/kexin type 9 (PCSK9), progranulin (PGRN), and fatty acid binding protein (FABP4). We also determined the affinity of each mAb towards its purified recombinant antigen and assessed whether the interactions were pH-dependent. Of the six mAbs studied, three did not appear to discriminate between the serum and recombinant forms of the antigen; one mAb bound serum antigen with a higher affinity than recombinant antigen; and two mAbs displayed a different affinity for serum antigen that could be explained by a pH-dependent interaction. Our results highlight the importance of taking pH into account when measuring the affinities of mAbs towards their serum antigens, since the pH of serum samples becomes increasingly alkaline upon aerobic handling.

  9. Lytic antibodies elicited by Trypanosoma cruzi infection recognize epitopes present on both bloodstream trypomastigote and epimastigote forms of parasite

    Directory of Open Access Journals (Sweden)

    Harumi A. Takehara

    1988-10-01

    Full Text Available Sera of Chaga's disease patients containing anti-T. cruzi lytic antibodies were submitted to affinity chromatography using Sepharose 4B conjugated with antigen extracted from epimasiigote or trypomasiigote forms of the parasite. Epimastigotes were obtained from culture at the exponential growth phase and the trypomastigotes from blood of infected and immunosuppressed mice. Antigen of both parasite forms was obtained by sonication of the parasites followed by centrifugation. Both antigens were then conjugated to activated Sepharose 4B. Affinity chromatography was performed by passing sera from chagasic patients through an immunoadsorbent column containing either epimasiigote or trypomasiigote antigens. Antibodies bound to the column were eluted with cold 0,2 M glycine buffer pH 2,8. The eluted antibodies were analysed regarding their isotype and lytic activity. The results showed that anti-T. cruzi lytic antibodies present in sera from chagasic patients are mainly located in the IgG isotype and recognize epitopes present in both trypomasiigote and epimastigote forms. A brief report of this work has already been published12.

  10. A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield

    Energy Technology Data Exchange (ETDEWEB)

    Pejchal, Robert; Doores, Katie J.; Walker, Laura M.; Khayat, Reza; Huang, Po-Ssu; Wang, Sheng-Kai; Stanfield, Robyn L.; Julien, Jean-Philippe; Ramos, Alejandra; Crispin, Max; Depetris, Rafael; Katpally, Umesh; Marozsan, Andre; Cupo, Albert; Maloveste, Sebastien; Liu, Yan; McBride, Ryan; Ito, Yukishige; Sanders, Rogier W.; Ogohara, Cassandra; Paulson, James C.; Feizi, Ten; Scanlan, Christopher N.; Wong, Chi-Huey; Moore, John P.; Olson, William C.; Ward, Andrew B.; Poignard, Pascal; Schief, William R.; Burton, Dennis R.; Wilson, Ian A. (UWASH); (Progenics); (ICL); (Weill-Med); (NIH); (JSTA); (Scripps); (Oxford)

    2015-10-15

    The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man{sub 9} at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short {beta}-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificify. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.

  11. Cancer vaccines: an update with special focus on ganglioside antigens.

    Science.gov (United States)

    Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

    2002-01-01

    Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by

  12. 76 FR 33419 - Nationally Recognized Statistical Rating Organizations

    Science.gov (United States)

    2011-06-08

    ... 232, 240, 249, et al. Nationally Recognized Statistical Rating Organizations; Proposed Rule #0;#0...-11] RIN 3235-AL15 Nationally Recognized Statistical Rating Organizations AGENCY: Securities and... rating organizations (``NRSROs''). In addition, in accordance with the Dodd-Frank Act, the Commission is...

  13. Recognizing Strokes in Tennis Videos Using Hidden Markov Models

    NARCIS (Netherlands)

    Petkovic, M.; Jonker, Willem; Zivkovic, Z.

    This paper addresses content-based video retrieval with an emphasis on recognizing events in tennis game videos. In particular, we aim at recognizing different classes of tennis strokes using automatic learning capability of Hidden Markov Models. Driven by our domain knowledge, a robust player

  14. Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens.

    Directory of Open Access Journals (Sweden)

    Mauro Bombaci

    Full Text Available The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS

  15. Effects of Co60 gamma radiation on the immunogenic and antigenic properties of Bothrops jararacussu venom

    International Nuclear Information System (INIS)

    Spencer, Patrick J.; Nascimento, Nanci do; Rogero, Jose R.

    1997-01-01

    Ionizing radiation has been successfully employed to attenuate animals toxins and venoms for immunizing antisera producing animals. However, the radiation effects on antigenicity and immunogenecity have not yet been elucidated. In the present work, we investigated the effects of gamma rays on the antigenic and immunogenicity have not yet been elucidated. In the present work, we investigated the effects of gamma rays on the antigenic and immunogenic behaviour of Bothrops jararacussu venon. Venom samples (2mg/ml in 150 mM NaCl) were irradiated with 500, 1000 and 2000 Gy of 60 Co gamma rays. These samples were submitted to antigen capture ELISA on plates coated with commercial bothropic antiserum. Results suggest a loss of reactivity of the 1000 and 2000 Gy irradiated samples. Antibodies against native and 2000 Gy irradiated venoms were produced in rabbits. Both sera able to bind native venom with a slightly higher titer for anti-irradiated serum. These data suggest that radiation promoted structural modification on the antigen molecules. However since the antibodies produced against irradiated antivenom were able to recognize native venom, there must have been preservation of some antigenic determinants. It has already been demosntrated that irradiation of proteins leads to structural modifications and unfolding of the molecules. Our data suggest that irradiation led to conformational epitopes destruction with preservation of linear epitopes and that the response against irradiated venom may be attributed to these linear antigenic determinants. (author). 8 refs., 3 figs

  16. Critical epitopes in the nucleocapsid protein of SFTS virus recognized by a panel of SFTS patients derived human monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Li Yu

    Full Text Available BACKGROUND: SFTS virus (SFTSV is a newly discovered pathogen to cause severe fever with thrombocytopenia syndrome (SFTS in human. Successful control of SFTSV epidemic requires better understanding of the antigen target in humoral immune responses to the new bunyavirus infection. METHODOLOGY/PRINCIPAL FINDINGS: We have generated a combinatorial Fab antibody phage library from two SFTS patients recovered from SFTSV infection. To date, 94 unique human antibodies have been generated and characterized from over 1200 Fab antibody clones obtained by screening the library with SFTS purified virions. All those monoclonal antibodies (MAbs recognized the nucleocapsid (N protein of SFTSV while none of them were reactive to the viral glycoproteins Gn or Gc. Furthermore, over screening 1000 mouse monoclonal antibody clones derived from SFTSV virions immunization, 462 clones reacted with N protein, while only 16 clones were reactive to glycoprotein. Furthermore, epitope mapping of SFTSV N protein was performed through molecular simulation, site mutation and competitive ELISA, and we found that at least 4 distinct antigenic epitopes within N protein were recognized by those human and mouse MAbs, in particular mutation of Glu10 to Ala10 abolished or significantly reduced the binding activity of nearly most SFTS patients derived MAbs. CONCLUSIONS/SIGNIFICANCE: The large number of human recombinant MAbs derived from SFTS patients recognized the viral N protein indicated the important role of the N protein in humoral responses to SFTSV infection, and the critical epitopes we defined in this study provided molecular basis for detection and diagnosis of SFTSV infection.

  17. Natural selection promotes antigenic evolvability

    NARCIS (Netherlands)

    Graves, C.J.; Ros, V.I.D.; Stevenson, B.; Sniegowski, P.D.; Brisson, D.

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide

  18. Recognizing Multi-user Activities using Body Sensor Networks

    DEFF Research Database (Denmark)

    Gu, Tao; Wang, Liang; Chen, Hanhua

    2011-01-01

    activity classes of data—for building activity models and design a scalable, noise-resistant, Emerging Pattern based Multi-user Activity Recognizer (epMAR) to recognize both single- and multi-user activities. We develop a multi-modal, wireless body sensor network for collecting real-world traces in a smart......The advances of wireless networking and sensor technology open up an interesting opportunity to infer human activities in a smart home environment. Existing work in this paradigm focuses mainly on recognizing activities of a single user. In this work, we address the fundamental problem...... of recognizing activities of multiple users using a wireless body sensor network, and propose a scalable pattern mining approach to recognize both single- and multi-user activities in a unified framework. We exploit Emerging Pattern—a discriminative knowledge pattern which describes significant changes among...

  19. Interpretation of sequential measurements of cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Petersen, P H

    2001-01-01

    patients with serological tumor markers should take into account the stochastic variation, i.e. the probability that observed increases and decreases may solely be due to analytical imprecision and normal intra-individual biological variation. The aim of this study was to provide a detailed characteristic......, the standard deviations, and the coefficients of variation differed among subjects, and iii) the steady state variability differed among the markers. In conclusion, our data indicate that the assessment of sequential CA 125, CEA, and TPA concentrations is more complex than hitherto recognized. We suggest......The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer...

  20. Western blotting using Strongyloides ratti antigen for the detection of IgG antibodies as confirmatory test in human strongyloidiasis

    Directory of Open Access Journals (Sweden)

    Luciana Pereira Silva

    2003-07-01

    Full Text Available The present study was conducted to evaluate the frequency of antigenic components recognized by serum IgG antibodies in Western blotting (WB using a Strongyloides ratti larval extract for the diagnosis of human strongyloidiasis. In addition, the WB results were compared to the enzyme-linked immunosorbent assay (ELISA and the indirect immunofluorescence antibody test (IFAT results. Serum samples of 180 individuals were analyzed (80 with strongyloidiasis, 60 with other intestinal parasitoses, and 40 healthy individuals. S. ratti was obtained from fecal culture of experimentally infected Rattus rattus. For IFAT, S. ratti larvae were used as antigen and S. ratti larval antigenic extracts were employed in WB and ELISA. Eleven S. ratti antigenic components were predominantly recognized by IgG antibodies in sera of patients with strongyloidiasis. There was a positive concordance for the three tests in 87.5% of the cases of strongyloidiasis. The negative concordance in the three tests was 94% and 97.5%, in patients with other intestinal parasitoses and healthy individuals, respectively. In cases of positive ELISA and negative IFAT results, diagnosis could be confirmed by WB. ELISA, IFAT, and WB using S. ratti antigens showed a high rate of sensitivity and specificity. In conclusion, WB using S. ratti larval extract was able to recognize 11 immunodominant antigenic components, showing to be a useful tool to define the diagnosis in cases of equivocal serology.

  1. Concepts and applications for influenza antigenic cartography

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

  2. Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cylotoxic T Lymphocytes

    Science.gov (United States)

    2008-11-01

    cell line CEA Carcinoembryonic antigen CTL Cytotoxic T lymphocyte Ck Cytokeratin FBP Folate binding protein FBS Fetal bovine serum GAPDH Glyceraldehyde-3...MHC molecules, and for their expres- sion of the tumor antigens carcinoembryonic antigen (CEA), FBP, Her-2/neu, MAGE-A1, MAGE-A2, MAGE- A3, MAGE-A4... carcinoembryonic antigen .27 We have applied that approach to the cancer/testis antigen TAG and have attempted to identify new peptide antigens presented

  3. Comprehensive mapping of common immunodominant epitopes in the West Nile virus nonstructural protein 1 recognized by avian antibody responses.

    Directory of Open Access Journals (Sweden)

    Encheng Sun

    Full Text Available West Nile virus (WNV is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1 of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for serological diagnostic reagents. To further define serological reagents for diagnostic use, the antigenic sites in NS1 that are targeted by host immune responses need to be identified and the potential diagnostic value of individual antigenic sites also needs to be defined. The present study describes comprehensive mapping of common immunodominant linear B-cell epitopes in the WNV NS1 using avian WNV NS1 antisera. We screened antisera from chickens, ducks and geese immunized with purified NS1 for reactivity against 35 partially overlapping peptides covering the entire WNV NS1. This study identified twelve, nine and six peptide epitopes recognized by chicken, duck and goose antibody responses, respectively. Three epitopes (NS1-3, 14 and 24 were recognized by antibodies elicited by immunization in all three avian species tested. We also found that NS1-3 and 24 were WNV-specific epitopes, whereas the NS1-14 epitope was conserved among the Japanese encephalitis virus (JEV serocomplex viruses based on the reactivity of avian WNV NS1 antisera against polypeptides derived from the NS1 sequences of viruses of the JEV serocomplex. Further analysis showed that the three common polypeptide epitopes were not recognized by antibodies in Avian Influenza Virus (AIV, Newcastle Disease Virus (NDV, Duck Plague Virus (DPV and Goose Parvovirus (GPV antisera. The knowledge and reagents generated in this study have potential applications in differential diagnostic approaches and

  4. Screening Donors for Rare Antigen Constellations.

    Science.gov (United States)

    Wagner, Franz F

    2009-01-01

    SCREENING BLOOD DONORS FOR RARE ANTIGEN CONSTELLATIONS HAS BEEN IMPLEMENTED USING SIMPLE PCR METHODS: PCR with enzyme digestion has been used to type donor cohorts for Dombrock antigens, and PCR with sequence-specific priming to identify donors negative for antigens of high frequency. The advantages and disadvantages of the methods as well as their current state is discussed.

  5. Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure.

    Directory of Open Access Journals (Sweden)

    Sophie Roetynck

    Full Text Available Multiparameter flow cytometry has revealed extensive phenotypic and functional heterogeneity of CD4 T cell responses in mice and humans, emphasizing the importance of assessing multiple aspects of the immune response in correlation with infection or vaccination outcome. The aim of this study was to establish and validate reliable and feasible flow cytometry assays, which will allow us to characterize CD4 T cell population in humans in field studies more fully.We developed polychromatic flow cytometry antibody panels for immunophenotyping the major CD4 T cell subsets as well as broadly characterizing the functional profiles of the CD4 T cells in peripheral blood. We then validated these assays by conducting a pilot study comparing CD4 T cell responses in distinct populations of healthy adults living in either rural or urban Kenya. This study revealed that the expression profile of CD4 T cell activation and memory markers differed significantly between African and European donors but was similar amongst African individuals from either rural or urban areas. Adults from rural Kenya had, however, higher frequencies and greater polyfunctionality among cytokine producing CD4 T cells compared to both urban populations, particularly for "Th1" type of response. Finally, endemic exposure to malaria in rural Kenya may have influenced the expansion of few discrete CD4 T cell populations with specific functional signatures.These findings suggest that environmentally driven T cell activation does not drive the dysfunction of CD4 T cells but is rather associated with greater magnitude and quality of CD4 T cell response, indicating that the level or type of microbial exposure and antigenic experience may influence and shape the functionality of CD4 T cell compartment. Our data confirm that it is possible and mandatory to assess multiple functional attributes of CD4 T cell response in the context of infection.

  6. Targeting lentiviral vectors to antigen-specific immunoglobulins.

    Science.gov (United States)

    Ziegler, Leslie; Yang, Lili; Joo, Kye il; Yang, Haiguang; Baltimore, David; Wang, Pin

    2008-09-01

    Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient method to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and in vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral surface. This engineered vector could specifically bind to cells expressing surface immunoglobulin recognizing CD20 (alphaCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing alphaCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin- specific cells to deliver a therapeutic effect. Such targeting lentivectors also could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology.

  7. Expression cloning of camelid nanobodies specific for Xenopus embryonic antigens.

    Directory of Open Access Journals (Sweden)

    Keiji Itoh

    Full Text Available Developmental biology relies heavily on the use of conventional antibodies, but their production and maintenance involves significant effort. Here we use an expression cloning approach to identify variable regions of llama single domain antibodies (known as nanobodies, which recognize specific embryonic antigens. A nanobody cDNA library was prepared from lymphocytes of a llama immunized with Xenopus embryo lysates. Pools of bacterially expressed cDNAs were sib-selected for the ability to produce specific staining patterns in gastrula embryos. Three different nanobodies were isolated: NbP1 and NbP3 stained yolk granules, while the reactivity of NbP7 was predominantly restricted to the cytoplasm and the cortex. The isolated nanobodies recognized specific protein bands in immunoblot analysis. A reverse proteomic approach identified NbP1 target antigen as EP45/Seryp, a serine protease inhibitor. Given the unique stability of nanobodies and the ease of their expression in diverse systems, we propose that nanobody cDNA libraries represent a promising resource for molecular markers for developmental biology.

  8. Identification of a peptide binding protein that plays a role in antigen presentation

    International Nuclear Information System (INIS)

    Lakey, E.K.; Margoliash, E.; Pierce, S.K.

    1987-01-01

    The helper T-cell response to globular proteins appears, in general, to require intracellular processing of the antigen, such that a peptide fragment containing the T-cell antigenic determinant is released and transported to and held on the surface of an Ia-expressing, antigen-presenting cell. However, the molecular details underlying these phenomena are largely unknown. The means by which antigenic peptides are anchored on the antigen-presenting cell surface was investigated. A cell surface protein is identified that was isolated by it ability to bind to a 24-amino acid peptide fragment of pigeon cytochrome c, residues 81-104, containing the major antigenic determinant for B10.A mouse T cells. This peptide binding protein, purified from [ 35 S]methionine-labeled cells, appears as two discrete bands of ≅72 and 74 kDa after NaDodSO 4 /PAGE. The protein can be eluted from the peptide affinity column with equivalent concentrations of either the antigenic pigeon cytochrome c peptide or the corresponding nonantigenic peptide of mouse cytochrome c. However, it does not bind to the native cytochromes c, either of pigeon or mouse, and thus the protein appears to recognize some structure available only in the free peptides. This protein plays a role in antigen presentation. Its expression is not major histocompatibility complex-restricted in that the blocking activity of the antisera can be absorbed on spleen cells from mice of different haplotypes. This peptide binding protein can be isolated from a variety of cell types, including B cells, T cells, and fibroblasts. The anchoring of processed peptides on the cell surface by such a protein may play a role in antigen presentation

  9. Involvement of a putative intercellular signal-recognizing G protein ...

    African Journals Online (AJOL)

    Involvement of a putative intercellular signal-recognizing G protein-coupled receptor in the engulfment of Salmonella by the protozoan Tetrahymena. PN Agbedanu, MT Brewer, TA Day, MJ Kimber, KL Anderson, SK Rasmussen, MA Rasmussen, SA Carlson ...

  10. EPA Recognizes Excellence and Innovation in Clean Water Infrastructure

    Science.gov (United States)

    Today, the U.S. Environmental Protection Agency recognized 28 clean water infrastructure projects for excellence & innovation within the Clean Water State Revolving Fund (CWSRF) program. Honored projects include large wastewater infrastructure projects.

  11. Identification of an Antigen from Normal Human Tissue That Crossreacts with the Carcinoembryonic Antigen

    Science.gov (United States)

    Kleist, S. Von; Chavanel, G.; Burtin, P.

    1972-01-01

    A glycoprotein present in normal human tissue is characterized that is neither organ- nor tumor-specific (nonspecific crossreacting antigen) and that crossreacts (by the Ouchterlony double-diffusion technique) with the carcinoembryonic antigen. This immunological relationship indicates common determinants on the molecules of both antigens. We demonstrate that the nonspecific crossreacting antigen is not a fragment of the carcinoembryonic antigen molecule. Images PMID:4115954

  12. Non-classical antigen processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4+ T cells

    Science.gov (United States)

    Matsuzaki, Junko; Tsuji, Takemasa; Luescher, Immanuel; Old, Lloyd J.; Shrikant, Protul; Gnjatic, Sacha; Odunsi, Kunle

    2014-01-01

    Tumor antigen-specific CD4+ T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4+ T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157–170 peptide vaccination in ovarian cancer patients. While both subsets similarly recognized exogenous NY-ESO-1 protein pulsed on DP04+ target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4+ T cells more efficiently recognized the short 8–9-mer peptides than the non-tumor-recognizing CD4+ T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways such as the proteasomal degradation and transporter-associated with antigen-processing (TAP)-mediated peptide transport were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacological inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrated that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple non-classical antigen-processing pathways. Harnessing direct tumor-recognizing ability of CD4+ T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment. PMID:24764581

  13. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells.

    Science.gov (United States)

    Matsuzaki, Junko; Tsuji, Takemasa; Luescher, Immanuel; Old, Lloyd J; Shrikant, Protul; Gnjatic, Sacha; Odunsi, Kunle

    2014-04-01

    Tumor antigen-specific CD4(+) T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4(+) T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157-170 peptide vaccination in patients with ovarian cancer. Although both subsets recognized exogenous NY-ESO-1 protein pulsed on DP04(+) target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4(+) T cells more efficiently recognized the short 8-9-mer peptides than the non-tumor-recognizing CD4(+) T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways, such as the proteasomal degradation and transporter-associated with antigen-processing-mediated peptide transport, were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacologic inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrate that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple nonclassical antigen-processing pathways. Harnessing the direct tumor-recognizing ability of CD4(+) T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment.

  14. Enzyme-labeled Antigen Method: Development and Application of the Novel Approach for Identifying Plasma Cells Locally Producing Disease-specific Antibodies in Inflammatory Lesions

    International Nuclear Information System (INIS)

    Mizutani, Yasuyoshi; Shiogama, Kazuya; Onouchi, Takanori; Sakurai, Kouhei; Inada, Ken-ichi; Tsutsumi, Yutaka

    2016-01-01

    In chronic inflammatory lesions of autoimmune and infectious diseases, plasma cells are frequently observed. Antigens recognized by antibodies produced by the plasma cells mostly remain unclear. A new technique identifying these corresponding antigens may give us a breakthrough for understanding the disease from a pathophysiological viewpoint, simply because the immunocytes are seen within the lesion. We have developed an enzyme-labeled antigen method for microscopic identification of the antigen recognized by specific antibodies locally produced in plasma cells in inflammatory lesions. Firstly, target biotinylated antigens were constructed by the wheat germ cell-free protein synthesis system or through chemical biotinylation. Next, proteins reactive to antibodies in tissue extracts were screened and antibody titers were evaluated by the AlphaScreen method. Finally, with the enzyme-labeled antigen method using the biotinylated antigens as probes, plasma cells producing specific antibodies were microscopically localized in fixed frozen sections. Our novel approach visualized tissue plasma cells that produced 1) autoantibodies in rheumatoid arthritis, 2) antibodies against major antigens of Porphyromonas gingivalis in periodontitis or radicular cyst, and 3) antibodies against a carbohydrate antigen, Strep A, of Streptococcus pyogenes in recurrent tonsillitis. Evaluation of local specific antibody responses expectedly contributes to clarifying previously unknown processes in inflammatory disorders

  15. A novel approach in recognizing magnetic material with simplified algorithm

    KAUST Repository

    Talukdar, Abdul Hafiz Ibne

    2011-04-01

    In this article a cost-effective and simple system (circuit and algorithm) which allows recognizing different kinds of films by their magneto-field conductive properties is demonstrated. The studied signals are generated by a proposed circuit. This signal was further analyzed (recognized) in frequency domain creating the Fourier frequency spectrum which is easily used to detect the response of magnetic sample. The novel algorithm in detecting magnetic field is presented here with both simulation and experimental results. © 2011 IEEE.

  16. Healthy human T-Cell Responses to Aspergillus fumigatus antigens.

    Directory of Open Access Journals (Sweden)

    Neelkamal Chaudhary

    2010-02-01

    Full Text Available Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H1-T(H17 and destructive allergic (T(H2 immunity. How Aspergillus allergens (Asp f proteins participate in the development of allergic sensitization is unknown.To determine whether Asp f proteins are strictly associated with T(H2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17 to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H1-responses to Asp f3 (a putative peroxismal membrane protein, Asp f9/16 (cell wall glucanase, Asp f11 (cyclophilin type peptidyl-prolyl isomerase and Asp f22 (enolase. Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals.Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.

  17. Healthy human T-Cell Responses to Aspergillus fumigatus antigens.

    Science.gov (United States)

    Chaudhary, Neelkamal; Staab, Janet F; Marr, Kieren A

    2010-02-17

    Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H)1-T(H)17) and destructive allergic (T(H)2) immunity. How Aspergillus allergens (Asp f proteins) participate in the development of allergic sensitization is unknown. To determine whether Asp f proteins are strictly associated with T(H)2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17) to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H)1-responses to Asp f3 (a putative peroxismal membrane protein), Asp f9/16 (cell wall glucanase), Asp f11 (cyclophilin type peptidyl-prolyl isomerase) and Asp f22 (enolase). Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals. Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.

  18. Antigen-specific T cell activation independently of the MHC: chimeric antigen receptor (CAR-redirected T cells.

    Directory of Open Access Journals (Sweden)

    Hinrich eAbken

    2013-11-01

    Full Text Available Adoptive T cell therapy has recently shown powerful in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR which consists in the extracellular part of an antibody-derived domain for binding with a tumor-associated antigen and in the intracellular part of a TCR-derived signaling moiety for T cell activation. The specificity of CAR mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR and review most significant progress recently made in early stage clinical trials to treat cancer.

  19. "RecognizeCane" : The new concept of a cane which recognizes the most common objects and safety clues.

    Science.gov (United States)

    Scherlen, Anne-Catherine; Dumas, Jean Claude; Guedj, Benjamin; Vignot, Alexandre

    2007-01-01

    This paper introduces the new concept of an electronic cane for blind people. While some systems inform the subject only of the presence of the object and its relative distance, RecognizeCane is also able to recognize most common objects and environment clues to increase the safety and confidence of the navigation process. The originality of RecognizeCane is the use of simple sensors, such as infrared, brilliance or water sensors to inform the subject of the presence, for example, of a stairway, a water puddle, a zebra crossing or a trash can. This cane does not use an embedded vision system. RecognizeCane is equipped with several sensors and microprocessors to collect sensor data and extract the desired information about the close environment by means of a dynamic analysis of output signals.

  20. MHC-restricted antigen presentation and recognition: constraints on gene, recombinant and peptide vaccines in humans

    Directory of Open Access Journals (Sweden)

    Cunha-Neto E.

    1999-01-01

    Full Text Available The target of any immunization is to activate and expand lymphocyte clones with the desired recognition specificity and the necessary effector functions. In gene, recombinant and peptide vaccines, the immunogen is a single protein or a small assembly of epitopes from antigenic proteins. Since most immune responses against protein and peptide antigens are T-cell dependent, the molecular target of such vaccines is to generate at least 50-100 complexes between MHC molecule and the antigenic peptide per antigen-presenting cell, sensitizing a T cell population of appropriate clonal size and effector characteristics. Thus, the immunobiology of antigen recognition by T cells must be taken into account when designing new generation peptide- or gene-based vaccines. Since T cell recognition is MHC-restricted, and given the wide polymorphism of the different MHC molecules, distinct epitopes may be recognized by different individuals in the population. Therefore, the issue of whether immunization will be effective in inducing a protective immune response, covering the entire target population, becomes an important question. Many pathogens have evolved molecular mechanisms to escape recognition by the immune system by variation of antigenic protein sequences. In this short review, we will discuss the several concepts related to selection of amino acid sequences to be included in DNA and peptide vaccines.

  1. Dengue virus-specific, human CD4+ CD8- cytotoxic T-cell clones: multiple patterns of virus cross-reactivity recognized by NS3-specific T-cell clones.

    OpenAIRE

    Kurane, I; Brinton, M A; Samson, A L; Ennis, F A

    1991-01-01

    Thirteen dengue virus-specific, cytotoxic CD4+ CD8- T-cell clones were established from a donor who was infected with dengue virus type 3. These clones were examined for virus specificity and human leukocyte antigen (HLA) restriction in cytotoxic assays. Six patterns of virus specificities were determined. Two serotype-specific clones recognized only dengue virus type 3. Two dengue virus subcomplex-specific clones recognized dengue virus types 2, 3, and 4, and one subcomplex-specific clone re...

  2. Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells.

    Science.gov (United States)

    Nuti, M; Turchi, V; Rughetti, A; Viacava, P; Masci, A M; Castagna, M; Frati, L

    1992-01-01

    Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. The Mycoplasma hominis P120 membrane protein contains a 216 amino acid hypervariable domain that is recognized by the human humoral immune response

    DEFF Research Database (Denmark)

    Nyvold, Charlotte Guldborg; Birkelund, Svend; Christiansen, Gunna

    1997-01-01

    In the antigenically heterogeneous species Mycoplasma hominis a monoclonal antibody, mAb 26.7D, was previously found to recognize a 120 kDa polypeptide from M. hominis 7488. This antibody did not react with the type strain PG21. The homologous gene from M. hominis PG21 was cloned and sequenced an...... response. Such a variable domain may be important in evasion of the host's immune response, and thus aid survival of the micro-organism....

  4. Drawing and Recognizing Chinese Characters with Recurrent Neural Network.

    Science.gov (United States)

    Zhang, Xu-Yao; Yin, Fei; Zhang, Yan-Ming; Liu, Cheng-Lin; Bengio, Yoshua

    2018-04-01

    Recent deep learning based approaches have achieved great success on handwriting recognition. Chinese characters are among the most widely adopted writing systems in the world. Previous research has mainly focused on recognizing handwritten Chinese characters. However, recognition is only one aspect for understanding a language, another challenging and interesting task is to teach a machine to automatically write (pictographic) Chinese characters. In this paper, we propose a framework by using the recurrent neural network (RNN) as both a discriminative model for recognizing Chinese characters and a generative model for drawing (generating) Chinese characters. To recognize Chinese characters, previous methods usually adopt the convolutional neural network (CNN) models which require transforming the online handwriting trajectory into image-like representations. Instead, our RNN based approach is an end-to-end system which directly deals with the sequential structure and does not require any domain-specific knowledge. With the RNN system (combining an LSTM and GRU), state-of-the-art performance can be achieved on the ICDAR-2013 competition database. Furthermore, under the RNN framework, a conditional generative model with character embedding is proposed for automatically drawing recognizable Chinese characters. The generated characters (in vector format) are human-readable and also can be recognized by the discriminative RNN model with high accuracy. Experimental results verify the effectiveness of using RNNs as both generative and discriminative models for the tasks of drawing and recognizing Chinese characters.

  5. Monoclonal antibodies recognize gly-leu-phe-gly repeat of nucleoporin nup98 of tetrahymena, yeasts, and humans.

    Science.gov (United States)

    Iwamoto, Masaaki; Asakawa, Haruhiko; Ohtsuki, Chizuru; Osakada, Hiroko; Koujin, Takako; Hiraoka, Yasushi; Haraguchi, Tokuko

    2013-04-01

    Nucleoporin Nup98, an essential component of the nuclear pore complex, has multifunctional roles in nuclear functions including transcriptional regulation and nucleocytoplasmic transport. These functions mostly depend on a Gly-Leu-Phe-Gly (GLFG) sequence appearing repetitively in the N-terminal region of Nup98. As the GLFG sequence is well conserved among Nup98s from a wide variety of species including humans, yeasts, and ciliates such as Tetrahymena thermophila, a specific antibody that recognizes the GLFG sequence is expected to detect various Nup98s from a wide-range of species. To generate monoclonal antibodies specific to the GLFG repeat of Nup98, we used two synthetic polypeptides derived from the macronuclear Nup98 of T. thermophila as an antigen. We obtained two monoclonal antibodies (MAbs), 13C2 and 21A10, that recognize Nup98s in indirect immunofluorescence staining and Western blot analysis of T. thermophila. Peptide array analysis of these monoclonal antibodies located the position of their epitopes at or near GLFG residues: the epitope recognized by the 13C2 MAb is FGxxN (x being any amino acid), and the epitope recognized by the 21A10 MAb is GLF. As expected by their epitopes, these monoclonal antibodies also recognize Nup98 homologs expressed by human cells and the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae, indicating that 13C2 and 21A10 MAbs recognize Nup98 epitopes common to phylogenetically distinct organisms. Thus, these MAbs are useful in studying a wide variety of biological phenomena that involve Nup98, ranging from ciliate nuclear dimorphism to NUP98-related human leukemia.

  6. The extended family of CD1d-restricted T cells: sifting through a mixed bag of TCRs, antigens and functions

    Directory of Open Access Journals (Sweden)

    Elodie eMacho-Fernandez

    2015-07-01

    Full Text Available Natural killer T (NKT cells comprise a family of specialized T cells that recognize lipid antigens presented by CD1d. Based on their T cell receptor (TCR usage and antigen-specificities, CD1d-restricted NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR α-chain and recognize α-galactosylceramide (α-GalCer, and type II NKT cells that use a more diverse αβ TCR repertoire and do not recognize α-GalCer. In addition, α-GalCer-reactive NKT cells that use non-canonical αβ TCRs and CD1d-restricted T cells that use γδ or δ/αβ TCRs have recently been identified, revealing further diversity among CD1d-restricted T cells. Importantly, in addition to their distinct antigen specificities, functional differences are beginning to emerge between the different members of the CD1d-restricted T cell family. In this review, while using type I NKT cells as comparison, we will focus on type II NKT cells and the other non-invariant CD1d-restricted T cell subsets, and discuss our current understanding of the antigens they recognize, the formation of stimulatory CD1d/antigen complexes, the modes of TCR-mediated antigen recognition, and the mechanisms and consequences of their activation that underlie their function in antimicrobial responses, antitumor immunity, and autoimmunity.

  7. The Extended Family of CD1d-Restricted NKT Cells: Sifting through a Mixed Bag of TCRs, Antigens, and Functions.

    Science.gov (United States)

    Macho-Fernandez, Elodie; Brigl, Manfred

    2015-01-01

    Natural killer T (NKT) cells comprise a family of specialized T cells that recognize lipid antigens presented by CD1d. Based on their T cell receptor (TCR) usage and antigen specificities, CD1d-restricted NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR α-chain and recognize α-galactosylceramide (α-GalCer), and type II NKT cells that use a more diverse αβ TCR repertoire and do not recognize α-GalCer. In addition, α-GalCer-reactive NKT cells that use non-canonical αβ TCRs and CD1d-restricted T cells that use γδ or δ/αβ TCRs have recently been identified, revealing further diversity among CD1d-restricted T cells. Importantly, in addition to their distinct antigen specificities, functional differences are beginning to emerge between the different members of the CD1d-restricted T cell family. In this review, while using type I NKT cells as comparison, we will focus on type II NKT cells and the other non-invariant CD1d-restricted T cell subsets, and discuss our current understanding of the antigens they recognize, the formation of stimulatory CD1d/antigen complexes, the modes of TCR-mediated antigen recognition, and the mechanisms and consequences of their activation that underlie their function in antimicrobial responses, anti-tumor immunity, and autoimmunity.

  8. Hand posture recognizer based on separator wavelet networks

    Science.gov (United States)

    Bouchrika, Tahani; Jemai, Olfa; Zaied, Mourad; Ben Amar, Chokri

    2015-12-01

    This paper presents a novel hand posture recognizer based on separator wavelet networks (SWNs). Aiming at creating a robust and rapid hand posture recognizer, we have contributed by proposing a new training algorithm for the wavelet network classifier based on fast wavelet transform (FWN). So, the contribution resides in reducing the number of WNs modeling training data. To make that, inspiring from the adaboost feature selection method, we thought to create SWNs (n-1 WNs for n classes) instead of modeling each training sample by its wavelet network (WN). By proposing the new training algorithm, the recognition phase will be positively influenced. It will be more rapid thanks to the reduction of the number of comparisons between test images WNs and training WNs. Comparisons with other works, employing universal hand posture datasets are presented and discussed. Obtained results have shown that the new hand posture recognizer is comparable to previously established ones.

  9. Recognizing Variable Environments The Theory of Cognitive Prism

    CERN Document Server

    Dong, Tiansi

    2012-01-01

    Normal adults do not have any difficulty in recognizing their homes. But can artificial systems do in the same way as humans? This book collects interdisciplinary evidences and presents an answer from the perspective of computing, namely, the theory of cognitive prism. To recognize an environment, an intelligent system only needs to classify objects, structures them based on the connection relation (not through measuring!), subjectively orders the objects, and compares with the target environment, whose knowledge is similarly structured. The intelligent system works, therefore, like a prism: when a beam of light (a scene) reaches (is perceived) to an optical prism (by an intelligent system), some light (objects) is reflected (are neglected), those passed through (the recognized objects) are distorted (are ordered differently). So comes the term 'cognitive prism'! Two fundamental propositions used in the theory can be informally stated as follow: an orientation relation is a kind of distance comparison relatio...

  10. Antigenicity of Dermatophilus congolensis hemolysin.

    Science.gov (United States)

    Skalka, B; Pospísil, L

    1993-05-01

    The separated cell-free form of hemolytic exosubstance was obtained from five strains of Dermatophilus congolensis. Three strains produced exosubstance with high activity, two strains produced exosubstance with lower intensity of activity. The separated forms exhibited the same hemolytic interactions as the native forms produced by growing strains, namely the antagonism with staphylococcal beta hemolysin and the synergism with staphylococcal delta hemolysin, streptococcal CAMP factor and rhodococcal equi factor. Rabbit sera obtained after intravenous or intraperitoneal application of the separated forms contained precipitation and neutralization antibodies. Cross tests of precipitation and neutralization proved antigen identity of hemolysins of different D. congolensis, strains which makes the serodiagnostics of this species possible.

  11. Production of antibodies which recognize opiate receptors on murine leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Bost, K.L.; Blalock, J.E.

    1988-01-01

    An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

  12. Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment

    Directory of Open Access Journals (Sweden)

    S. Montes-Moreno

    2011-01-01

    Full Text Available Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL and classical Hodgkin Lymphoma (CHL. This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

  13. Predictive Value of Carcinoembryonic and Carbohydrate Antigen 19-9 Related to Some Clinical, Endoscopic and Histological Colorectal Cancer Characteristics

    Directory of Open Access Journals (Sweden)

    Tomašević Ratko

    2016-09-01

    Full Text Available Background: Colorectal cancer (CRC is an important oncological and public health problem worldwide, including Serbia. Unfortunately, half of the patients are recognized in an advanced stage of the disease, therefore, early detection through specific tumor biomarkers, such as carcinoembryonic (CEA and carbohydrate antigen 19-9 (CA 19-9, is the only way to cope with CRC expansion.

  14. Inhibition, by vinca alkaloids and colchicine, of antigenic modulation induced by anti-CD19 monoclonal antibodies

    NARCIS (Netherlands)

    de Rie, M. A.; Zeijlemaker, W. P.; von dem Borne, A. E.

    1988-01-01

    Several clinical trials have been reported in which monoclonal antibodies (McAb) were used for therapy of lymphoid malignancies. Such trials have shown that infusion of McAb recognizing lymphoid antigens, is well-tolerated, and leads to the coating of tumor cells and tumor regression in some

  15. Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably Presented by HLA-B*07

    NARCIS (Netherlands)

    Marino, Fabio; Mommen, Geert P M; Jeko, Anita; Meiring, Hugo D; van Gaans-van den Brink, Jacqueline A M; Scheltema, Richard A; van Els, Cécile A C M; Heck, Albert J R

    Alterations in protein post-translational modification (PTM) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related human leukocyte antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA

  16. Characterization of murine B-cell epitopes on the Mycobacterium leprae proline-rich antigen by use of synthetic peptides

    NARCIS (Netherlands)

    Klatser, P. R.; de Wit, M. Y.; Kolk, A. H.; Hartskeerl, R. A.

    1991-01-01

    Using synthetic peptides representing overlapping sequences of the 100-amino-acid-long N-terminal region of the proline-rich antigen of Mycobacterium leprae (PRA), we have mapped the epitopes in the primary structure of PRA recognized by four monoclonal antibodies. The M. leprae-specific monoclonal

  17. Synthetic Peptides as Potential Antigens for Cutaneous Leishmaniosis Diagnosis.

    Science.gov (United States)

    Link, Juliana Seger; Alban, Silvana Maria; Soccol, Carlos Ricardo; Pereira, Gilberto Vinicius Melo; Thomaz Soccol, Vanete

    2017-01-01

    This work's goal was to research new candidate antigens for cutaneous leishmaniosis (CL). In order to reach the goal, we used random peptide phage display libraries screened using antibodies from Leishmania braziliensis patients. After selection, three peptides (P1, P2, and P3) were synthesized using Fmoc chemistry. The peptides individually or a mixture of them (MIX) was subsequently emulsified in complete and incomplete Freund's adjuvant and injected subcutaneously in golden hamsters. Sera from the hamsters administered with P1 presented antibodies that recognized proteins between 76 and 150 kDa from L. braziliensis . Sera from hamsters which had peptides P2 and P3, as well as the MIX, administered presented antibodies that recognized proteins between 52 and 76 kDa of L. braziliensis . The research on the similarity of the peptides' sequences in protein databases showed that they match a 63 kDa glycoprotein. The three peptides and the MIX were recognized by the sera from CL patients by immunoassay approach (ELISA). The peptides' MIX showed the best performance (79% sensitivity) followed by the P1 (72% sensitivity), and the AS presented 91% sensitivity. These results show a new route for discovering molecules for diagnosis or for immunoprotection against leishmaniosis.

  18. The molecular relationship between antigenic domains and epitopes on hCG.

    Science.gov (United States)

    Berger, Peter; Lapthorn, Adrian J

    2016-08-01

    Antigenic domains are defined to contain a limited number of neighboring epitopes recognized by antibodies (Abs) but their molecular relationship remains rather elusive. We thoroughly analyzed the antigenic surface of the important pregnancy and tumor marker human chorionic gonadotropin (hCG), a cystine knot (ck) growth factor, and set antigenic domains and epitopes in molecular relationships to each other. Antigenic domains on hCG, its free hCGα and hCGβ subunits are dependent on appropriate inherent molecular features such as molecular accessibility and protrusion indices that determine bulging structures accessible to Abs. The banana-shaped intact hCG comprises ∼7500Å(2) of antigenic surface with minimally five antigenic domains that encompass a continuum of overlapping non-linear composite epitopes, not taking into account the C-terminal peptide extension of hCGβ (hCGβCTP). Epitopes within an antigenic domain are defined by specific Abs, that bury nearly 1000Å(2) of surface accessible area on the antigen and recognize a few up to 15 amino acid (aa) residues, whereby between 2 and 5 of these provide the essential binding energy. Variability in Ab binding modes to the contact aa residues are responsible for the variation in affinity and intra- and inter-species specificity, e.g. cross-reactions with luteinizing hormone (LH). Each genetically distinct fragment antigen binding (Fab) defines its own epitope. Consequently, recognition of the same epitope by different Abs is only possible in cases of genetically identical sequences of its binding sites. Due to combinatorial V(D)J gene segment variability of heavy and light chains, Abs defining numerous epitopes within an antigenic domain can be generated by different individuals and species. Far more than hundred Abs against the immuno-dominant antigenic domains of either subunit at both ends of the hCG-molecule, the tips of peptide loops one and three (Ł1+3) protruding from the central ck, encompassing h

  19. Mucosal-Associated Invariant T Cells: New Insights into Antigen Recognition and Activation

    Directory of Open Access Journals (Sweden)

    Xingxing Xiao

    2017-11-01

    Full Text Available Mucosal-associated invariant T (MAIT cells, a novel subpopulation of innate-like T cells that express an invariant T cell receptor (TCRα chain and a diverse TCRβ chain, can recognize a distinct set of small molecules, vitamin B metabolites, derived from some bacteria, fungi but not viruses, in the context of an evolutionarily conserved major histocompatibility complex-related molecule 1 (MR1. This implies that MAIT cells may play unique and important roles in host immunity. Although viral antigens are not recognized by this limited TCR repertoire, MAIT cells are known to be activated in a TCR-independent mechanism during some viral infections, such as hepatitis C virus and influenza virus. In this article, we will review recent works in MAIT cell antigen recognition, activation and the role MAIT cells may play in the process of bacterial and viral infections and pathogenesis of non-infectious diseases.

  20. Isolation of Fasciola hepatica tegument antigens.

    OpenAIRE

    Hillyer, G V

    1980-01-01

    Fasciola hepatica tegument antigens were isolated from intact worms in the cold by using Nonidet P-40. Proof of the tegumental nature of the antigens was shown by the peroxidase-antiperoxidase immunocytochemical technique at the light microscope level. The potential of F. hepatica tegument antigens for the immunodiagnosis of rabbit and human fascioliasis was shown by Ouchterlony immunodiffusion, although cross-reactivity was evident in one of six serum samples from patients infected with Schi...

  1. Antimelanoma CTL recognizes peptides derived from an ORF transcribed from the antisense strand of the 3′ untranslated region of TRIT1

    Directory of Open Access Journals (Sweden)

    Rolf K Swoboda

    2014-01-01

    Full Text Available Noncoding regions of the genome play an important role in tumorigenesis of cancer. Using expression cloning, we have identified a cytotoxic T lymphocyte (CTL–defined antigen that recognizes a protein sequence derived from an open reading frame transcribed from the reverse strand in the 3′ untranslated region of tRNA isopentenyltransferase 1 (TRIT1. A peptide derived from this open reading frame (ORF sequence and predicted to bind to HLA-B57, sensitized HLA-B57+ tumor cells to lysis by CTL793. The peptide also induced a CTL response in peripheral blood mononuclear cells (PBMC of patient 793 and in two other melanoma patients. The CTL lysed peptide-pulsed HLA-B57+ target cells and melanoma cells with endogenous antigen expression. The recognition of this antigen is not limited to HLA-B57-restricted CTLs. An HLA-A2 peptide derived from the ORF was able to induce CTLs in PBMC of 2 HLA-A2+ patients. This study describes for the first time a CTL-defined melanoma antigen that is derived from an ORF on the reverse strand of the putative tumor suppressor gene TRIT1. This antigen has potential use as a vaccine or its ability to induce CTLs in vitro could be used as a predictive biomarker.

  2. Screening of random peptide library of hemagglutinin from pandemic 2009 A(H1N1 influenza virus reveals unexpected antigenically important regions.

    Directory of Open Access Journals (Sweden)

    Wanghui Xu

    Full Text Available The antigenic structure of the membrane protein hemagglutinin (HA from the 2009 A(H1N1 influenza virus was dissected with a high-throughput screening method using complex antisera. The approach involves generating yeast cell libraries displaying a pool of random peptides of controllable lengths on the cell surface, followed by one round of fluorescence-activated cell sorting (FACS against antisera from mouse, goat and human, respectively. The amino acid residue frequency appearing in the antigenic peptides at both the primary sequence and structural level was determined and used to identify "hot spots" or antigenically important regions. Unexpectedly, different antigenic structures were seen for different antisera. Moreover, five antigenic regions were identified, of which all but one are located in the conserved HA stem region that is responsible for membrane fusion. Our findings are corroborated by several recent studies on cross-neutralizing H1 subtype antibodies that recognize the HA stem region. The antigenic peptides identified may provide clues for creating peptide vaccines with better accessibility to memory B cells and better induction of cross-neutralizing antibodies than the whole HA protein. The scheme used in this study enables a direct mapping of the antigenic regions of viral proteins recognized by antisera, and may be useful for dissecting the antigenic structures of other viral proteins.

  3. Identification of antigenic Sarcoptes scabiei proteins for use in a diagnostic test and of non-antigenic proteins that may be immunomodulatory.

    Directory of Open Access Journals (Sweden)

    Marjorie S Morgan

    2017-06-01

    Full Text Available Scabies, caused by the mite, Sarcoptes scabiei, infects millions of humans, and many wild and domestic mammals. Scabies mites burrow in the lower stratum corneum of the epidermis of the skin and are the source of substances that are antigenic or modulate aspects of the protective response of the host. Ordinary scabies is a difficult disease to diagnose.The goal of this project was to identify S. scabiei proteins that may be candidate antigens for use in a diagnostic test or may be used by the mite to modulate the host's protective response.An aqueous extract of S. scabiei was separated by 2-dimensional electrophoresis and proteins were identified by mass spectrometry. A parallel immunoblot was probed with serum from patients with ordinary scabies to identify IgM and/or IgG-binding antigens. The genes coding for 23 selected proteins were cloned into E. coli and the expressed recombinant proteins were screened with serum from patients with confirmed ordinary scabies.We identified 50 different proteins produced by S. scabiei, 34 of which were not previously identified, and determined that 66% were recognized by patient IgM and/or IgG. Fourteen proteins were screened for use in a diagnostic test but none possessed enough sensitivity and specificity to be useful. Six of the 9 proteins selected for the possibility that they may be immunomodulatory were not recognized by antibodies in patient serum.Thirty-three proteins that bound IgM and/or IgG from the serum of patients with ordinary scabies were identified. None of the 14 tested were useful for inclusion in a diagnostic test. The identities of 16 proteins that are not recognized as antigens by infected patients were also determined. These could be among the molecules that are responsible for this mite's ability to modulate its host's innate and adaptive immune responses.

  4. Identification of antigenic Sarcoptes scabiei proteins for use in a diagnostic test and of non-antigenic proteins that may be immunomodulatory.

    Science.gov (United States)

    Morgan, Marjorie S; Rider, S Dean; Arlian, Larry G

    2017-06-01

    Scabies, caused by the mite, Sarcoptes scabiei, infects millions of humans, and many wild and domestic mammals. Scabies mites burrow in the lower stratum corneum of the epidermis of the skin and are the source of substances that are antigenic or modulate aspects of the protective response of the host. Ordinary scabies is a difficult disease to diagnose. The goal of this project was to identify S. scabiei proteins that may be candidate antigens for use in a diagnostic test or may be used by the mite to modulate the host's protective response. An aqueous extract of S. scabiei was separated by 2-dimensional electrophoresis and proteins were identified by mass spectrometry. A parallel immunoblot was probed with serum from patients with ordinary scabies to identify IgM and/or IgG-binding antigens. The genes coding for 23 selected proteins were cloned into E. coli and the expressed recombinant proteins were screened with serum from patients with confirmed ordinary scabies. We identified 50 different proteins produced by S. scabiei, 34 of which were not previously identified, and determined that 66% were recognized by patient IgM and/or IgG. Fourteen proteins were screened for use in a diagnostic test but none possessed enough sensitivity and specificity to be useful. Six of the 9 proteins selected for the possibility that they may be immunomodulatory were not recognized by antibodies in patient serum. Thirty-three proteins that bound IgM and/or IgG from the serum of patients with ordinary scabies were identified. None of the 14 tested were useful for inclusion in a diagnostic test. The identities of 16 proteins that are not recognized as antigens by infected patients were also determined. These could be among the molecules that are responsible for this mite's ability to modulate its host's innate and adaptive immune responses.

  5. Lessons from Tiananmen Square: Recognizing Bias in News Reporting.

    Science.gov (United States)

    Braun, Joseph A., Jr.

    1990-01-01

    Recommends teaching students to recognize bias in news reports and how personal preferences infringe on objective judgment. Provides two class activities designed to help students understand this concept. Uses the Cinderella story from three cultures and group discussion to illustrate this technique. (NL)

  6. Recognizing Risk-of-Failure in Communication Design Projects

    Science.gov (United States)

    Yee, Joyce; Lievesley, Matthew; Taylor, Louise

    2009-01-01

    The pace of commercial graphic design practice presents very few opportunities to conduct user research after a project's launch. This makes the design team's ability to anticipate and address risks during the design development phase even more important, recognized in the astute observation from Tim Brown, CEO of leading international design…

  7. Subsistence fishers were legally recognized in South Africa for the ...

    African Journals Online (AJOL)

    denise

    defining a subsistence fisher, (2) current management practices, (3) resource use and (4) livelihood strategies. Feedback from fishers ... stances of fisheries management in South Africa, and it must be recognized that attitudes will only change when ...... Resources: Organising, Negotiating and Learning by Doing. Cameroon ...

  8. Recognizing, explaining and countering norm transgressive behaviour on social media

    NARCIS (Netherlands)

    Padje, E.D.H.

    2016-01-01

    In this thesis, it is researched how norm transgressive behaviour exhibited on the Dutch domains of social media can be recognized, explained and countered. An analysis of four comment threads is conducted, of which the comments can be found on the Facebook pages of three Dutch news sites and on a

  9. Professional Development Recognizing Technology Integration Modeled after the TPACK Framework

    Science.gov (United States)

    McCusker, Laura

    2017-01-01

    Public school teachers within a Pennsylvania intermediate unit are receiving inadequate job-embedded professional development that recognizes knowledge of content, pedagogy, and technology integration, as outlined by Mishra and Koehler's Technological Pedagogical Content Knowledge (TPACK) framework (2006). A school environment where teachers are…

  10. Recognize the Signs: Reading Young Adult Literature to Address Bullying

    Science.gov (United States)

    Pytash, Kristine E.; Morgan, Denise N.; Batchelor, Katherine E.

    2013-01-01

    This article summarizes preservice teachers' experiences in a book club that read young adult literature focused on issues related to bullying. Preservice teachers learned to recognize various incidents of bullying in the books. They also began to consider how they might handle incidents of bullying in their future classrooms. (Contains 2 figures.)

  11. Recognizing Job Safety Hazards. Module SH-09. Safety and Health.

    Science.gov (United States)

    Center for Occupational Research and Development, Inc., Waco, TX.

    This student module on recognizing job safety hazards is one of 50 modules concerned with job safety and health. This module details employee and employer responsibilities in correcting and monitoring safety hazards. Following the introduction, 10 objectives (each keyed to a page in the text) the student is expected to accomplish are listed (e.g.,…

  12. Shady strategic behavior : Recognizing strategic behavior of Dark Triad followers

    NARCIS (Netherlands)

    Schyns, Birgit; Wisse, Barbara; Sanders, Stacey

    2018-01-01

    The importance of strategic behavior in organizations has long been recognized. However, so far the literature has primarily focused on leaders’ strategic behavior, largely ignoring followers’ strategic behavior. In the present paper, we take a follower trait perspective to strategic follower

  13. QMODULE: CAMAC modules recognized by the QAL compiler

    International Nuclear Information System (INIS)

    Kellogg, M.; Minor, M.M.; Shlaer, S.; Spencer, N.; Thomas, R.F. Jr.; van der Beken, H.

    1977-10-01

    The compiler for the Q Analyzer Language, QAL, recognizes a certain set of CAMAC modules as having known characteristics. The conventions and procedures used to describe these modules are discussed as well as the tools available to the user for extending this set as required

  14. Structural elements recognized by abacavir-induced T cells

    DEFF Research Database (Denmark)

    Yerly, Daniel; Pompeu, Yuri Andreiw; Schutte, Ryan J.

    2017-01-01

    of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context...

  15. Students' Abstraction in Recognizing, Building with and Constructing a Quadrilateral

    Science.gov (United States)

    Budiarto, Mega Teguh; Rahaju, Endah Budi; Hartono, Sugi

    2017-01-01

    This study aims to implement empirically students' abstraction with socio-cultural background of Indonesia. Abstraction is an activity that involves a vertical reorganization of previously constructed mathematics into a new mathematical structure. The principal components of the model are three dynamic nested epistemic actions: recognizing,…

  16. Cultural characters of a newly recognized group of hospital staphylococci.

    Science.gov (United States)

    Jevons, M P; John, M; Parker, M T

    1966-07-01

    Members of a newly recognized group of hospital staphylococci, which are believed to have arisen from 83A staphylococci by lysogenization, differ from them in several cultural characters. Some but not all of these characters appear to be determined by the carriage of phage.

  17. DOD's Comptroller Recognizes NPS DRMI Director With Prestigious Award [video

    OpenAIRE

    2017-01-01

    NPS Professor Natalie Webb, Executive Director for the university’s Defense Resources Management Institute (DRMI), has been recognized by Under Secretary of Defense (Comptroller) The Honorable Mike McCord with the Office of the Secretary of Defense Award for Outstanding Achievement.

  18. 40 CFR 105.15 - How are award winners recognized?

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false How are award winners recognized? 105.15 Section 105.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER... ceremony as recognition for an outstanding technological achievement or an innovative process, method or...

  19. 76 FR 10500 - Nationally Recognized Testing Laboratories Fees

    Science.gov (United States)

    2011-02-25

    .... OSHA-2007-0031] Nationally Recognized Testing Laboratories Fees AGENCY: Occupational Safety and Health Administration (OSHA), Labor. ACTION: Final rule. SUMMARY: The Occupational Safety and Health Administration (OSHA) is adjusting the approach it uses for calculating the fees the Agency charges Nationally...

  20. Bordetella bronchiseptica antigen enhances the production of Mycoplasma hyopneumoniae antigen-specific immunoglobulin G in mice.

    Science.gov (United States)

    Yim, Seol-Hwa; Hahn, Tae-Wook; Joo, Hong-Gu

    2017-09-30

    We previously demonstrated that Bordetella ( B .) bronchiseptica antigen (Ag) showed high immunostimulatory effects on mouse bone marrow cells (BMs) while Mycoplasma ( M .) hyopneumoniae Ag showed low effects. The focus of this study was to determine if B. bronchiseptica Ag can enhance the M. hyopneumoniae Ag-specific immune response and whether the host's immune system can recognize both Ags. MTT assay results revealed that each or both Ags did not significantly change BM metabolic activity. Flow cytometry analysis using carboxyfluorescein succinimidyl ester showed that B. bronchiseptica Ag can promote the division of BMs. In cytokine and nitric oxide (NO) assays, B. bronchiseptica Ag boosted production of tumor necrosis factor-alpha in M. hyopneumoniae Ag-treated BMs, and combined treatment with both Ags elevated the level of NO in BMs compared to that from treatment of M. hyopneumoniae Ag alone. Immunoglobulin (Ig)G enzyme-linked immunosorbent assay using the sera of Ag-injected mice clearly indicated that B. bronchiseptica Ag can increase the production of M. hyopneumoniae Ag-specific IgG. This study provided information valuable in the development of M. hyopneumoniae vaccines and showed that B. bronchiseptica Ag can be used both as a vaccine adjuvant and as a vaccine Ag.

  1. Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics.

    Science.gov (United States)

    Tanaka, Toshihiro; Zhang, Weici; Sun, Ying; Shuai, Zongwen; Chida, Asiya Seema; Kenny, Thomas P; Yang, Guo-Xiang; Sanz, Ignacio; Ansari, Aftab; Bowlus, Christopher L; Ippolito, Gregory C; Coppel, Ross L; Okazaki, Kazuichi; He, Xiao-Song; Leung, Patrick S C; Gershwin, M Eric

    2017-09-01

    A major problem in autoimmunity has been identification of the earliest events that lead to breach of tolerance. Although there have been major advances in dissecting effector pathways and the multilineage immune responses to mitochondrial self-antigens in primary biliary cholangitis, the critical links between environmental factors and tolerance remain elusive. We hypothesized that environmental xenobiotic modification of the E2 subunit of the pyruvate dehydrogenase (PDC-E2) inner lipoyl domain can lead to loss of tolerance to genetically susceptible hosts. Previously we demonstrated that serum anti-PDC-E2 autoantibodies cross-react with the chemical xenobiotics 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid and further that there is a high frequency of PDC-E2-specific peripheral plasmablasts. Herein we generated 104 recombinant monoclonal antibodies (mAbs) based on paired heavy-chain and light-chain variable regions of individual plasmablasts derived from primary biliary cholangitis patients. We identified 32 mAbs reactive with native PDC-E2, including 20 specific for PDC-E2 and 12 cross-reactive with both PDC-E2 and 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid. A lower frequency of replacement somatic hypermutations, indicating a lower level of affinity maturation, was observed in the complementarity-determining regions of the cross-reactive mAbs in comparison to mAbs exclusively recognizing PDC-E2 or those for irrelevant antigens. In particular, when the highly mutated heavy-chain gene of a cross-reactive mAb was reverted to the germline sequence, the PDC-E2 reactivity was reduced dramatically, whereas the xenobiotic reactivity was retained. Importantly, cross-reactive mAbs also recognized lipoic acid, a mitochondrial fatty acid that is covalently bound to PDC-E2. Our data reflect that chemically modified lipoic acid or lipoic acid itself, through molecular mimicry, is the initial target that leads to the development of primary biliary

  2. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells

    DEFF Research Database (Denmark)

    Sette, A; Buus, S; Colon, S

    1987-01-01

    A detailed analysis of the residues within an immunogenic peptide that endow it with the capacity to interact with Ia and to be recognized by T cells is presented. Ia interacts with only a few of the peptide residues and overall exhibits a very broad specificity. Some residues appear to interact...... both with Ia and with T cells, leading to a model in which a peptide antigen is 'sandwiched' between Ia and the T-cell receptor....

  3. Parallel detection of antigen-specific T cell responses by combinatorial encoding of MHC multimers

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Kvistborg, Pia; Frøsig, Thomas Mørch

    2012-01-01

    Fluorescently labeled multimeric complexes of peptide-MHC, the molecular entities recognized by the T cell receptor, have become essential reagents for detection of antigen-specific CD8(+) T cells by flow cytometry. Here we present a method for high-throughput parallel detection of antigen-specif......(+) immune responses during cancer and infectious disease or after immunotherapy. One panel of 28 combinatorially encoded MHC multimers can be prepared in 4 h. Staining and detection takes a further 3 h.......Fluorescently labeled multimeric complexes of peptide-MHC, the molecular entities recognized by the T cell receptor, have become essential reagents for detection of antigen-specific CD8(+) T cells by flow cytometry. Here we present a method for high-throughput parallel detection of antigen......-specific T cells by combinatorial encoding of MHC multimers. Peptide-MHC complexes are produced by UV-mediated MHC peptide exchange and multimerized in the form of streptavidin-fluorochrome conjugates. Eight different fluorochromes are used for the generation of MHC multimers and, by a two...

  4. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  5. Antigenic cartography of H1N1 influenza viruses using sequence-based antigenic distance calculation.

    Science.gov (United States)

    Anderson, Christopher S; McCall, Patrick R; Stern, Harry A; Yang, Hongmei; Topham, David J

    2018-02-12

    The ease at which influenza virus sequence data can be used to estimate antigenic relationships between strains and the existence of databases containing sequence data for hundreds of thousands influenza strains make sequence-based antigenic distance estimates an attractive approach to researchers. Antigenic mismatch between circulating strains and vaccine strains results in significantly decreased vaccine effectiveness. Furthermore, antigenic relatedness between the vaccine strain and the strains an individual was originally primed with can affect the cross-reactivity of the antibody response. Thus, understanding the antigenic relationships between influenza viruses that have circulated is important to both vaccinologists and immunologists. Here we develop a method of mapping antigenic relationships between influenza virus stains using a sequence-based antigenic distance approach (SBM). We used a modified version of the p-all-epitope sequence-based antigenic distance calculation, which determines the antigenic relatedness between strains using influenza hemagglutinin (HA) genetic coding sequence data and provide experimental validation of the p-all-epitope calculation. We calculated the antigenic distance between 4838 H1N1 viruses isolated from infected humans between 1918 and 2016. We demonstrate, for the first time, that sequence-based antigenic distances of H1N1 Influenza viruses can be accurately represented in 2-dimenstional antigenic cartography using classic multidimensional scaling. Additionally, the model correctly predicted decreases in cross-reactive antibody levels with 87% accuracy and was highly reproducible with even when small numbers of sequences were used. This work provides a highly accurate and precise bioinformatics tool that can be used to assess immune risk as well as design optimized vaccination strategies. SBM accurately estimated the antigenic relationship between strains using HA sequence data. Antigenic maps of H1N1 virus strains reveal

  6. Purification of nonlipopolysaccharide antigen from Brucella abortus during preparation of antigen used for indirect hemolysis test.

    OpenAIRE

    Hoffmann, E M; Houle, J J

    1986-01-01

    The indirect hemolysis test (IHLT) for the diagnosis of brucellosis uses a lipopolysaccharide (LPS) antigen obtained by dimethyl sulfoxide extraction of Brucella abortus. We showed that a non-LPS antigen can be obtained as a by-product of the IHLT antigen preparation. The antigen was purified to homogeneity by a combination of gel-filtration chromatography and ion-exchange chromatography. The substance contained 8% protein and about 65% carbohydrate. The molecular weight of the primary unit w...

  7. Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Sørensen, Sofie Sølvsten; Mosgaard, Berit Jul

    2011-01-01

    The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease.......The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease....

  8. Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen

    DEFF Research Database (Denmark)

    Sharifzadeh, Zahra; Rahbarizadeh, Fatemeh; Shokrgozar, Mohammad Ali

    2013-01-01

    The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies that specific......The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies...... that specifically recognize the TAG-72 antigen. All selected nanobodies were shown to selectively bind to this cancer-related molecule with low-nanomolar affinities and do not cross-react with other antigens, such as MUC1 or HER2. Furthermore, they can detect TAG-72 in concentrations as low as 5 U/ml which...... nanobody recognizes a distinct epitope on the TAG-72 antigen that is different from the one recognized by the mouse anti-TAG-72 antibody, CC49. Considering their high specificity, reduced immunogenicity and multi-targeting behavior, these oligoclonal nanobodies represent a promising tool to target TAG-72...

  9. A computational framework for influenza antigenic cartography.

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2010-10-07

    Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI) assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses) and reference antisera (antibodies). Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS). In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses), we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  10. rOv-ASP-1, a recombinant secreted protein of the helminth Onchocercavolvulus, is a potent adjuvant for inducing antibodies to ovalbumin, HIV-1 polypeptide and SARS-CoV peptide antigens.

    Science.gov (United States)

    MacDonald, Angus J; Cao, Long; He, Yuxian; Zhao, Qian; Jiang, Shibo; Lustigman, Sara

    2005-05-16

    We studied the adjuvanticity of recombinant Onchocerca volvulus activation associated protein-1 (rOv-ASP-1) for ovalbumin (OVA) in mice. After a single immunization and one boost, rOv-ASP-1 exceeded the efficacy of alum or MPL + TDM adjuvants in terms of end-point total IgG or IgG1 and IgG2a anti-OVA titres. Using the helminth-derived adjuvant, IgG isotype responses to OVA were of a mixed Th1/Th2 profile and spleen cell cytokines exclusively Th1-type. The potent adjuvanticity of rOv-ASP-1 was confirmed in mice vaccinated with a 37-mer peptide from the S protein of SARS-CoV and an HIV-1 gp120-CD4 chimeric polypeptide antigen. Unusually for a helminth product, the rOv-ASP-1 adjuvant augmented not only Th2 but also Th1 responses, the latter property being of potential utility in stimulating anti-viral immune responses.

  11. Diagnostic Values of Carcinoembryonic Antigen, Cancer Antigen 15-3 and Cancer Antigen 125 Levels in Nipple Discharge.

    Science.gov (United States)

    Zhao, Song; Gai, Xiaodong; Wang, Yongmei; Liang, Weili; Gao, Haidong; Zhang, Kai; Wang, Huimin; Liu, Yanhong; Wang, Jianli; Ma, Rong

    2015-12-31

    An expedient and cost-effective diagnostic tool is needed to complement galactography and exfoliative cytology for detection of benign or malignant breast diseases with nipple discharge. The aim of this prospective study is to explore the utility of carcinoembryonic antigen, cancer antigen 15-3 and cancer antigen 125 levels in nipple discharge for the diagnosis of various breast diseases. We evaluated the pre-operative tumor marker levels in 153 nipple discharge samples collected from one or both breasts of 142 women undergoing surgery. Patients with nipple discharge underwent auxiliary examination (ultrasonography, exfoliative cytology, ductoscopy and galactography). Statistically higher levels of carcinoembryonic antigen and cancer antigen 15-3 were found in patients in the malignant group as compared to those in the benign group. No statistically significant difference in the level of cancer antigen 125 (P = 0.895). Sensitivities of carcinoembryonic antigen and cancer antigen 15-3 for diagnosing breast cancer were 74.42% and 58.14%, and specificities were 87.27% and 80.00% where as the cutoff values with max-sum of sensitivity and specificity were 224.3 ng/ml and 1368.2 U/ml, respectively. The following sensitivities for telling malignant from benign could be determined: exfoliative cytology 46.67%, ultrasonography 76.74%, galactography 75.00%, and ductoscopy 0%. Exfoliative cytology was found to be a valuable alternative method for differentiating benign from malignancy. Thus, tumor marker analysis of nipple discharge fluid for carcinoembryonic antigen and cancer antigen 15-3 would enhance the accurate assessment and treatment planning for patients with nipple discharge.

  12. Monoclonal antibodies against rat leukocyte surface antigens

    NARCIS (Netherlands)

    van den Berg, T. K.; Puklavec, M. J.; Barclay, A. N.; Dijkstra, C. D.

    2001-01-01

    Monoclonal antibodies have proven to be powerful tools for studying the properties of leukocyte surface antigens and the cells that express them. In the past decades many monoclonal antibodies (mAb) for identifying the different rat leukocyte surface antigens have been described. A list of mAb is

  13. Prostate-Specific Antigen (PSA) Test

    Science.gov (United States)

    ... antigen level New England Journal of Medicine 2004;350(22):2239-2246. [PubMed Abstract] Barry ... antigen testing for early diagnosis of prostate cancer. New England Journal of Medicine 2001;344(18):1373-1377. [PubMed Abstract] Pinsky ...

  14. Evaluation of an Antigen-Antibody

    African Journals Online (AJOL)

    GB

    1. ABSTRACT. BACKGROUND: Development of “combination” assays detecting in parallel, within a single test,. Hepatitis C Virus (HCV) antigens and antibodies, not ... considered above threshold of detection for antigen proteins suggested a lack of sensitivity by this assay ..... Hepatic veno-occlusive disease (sinusoidal.

  15. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

    Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

    2005-01-01

    Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination

  16. Vaccination and antigenic drift in influenza.

    Science.gov (United States)

    Boni, Maciej F

    2008-07-18

    The relationship between influenza antigenic drift and vaccination lies at the intersection of evolutionary biology and public health, and it must be viewed and analyzed in both contexts simultaneously. In this paper, 1 review what is known about the effects of antigenic drift on vaccination and the effects of vaccination on antigenic drift, and I suggest some simple ways to detect the presence of antigenic drift in seasonal influenza data. If antigenic drift occurs on the time scale of a single influenza season, it may be associated with the presence of herd immunity at the beginning of the season and may indicate a need to monitor for vaccine updates at the end of the season. The relationship between antigenic drift and vaccination must also be viewed in the context of the global circulation of influenza strains and the seeding of local and regional epidemics. In the data sets I consider--from New Zealand, New York, and France--antigenic drift can be statistically detected during some seasons, and seeding of epidemics appears to be endogenous sometimes and exogenous at other times. Improved detection of short-term antigenic drift and epidemic seeding would significantly benefit influenza monitoring efforts and vaccine selection.

  17. Computational and Experimental Validation of B and T-Cell Epitopes of the In Vivo Immune Response to a Novel Malarial Antigen

    Science.gov (United States)

    2013-08-16

    only recognize linear peptide fragments of antigens presented by various MHC molecules on antigen-presenting cells (APC). Current methods for...and sequence analysis of a-helical regions displayed distinct amphipathic character suggesting that appropriate helical packing is critical to the...immunoproteasomes. The PfCelTOS protein was subjected to proteasomal cleavage to identify peptides that could potentially bind to MHC molecules and

  18. Human sperm protein encyclopedia and alloantigen index: mining novel allo-antigens using sera from ASA-positive infertile patients and vasectomized men.

    Science.gov (United States)

    Shetty, Jagathpala; Bronson, Richard A; Herr, John C

    2008-01-01

    Anti-sperm antibodies (ASA) are an important cause of immunological infertility. The objective of this study was to identify immunodominant sperm antigens recognized by anti-sperm antibodies (ASA) in serum samples of infertile men, women and vasectomized men. High-resolution two-dimensional gel electrophoresis was employed to separate human sperm proteins using isoelectric focusing (IEF) or nonequilibrium pH gradient electrophoresis (NEPHGE), followed by PAGE and Western blotting. Serum samples from five infertile male and five infertile female subjects that contained ASA as assayed by the immunobead binding test (IBT), were analyzed by Western blotting using NEPHGE gels followed by enhanced chemiluminescence (ECL) to identify the basic sperm antigens reactive to the sera. Serum samples from five fertile male and five fertile female subjects that were ASA-negative by IBT were used as controls. Serum samples from six vasectomized men collected before vasectomy and at different time intervals until 6 months after vasectomy were analyzed by Western blotting using IEF gels. The ECL blots were analyzed to compare immunoreactivity between serum samples from fertile and infertile subjects and identify antigens unique to sera of the infertile subjects. Similarly, immunoreactivity between serum samples from pre- and post-vasectomy was compared to identify antigens unique to sera collected following vasectomy. Five allo-antigenic basic protein spots were recognized by sera from infertile males but not from fertile subjects. Five sperm iso-antigenic basic spots were recognized by infertile female subjects. Two among six of the vasectomized men's sera showed a difference in the Western blot profile 6 months after vasectomy, recognizing at least one new protein spot in each case when compared to pre-vasectomy sera. The acrosomal protein SP-10 was identified as an alloantigen recognized by a post-vasectomy serum. Molecular identities of the known allo- and iso-antigens

  19. Recognizing intentions in infant-directed speech: evidence for universals.

    Science.gov (United States)

    Bryant, Gregory A; Barrett, H Clark

    2007-08-01

    In all languages studied to date, distinct prosodic contours characterize different intention categories of infant-directed (ID) speech. This vocal behavior likely exists universally as a species-typical trait, but little research has examined whether listeners can accurately recognize intentions in ID speech using only vocal cues, without access to semantic information. We recorded native-English-speaking mothers producing four intention categories of utterances (prohibition, approval, comfort, and attention) as both ID and adult-directed (AD) speech, and we then presented the utterances to Shuar adults (South American hunter-horticulturalists). Shuar subjects were able to reliably distinguish ID from AD speech and were able to reliably recognize the intention categories in both types of speech, although performance was significantly better with ID speech. This is the first demonstration that adult listeners in an indigenous, nonindustrialized, and nonliterate culture can accurately infer intentions from both ID speech and AD speech in a language they do not speak.

  20. Federally-Recognized Tribes of the Columbia-Snake Basin.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration

    1997-11-01

    This is an omnibus publication about the federally-recognized Indian tribes of the Columbia-Snake river basin, as presented by themselves. It showcases several figurative and literal snapshots of each tribe, bits and pieces of each tribe`s story. Each individual tribe or tribal confederation either submitted its own section to this publication, or developed its own section with the assistance of the writer-editor. A federally-recognized tribe is an individual Indian group, or confederation of Indian groups, officially acknowledged by the US government for purposes of legislation, consultation and benefits. This publication is designed to be used both as a resource and as an introduction to the tribes. Taken together, the sections present a rich picture of regional indian culture and history, as told by the tribes.

  1. Analysis of Gait Pattern to Recognize the Human Activities

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    2014-09-01

    Full Text Available Human activity recognition based on the computer vision is the process of labelling image sequences with action labels. Accurate systems for this problem are applied in areas such as visual surveillance, human computer interaction and video retrieval. The challenges are due to variations in motion, recording settings and gait differences. Here we propose an approach to recognize the human activities through gait. Activity recognition through Gait is the process of identifying an activity by the manner in which they walk. The identification of human activities in a video, such as a person is walking, running, jumping, jogging etc are important activities in video surveillance. We contribute the use of Model based approach for activity recognition with the help of movement of legs only. Experimental results suggest that our method are able to recognize the human activities with a good accuracy rate and robust to shadows present in the videos.

  2. Slice&Dice: Recognizing Food Preparation Activities Using Embedded Accelerometers

    Science.gov (United States)

    Pham, Cuong; Olivier, Patrick

    Within the context of an endeavor to provide situated support for people with cognitive impairments in the kitchen, we developed and evaluated classifiers for recognizing 11 actions involved in food preparation. Data was collected from 20 lay subjects using four specially designed kitchen utensils incorporating embedded 3-axis accelerometers. Subjects were asked to prepare a mixed salad in our laboratory-based instrumented kitchen environment. Video of each subject's food preparation activities were independently annotated by three different coders. Several classifiers were trained and tested using these features. With an overall accuracy of 82.9% our investigation demonstrated that a broad set of food preparation actions can be reliably recognized using sensors embedded in kitchen utensils.

  3. Recognizing and treating toilet-seat contact dermatitis in children.

    Science.gov (United States)

    Litvinov, Ivan V; Sugathan, Paramoo; Cohen, Bernard A

    2010-02-01

    Toilet-seat contact dermatitis is a common condition around the world and is reemerging in the United States. It can be easily recognized and treated. However, few practitioners consider this diagnosis, which results in a delay in treatment and often exacerbation of the skin eruption. In the past, exposure to wooden toilet seats and associated varnish, lacquers, and paints led to the development of an allergic contact dermatitis on the buttocks and posterior thighs. In recent years, most public facilities have changed to plastic seats, resulting in a change in the clinical presentation of toilet-seat dermatitis. We present 5 cases of toilet-seat dermatitis in children from the United States and India and review the history, presentation, and clinical course of the disease. Our findings suggest that toilet-seat dermatitis is more common than previously recognized and should be considered in any child with a dermatitis that involves the buttocks and posterior thighs.

  4. Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI).

    Science.gov (United States)

    Scheiblhofer, Sandra; Ritter, Uwe; Thalhamer, Josef; Weiss, Richard

    2013-01-01

    The gene gun technology can not only be employed for efficient transfer of gene vaccines into upper layers of the skin, but also for application of protein antigens. As a tissue rich in professional antigen presenting cells, the skin represents an attractive target for immunizations. In this chapter we present a method for delivery of the model antigen ovalbumin into the skin of mice termed epidermal antigen incorporation and describe in detail how antigen-specific proliferation in draining lymph nodes can be followed by flow cytometry.

  5. Specific and common antigens of Trichomonas vaginalis detected by monoclonal antibodies.

    Science.gov (United States)

    Torian, B E; Connelly, R J; Stephens, R S; Stibbs, H H

    1984-01-01

    Monoclonal antibodies to Trichomonas vaginalis were prepared by immunizing mice with a cloned isolate of T. vaginalis. Eight antibodies reacted with the same four isolates or strains but did not react with the other T. vaginalis strains or isolates tested. All eight antibodies reacted uniformly with both the body and flagella of T. vaginalis in the immunofluorescence assay but were unreactive by immunoblotting. The antigen(s) recognized by these antibodies was determined to be present on the surface membrane by indirect immunofluorescence assay of live organisms. The antigen(s) was found to be sensitive to periodate oxidation but resistant to pronase digestion. In addition, one monoclonal antibody was derived which reacted with all T. vaginalis isolates or strains tested, as well as with Trichomonas gallinae, Tritrichomonas foetus, and Giardia lamblia. This antibody reacted with the body but not the flagella of Formalin-fixed protozoa in the immunofluorescence assay but failed to react with live organisms. The antigen was found to be periodate resistant but pronase labile. In the immunoblot assay, this antibody detected a single T. vaginalis polypeptide with a molecular weight of 62,000. Images PMID:6360900

  6. Carbohydrates as T-cell antigens with implications in health and disease.

    Science.gov (United States)

    Sun, Lina; Middleton, Dustin R; Wantuch, Paeton L; Ozdilek, Ahmet; Avci, Fikri Y

    2016-10-01

    Glycosylation is arguably the most ubiquitous post-translational modification on proteins in microbial and mammalian cells. During the past few years, there has been intensive research demonstrating that carbohydrates, either in pure forms or in conjunction with proteins or lipids, evoke and modulate adaptive immune responses. We now know that carbohydrates can be directly recognized by T cells or participate in T-cell stimulation as components of T-cell epitopes. T-cell recognition of carbohydrate antigens takes place via their presentation by major histocompatibility complex pathways on antigen-presenting cells. In this review, we summarize studies on carbohydrates as T-cell antigens modulating adaptive immune responses. Through discussion of glycan-containing antigens, such as glycoproteins, glycolipids, zwitterionic polysaccharides and carbohydrate-based glycoconjugate vaccines, we will illustrate the key molecular and cellular interactions between carbohydrate antigens and T cells and the implications of these interactions in health and disease. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Flow Virometry to Analyze Antigenic Spectra of Virions and Extracellular Vesicles.

    Science.gov (United States)

    Arakelyan, Anush; Fitzgerald, Wendy; Zicari, Sonia; Vagida, Murad; Grivel, Jean-Charles; Margolis, Leonid

    2017-01-25

    Cells release small extracellular vesicles (EVs) into the surrounding media. Upon virus infection cells also release virions that have the same size of some of the EVs. Both virions and EVs carry proteins of the cells that generated them and are antigenically heterogeneous. In spite of their diversity, both viruses and EVs were characterized predominantly by bulk analysis. Here, we describe an original nanotechnology-based high throughput method that allows the characterization of antigens on individual small particles using regular flow cytometers. Viruses or extracellular vesicles were immunocaptured with 15 nm magnetic nanoparticles (MNPs) coupled to antibodies recognizing one of the surface antigens. The captured virions or vesicles were incubated with fluorescent antibodies against other surface antigens. The resultant complexes were separated on magnetic columns from unbound antibodies and analyzed with conventional flow cytometers triggered on fluorescence. This method has wide applications and can be used to characterize the antigenic composition of any viral- and non-viral small particles generated by cells in vivo and in vitro. Here, we provide examples of the usage of this method to evaluate the distribution of host cell markers on individual HIV-1 particles, to study the maturation of individual Dengue virions (DENV), and to investigate extracellular vesicles released into the bloodstream.

  8. Challenging dentistry to recognize and respond to family violence.

    Science.gov (United States)

    Aved, Barbara M; Meyers, Larry; Burmas, Elita Lin

    2007-08-01

    Few studies have examined efforts to engage the dental community about roles and responsibilities in recognizing and responding to family violence through targeted educational programs. Evaluation of the Dental Professionals Against Violence course showed 1,213 dental professionals gained knowledge and confidence about identifying and appropriately responding where abuse/violence in patients was suspected. Practice changes included increased awareness of signs and symptoms of abuse among patients and application of the training materials for office staff.

  9. Effects of Facial Expressions on Recognizing Emotions in Dance Movements

    OpenAIRE

    Nao Shikanai; Kozaburo Hachimura

    2011-01-01

    Effects of facial expressions on recognizing emotions expressed in dance movements were investigated. Dancers expressed three emotions: joy, sadness, and anger through dance movements. We used digital video cameras and a 3D motion capturing system to record and capture the movements. We then created full-video displays with an expressive face, full-video displays with an unexpressive face, stick figure displays (no face), or point-light displays (no face) from these data using 3D animation so...

  10. Recognizing primary emotions in communication in adults with intellectual disability

    Directory of Open Access Journals (Sweden)

    Đorđević Mirjana

    2017-01-01

    Full Text Available The ability to recognize emotions helps people understand social situations and plan their own behavior in specific social contexts. Paralinguistic segments of communication (facial expression and prosodic characteristics significantly contribute to drawing conclusions on the speaker's emotions, and according to some authors, they are considered even more dominant and more reliable than linguistic segments in decoding emotions tasks. The aim of this paper was to determine the ability to recognize primary emotions in communication with the help of paralinguistic indicators, in adults with mild and moderate intellectual disability. The sample consisted of 60 adult participants with mild (N=25 and moderate (N=35 intellectual disability, equal with regard to gender and type of housing. The participants with mild intellectual disability were aged 20-55 (M=31.24; SD=8.84, while those with moderate intellectual disability were 22-55 years of age (M=34.17; SD=8.76. The Assessment Battery for Communication, ABaCo, (Sacco et al., 2008 was used for assessing the ability to understand emotions in communication. The obtained results showed that adults with intellectual disability experienced most difficulties in detecting fear. By applying the T test for independent samples, it was determined that there were no statistically significant differences between men and women both with mild and moderate ID with regard to their ability to recognize emotions (p>0,05. With regard to the type of housing, statistically significant differences were obtained only in the group of participants with moderate intellectual disability in detecting fear (t (33=-3.51; p=0.01, in favor of those who lived in institutions. The length of living in an institution positively and moderately correlated with the ability to recognize anger in adults with intellectual disability (r=0.46, p<0.05.

  11. Smart responsive microcapsules capable of recognizing heavy metal ions.

    Science.gov (United States)

    Pi, Shuo-Wei; Ju, Xiao-Jie; Wu, Han-Guang; Xie, Rui; Chu, Liang-Yin

    2010-09-15

    Smart responsive microcapsules capable of recognizing heavy metal ions are successfully prepared with oil-in-water-in-oil double emulsions as templates for polymerization in this study. The microcapsules are featured with thin poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (P(NIPAM-co-BCAm)) membranes, and they can selectively recognize special heavy metal ions such as barium(II) or lead(II) ions very well due to the "host-guest" complexation between the BCAm receptors and barium(II) or lead(II) ions. The stable BCAm/Ba(2+) or BCAm/Pb(2+) complexes in the P(NIPAM-co-BCAm) membrane cause a positive shift of the volume phase transition temperature of the crosslinked P(NIPAM-co-BCAm) hydrogel to a higher temperature, and the repulsion among the charged BCAm/Ba(2+) or BCAm/Pb(2+) complexes and the osmotic pressure within the P(NIPAM-co-BCAm) membranes result in the swelling of microcapsules. Induced by recognizing barium(II) or lead(II) ions, the prepared microcapsules with P(NIPAM-co-BCAm) membranes exhibit isothermal and significant swelling not only in outer and inner diameters but also in the membrane thickness. The proposed microcapsules in this study are highly attractive for developing smart sensors and/or carriers for detection and/or elimination of heavy metal ions. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Human antigen-specific regulatory T cells generated by T cell receptor gene transfer.

    Directory of Open Access Journals (Sweden)

    Todd M Brusko

    2010-07-01

    Full Text Available Therapies directed at augmenting regulatory T cell (Treg activities in vivo as a systemic treatment for autoimmune disorders and transplantation may be associated with significant off-target effects, including a generalized immunosuppression that may compromise beneficial immune responses to infections and cancer cells. Adoptive cellular therapies using purified expanded Tregs represents an attractive alternative to systemic treatments, with results from animal studies noting increased therapeutic potency of antigen-specific Tregs over polyclonal populations. However, current methodologies are limited in terms of the capacity to isolate and expand a sufficient quantity of endogenous antigen-specific Tregs for therapeutic intervention. Moreover, FOXP3+ Tregs fall largely within the CD4+ T cell subset and are thus routinely MHC class II-specific, whereas class I-specific Tregs may function optimally in vivo by facilitating direct tissue recognition.To overcome these limitations, we have developed a novel means for generating large numbers of antigen-specific Tregs involving lentiviral T cell receptor (TCR gene transfer into in vitro expanded polyclonal natural Treg populations. Tregs redirected with a high-avidity class I-specific TCR were capable of recognizing the melanoma antigen tyrosinase in the context of HLA-A*0201 and could be further enriched during the expansion process by antigen-specific reactivation with peptide loaded artificial antigen presenting cells. These in vitro expanded Tregs continued to express FOXP3 and functional TCRs, and maintained the capacity to suppress conventional T cell responses directed against tyrosinase, as well as bystander T cell responses. Using this methodology in a model tumor system, murine Tregs designed to express the tyrosinase TCR effectively blocked antigen-specific effector T cell (Teff activity as determined by tumor cell growth and luciferase reporter-based imaging.These results support the

  13. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Marc Schmitz

    2012-02-01

    Full Text Available Prostate cancer (PCa is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8+ cytotoxic T lymphocytes (CTLs efficiently recognize and destroy tumor cells. CD4+ T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  14. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  15. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Mustafa, A S; Amoudy, H A; Wiker, H G

    1998-01-01

    We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r......-gamma secretion showed that the most frequently recognized antigen was ESAT-6, followed by MPT59, GroES, MPB70, MPT64, DnaK, GroEL and PstS. The frequency of ESAT-6 responders, as measured both by proliferation (18/19) and secretion of IFN-gamma (16/19) was comparable to the results obtained with whole-cell M...

  16. Study of the antigenic cross reactivity between carcinoembryonic antigen and "nonspecific cross reacting antigens" (NCA and NCA 2).

    Science.gov (United States)

    Neveu, T.; Staebler, D.; Chavanel, G.; Burtin, P.

    1975-01-01

    The immunochemical relationship between CEA, NCA and NCA 2 was studied in guinea-pigs. Strong cross reactions were found between these antigens, either in delayed or anaphylactic reactions. Some specific determinants for each antigen could still be demonstrated. Delayed hypersensitivity is likely to be due to the protein moiety of the molecules while anaphylactic reactivity could probably be related to their glucidic parts. Consequently, CEA and NCA have common antigenic determinants on their glucidic and peptidic moieties, perhaps more on the latter ones. PMID:50854

  17. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    Energy Technology Data Exchange (ETDEWEB)

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  18. CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

    Directory of Open Access Journals (Sweden)

    Vanesa Alonso-Camino

    2013-01-01

    Full Text Available A human single-chain variable fragment (scFv antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs. The repertoire was fused to a first-generation T cell receptor ζ (TCRζ-based chimeric antigen receptor (CAR. We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2 bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR and the selection context (cell synapse, which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells.

  19. Molecular cloning, characterization and antigenicity of Babesia sp. BQ1 (Lintan) (Babesia cf. motasi) apical membrane antigen-1 (AMA-1).

    Science.gov (United States)

    Niu, Qingli; Liu, Zhijie; Yang, Jifei; Guan, Guiquan; Pan, Yuping; Luo, Jianxun; Yin, Hong

    2017-04-01

    Apical membrane antigen-1 (AMA-1) has been described as a potential vaccine candidate in apicomplexan parasites. Here we characterize the ama-1 gene. The full-length ama-1 gene of Babesia sp. BQ1 (Lintan) (BLTAMA-1) is 1785 bp, which contains an open reading frame (ORF) encoding a 65-kDa protein of 594 amino acid residues; by definition, the 5' UTR precedes the first methionine of the ORF. Phylogenetic analysis based on AMA-1 amino acid sequences clearly separated Piroplasmida from other Apicomplexa parasites. The Babesia sp. BQ1 (Lintan) AMA-1 sequence is most closely associated with that of B. ovata and B. bigemina, with high bootstrap value. A recombinant protein encoding a conserved region and containing ectodomains I and II of BLTAMA-1 was constructed. BLTrAMA-1-DI/DII proteins were tested for reactivity with sera from sheep infected by Babesia sp. BQ1 (Lintan). In Western-blot analysis, native Babesia sp. BQ1 (Lintan) AMA-1 proteins were recognized by antibodies raised in rabbits against BLTrAMA-1 in vitro. The results of this study are discussed in terms of gene characterization, taxonomy and antigenicity.

  20. Posttransplant chimeric antigen receptor therapy.

    Science.gov (United States)

    Smith, Melody; Zakrzewski, Johannes; James, Scott; Sadelain, Michel

    2018-03-08

    Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD. © 2018 by The American Society of Hematology.

  1. Demonstration of Antigenic Identity Between Purified Equine Infectious Anemia Virus and an Antigen Extracted from Infected Horse Spleen

    Science.gov (United States)

    Nakajima, Hideo; Norcross, Neil L.; Coggins, Leroy

    1972-01-01

    Antigenic relationship between purified equine infectious anemia (EIA) virus and spleen-derived antigen from EIA-infected horses was examined by immunodiffusion. Identical antigenicity of these two antigens has been proven because precipitation lines formed between the two antigens and EIA antiserum connected with each other. The results indicate that the antigenic substance derived from infected spleen is a component of EIA virus. Images PMID:4629262

  2. Engineering support vector machine kernels that recognize translation initiation sites.

    Science.gov (United States)

    Zien, A; Rätsch, G; Mika, S; Schölkopf, B; Lengauer, T; Müller, K R

    2000-09-01

    In order to extract protein sequences from nucleotide sequences, it is an important step to recognize points at which regions start that code for proteins. These points are called translation initiation sites (TIS). The task of finding TIS can be modeled as a classification problem. We demonstrate the applicability of support vector machines for this task, and show how to incorporate prior biological knowledge by engineering an appropriate kernel function. With the described techniques the recognition performance can be improved by 26% over leading existing approaches. We provide evidence that existing related methods (e.g. ESTScan) could profit from advanced TIS recognition.

  3. Recognizing and Treating Malaria in U.S. Residents

    Centers for Disease Control (CDC) Podcasts

    2010-06-09

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: It's a Small World After All: Dengue and Malaria in U.S. Residents - Recognizing and Treating These Mosquito-borne Diseases. CDC's David Townes discusses clinical presentation, transmission, prevention strategies, new treatments, and malaria resources available to health care providers.  Created: 6/9/2010 by Division of Parasitic Diseases and Malaria, Center for Global Health and Emergency Communication System (ECS)/Joint Information Center (JIC); Office of Public Health Preparedness and Response (OPHPR).   Date Released: 6/15/2010.

  4. Recognizing the Stranger: Recognition Scenes in the Gospel of John

    DEFF Research Database (Denmark)

    Larsen, Kasper Bro

    Recognizing the Stranger is the first monographic study of recognition scenes and motifs in the Gospel of John. The recognition type-scene (anagnōrisis) was a common feature in ancient drama and narrative, highly valued by Aristotle as a touching moment of truth, e.g., in Oedipus’ tragic self......-discovery and Odysseus’ happy homecoming. The book offers a reconstruction of the conventions of the genre and argues that it is one of the most recurrent and significant literary forms in the Gospel. When portraying Jesus as the divine stranger from heaven, the Gospel employs and transforms the formal and ideological...

  5. Indirect haemagglutination reaction with Sarcocystis dispersa antigen.

    Science.gov (United States)

    Cerva, L; Cerná, Z

    1982-01-01

    A description is given of the preparation of antigen from Sarcocystis dispersa cystozoites and the procedure of the indirect haemagglutination test (IHA). The antibodies against this antigen were detected in experimentally infected mice from day 20 p.i. (1: 640). In the following weeks the antibody titres reached the value of 1: 40,960. The sera of pigs, sheep and horses spontaneously infected with other Sarcocystis species reacted with this antigen in low titres only. The bovine sera gave negative reactions even in cases when Sarcocystis cysts were present in the muscles of the examined animals. A possible application of IHA for the research and diagnostic purposes is discussed.

  6. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Buffalo, Cosmo Z.; Bahn-Suh, Adrian J.; Hirakis, Sophia P.; Biswas, Tapan; Amaro, Rommie E.; Nizet, Victor; Ghosh, Partho

    2016-09-05

    No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently ~90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant ‘reading head’ in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M–C4BP interaction, and also inform a path towards vaccine design.

  7. Recognizing induced emotions of happiness and sadness from dance movement.

    Science.gov (United States)

    Van Dyck, Edith; Vansteenkiste, Pieter; Lenoir, Matthieu; Lesaffre, Micheline; Leman, Marc

    2014-01-01

    Recent research revealed that emotional content can be successfully decoded from human dance movement. Most previous studies made use of videos of actors or dancers portraying emotions through choreography. The current study applies emotion induction techniques and free movement in order to examine the recognition of emotional content from dance. Observers (N = 30) watched a set of silent videos showing depersonalized avatars of dancers moving to an emotionally neutral musical stimulus after emotions of either sadness or happiness had been induced. Each of the video clips consisted of two dance performances which were presented side-by-side and were played simultaneously; one of a dancer in the happy condition and one of the same individual in the sad condition. After every film clip, the observers were asked to make forced-choices concerning the emotional state of the dancer. Results revealed that observers were able to identify the emotional state of the dancers with a high degree of accuracy. Moreover, emotions were more often recognized for female dancers than for their male counterparts. In addition, the results of eye tracking measurements unveiled that observers primarily focus on movements of the chest when decoding emotional information from dance movement. The findings of our study show that not merely portrayed emotions, but also induced emotions can be successfully recognized from free dance movement.

  8. Recognizing induced emotions of happiness and sadness from dance movement.

    Directory of Open Access Journals (Sweden)

    Edith Van Dyck

    Full Text Available Recent research revealed that emotional content can be successfully decoded from human dance movement. Most previous studies made use of videos of actors or dancers portraying emotions through choreography. The current study applies emotion induction techniques and free movement in order to examine the recognition of emotional content from dance. Observers (N = 30 watched a set of silent videos showing depersonalized avatars of dancers moving to an emotionally neutral musical stimulus after emotions of either sadness or happiness had been induced. Each of the video clips consisted of two dance performances which were presented side-by-side and were played simultaneously; one of a dancer in the happy condition and one of the same individual in the sad condition. After every film clip, the observers were asked to make forced-choices concerning the emotional state of the dancer. Results revealed that observers were able to identify the emotional state of the dancers with a high degree of accuracy. Moreover, emotions were more often recognized for female dancers than for their male counterparts. In addition, the results of eye tracking measurements unveiled that observers primarily focus on movements of the chest when decoding emotional information from dance movement. The findings of our study show that not merely portrayed emotions, but also induced emotions can be successfully recognized from free dance movement.

  9. Effects of Facial Expressions on Recognizing Emotions in Dance Movements

    Directory of Open Access Journals (Sweden)

    Nao Shikanai

    2011-10-01

    Full Text Available Effects of facial expressions on recognizing emotions expressed in dance movements were investigated. Dancers expressed three emotions: joy, sadness, and anger through dance movements. We used digital video cameras and a 3D motion capturing system to record and capture the movements. We then created full-video displays with an expressive face, full-video displays with an unexpressive face, stick figure displays (no face, or point-light displays (no face from these data using 3D animation software. To make point-light displays, 13 markers were attached to the body of each dancer. We examined how accurately observers were able to identify the expression that the dancers intended to create through their dance movements. Dance experienced and inexperienced observers participated in the experiment. They watched the movements and rated the compatibility of each emotion with each movement on a 5-point Likert scale. The results indicated that both experienced and inexperienced observers could identify all the emotions that dancers intended to express. Identification scores for dance movements with an expressive face were higher than for other expressions. This finding indicates that facial expressions affect the identification of emotions in dance movements, whereas only bodily expressions provide sufficient information to recognize emotions.

  10. Patient Selection in Plastic Surgery: Recognizing Body Dysmorphic Disorder

    Directory of Open Access Journals (Sweden)

    Cihan Sahin

    2013-04-01

    Full Text Available Plastic surgery is a branch of medicine that provides significant improvements to the people with positive changes. But first of all, this branch has a characteristic which requires analysing patients' psychological situation very carefully. Plastic surgeons are often confronted by patients with mental disorders seeking aesthetic surgery. It is imperative for surgeons to recognize possible underlying psychiatric illnesses. Common psychiatric conditions seen in cosmetic surgery patients include body dysmorphic disorder (BDD, narcissistic personality disorder and histrionic personality disorders. BDD is of particular importance to plastic surgeons. Because outrageous dissatisfaction with one's appearance may conceal psychopathologic traits that are not always easily recognizable, and which, if neglected, may result in serious iatrogenic and medicolegal consequences, we hope that this paper will help plastic surgeons in ultimately preventing patient and surgeon dissatisfaction within the population of patients with psychiatric disorders, and should recognize the diagnostic features of body dysmorphic disorder and screen psychologically unstable patients who may never be satisfied with surgery. [Arch Clin Exp Surg 2013; 2(2.000: 109-115

  11. Recognizing Induced Emotions of Happiness and Sadness from Dance Movement

    Science.gov (United States)

    Van Dyck, Edith; Vansteenkiste, Pieter; Lenoir, Matthieu; Lesaffre, Micheline; Leman, Marc

    2014-01-01

    Recent research revealed that emotional content can be successfully decoded from human dance movement. Most previous studies made use of videos of actors or dancers portraying emotions through choreography. The current study applies emotion induction techniques and free movement in order to examine the recognition of emotional content from dance. Observers (N = 30) watched a set of silent videos showing depersonalized avatars of dancers moving to an emotionally neutral musical stimulus after emotions of either sadness or happiness had been induced. Each of the video clips consisted of two dance performances which were presented side-by-side and were played simultaneously; one of a dancer in the happy condition and one of the same individual in the sad condition. After every film clip, the observers were asked to make forced-choices concerning the emotional state of the dancer. Results revealed that observers were able to identify the emotional state of the dancers with a high degree of accuracy. Moreover, emotions were more often recognized for female dancers than for their male counterparts. In addition, the results of eye tracking measurements unveiled that observers primarily focus on movements of the chest when decoding emotional information from dance movement. The findings of our study show that not merely portrayed emotions, but also induced emotions can be successfully recognized from free dance movement. PMID:24587026

  12. Phages recognizing the Indium Nitride semiconductor surface via their peptides.

    Science.gov (United States)

    Estephan, Elias; Saab, Marie-Belle; Martin, Marta; Larroque, Christian; Cuisinier, Frédéric J G; Briot, Olivier; Ruffenach, Sandra; Moret, Matthieu; Gergely, Csilla

    2011-02-01

    Considerable advances in materials science are expected via the use of selected or designed peptides to recognize material, control their growth, or to assemble them into elaborate novel devices. Identifying specific peptides for a number of technologically useful materials has been the challenge of many research groups in recent years. This can be accomplished by using affinity-based bio-panning methods such as phage display technologies. In this work, a combinatorial library including billions of clones of genetically engineered M13 bacteriophage was used to select peptides that could recognize improved indium nitride (InN) semiconductor (SC) material. Several rounds of biopanning were necessary to select the phage with the higher affinity from the low variant library. The DNA of this specific phage was extracted and sequenced to set up the related specific adherent peptide. Atomic force microscopy (AFM) is used to demonstrate the real affinity of a selected phage for the InN surface. Due to the possibility of its functionalization with biomolecules and its important physical properties, InN is a promising candidate for developing affinity-based optical and electrical biosensors and/or for biomimetic applications. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

  13. Comparison of concept recognizers for building the Open Biomedical Annotator

    Directory of Open Access Journals (Sweden)

    Rubin Daniel

    2009-09-01

    Full Text Available Abstract The National Center for Biomedical Ontology (NCBO is developing a system for automated, ontology-based access to online biomedical resources (Shah NH, et al.: Ontology-driven indexing of public datasets for translational bioinformatics. BMC Bioinformatics 2009, 10(Suppl 2:S1. The system's indexing workflow processes the text metadata of diverse resources such as datasets from GEO and ArrayExpress to annotate and index them with concepts from appropriate ontologies. This indexing requires the use of a concept-recognition tool to identify ontology concepts in the resource's textual metadata. In this paper, we present a comparison of two concept recognizers – NLM's MetaMap and the University of Michigan's Mgrep. We utilize a number of data sources and dictionaries to evaluate the concept recognizers in terms of precision, recall, speed of execution, scalability and customizability. Our evaluations demonstrate that Mgrep has a clear edge over MetaMap for large-scale service oriented applications. Based on our analysis we also suggest areas of potential improvements for Mgrep. We have subsequently used Mgrep to build the Open Biomedical Annotator service. The Annotator service has access to a large dictionary of biomedical terms derived from the United Medical Language System (UMLS and NCBO ontologies. The Annotator also leverages the hierarchical structure of the ontologies and their mappings to expand annotations. The Annotator service is available to the community as a REST Web service for creating ontology-based annotations of their data.

  14. How well do nurses recognize malnutrition in elderly patients?

    Science.gov (United States)

    Suominen, M H; Sandelin, E; Soini, H; Pitkala, K H

    2009-02-01

    Malnutrition is a common and underrecognized clinical problem among aged institutionalized patients. The aim of this study was to investigate how well nurses recognize malnutrition in elderly patients in long-term care hospitals in Helsinki. In this descriptive, cross-sectional study, the nutritional status of 1043 elderly patients was assessed with the Mini Nutritional Assessment (MNA), their body mass indices (BMIs) (kg m(-2)) were counted, and factors related to their nutritional care were queried using a structured questionnaire. In addition, we asked the opinions of 53 nurses on whether they considered their patients to suffer from malnutrition. All the long-term care hospitals in Helsinki, Finland participated in this study. The mean age of the patients was 81 years. The nurses considered only 15.2% of the patients to be malnourished, although the MNA showed that 56.7% were malnourished (MNApatients having a BMI24 but MNApatients considered to be malnourished received snacks and nutritional supplements less than the patients that the nurses considered to have normal nutritional status. However, only one in six of the malnourished patients received oral nutritional supplements. The nurses recognized malnutrition in their aged patients poorly. Nutrition education for nurses is urgently needed, as malnutrition and weight loss have been considered significant problems, and the benefits of nutritional care are well established.

  15. IgG autoantibodies from bullous pemphigoid (BP) patients bind antigenic sites on both the extracellular and the intracellular domains of the BP antigen 180.

    Science.gov (United States)

    Perriard, J; Jaunin, F; Favre, B; Büdinger, L; Hertl, M; Saurat, J H; Borradori, L

    1999-02-01

    Bullous pemphigoid (BP) and gestational pemphigoid (PG) are subepidermal blistering disorders associated with autoantibodies directed against two components of hemidesmosomes: the BP antigen 180 (BP180) and the BP antigen 230 (BP230). Autoantibodies against the extracellular domain (ECD) of BP180 are thought to play an initiatory role in subepidermal blister formation. To characterize the targeted antigenic sites on BP180, we have assessed the reactivity of sera from BP and PG patients against eukaryotic recombinant proteins encompassing various portions of the ECD and the intracellular domain (ICD) of BP180. Twenty-two of 22 (100%) BP sera that immunoblotted BP180 in keratinocyte extracts, bound a mutant form consisting of the entire ECD of BP180, whereas only three of these 22 sera (14%) reacted against the ECD of BP180 lacking the NC16A membrane proximal region. Thirteen out of the 22 (59%) BP sera recognized the ICD of BP180. Circulating IgG from a representative BP patient that was affinity purified against the ECD of BP180 did not bind the ICD when reblotted, indicating that there was no antigenic cross-reactivity between the ECD and the ICD of BP180. Reactivity against the ICD of BP180 was further ascertained by immunofluorescence microscopy studies showing that nine of the 22 (41%) BP sera stained COS-7 cells expressing the ICD of BP180. Using deletion mutants of the ICD of BP180, the majority of the sera was found to recognize the central region of the ICD of BP180. Specifically, an immunodominant region was localized to an 87-amino acid segment located towards the NH2-terminus of BP180. In contrast to BP sera, five of six (83%) PG sera contained IgG that recognized exclusively the NC16A region, whereas none bound to the ICD of BP180. Together, the results indicate that in BP, autoantibody reactivity to BP180 is not exclusively restricted to the NC16A region, but that additional antigenic determinants exist on the ICD of BP180. The observed heterogeneous

  16. Tissue polypeptide antigen activity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Bach, F; Söletormos, Georg; Dombernowsky, P

    1991-01-01

    Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis...

  17. HLA antigens in three populations of India.

    Science.gov (United States)

    Papiha, S S; Wentzel, J; Shah, K C; Roberts, D F

    1989-01-01

    In blood samples from a Hindu population of Uttar Pradesh (North India) and from two Muslim groups, one from Andhra Pradesh (South India) and the other from Gujurat (West India), frequencies of 38 HLA-A, -B and -C antigens were investigated. Eight antigens - A23, A25, A29, A32, Bw45, B21, Bw22 and Bw53 - were absent in the Hindu population, four different antigens - A29, Bw52, B14 and Bw42 - were absent in Hyderabad Muslims, two antigens - A31 and Bw45 - were lacking in Surat Muslims. The three populations showed considerable genetic heterogeneity. The genetic difference between the two Muslim groups was small, but the Hindu population showed pronounced differences from each of the Muslim groups.

  18. 9 CFR 113.407 - Pullorum antigen.

    Science.gov (United States)

    2010-01-01

    ... determined by a colorimetric method. (2) The phenol content for Pullorum Tube Antigen shall be 0.55 ±0.05 percent as determined by direct titration with a standardized bromide-bromate solution. (d) Sensitivity...

  19. 78 FR 37795 - Draft NOAA Procedures for Government to Government Consultation With Federally Recognized Indian...

    Science.gov (United States)

    2013-06-24

    ... affect tribal governments, their economic and social development activities, and their lands and... policy recognized the unique legal and political status of federally recognized American Indian and...

  20. Carcinoembryonic antigen in thyroid cancer

    International Nuclear Information System (INIS)

    Weissel, M.; Hoefer, R.

    1982-01-01

    In order to investigate the usefulness of determining the serum concentrations of carcinoembryonic antigen (CEA) as a specific tumor marker in thyroid cancer, CEA serum levels were measured (enzymeimmunoassay, Abbott-Kit) repeatedly at the routine followup checks performed at various intervals after total thyroidectomy, in 65 patients with papillary, 82 with follicular, 25 with mixed type (papillary/follicular), 8 with anaplastic, and in 18 patients with medullary thyroid cancer. The postoperative observation period of these patients ranged from 2 to 36 months. Calcitonin serum levels were additionally determined in patients with medullary carcinoma (radioimmunoassay kit of Immuno-Nuclear Corp.). In the family of one patient with medullary carcinoma we also had an opportunity to investigate, within the framework of family screening (pentagastrin tests, etc.), the value of preoperative CEA determination. In the patients with ''non-medullary'' histological types of thyroid cancer, the maximum CEA serum concentration was 9.8 ng/ml. 6% of the patients with papillary, 9% of the patients with follicular, and 8% of those with mixed type thyroid cancer had serum levels above the upper limit of our normal range (5 ng/ml). All patients with anaplastic carcinoma had values below 3 ng/ml. The values quoted represent maximal values and were confirmed at various follow-up checks. However, 1 year after thyroidectomy, a female patient with follicular thyroid carcinoma developed an adenocarcinoma of the rectum: The CEA levels measured in this patient were: 4.2 ng/ml 3 weeks after thyroidectomy, 8.4 ng/ml 6 months later, and 37 ng/ml 1 week before operation on the rectum. In none of the other patients with elevated CEA levels were metastases of thyroid cancer, or any other malignancy, detected. (orig.) [de

  1. Antigenic variation in vector-borne pathogens.

    OpenAIRE

    Barbour, A. G.; Restrepo, B. I.

    2000-01-01

    Several pathogens of humans and domestic animals depend on hematophagous arthropods to transmit them from one vertebrate reservoir host to another and maintain them in an environment. These pathogens use antigenic variation to prolong their circulation in the blood and thus increase the likelihood of transmission. By convergent evolution, bacterial and protozoal vector-borne pathogens have acquired similar genetic mechanisms for successful antigenic variation. Borrelia spp. and Anaplasma marg...

  2. Allosensibilisation to erythrocyte antigens (literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2015-01-01

    Full Text Available In this article literature review of the causes of allosensibilisation to erythrocyte antigens are presented. It is shown that the ability to produce antierythrocyte antibodies is affected by many factors, principal of whom it is difficult to identify. For the allosensibilisation development requires genetically determined differences in erythrocyte antigens phenotypes of donor and recipient, mother and fetus, which can lead to immune response and antibodies production. The biochemical nature of erythrocyte antigens, antigen dose (the amount of transfused doses, the number of antigens determinants on donor and fetus erythrocytes, the number of pregnancies are important. Individual patient characteristics: age, gender, diseases, the use of immunosuppressive therapy and the presence of inflammatory processes, are also relevant. Note that antibody to one erythrocyte antigens have clinical value, and to the other – have no. The actual data about frequency of clinically significant antibodies contribute to the development of post-transfusion hemolytic complications prophylaxis as well as the improvement of laboratory diagnosis of hemolytic disease of the newborn in the presence of maternal antierythrocyte antibodies.

  3. [Antigenic relations of several strains of Naegleria].

    Science.gov (United States)

    Zubiaur, E; Alonso, P

    1987-02-01

    In previous papers different aspects of one strain of Naegleria lovaniensis (Aq/9/1/45D) and two strains of N. gruberi (1518/le and 1518/lf) have been studied. From the results obtained it can be concluded that each strain behaves differently; no more similarities have been found between both N. gruberi strains, than between each of these and N. lovaniensis. Such an event has prompted us to characterize their antigenic relationships by means of an immunoprecipitation assay (double diffusion in plate). Each antiserum was tested against the different antigenic extracts. For N. lovaniensis, besides the whole extract, two fractions (particulate and soluble) and their respective antisera were assayed separately. No reaction occurred between any of the anti-N. lovaniensis sera and either of the two N. gruberi extracts. The antiserum to N. gruberi 1518/lf reacted only with its homologue and with N. lovaniensis antigens. Both N. lovaniensis fractions share some antigenic components being more complex the antigenic structure of the soluble fraction. Therefore no more similarities occur between both N. gruberi strains than between each one and N. lovaniensis, rather N. gruberi 1518/le exhibits more antigenic relationships with N. lovaniensis than with 1518/lf strains. In view of such results the species N. gruberi should be taxonomically reconsidered, criterium shared by other authors.

  4. Designed ankyrin repeat proteins: a new approach to mimic complex antigens for diagnostic purposes?

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    Stefanie Hausammann

    Full Text Available Inhibitory antibodies directed against coagulation factor VIII (FVIII can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures.

  5. Immunohistochemical diagnosis of Alport's syndrome in paraffin-embedded renal sections: antigen retrieval with autoclave heating.

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    Naito, Ichiro; Ninomiya, Yoshifumi; Nomura, Shinsuke

    2003-03-01

    Alport's syndrome (AS) is a hereditary renal disease caused by mutations in the genes encoding collagen type IV. Immunohistochemical analysis of the alpha chains of collagen type IV has been found to be useful for the diagnosis of this disease. The monoclonal antibodies (mAbs) generated by us recognize alpha 1(IV) through alpha 6(IV) chains of collagen type IV on fresh-frozen sections but not on paraffin-embedded sections. Antigen retrieval by autoclave heating has been found to restore the epitopes recognized by the mAbs; however the heating conditions had not been well established. In this study, the heating conditions were carefully examined using renal sections obtained from AS and non-AS patients. The heating was performed in an autoclave, at 105 degrees -127 degrees C for 6-8 min. During the heating, the sections were immersed in 0.2 N HCl solution (pH 0.9). Then, the mAbs were applied for 30 min, and the bound mAbs were detected using the LSAB kit. The optimal temperature for the antigen retrieval varied among specimens, and was dependent on the type of basement membrane examined. Thus, it was considered that heating at two or three different temperatures could be helpful for the precise diagnosis of AS. Adopting the antigen retrieval method could extend the possibility of immunohistochemical diagnosis of AS to cases without using fresh-frozen sections.

  6. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

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    Sandra M. McLachlan

    2017-12-01

    Full Text Available Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg, thyroid peroxidase (TPO, and the thyrotropin receptor (TSHR A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of spontaneously arising pathogenic TSHR antibodies in transgenic human thyrotropin receptor/NOD.H2h4 mice by injecting a non-pathogenic form of TSHR A-subunit protein also provides evidence for original antigenic sin. From other studies, antigen presentation by B cells, not dendritic cells, is likely responsible for original antigenic sin. Recognition of restricted epitopes on the large glycosylated thyroid autoantigens (60-kDa A-subunit, 100-kDa TPO, and 600-kDa Tg facilitates exploring the amino acid locations in the immunodominant regions. Epitope spreading has also been revealed by autoantibodies in thyroid autoimmunity. In humans, and in mice that spontaneously develop autoimmunity to all three thyroid autoantigens, autoantibodies develop first to Tg and later to TPO and the TSHR A-subunit. The pattern of intermolecular epitope spreading is related in part to the thyroidal content of Tg, TPO and TSHR A-subunit and to the molecular sizes of these proteins. Importantly, the epitope spreading pattern provides a rationale for future antigen-specific manipulation to block the development of all thyroid autoantibodies by inducing tolerance to Tg, first in the autoantigen cascade. Because of its abundance, Tg may be the autoantigen of choice to explore antigen-specific treatment, preventing the development of pathogenic TSHR antibodies.

  7. Viral Escape Mutant Epitope Maintains TCR Affinity for Antigen yet Curtails CD8 T Cell Responses.

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    Shayla K Shorter

    Full Text Available T cells have the remarkable ability to recognize antigen with great specificity and in turn mount an appropriate and robust immune response. Critical to this process is the initial T cell antigen recognition and subsequent signal transduction events. This antigen recognition can be modulated at the site of TCR interaction with peptide:major histocompatibility (pMHC or peptide interaction with the MHC molecule. Both events could have a range of effects on T cell fate. Though responses to antigens that bind sub-optimally to TCR, known as altered peptide ligands (APL, have been studied extensively, the impact of disrupting antigen binding to MHC has been highlighted to a lesser extent and is usually considered to result in complete loss of epitope recognition. Here we present a model of viral evasion from CD8 T cell immuno-surveillance by a lymphocytic choriomeningitis virus (LCMV escape mutant with an epitope for which TCR affinity for pMHC remains high but where the antigenic peptide binds sub optimally to MHC. Despite high TCR affinity for variant epitope, levels of interferon regulatory factor-4 (IRF4 are not sustained in response to the variant indicating differences in perceived TCR signal strength. The CD8+ T cell response to the variant epitope is characterized by early proliferation and up-regulation of activation markers. Interestingly, this response is not maintained and is characterized by a lack in IL-2 and IFNγ production, increased apoptosis and an abrogated glycolytic response. We show that disrupting the stability of peptide in MHC can effectively disrupt TCR signal strength despite unchanged affinity for TCR and can significantly impact the CD8+ T cell response to a viral escape mutant.

  8. PMab-38 Recognizes Canine Podoplanin of Squamous Cell Carcinomas.

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    Kaneko, Mika K; Honma, Ryusuke; Ogasawara, Satoshi; Fujii, Yuki; Nakamura, Takuro; Saidoh, Noriko; Takagi, Michiaki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-10-01

    Podoplanin, a type I transmembrane protein, is expressed in lymphatic endothelial cells. Although we previously developed an anticanine podoplanin monoclonal antibody (mAb), PMab-38, immunohistochemistry (IHC) showed that it did not react with canine lymphatic endothelial cells. Here, we determined whether PMab-38 recognizes canine podoplanin of squamous cell carcinomas (SCCs) and clarified its epitope. In IHC, PMab-38 reacted with 83% of SCCs (15/18 cases). Flow cytometry showed that the epitope of PMab-38 was different from that of the platelet aggregation-stimulating domain of the N-terminus, which was detected by almost all antipodoplanin mAbs such as D2-40 or NZ-1. PMab-38 is expected to be useful for investigating the function of podoplanin in canine tumors.

  9. Recognizing Dementia: Constructing Deconstruction in a Danish Memory Clinic.

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    Gjødsbøl, Iben M; Svendsen, Mette N

    2017-03-06

    This article investigates how a person with dementia is made up through intersubjective acts of recognition. Based on ethnographic fieldwork in a Danish memory clinic, we show that identification of disease requires patients to be substituted by their relatives in constructing believable medical narratives; yet during memory testing, patients are not allowed any substitution to clearly expose cognitive shortcomings. In combining works of theorists Ian Hacking and Paul Ricoeur, we argue that the clinical identification of dementia unmakes the knowing subject, a deconstruction that threatens to misrecognize and humiliate the person under examination. The article ends by proposing that dementia be the condition that forces us to rethink our ways of recognizing persons more generally. Thus, dementia diagnostics provide insights into different enactments of the person that invite us to explore practices of substitution and modes of interaction emerging when our fundamental dependency becomes unquestionable. © 2017 by the American Anthropological Association.

  10. Serendipitous learning: Recognizing and fostering the potential of microblogging

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    Ilona Buchem

    2013-03-01

    Full Text Available This paper introduces the concept of serendipitous learning in the context of microblogging and discusses the potential of unplanned and unexpected discoveries for learning. Serendipitous learning as a subset of incidental learning refers to learning through gaining new insights, discovering unrevealed aspects and recognizing seemingly unrelated connections. This type of learning can occur by chance and as a by-product of other activities like information browsing through social status updates in microblogs. It is argued that engaging in microblogging in an open social network of users frequently generating new information enhances the possibilities of serendipitous discovery. The paper discusses possible factors facilitating serendipitous learning and concludes with recommendations for future research.

  11. Perceptron Genetic to Recognize Openning Strategy Ruy Lopez

    Science.gov (United States)

    Azmi, Zulfian; Mawengkang, Herman

    2018-01-01

    The application of Perceptron method is not effective for coding on hardware based systems because it is not real time learning. With Genetic algorithm approach in calculating and searching the best weight (fitness value) system will do learning only one iteration. And the results of this analysis were tested in the case of the introduction of the opening pattern of chess Ruy Lopez. The Analysis with Perceptron Model with Algorithm Approach Genetics from group Artificial Neural Network for open Ruy Lopez. The data is processed with base open chess, with step eight a position white Pion from end open chess. Using perceptron method have many input and one output process many weight and refraction until output equal goal. Data trained and test with software Matlab and system can recognize the chess opening Ruy Lopez or Not open Ruy Lopez with Real time.

  12. Truncated Autoinducing Peptide Conjugates Selectively Recognize and Kill Staphylococcus aureus.

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    Tsuchikama, Kyoji; Shimamoto, Yasuhiro; Anami, Yasuaki

    2017-06-09

    The accessory gene regulator (agr) of Staphylococcus aureus coordinates various pathogenic events and is recognized as a promising therapeutic target for virulence control. S. aureus utilizes autoinducing peptides (AIPs), cyclic-peptide signaling molecules, to mediate the agr system. Despite the high potency of synthetic AIP analogues in agr inhibition, the potential of AIP molecules as a delivery vehicle for antibacterial agents remains unexplored. Herein, we report that truncated AIP scaffolds can be fused with fluorophore and cytotoxic photosensitizer molecules without compromising their high agr inhibitory activity, binding affinity to the receptor AgrC, or cell specificity. Strikingly, a photosensitizer-AIP conjugate exhibited 16-fold greater efficacy in a S. aureus cell-killing assay than a nontargeting analogue. These findings highlight the potential of truncated AIP conjugates as useful chemical tools for in-depth biological studies and as effective anti-S. aureus agents.

  13. Recognizing the value of assistance dogs in society.

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    Audrestch, Hilary M; Whelan, Chantelle T; Grice, David; Asher, Lucy; England, Gary C W; Freeman, Sarah L

    2015-10-01

    Assistance dogs are specially trained to undertake a variety of tasks to help individuals with disabilities. This review gives an overview of the different types of assistance dogs in the UK, including guide dogs, hearing dogs, mobility assistance dogs, service dogs and dual-purpose dogs. The literature describes many benefits of assistance dogs, including their impact on physical wellbeing and safety of their 'owners,' as well as on psychological wellbeing and social inclusion. The role of assistance dogs in society is widely recognized by the public, but is not currently acknowledged in government social policy. The current evidence on the benefits of assistance dogs is limited by the type and scale of current research. This article highlights the need for independent funding for high quality research to enable social care and policy makers to make evidence-based decisions on the value of assistance dogs to people with disabilities. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. T cells recognizing a peptide contaminant undetectable by mass spectrometry

    DEFF Research Database (Denmark)

    Brezar, Vedran; Culina, Slobodan; Østerbye, Thomas

    2011-01-01

    Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility...... of the contaminant, further underlining the immunodominance of IGRP(206-214). If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results....... complex (MHC) Class I-restricted ß-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid...

  15. Chimpanzees recognize their own delayed self-image.

    Science.gov (United States)

    Hirata, Satoshi; Fuwa, Kohki; Myowa, Masako

    2017-08-01

    Unlike mirror self-recognition, recognizing one's own image in delayed video footage may indicate the presence of a concept of self that extends across time and space. While humans typically show this ability around 4 years of age, it is unknown whether this capacity is found in non-human animals. In this study, chimpanzees performed a modified version of the mark test to investigate whether chimpanzees could remove stickers placed on the face and head while watching live and delayed video images. The results showed that three of five chimpanzees consistently removed the mark in delayed-viewing conditions, while they removed the stickers much less frequently in control video conditions which lacked a link to their current state. These findings suggest that chimpanzees, like human children at the age of 4 years and more, can comprehend temporal dissociation in their concept of self.

  16. Combined pulmonary fibrosis and emphysema: an increasingly recognized condition

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    Olívia Meira Dias

    2014-06-01

    Full Text Available Combined pulmonary fibrosis and emphysema (CPFE has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis.

  17. The Ocular Conjunctiva as a Mucosal Immunization Route: A Profile of the Immune Response to the Model Antigen Tetanus Toxoid

    Science.gov (United States)

    Belij, Sandra; Marinkovic, Emilija; Stojicevic, Ivana; Montanaro, Jacqueline; Stein, Elisabeth; Bintner, Nora; Stojanovic, Marijana

    2013-01-01

    Background In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen. Materials and methods BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 × LD50) of tetanus toxin. Results The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFNγ and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p<0.05). Conclusion Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively. PMID

  18. The ocular conjunctiva as a mucosal immunization route: a profile of the immune response to the model antigen tetanus toxoid.

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    Talin Barisani-Asenbauer

    Full Text Available BACKGROUND: In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd, a model antigen. MATERIALS AND METHODS: BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 × LD50 of tetanus toxin. RESULTS: The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFNγ and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p<0.05. CONCLUSION: Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more

  19. Identification of putative new Escherichia coli flagellar antigens from human origin using serology, PCR-RFlP and DNA sequencing methods

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    Monique Ribeiro Tiba

    Full Text Available Escherichia coli has been isolated frequently, showing flagellar antigens that are not recognized by any of the 53 antisera, provided by the most important reference center of E. coli, The International Escherichia and Klebsiella Center (WHO of the Statens Serum Institute, Copenhagen, Denmark. The objective of this study was to characterize flagellar antigens of E. coli that express non-typeable H antigens. The methods used were serology, PCR-RFLP and DNA sequencing. This characterization was performed by gene amplification of the fliC (flagellin protein by polymerase chain reaction in all 53 standards E.coli strains for the H antigens and 20 E. coli strains for which the H antigen was untypeable. The amplicons were digested by restriction enzymes, and different restriction enzyme profiles were observed. Anti-sera were produced in rabbits, for the non-typeable strains, and agglutination tests were carried out. In conclusion,the results showed that although non-typeable and typable H antigens strains had similar flagellar antigens, the two types of strains were distinct in terms of nucleotide sequence, and did not phenotypically react with the standard antiserum, as expected. Thirteen strains had been characterized as likely putative new H antigen using PCR-RFLP techniques, DNA sequencing and/or serology.

  20. How T lymphocytes see antigen

    Science.gov (United States)

    Chakraborty, Arup K.

    2009-03-01

    Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (``on'' or ``off''), and how this molecular machinery coupled with frustration (a la spin glasses) plays a key role in designing the special properties of the T cell repertoire during development in the thymus.

  1. VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines

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    Flower Darren R

    2007-01-01

    Full Text Available Abstract Background Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC transformation of protein sequences into uniform vectors of principal amino acid properties. Results Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without

  2. A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity

    Energy Technology Data Exchange (ETDEWEB)

    Doores, Katie J.; Fulton, Zara; Hong, Vu; Patel, Mitul K.; Scanlan, Christopher N.; Wormald, Mark R.; Finn, M.G.; Burton, Dennis R.; Wilson, Ian A.; Davis, Benjamin G. (Scripps); (Oxford)

    2011-08-24

    Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120.

  3. Serological diagnosis of North American Paragonimiasis by Western blot using Paragonimus kellicotti adult worm antigen.

    Science.gov (United States)

    Fischer, Peter U; Curtis, Kurt C; Folk, Scott M; Wilkins, Patricia P; Marcos, Luis A; Weil, Gary J

    2013-06-01

    Abstract. We studied the value of an IgG Western blot (WB) with Paragonimus kellicotti (Pk) antigen for diagnosis of North American paragonimiasis. The test was evaluated with sera from patients with Pk and Paragonimus westermani infections, with control sera from patients with other helminth infections, and sera from healthy Americans. All 11 proven Pk infection sera and two samples from suspected cases that were negative by P. westermani WB at the Centers for Disease Control and Prevention (CDC) contained antibodies to antigens at 34 kDa and at 21/23 kDa. Seven of 7 P. westermani sera contained antibodies to the 34 kDa antigen, but only 2 recognized the 21/23 kDa doublet. No control samples were reactive with these antigens. Antibody reactivity declined after praziquantel treatment. Thus, the P. kellicotti WB appears to be superior to P. westermani WB for diagnosing Pk infections, and it may be useful for assessing responses to treatment.

  4. Serodiagnosis of toxocariasis by ELISA using crude antigen of Toxocara canis larvae.

    Science.gov (United States)

    Jin, Yan; Shen, Chenghua; Huh, Sun; Sohn, Woon-Mok; Choi, Min-Ho; Hong, Sung-Tae

    2013-08-01

    Toxocariasis is a worldwide zoonosis caused by larvae of ascarid nematodes of dogs or cats, Toxocara canis or T. cati. Diagnosis of human toxocariasis currently relies on serology that uses T. canis excretory-secretory antigen to detect specific IgG antibodies by ELISA. We investigated the serodiagnostic efficacy of ELISA using crude antigen of T. canis larvae (TCLA). Serum specimens of 64 clinically confirmed toxocariasis, 115 healthy controls, and 119 other tissue-invading helminthiases were screened by ELISA using TCLA. The ELISA using TCLA showed 92.2% (59/64 patient samples) sensitivity and 86.6% (103/119) specificity. Its positive diagnostic predictivity was 78.7% and negative predictivity was 97.8%. No serum of healthy controls reacted but that of anisakiasis (45.5%), gnathostomiasis (19.2%), clonorchiasis (15.8%), sparganosis (11.1%), and cysticercosis (6.3%) cross-reacted. Immunoblot analysis on TCLA recognized antigenic proteins of 28- and 30-kDa bands in their dominant protein quantity and strong blotting reactivity. The present results indicate that the ELISA using our TCLA antigen is acceptable by the sensitivity and specificity for serodiagnosis of human toxocariasis. ELISA with TCLA is recommended to make differential diagnosis for patients with any sign of organ infiltration and eosinophilia.

  5. Nuclear lamins and peripheral nuclear antigens during fertilization and embryogenesis in mice and sea urchins

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    Schatten, G.; Schatten, H.; Simerly, C.; Maul, G.G.; Chaly, N.

    1985-07-01

    Nuclear structural changes during fertilization and embryogenesis in mice and sea urchins are traced using four antibodies. The oocytes from virgin female mice, morulae and blastocytes from mated females, and gametes from the sea urchin Lytechnius variegatis are studied using mouse monoclonal antibodies to nuclear lamin A/C, monoclonal antibody to P1, human autoimmune antibodies to lamin A/C, and to lamin B. The mouse fertilization data reveal no lamins on the oocyte; however, lamins are present on the pronuclei, and chromosomes are found on the oocytes and pronuclei. It is detected that on the sea urchin sperm the lamins are reduced to acrosomal and centriolar fossae and peripheral antigens are around the sperm nucleus. The mouse sperm bind lamin antibodies regionally and do not contain antigens. Lamins and antigens are observed on both pronuclei and chromosomes during sea urchin fertilization. Mouse embryogenesis reveals that lamin A/C is not recognized at morula and blastocyst stages; however, lamin B stains are retained. In sea urchin embryogenesis lamin recognition is lost at the blastrula, gastrula, and plutei stages. It is noted that nuclear lamins lost during spermatogenesis are restored at fertilization and peripheral antigens are associated with the surface of chromosomes during meiosis and mitosis and with the periphery of the pronuclei and nuclei during interphase. 32 references.

  6. Outer membrane proteins analysis of Shigella sonnei and evaluation of their antigenicity in Shigella infected individuals.

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    Hemavathy Harikrishnan

    Full Text Available Bacillary dysentery caused by infection with Shigella spp. remains as serious and common health problem throughout the world. It is a highly multi drug resistant organism and rarely identified from the patient at the early stage of infection. S. sonnei is the most frequently isolated species causing shigellosis in industrialized countries. The antigenicity of outer membrane protein of this pathogen expressed during human infection has not been identified to date. We have studied the antigenic outer membrane proteins expressed by S. sonnei, with the aim of identifying presence of specific IgA and IgG in human serum against the candidate protein biomarkers. Three antigenic OMPs sized 33.3, 43.8 and 100.3 kDa were uniquely recognized by IgA and IgG from patients with S. sonnei infection, and did not cross-react with sera from patients with other types of infection. The antigenic proteome data generated in this study are a first for OMPs of S. sonnei, and they provide important insights of human immune responses. Furthermore, numerous prime candidate proteins were identified which will aid the development of new diagnostic tools for the detection of S. sonnei.

  7. A T Helper Cell 2 (Th2) Immune Response against Non-self Antigens Modifies the Cytokine Profile of Autoimmune T Cells and Protects against Experimental Allergic Encephalomyelitis

    Science.gov (United States)

    Falcone, Marika; Bloom, Barry R.

    1997-01-01

    in which the autoreactive T cells were engaged by the encephalitogenic stimulus were able to bias their cytokine profile towards a protective Th2 phenotype. This interpretation is supported by the observation that the protective effect of preimmunization with KLH was overcome by rm– IL-12, which inhibited the production of IL-4 by the Th1 cells and biased the autoimmune response to a predominantly Th1 type. Since IL-4 mRNA could not be detected by reverse transcriptase PCR in the CNS, the protective effect was inferred to be mediated by Th2 cells in the lymphoid system, and not the target organ. We conclude that exogenous, nonself antigens that can induce Th2 responses, can modify the cytokine environment sufficiently to alter the cytokine phenotype of inflammatory, autoreactive T cell clones, and ultimately, to provide significant protection against EAE and possibly other T cell–mediated autoimmune diseases. PMID:9120396

  8. A T helper cell 2 (Th2) immune response against non-self antigens modifies the cytokine profile of autoimmune T cells and protects against experimental allergic encephalomyelitis.

    Science.gov (United States)

    Falcone, M; Bloom, B R

    1997-03-03

    which the autoreactive T cells were engaged by the encephalitogenic stimulus were able to bias their cytokine profile towards a protective Th2 phenotype. This interpretation is supported by the observation that the protective effect of preimmunization with KLH was overcome by rm-IL-12, which inhibited the production of IL-4 by the Th1 cells and biased the autoimmune response to a predominantly Th1 type. Since IL-4 mRNA could not be detected by reverse transcriptase PCR in the CNS, the protective effect was inferred to be mediated by Th2 cells in the lymphoid system, and not the target organ. We conclude that exogenous, nonself antigens that can induce Th2 responses, can modify the cytokine environment sufficiently to alter the cytokine phenotype of inflammatory, autoreactive T cell clones, and ultimately, to provide significant protection against EAE and possibly other T cell-mediated autoimmune diseases.

  9. MHC-I-restricted epitopes conserved among variola and other related orthopoxviruses are recognized by T cells 30 years after vaccination

    DEFF Research Database (Denmark)

    Tang, Sheila Tuyet; Wang, M.; Lamberth, K.

    2008-01-01

    lymphocyte epitopes. Eight epitopes were confirmed to stimulate IFN-gamma release by T cells in smallpox-vaccinated subjects. The epitopes were restricted by five supertypes (HLA-A1, -A2, -A24 -A26 and -B44). Significant T cell responses were detected against 8 of 45 peptides with an HLA class I affinity......It is many years since the general population has been vaccinated against smallpox virus. Here, we report that human leukocyte antigen (HLA) class I restricted T cell epitopes can be recognized more than 30 years after vaccination. Using bioinformatic methods, we predicted 177 potential cytotoxic T...

  10. Prostate-related antigen-derived new peptides having the capacity of inducing prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients.

    Science.gov (United States)

    Harada, Mamoru; Matsueda, Satoko; Yao, Akihisa; Ogata, Rika; Noguchi, Masanori; Itoh, Kyogo

    2004-09-01

    Prostate-related antigens, including prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP), can be targets in specific immunotherapy for prostate cancer. In this study, we attempted to newly identify epitope peptides from these 2 antigens, which are immunogenic in human histocompatibility leukocyte antigen (HLA)-A2+ prostate cancer patients. Twenty-nine peptides (PSMA with 15 and PAP with 14) were prepared based on the HLA-A2 binding motif. Based on our previous finding that antigenic peptides recognized by both cellular and humoral immune systems are useful for peptide-based immunotherapy, peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs). As a result, PSMA441-450 and PAP112-120 peptides were found to be frequently recognized by IgG in plasma from prostate cancer patients. These 2 candidates effectively induced HLA-A2-restricted and prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. In addition, their cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. These results indicate that these PSMA441-450 and PAP112-120 peptides could be promising candidates for peptide-based immunotherapy for HLA-A2(+) prostate cancer.

  11. Functional role of BK virus tumor antigens in transformation.

    OpenAIRE

    Nakshatri, H; Pater, M M; Pater, A

    1988-01-01

    We have examined the role of the human papovavirus BK virus (BKV) tumor (T) antigen(s) in the maintenance of transformation and have identified the domain of T antigen essential for transformation. BKV-transformed BHK 21 and NIH 3T3 cells expressing antisense T-antigen RNA lose their ability to grow in soft agar, indicating the need for the continued expression of T antigen for the maintenance of the transformed phenotype. Experiments using translation termination linker insertion and deletio...

  12. Antigenic diversity of H5 highly pathogenic avian influenza viruses of clade 2.3.4.4 isolated in Asia.

    Science.gov (United States)

    Ohkawara, Ayako; Okamatsu, Masatoshi; Ozawa, Makoto; Chu, Duc-Huy; Nguyen, Lam Thanh; Hiono, Takahiro; Matsuno, Keita; Kida, Hiroshi; Sakoda, Yoshihiro

    2017-05-01

    H5 highly pathogenic avian influenza viruses (HPAIV) have spread in both poultry and wild birds since late 2003. Continued circulation of HPAIV in poultry in several regions of the world has led to antigenic drift. In the present study, we analyzed the antigenic properties of H5 HPAIV isolated in Asia using four neutralizing mAbs recognizing hemagglutinin, which were established using A/chicken/Kumamoto/1-7/2014 (H5N8), belonging to clade 2.3.4.4 and also using polyclonal antibodies. Viruses of clades 1.1, 2.3.2.1, 2.3.4, and 2.3.4.4 had different reactivity patterns to the panel of mAbs, thereby indicating that the antigenicity of the viruses of clade 2.3.4.4 were similar but differed from the other clades. In particular, the antigenicity of the viruses of clade 2.3.4.4 differed from those of the viruses of clades 2.3.4 and 2.3.2.1, which suggests that the recent H5 HPAIV have further evolved antigenically divergent. In addition, reactivity of antiserum suggests that the antigenicity of viruses of clade 2.3.4.4 differed slightly among groups A, B, and C. Vaccines are still used in poultry in endemic countries, so the antigenicity of H5 HPAIV should be monitored continually to facilitate control of avian influenza. The panel of mAbs established in the present study will be useful for detecting antigenic drift in the H5 viruses that emerge from the current strains. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  13. Acute lymphoblastic leukemia-derived dendritic cells express tumor associated antigens: PNPT1, PMPCB, RHAMM, BSG and ERCC1.

    Science.gov (United States)

    Luczynski, W; Kowalczuk, O; Stasiak-Barmuta, A; Ilendo, E; Krawczuk-Rybak, M; Chyczewski, L

    2009-01-01

    In all types of leukemia both in children and adults there is a need for novel therapies that could reduce the risk of relapse after standard treatment. Acute lymphoblastic leukemia (ALL) cells are ineffective antigen presenting cells, but as shown by many authors including results from our laboratory, stimulation with CD40L restores their antigen expressing capacity. The development of T-cell therapies for leukemic patients can be based on discovery of leukemia-associated antigens (LAA) which could be recognized by the host immune system. The aim of our present study was to test the hypothesis that leukemia-derived dendritic cells maintain the expression of tumor associated antigens. Twenty five children with B-cell precursor ALL were prospectively enrolled into the study. The mononuclear cells from peripheral blood or bone marrow were cultured and stimulated (or not) with CD40L and IL-4. The assessment of costimulatory/adhesion molecules with the use of flow cytometry and real-time RT PCR were used to confirm the possibility of turning ALL cells into dendritic-like cells. Additionally 22 tumor associated antigens mRNA levels were determined by real-time PCR technique with the TaqMan chemistry using ready-to-use Low Density Arrays for Gene Expression. The results of the study showed maintained expression and even up-regulation of some (PNPT1, PMPCB, HMMR/RHAMM, BSG and ERCC1) tumor associated antigens in CD40-activated leukemic cells. CD40L stimulation leading to the differentiation of leukemic cells into DCs which combine both antigen presenting function and expression of tumor associated antigens represents an interesting approach in cancer immunotherapy.

  14. H-2 restriction: Independent recognition of H-2 and foreign antigen by a single receptor

    Science.gov (United States)

    Siliciano, Robert F.; Zacharchuk, Charles M.; Shin, Hyun S.

    1980-01-01

    We describe two situations in which the recognition of hapten can compensate for the lack of recognition of appropriate H-2 gene products in hapten-specific, H-2 restricted, T lymphocyte-mediated cytolysis. First, we show that although recognition of appropriate H-2 gene products is essential for the lysis of target cells bearing a low hapten density, significant hapten-specific lysis of H-2 inappropriate target cells is observed at high levels of target cell derivatization. Secondly, we show that hapten-conjugated anti-H-2 antibody inhibits cytolysis poorly even though its binding to target cell H-2 antigens is equivalent to that of underivatized antibody. These results suggest that hapten and H-2 are recognized independently and are therefore inconsistent with the altered-self model. Although our data do not exclude the dual-recognition model, we prefer to interpret them within the framework of a single-receptor model in which hapten and H-2 are recognized independently by receptors of identical idiotype on the T cell. We postulate that the affinity of these receptors for the relevant H-2 gene product is low enough so that the T cell is not activated by encounters with normal-self cells expressing that H-2 gene product. However, when self cells express in addition a foreign antigen that can also be recognized by the same receptor, then the force of T cell-target cell interaction may be increased sufficiently to activate T cell effector function. PMID:6966404

  15. How protein recognizes ladder-like polycyclic ethers. Interactions between ciguatoxin (CTX3C) fragments and its specific antibody 10C9.

    Science.gov (United States)

    Ui, Mihoko; Tanaka, Yoshikazu; Tsumuraya, Takeshi; Fujii, Ikuo; Inoue, Masayuki; Hirama, Masahiro; Tsumoto, Kouhei

    2008-07-11

    Ciguatoxins are a family of marine toxins composed of transfused polycyclic ethers. It has not yet been clarified at the atomic level on the pathogenic mechanism of these toxins or the interaction between a polycyclic ether compounds and a protein. Using the crystal structures of anti-ciguatoxin antibody 10C9 Fab in ligand-free form and in complexes with ABCD-ring (CTX3C-ABCD) and ABCDE-ring (CTX3C-ABCDE) fragments of the antigen CTX3C at resolutions of 2.6, 2.4, and 2.3 angstroms, respectively, we elucidated the mechanism of the interaction between the polycyclic ethers and the antibody. 10C9 Fab has an extraordinarily large and deep binding pocket at the center of the variable region, where CTX3C-ABCD or CTX3C-ABCDE binds longitudinally in the pocket via hydrogen bonds and van der Waals interactions. Upon antigen-antibody complexation, 10C9 Fab adjusts to the antigen fragments by means of rotational motion in the variable region. In addition, the antigen fragment lacking the E-ring induces a large motion in the constant region. Consequently, the thermostability of 10C9 Fab is enhanced by 10 degrees C upon complexation with CTX3C-ABCDE but not with CTX3C-ABCD. The crystal structures presented in this study also show that 10C9 Fab recoginition of CTX3C antigens requires molecular rearrangements over the entire antibody structure. These results further expand the fundamental understanding of the mechanism by which ladder-like polycyclic ethers are recognized and may be useful for the design of novel therapeutic agents by antibodies, marine toxins, or new diagnostic reagents for the detection and targeting of members of the polycyclic ether family.

  16. Recognition of melanoma-derived antigens by CTL: possible mechanisms involved in down-regulating anti-tumor T-cell reactivity

    DEFF Research Database (Denmark)

    Rivoltini, L; Loftus, D J; Squarcina, P

    1998-01-01

    Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine...

  17. Antigenic determinant of the Lancefield group H antigen of Streptococcus sanguis.

    Science.gov (United States)

    Rosan, B; Argenbright, L

    1982-01-01

    Previous studies indicated that the teichoic acid isolated from strains of Streptococcus sanguis was group specific and defined the Lancefield group H streptococci. To determine the specific antigenic determinants, the antigen was extracted from a group H streptococcus (ATCC 903) by the phenol-water method and purified by column chromatography. The isolated antigen had a glycerol/phosphate/glucose molar ratio of 1:0.9:0.3; the lipid concentration was 7.6% of its dry weight. No nucleic acids were detected, and amino acids constituted approximately 2% of the dry weight. The minimum concentration of antigen required to sensitize erythrocytes for hemagglutination with a 1:1,000 dilution of either group H antiserum or antiteichoic acid serum was 0.02 microgram/ml. Hemagglutination inhibition studies suggested that the major antigenic determinant consisted of an alpha-glucose linked to the glycerol phosphate backbone. Images PMID:6185428

  18. High-throughput identification of potential minor histocompatibility antigens by MHC tetramer-based screening

    DEFF Research Database (Denmark)

    Hombrink, Pleun; Hadrup, Sine R; Bakker, Arne

    2011-01-01

    -cell infusion difficult. This study represents the first attempt of genome-wide prediction of MiHA, coupled to the isolation of T-cell populations that react with these antigens. In this unbiased high-throughput MiHA screen, both the possibilities and pitfalls of this approach were investigated. First, 973...... polymorphic peptides expressed by hematopoietic stem cells were predicted and screened for HLA-A2 binding. Subsequently a set of 333 high affinity HLA-A2 ligands was identified and post transplantation samples from allo-SCT patients were screened for T-cell reactivity by a combination of p......MHC-tetramer-based enrichment and multi-color flow cytometry. Using this approach, 71 peptide-reactive T-cell populations were generated. The isolation of a T-cell line specifically recognizing target cells expressing the MAP4K1(IMA) antigen demonstrates that identification of MiHA through this approach is in principle...

  19. Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer

    Directory of Open Access Journals (Sweden)

    Marc Cartellieri

    2010-01-01

    Full Text Available CD4+ and CD8+ T lymphocytes are powerful components of adaptive immunity, which essentially contribute to the elimination of tumors. Due to their cytotoxic capacity, T cells emerged as attractive candidates for specific immunotherapy of cancer. A promising approach is the genetic modification of T cells with chimeric antigen receptors (CARs. First generation CARs consist of a binding moiety specifically recognizing a tumor cell surface antigen and a lymphocyte activating signaling chain. The CAR-mediated recognition induces cytokine production and tumor-directed cytotoxicity of T cells. Second and third generation CARs include signal sequences from various costimulatory molecules resulting in enhanced T-cell persistence and sustained antitumor reaction. Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients. However, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells.

  20. The antibody response to well-defined malaria antigens after acute malaria in individuals living under continuous malaria transmission

    DEFF Research Database (Denmark)

    Petersen, E; Høgh, B; Dziegiel, Morten Hanefeld

    1992-01-01

    The IgG and IgM antibody responses to the C-terminal 783 amino acids of the P. falciparum glutamate-rich protein, GLURP489-1271, expressed as an E. coli fusion protein, the IgG response to a 18-mer synthetic peptide EDKNEKGQHEIVEVEEIL (GLURP899-916) representing the C-terminal repeats of GLURP......, and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing...

  1. [Enterobacterial antigen in human peripheral blood lymphocytes].

    Science.gov (United States)

    Faure-Fontenla, M A; García-Tamayo, F

    1989-11-01

    The following study has as prior history the research reports which have shown the existence of an antigenic tissue deposit in gram-negative enterobacteria. The antigens of the enterobacteria have also been found in the lymphocytic membranes and cytoplasm. Since intestinal lymphoid tissue cells can recirculate by means of the thoracic duct to the peripheral venous system, it was proposed that the circulating lymphocytes in healthy people could also contain small amounts of a common enterobacterial antigen. The study was carried out in 15 human venous blood samples, of which the lymphocytic population was separated to later be used in the preparation of 15 alcohol soluble extracts. This material was used for inhibiting the immuno-hemolysis assay in three occasions in order to show the presence of antigens shared by different enterobacterias, using as reference a fraction separated from the LPS of Escherichia coli 08. The results showed that the human lymphocytes also had antigenic determinants common to gram-negative bacteria.

  2. Production of monoclonal antibodies anti-Taenia crassiceps cysticerci with cross-reactivity with Taenia solium antigens

    Directory of Open Access Journals (Sweden)

    ESPÍNDOLA Noeli M.

    2000-01-01

    Full Text Available We describe the production of the potential monoclonal antibodies (MoAbs using BALB/c mice immunized with vesicular fluid (VF-Tcra (T. crassiceps antigen. Immune sera presented anti-VF-Tcra (<20kD IgG and IgM antibodies with cross-reactivity with T. solium (Tso antigen (8-12, 14, and 18 kD. After cell fusion, we selected 33 anti-Tcra and anti-Tso reactive IgM-clones and 53 anti-Tcra specific IgG-clones, 5 of them also recognizing Tso antigens. Two clones identified the 8-14 and 18kD peptides of VF-Tcra.

  3. Antigenic differentiation of classical swine fever vaccinal strain PAV-250 from other strains, including field strains from Mexico.

    Science.gov (United States)

    Mendoza, Susana; Correa-Giron, Pablo; Aguilera, Edgar; Colmenares, Germán; Torres, Oscar; Cruz, Tonatiuh; Romero, Andres; Hernandez-Baumgarten, Eliseo; Ciprián, Abel

    2007-10-10

    Twenty-nine classical swine fever virus (CSFv) strains were grown in the PK15 or SK6 cell lines. Antigenic differentiation studies were performed using monoclonal antibodies (McAbs), produced at Lelystad (CDI-DLO), The Netherlands. The monoclonals which were classified numerically as monoclonals 2-13. Epitope map patterns that resulted from the reactivity with McAbs were found to be unrelated to the pathogenicity of the viruses studied. Antigenic determinants were recognized by McAbs 5 and 8, were not detected in some Mexican strains; however, sites for McAb 6 were absent in all strains. The PAV-250 vaccine strain was recognized by all MAbs, except by MAb 6. Furthermore, the Chinese C-S vaccine strain was found to be very similar to the GPE(-) vaccine. None of the studied Mexican vaccines or field strains was found to be similar to the PAV-250 vaccine strain.

  4. A novel protein that recognizes DNA strand break

    Energy Technology Data Exchange (ETDEWEB)

    Narumi, Issay; Satoh, Katsuya; Kikuchi, Masahiro [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2002-03-01

    By analyzing a DNA damage-sensitive mutant of the radioresistant bacterium Deinococcus radiodurans, we discovered that a novel protein participates in the extreme radiation resistance of this bacterium. The protein (designated PprA for promoting prominent repair) can recognize DNA strand breaks. PprA could bind to double-stranded DNA (dsDNA) in the open circular form and to linear dsDNA, but could not bind to either dsDNA in the closed circular form or single-stranded DNA (ssDNA). Further, under conditions where a substantial amount of degradation of naked DNA fragments would normally result from the activity of E. coli exonuclease III, no DNA degradation was observed when the DNA fragments were preincubated with PprA. These suggest that PprA would protect irradiation-damaged DNA from exonuclease-mediated degradation and consequent DNA repair processes could function. Beside DNA-binding ability, PprA could promote the activities of DNA repair enzymes such as DNA ligase and RecA, suggesting that PprA functions as a DNA repair-promoting protein to potentiate the effectiveness of DNA repair. These properties enable PprA to use the widespread application in vivo and in vitro. (author)

  5. Recognizing a heart attack: the process of determining illness.

    Science.gov (United States)

    Scherck, K A

    1997-07-01

    To examine the process by which patients with acute myocardial infarction recognize illness and the need for medical treatment. Descriptive, exploratory, qualitative. The coronary care and progressive care units of two midwestern medical centers. Thirty men and women with a diagnosis of acute myocardial infarction. Open-ended interviews were conducted on the fourth or fifth day of hospitalization. All interviews were recorded on audiotape and transcribed. Data were analyzed by using grounded theory methods. Findings of the study indicated that determining illness and the need for medical attention was often a difficult process involving phases. The first phase involved attending to or ignoring bodily sensations as they come and go or additional sensations develop. Some subjects moved precipitously to seeking treatment; others took days to attend to bodily sensations. The second phase involved comparing sensations with those from a previously experienced illness or with the subject's concept of sensations likely to accompany common ailments such as indigestion or flu or more serious illnesses such as ulcer, gallbladder disease, or heart attack. The quality of sensations experienced had an important influence on assigning probable cause and deciding that medical attention is warranted. The disruptive nature of signs and symptoms and how closely signs and symptoms matched the subject's prototype for a heart attack greatly influenced the determination that illness was present and healthcare was needed. These findings have implications for educating the public about the complex and variable manifestations of a heart attack.

  6. Recognizing genes and other components of genomic structure

    Energy Technology Data Exchange (ETDEWEB)

    Burks, C. (Los Alamos National Lab., NM (USA)); Myers, E. (Arizona Univ., Tucson, AZ (USA). Dept. of Computer Science); Stormo, G.D. (Colorado Univ., Boulder, CO (USA). Dept. of Molecular, Cellular and Developmental Biology)

    1991-01-01

    The Aspen Center for Physics (ACP) sponsored a three-week workshop, with 26 scientists participating, from 28 May to 15 June, 1990. The workshop, entitled Recognizing Genes and Other Components of Genomic Structure, focussed on discussion of current needs and future strategies for developing the ability to identify and predict the presence of complex functional units on sequenced, but otherwise uncharacterized, genomic DNA. We addressed the need for computationally-based, automatic tools for synthesizing available data about individual consensus sequences and local compositional patterns into the composite objects (e.g., genes) that are -- as composite entities -- the true object of interest when scanning DNA sequences. The workshop was structured to promote sustained informal contact and exchange of expertise between molecular biologists, computer scientists, and mathematicians. No participant stayed for less than one week, and most attended for two or three weeks. Computers, software, and databases were available for use as electronic blackboards'' and as the basis for collaborative exploration of ideas being discussed and developed at the workshop. 23 refs., 2 tabs.

  7. Recognizing sights, smells, and sounds with gnostic fields.

    Science.gov (United States)

    Kanan, Christopher

    2013-01-01

    Mammals rely on vision, audition, and olfaction to remotely sense stimuli in their environment. Determining how the mammalian brain uses this sensory information to recognize objects has been one of the major goals of psychology and neuroscience. Likewise, researchers in computer vision, machine audition, and machine olfaction have endeavored to discover good algorithms for stimulus classification. Almost 50 years ago, the neuroscientist Jerzy Konorski proposed a theoretical model in his final monograph in which competing sets of "gnostic" neurons sitting atop sensory processing hierarchies enabled stimuli to be robustly categorized, despite variations in their presentation. Much of what Konorski hypothesized has been remarkably accurate, and neurons with gnostic-like properties have been discovered in visual, aural, and olfactory brain regions. Surprisingly, there have not been any attempts to directly transform his theoretical model into a computational one. Here, I describe the first computational implementation of Konorski's theory. The model is not domain specific, and it surpasses the best machine learning algorithms on challenging image, music, and olfactory classification tasks, while also being simpler. My results suggest that criticisms of exemplar-based models of object recognition as being computationally intractable due to limited neural resources are unfounded.

  8. Recognizing sights, smells, and sounds with gnostic fields.

    Directory of Open Access Journals (Sweden)

    Christopher Kanan

    Full Text Available Mammals rely on vision, audition, and olfaction to remotely sense stimuli in their environment. Determining how the mammalian brain uses this sensory information to recognize objects has been one of the major goals of psychology and neuroscience. Likewise, researchers in computer vision, machine audition, and machine olfaction have endeavored to discover good algorithms for stimulus classification. Almost 50 years ago, the neuroscientist Jerzy Konorski proposed a theoretical model in his final monograph in which competing sets of "gnostic" neurons sitting atop sensory processing hierarchies enabled stimuli to be robustly categorized, despite variations in their presentation. Much of what Konorski hypothesized has been remarkably accurate, and neurons with gnostic-like properties have been discovered in visual, aural, and olfactory brain regions. Surprisingly, there have not been any attempts to directly transform his theoretical model into a computational one. Here, I describe the first computational implementation of Konorski's theory. The model is not domain specific, and it surpasses the best machine learning algorithms on challenging image, music, and olfactory classification tasks, while also being simpler. My results suggest that criticisms of exemplar-based models of object recognition as being computationally intractable due to limited neural resources are unfounded.

  9. Perceiving action identity: how pianists recognize their own performances.

    Science.gov (United States)

    Repp, Bruno H; Knoblich, Günther

    2004-09-01

    Can skilled performers, such as artists or athletes, recognize the products of their own actions? We recorded 12 pianists playing 12 mostly unfamiliar musical excerpts, half of them on a silent keyboard. Several months later, we played these performances back and asked the pianists to use a 5-point scale to rate whether they thought they were the person playing each excerpt (1 = no, 5 = yes). They gave their own performances significantly higher ratings than any other pianist's performances. In two later follow-up tests, we presented edited performances from which differences in tempo, overall dynamic (i.e., intensity) level, and dynamic nuances had been removed. The pianists' ratings did not change significantly, which suggests that the remaining information (expressive timing and articulation) was sufficient for self-recognition. Absence of sound during recording had no significant effect. These results are best explained by the hypothesis that an observer's action system is most strongly activated during perception of self-produced actions.

  10. Do pastoral care providers recognize nurses as spiritual care providers?

    Science.gov (United States)

    Cavendish, Roberta; Edelman, Maryann; Naradovy, Linda; Bajo, Maryann McPartlan; Perosi, Irene; Lanza, Melissa

    2007-01-01

    This descriptive qualitative study was conducted to explicate pastoral care providers' perceptions of nurses as spiritual providers. Spirituality is especially meaningful in contemporary society as a whole with spiritual care an expectation of hospitalized patients. Spiritual care given by nurses is grounded in nursing's history, inherent in its philosophical framework, and supported by research and professional mandates. In hospitals today, the primary responsibility for the spiritual care of patients resides with pastoral care providers. Collaboration between pastoral care providers and nurses may improve patients' spiritual care outcomes. Before collaboration can occur, it is important to learn whether pastoral care providers recognize nurses as spiritual providers. Guided by qualitative research methods, participants were sought until data saturation occurred. This qualitative study consisted of 8 participants who were experienced, full-time pastoral care providers from general and religious-affiliated hospitals. Data were collected through audiotaped open-ended interviews, a demographic data form, and exploratory questions or probes. The analysis included concurrent data collection, constant examination of conceptual interactions, linkages, and the conditions under which they occurred. Themes emerged: quest, conscious response, and essence of caring. Pastoral care providers perceive nurses as spiritual providers. Few felt comfortable initiating collaboration. Study findings are not generalizable.

  11. [Is the parasite fauna of Poland well recognized?].

    Science.gov (United States)

    Pojmańska, Teresa; Niewiadomska, Katarzyna

    2003-01-01

    The studies of parasite fauna have in Poland a long tradition. Generally the helmint fauna of all groups of vertebrates was more or less examined and as much as over 100 species of Monogenea, almost 400 Digenea, over 250 Cestoda, about 500 Nematoda and 32 Acanthocephala have been recorded. The best recognized are the helminths of fish (especially those of Cyprinidae, Esocidae, Percidae and Salmonidae), frogs examined in various regions of Poland, some birds (especially connected with water environment: Anseriformes, Ciconiformes, Podicipediformes), most of insectivores (although examined only in few localities), European bisons, deers, foxes and wild boars (all under permanent monitoring), as well as domestic animals (cattle, horses, sheeps) and pets. Such groups like some amphibians, reptiles, bats, carniwores, some birds (especially Passeriformes, Charadriiformes, falcons and eagles) need further exploration, as some host species were not the subject of parasitological investigation. In some cases it will be rather difficult goal, as most of these animals are under strict preservation, and only dead (naturally or accidentally) specimens can be autopsied.

  12. A deep convolutional neural network for recognizing foods

    Science.gov (United States)

    Jahani Heravi, Elnaz; Habibi Aghdam, Hamed; Puig, Domenec

    2015-12-01

    Controlling the food intake is an efficient way that each person can undertake to tackle the obesity problem in countries worldwide. This is achievable by developing a smartphone application that is able to recognize foods and compute their calories. State-of-art methods are chiefly based on hand-crafted feature extraction methods such as HOG and Gabor. Recent advances in large-scale object recognition datasets such as ImageNet have revealed that deep Convolutional Neural Networks (CNN) possess more representation power than the hand-crafted features. The main challenge with CNNs is to find the appropriate architecture for each problem. In this paper, we propose a deep CNN which consists of 769; 988 parameters. Our experiments show that the proposed CNN outperforms the state-of-art methods and improves the best result of traditional methods 17%. Moreover, using an ensemble of two CNNs that have been trained two different times, we are able to improve the classification performance 21:5%.

  13. Recognizing Presentations of Pemphigoid Gestationis: A Case Study

    Directory of Open Access Journals (Sweden)

    Sadie Henry

    2014-01-01

    Full Text Available Introduction. Pemphigoid gestationis (PG is an autoimmune blistering disease that occurs in approximately 1 in 50,000 pregnancies. Failing to recognize PG may lead to inadequate maternal treatment and possible neonatal complications. Case Report. At 18 weeks of gestation, a 36-year-old otherwise healthy Caucasian G4P1 presented with pruritic papules on her anterior thighs, initially treated with topical steroids. At 31 weeks of gestation, she was switched to oral steroids after her rash and pruritus worsened. The patient had an uncomplicated SVD of a healthy female infant at 37 weeks of gestation and was immediately tapered off steroid treatment, resulting in a severe postpartum flare of her disease. Discussion. This case was similar to reported cases of pruritic urticarial papules followed by blisters; however, this patient had palm, sole, and mucous membrane involvement, which is rare. Biopsy for direct immunofluorescence or ELISA is the preferred test for diagnosis. Previous case reports describe severe postdelivery flares that require higher steroid doses. Obstetrical providers need to be familiar with this disease although it is rare, as this condition can be easily confused with other dermatoses of pregnancy. Adequate treatment is imperative for the physical and psychological well-being of the mother and infant.

  14. Diversity in warning coloration is easily recognized by avian predators.

    Science.gov (United States)

    Arenas, L M; Stevens, M

    2017-07-01

    Warning coloration is a widespread strategy to alert predators about prey unprofitability. The success of this strategy partly depends on predators being able to learn and recognize certain signals as indicators of toxicity, and theory predicts that this is easier if signals converge on similar colours. However, the diversity in warning signal form is astonishing, contradicting predictions. Here, we quantified ladybird signal diversity with respect to avian vision, measuring how unique and discernible each signal is from one another. In addition, we measured signal conspicuousness against a series of backgrounds, namely an average green, average brown, and where we collected each species, to determine whether signals are more contrasting against the ladybirds' local substrates than compared to average ones. This allowed us to establish whether there are local adaptations in conspicuousness that promote signal diversity. We found that while ladybird signals are unique and recognizable, specialist species are more contrasting against the background they are most commonly found on. However, overall our study suggests that warning signals have evolved to be effective against a wide range of natural backgrounds, partly explaining the success of this strategy in nature. © 2017 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.

  15. The repertoire of glycosphingolipids recognized by Vibrio cholerae.

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    John Benktander

    Full Text Available The binding of cholera toxin to the ganglioside GM1 as the initial step in the process leading to diarrhea is nowadays textbook knowledge. In contrast, the knowledge about the mechanisms for attachment of Vibrio cholerae bacterial cells to the intestinal epithelium is limited. In order to clarify this issue, a large number of glycosphingolipid mixtures were screened for binding of El Tor V. cholerae. Several specific interactions with minor complex non-acid glycosphingolipids were thereby detected. After isolation of binding-active glycosphingolipids, characterization by mass spectrometry and proton NMR, and comparative binding studies, three distinct glycosphingolipid binding patterns were defined. Firstly, V. cholerae bound to complex lacto/neolacto glycosphingolipids with the GlcNAcβ3Galβ4GlcNAc sequence as the minimal binding epitope. Secondly, glycosphingolipids with a terminal Galα3Galα3Gal moiety were recognized, and the third specificity was the binding to lactosylceramide and related compounds. V. cholerae binding to lacto/neolacto glycosphingolipids, and to the other classes of binding-active compounds, remained after deletion of the chitin binding protein GbpA. Thus, the binding of V. cholerae to chitin and to lacto/neolacto containing glycosphingolipids represents two separate binding specificities.

  16. Pediatric rheumatology: An under-recognized subspecialty in India

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    Akhila Kavirayani

    2017-01-01

    Full Text Available Pediatrics in India at the levels of both undergraduate and postgraduate training is often viewed upon as an acute disease specialty with little emphasis on chronic medical musculoskeletal diseases. Pediatric rheumatology is an under-recognized subspecialty of pediatrics which deals specifically with childhood arthritis, noninflammatory joint pains, connective tissue diseases, autoimmune diseases, vasculitis, and other rare inflammatory disorders. This article aims to give a bird's eye view of the repertoire of commonly encountered problems seen by a pediatric rheumatologist, via a classical case vignette for each topic followed by discussion. There is also mention of some rare diseases managed within pediatric rheumatology to give a flavor of the spectrum of diseases encountered. This is to raise awareness of the importance of pediatric rheumatology as a subspecialty within India and to prompt readers to seek specialist advice when encountering challenging cases. Pediatric rheumatologists network and work collaboratively with many other specialties such as ophthalmology, dermatology, neurology, orthopedics, nephrology, infectious diseases, immunology, and gastroenterology for combined care of diverse conditions. There is an unmet need in India to develop a training program for pediatric rheumatology so that shared care pathways with sensitized pediatricians and other specialists can be developed nationwide, to serve these children better to achieve optimal outcomes.

  17. Micturition Syncope in Childhood: How to Recognize and Manage It.

    Science.gov (United States)

    Marzuillo, Pierluigi; Guarino, Stefano; Tipo, Vincenzo; Apicella, Andrea; Grandone, Anna; Diplomatico, Mario; Polito, Cesare; Miraglia Del Giudice, Emanuele; La Manna, Angela; Perrone, Laura

    2017-11-14

    Frequently, general pediatricians could face a patient with syncope, which represents approximately 1% to 3% of emergency visits. Micturition syncope is a transient loss of consciousness with onset immediately before, during, or after micturition. Literature evidence indicates that healthy young men are a population with major risk for presenting micturition syncope, with a peak of incidence around 40 to 50 years of age. Usually, this syncope occurs in the morning, after wake-up, or, more generally, when the male patients assume the orthostatic position after a period of supine position in a warm bed. No information on micturition syncope clinical presentation and prevalence in childhood is available in the literature, and probably, this kind of syncope is unrecognized in childhood. We describe 4 unreported pediatric patients with a diagnosis of micturition syncope and well-defined clinical presentation. In all patients, the syncope has been presented in the same conditions: in the morning; after wake-up; in an orthostatic position; just before, after, or during urinary bladder voiding; and with spontaneous recovery in few minutes. Interestingly, 1 patient presented with the syncope during urinary bladder voiding by autocatheterization. In our patients, all investigations made as the first approach in the pediatric emergency department did not show any abnormal results, possibly underlying the syncope episodes. By describing our experience, we want to underline the clinical presentation of micturition syncope and give to the clinicians the elements to recognize and manage it easily in children.

  18. Structural basis of Zika virus helicase in recognizing its substrates

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    Hongliang Tian

    2016-07-01

    Full Text Available Abstract The recent explosive outbreak of Zika virus (ZIKV infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn2+ and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn2+. The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.

  19. Random Deep Belief Networks for Recognizing Emotions from Speech Signals

    Directory of Open Access Journals (Sweden)

    Guihua Wen

    2017-01-01

    Full Text Available Now the human emotions can be recognized from speech signals using machine learning methods; however, they are challenged by the lower recognition accuracies in real applications due to lack of the rich representation ability. Deep belief networks (DBN can automatically discover the multiple levels of representations in speech signals. To make full of its advantages, this paper presents an ensemble of random deep belief networks (RDBN method for speech emotion recognition. It firstly extracts the low level features of the input speech signal and then applies them to construct lots of random subspaces. Each random subspace is then provided for DBN to yield the higher level features as the input of the classifier to output an emotion label. All outputted emotion labels are then fused through the majority voting to decide the final emotion label for the input speech signal. The conducted experimental results on benchmark speech emotion databases show that RDBN has better accuracy than the compared methods for speech emotion recognition.

  20. Evaluation of protective immune responses induced by DNA vaccines encoding Toxoplasma gondii surface antigen 1 (SAG1) and 14-3-3 protein in BALB/c mice.

    Science.gov (United States)

    Meng, Min; He, Shenyi; Zhao, Guanghui; Bai, Yang; Zhou, Huaiyu; Cong, Hua; Lu, Gang; Zhao, Qunli; Zhu, Xing-Quan

    2012-11-26

    Toxoplasmosis, caused by an obligate intracellular protozoan parasite Toxoplasma gondii, has been a serious clinical and veterinary problem. Effective DNA vaccines against T. gondii can prevent and control the spread of toxoplasmosis, which is important for both human health and the farming industry. The T. gondii 14-3-3 protein has been proved to be antigenic and immunogenic and was a potential vaccine candidate against toxoplasmosis. In this study, we evaluated the immune responses induced by recombinant plasmids encoding T. gondii surface antigen 1 (SAG1) and 14-3-3 protein by immunizing BALB/c mice intramuscularly. In the present study, BALB/c mice were randomly divided into five groups, including three experimental groups (pSAG1, p14-3-3 and pSAG1/14-3-3) and two control groups (PBS and pBudCE4.1), and were immunized intramuscularly three times. The levels of IgG antibodies and cytokine production in mouse sera were determined by enzyme-linked immunosorbent assays (ELISA). Two weeks after the last immunization, all mice were challenged intraperitoneally (i.p.) with 1×10(4) tachyzoites of T. gondii and the survival time of mice was observed and recorded every day. Mice vaccinated with pSAG1, p14-3-3 or pSAG1/14-3-3 developed high levels of IgG2a and gamma interferon (IFN-γ) and low levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) compared to control groups (PBS or pBudCE4.1), which suggested a modulated Th1 type immune response (Pmice in experimental groups was longer than control groups (Pmice and was a novel DNA vaccine candidate against toxoplasmosis, and the immune protective efficacy elicited by SAG1 gene was also demonstrated. Our results also showed multi-gene vaccine significantly enhanced immune responses and protective efficacy and was superior to the single-gene vaccine.

  1. Identification, characterization and immunogenicity of an O-antigen capsular polysaccharide of Francisella tularensis.

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    Michael A Apicella

    2010-07-01

    Full Text Available Capsular polysaccharides are important factors in bacterial pathogenesis and have been the target of a number of successful vaccines. Francisella tularensis has been considered to express a capsular antigen but none has been isolated or characterized. We have developed a monoclonal antibody, 11B7, which recognizes the capsular polysaccharide of F. tularensis migrating on Western blot as a diffuse band between 100 kDa and 250 kDa. The capsule stains poorly on SDS-PAGE with silver stain but can be visualized using ProQ Emerald glycoprotein stain. The capsule appears to be highly conserved among strains of F. tularensis as antibody 11B7 bound to the capsule of 14 of 14 F. tularensis type A and B strains on Western blot. The capsular material can be isolated essentially free of LPS, is phenol and proteinase K resistant, ethanol precipitable and does not dissociate in sodium dodecyl sulfate. Immunoelectron microscopy with colloidal gold demonstrates 11B7 circumferentially staining the surface of F. tularensis which is typical of a polysaccharide capsule. Mass spectrometry, compositional analysis and NMR indicate that the capsule is composed of a polymer of the tetrasaccharide repeat, 4-alpha-D-GalNAcAN-(1->4-alpha-D-GalNAcAN-(1->3-beta-D-QuiNAc-(1->2-beta-D-Qui4NFm-(1-, which is identical to the previously described F. tularensis O-antigen subunit. This indicates that the F. tularensis capsule can be classified as an O-antigen capsular polysaccharide. Our studies indicate that F. tularensis O-antigen glycosyltransferase mutants do not make a capsule. An F. tularensis acyltransferase and an O-antigen polymerase mutant had no evidence of an O-antigen but expressed a capsular antigen. Passive immunization of BALB/c mice with 75 microg of 11B7 protected against a 150 fold lethal challenge of F. tularensis LVS. Active immunization of BALB/c mice with 10 microg of capsule showed a similar level of protection. These studies demonstrate that F. tularensis

  2. Identification of early diagnostic antigens from major excretory-secretory proteins of Trichinella spiralis muscle larvae using immunoproteomics.

    Science.gov (United States)

    Wang, Li; Cui, Jing; Hu, Dan Dan; Liu, Ruo Dan; Wang, Zhong Quan

    2014-01-22

    The excretory-secretory (ES) proteins of Trichinella spiralis muscle larvae (ML) come mainly from the excretory granules of the stichosome and the cuticles (membrane proteins), are directly exposed to the host's immune system, and are the main target antigens, which induce the immune responses. Although the ES proteins are the most commonly used diagnostic antigens for trichinellosis, their main disadvantage are the false negative results during the early stage of infection. The aim of this study was to identify early specific diagnostic antigens from the main components of T. spiralis muscle larval ES proteins. Two-dimensional electrophoresis (2-DE) combined with Western blot were used to screen the early diagnostic antigens from the main components of T. spiralis muscle larval ES proteins. The protein spots recognized by the sera from BALB/c mice infected with T. spiralis at 18 days post-infection (dpi) were identified by MALDI-TOF/TOF-MS and putatively annotated using GO terms obtained from the InterPro databases. The ES proteins were analyzed by 2-DE, and more than 33 protein spots were detected with molecular weight varying from 40 to 60 kDa and isoelectric point (pI) from 4 to 7. When probed with the sera from infected mice at 18 dpi, 21 protein spots were recognized and then identified, and they were characterized to correlate with five different proteins of T. spiralis, including two serine proteases, one deoxyribonuclease (DNase) II, and two kinds of trypsin. The five proteins were functionally categorized into molecular function and biological process according to GO hierarchy. 2-DE and Western blot combined with MALDI-TOF/TOF-MS were used to screen the diagnostic antigens from the main components of T. spiralis muscle larval ES proteins. The five proteins of T. spiralis identified (two serine proteases, DNase II and two kinds of trypsin) might be the early specific diagnostic antigens of trichinellosis.

  3. Cloning and Expression of Genes for Dengue Virus Type-2 Encoded-Antigens for Rapid Diagnosis and Vaccine Development

    Science.gov (United States)

    1990-12-12

    problem associated with monovalent dengue vaccines is that individuals infected with one serotype are fully susceptible to infection with other...replication and virion assembly. Use of synthetic peptides encoding the epitopes of viral antigens recognized by host immune system has augmented our...Della-Porta and Westaway, 1977; Kitano et al., 1974; Heinz et al., 1981). In order to develop a subunit vaccine against dengue virus, it is important to

  4. In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

    OpenAIRE

    Chamakh-Ayari, Rym; Bras-Gonçalves, Rachel; Bahi-Jaber, Narges; Petitdidier, Elodie; Markikou-Ouni, Wafa; Aoun, Karim; Moreno, Javier; Carrillo, Eugenia; Salotra, Poonam; Kaushal, Himanshu; Negi, Narender Singh; Arevalo, Jorge; Falconi-Agapito, Francesca; Privat, Angela; Cruz, Maria

    2014-01-01

    PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb)...

  5. HLA antigens, epilepsy and cytomegalovirus infection.

    Science.gov (United States)

    Iannetti, P; Morellini, M; Raucci, U; Cappellacci, S

    1988-01-01

    Thirty-one epileptic patients, selected from among 900 children with previous febrile convulsions and subsequent epilepsy, were typed for HLA antigens. In 16 of the 31 patients CMV was isolated from the urine shortly after the appearance of spontaneous fits; in the remaining 15 patients the virus was never detected. All the examined children were typed for 14 HLA-A, 23 HLA-B, 7 HLA-C and 9 HLA-DR specificities, and compared with a group of healthy subjects. The HLA-A11 antigen was present in 25% of the children with chronic CMV infection and epilepsy, and absent in patients with epilepsy but without CMV infection (p less than 0.02). The possibility that the A11 antigen is a marker of the predisposing genes for CMV infection in children with epilepsy following FC is proposed.

  6. Antigenic typing Polish isolates of canine parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Mizak, B. [National Veterinary Research Institute, Pulawy (Poland); Plucienniczak, A. [Polish Academy ofd Sciences. Microbiology and Virology Center, Lodz (Poland)

    1995-12-31

    Polish strains of canine parvovirus isolated between 1982 and 1993 were examined to determine the extent to which the virus has evolved antigenically and genetically over eleven years. Two CPV isolates obtained in Warsaw in 1982 and Pulawy in 1993, were examined using monoclonal antibody typing, restriction analysis and sequencing VP-2 protein gene. Five other isolates from Warsaw and Pulawy were tested with the panel of monoclonal antibodies specific to CPV-2, CPV-2a and common for canine parvovirus, feline panleukopenia virus and milk enteritis virus. Results of the studies demonstrated that all isolates tested represented CPV-2a antigenic type. Rapid antigenic strain replacement recorded by Parrish and Senda in the U.S.A and Japan was not confirmed in Poland. (author). 30 refs, 2 tabs.

  7. Idiopathic focal segmental glomerulosclerosis and HLA antigens

    Directory of Open Access Journals (Sweden)

    M. Gerbase-DeLima

    1998-03-01

    Full Text Available The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS. HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P<0.05. In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease

  8. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  9. Intravenous IgA complexed with antigen reduces primary antibody response to the antigen and anaphylaxis upon antigen re-exposure by inhibiting Th1 and Th2 activation in mice.

    Science.gov (United States)

    Yamaki, Kouya; Miyatake, Kenji; Nakashima, Takayuki; Morioka, Ayumi; Yamamoto, Midori; Ishibashi, Yuki; Ito, Ayaka; Kuranishi, Ayu; Yoshino, Shin

    2014-10-01

    Serum IgG, IgE and IgM have been shown to enhance the primary antibody responses upon exposure to the soluble antigens recognized by those antibodies. However, how IgA affects these responses remains unknown. We investigated the effects of intravenously administered monoclonal IgA on the immune responses in mice. DBA/1J mice were immunized with ovalbumin in the presence or absence of anti-ovalbumin monoclonal IgA. The Th1 and Th2 immune responses to ovalbumin and the anaphylaxis induced by re-exposure to ovalbumin were measured. IgA complexed with antigen attenuated the primary antibody responses to the antigen in mice, in contrast to IgG2b and IgE. The primary antibody responses, i.e. the de novo synthesis of anti-ovalbumin IgG2a, IgG1 and IgE in the serum, and the subsequent anaphylaxis induced with re-exposure to ovalbumin were reduced by the co-injection of anti-ovalbumin monoclonal IgA at ovalbumin immunization. The Th1, Th2 and Tr1 cytokines interferon-γ, interleukin-4 and interleukin-10, respectively, released from ovalbumin-restimulated cultured splenocytes collected from allergic mice were also reduced by the treatment. The induction of interferon-γ and interleukin-4 secretion by splenocytes from ovalbumin-immunized mice stimulated in vitro with ovalbumin was also significantly reduced by the antigen complexed with anti-ovalbumin IgA. These data suggest that the direct inhibition of Th1 and Th2 activation by anti-ovalbumin monoclonal IgA participates in the inhibition of the primary antibody responses. IgA plays important immunosuppressive roles under physiological and pathological conditions and is a promising candidate drug for the treatment of immune disorders.

  10. Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma.

    Science.gov (United States)

    Zheng, Long; Hu, Peisheng; Wolfe, Brandon; Gonsalves, Caryn; Ren, Luqing; Khawli, Leslie A; Kaslow, Harvey R; Epstein, Alan L

    2017-12-20

    T cells expressing chimeric antigen receptors (CARs) recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR) on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgamma null (NSG) mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP) in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies.

  11. Lym-1 Chimeric Antigen Receptor T Cells Exhibit Potent Anti-Tumor Effects against B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Long Zheng

    2017-12-01

    Full Text Available T cells expressing chimeric antigen receptors (CARs recognizing CD19 epitopes have produced remarkable anti-tumor effects in patients with B-cell malignancies. However, cancer cells lacking recognized epitopes can emerge, leading to relapse and death. Thus, CAR T cells targeting different epitopes on different antigens could improve immunotherapy. The Lym-1 antibody targets a conformational epitope of Human Leukocyte Antigen-antigen D Related (HLA-DR on the surface of human B-cell lymphomas. Lym-1 CAR T cells were thus generated for evaluation of cytotoxic activity towards lymphoma cells in vitro and in vivo. Human T cells from healthy donors were transduced to express a Lym-1 CAR, and assessed for epitope-driven function in culture and towards Raji xenografts in NOD-scidIL2Rgammanull (NSG mice. Lym-1 CAR T cells exhibited epitope-driven activation and lytic function against human B-cell lymphoma cell lines in culture and mediated complete regression of Raji/Luciferase-Green fluorescent protein (Raji/Luc-GFP in NSG mice with similar or better reactivity than CD19 CAR T cells. Lym-1 CAR transduction of T cells is a promising immunotherapy for patients with Lym-1 epitope positive B-cell malignancies.

  12. The role of MHC class II antigenic determinants in the function of human antigen binding T8+ cells, monocytes and helper and suppressor factors.

    Science.gov (United States)

    Lehner, T; Jones, T

    1984-06-01

    The role of MHC class II antigens was investigated in the process of antigen binding by T8+ cells and monocytes (Mo) and in the functions of helper factor (HF) and suppressor factor (SF). Monoclonal antibodies (MoAbs) to HLA-DR, DC and SB determinants were used in immunofluorescence, inhibition of antigen binding and affinity chromatography of HF and SF. Indirect immunofluorescence studies suggest that T lymphocytes from peripheral blood of healthy subjects have a small proportion of cells expressing HLA-DR, beta chain determinants (1.4-3.8%). These belong predominantly to the T8+ subset of cells (4.6-8.8%), with only a very small proportion in the T4+ cells (0.1-1.8%). However, DC1 on DRw6+ T cells and SB2,3 on any HLA typed cells were found in significantly greater proportion than the DR antigens in both T8+ and T4+ cells, though this was again greater on T8+ (30 and 25%) than T4+ (8.3 and 14.4%) cells. Although Mo had a greatly increased proportion of cells with DR-beta chain determinants (27-45%) than the T8+ cells, the converse was found with DC1 and SB2,3 determinants (13.9 and 11.4%). Inhibition of 125I-streptococcal antigen (SA) binding to T8+ cells and to Mo by MoAbs to the class II antigens showed that DR-beta chain monomorphic or polymorphic antibodies and DC1 antibodies inhibited binding to both cell types by 66-94%. However, MoAbs to DR-alpha chains or to the SB2,3 determinant failed to yield significant inhibition. Affinity chromatography studies of HF and SF revealed that the DR-beta chain monomorphic and DC1 antibodies bound HF and SF activities and that this was not found with the DR-beta chain polymorphic or SB2,3 antibodies. The results of inhibition of 125I-SA binding to T8+ cells and Mo, and absorption of HF and SF by affinity chromatography with MoAbs suggest four categories of recognition of human MHC class II antigenic determinants. (1) Class II determinants shared by the T8+ cells, Mo, HF and SF and recognized by MoAbs to monomorphic beta

  13. Original antigenic sin: A comprehensive review.

    Science.gov (United States)

    Vatti, Anup; Monsalve, Diana M; Pacheco, Yovana; Chang, Christopher; Anaya, Juan-Manuel; Gershwin, M Eric

    2017-09-01

    The concept of "original antigenic sin" was first proposed by Thomas Francis, Jr. in 1960. This phenomenon has the potential to rewrite what we understand about how the immune system responds to infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been demonstrated to occur in several infectious diseases in both animals and humans, including human influenza infection and dengue fever. The basis of "original antigenic sin" requires immunological memory, and our immune system ability to autocorrect. In the context of viral infections, it is expected that if we are exposed to a native strain of a pathogen, we should be able to mount a secondary immune response on subsequent exposure to the same pathogen. "Original antigenic sin" will not contradict this well-established immunological process, as long as the subsequent infectious antigen is identical to the original one. But "original antigenic sin" implies that when the epitope varies slightly, then the immune system relies on memory of the earlier infection, rather than mount another primary or secondary response to the new epitope which would allow faster and stronger responses. The result is that the immunological response may be inadequate against the new strain, because the immune system does not adapt and instead relies on its memory to mount a response. In the case of vaccines, if we only immunize to a single strain or epitope, and if that strain/epitope changes over time, then the immune system is unable to mount an accurate secondary response. In addition, depending of the first viral exposure the secondary immune response can result in an antibody-dependent enhancement of the disease or at the opposite, it could induce anergy. Both of them triggering loss of pathogen control and inducing aberrant clinical consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Nanoscale artificial antigen presenting cells for cancer immunotherapy.

    Science.gov (United States)

    Rhodes, Kelly R; Green, Jordan J

    2018-03-07

    Exciting developments in cancer nanomedicine include the engineering of nanocarriers to deliver drugs locally to tumors, increasing efficacy and reducing off-target toxicity associated with chemotherapies. Despite nanocarrier advances, metastatic cancer remains challenging to treat due to barriers that prevent nanoparticles from gaining access to remote, dispersed, and poorly vascularized metastatic tumors. Instead of relying on nanoparticles to directly destroy every tumor cell, immunotherapeutic approaches target immune cells to train them to recognize and destroy tumor cells, which, due to the amplification and specificity of an adaptive immune response, may be a more effective approach to treating metastatic cancer. One novel technology for cancer immunotherapy is the artificial antigen presenting cell (aAPC), a micro- or nanoparticle-based system that mimics an antigen presenting cell by presenting important signal proteins to T cells to activate them against cancer. Signal 1 molecules target the T cell receptor and facilitate antigen recognition by T cells, signal 2 molecules provide costimulation essential for T cell activation, and signal 3 consists of secreted cues that further stimulate T cells. Classic microscale aAPCs present signal 1 and 2 molecules on their surface, and biodegradable polymeric aAPCs offer the additional capability of releasing signal 3 cytokines and costimulatory molecules that modulate the T cell response. Although particles of approximately 5-10 μm in diameter may be considered the optimal size of an aAPC for ex vivo cellular expansion, nanoscale aAPCs have demonstrated superior in vivo pharmacokinetic properties and are more suitable for systemic injection. As sufficient surface contact between T cells and aAPCs is essential for activation, nano-aAPCs with microscale contact surface areas have been created through engineering approaches such as shape manipulation and nanoparticle clustering. These design strategies have

  15. Immunogenicity of Novel DosR Regulon-Encoded Candidate Antigens of Mycobacterium tuberculosis in Three High-Burden Populations in Africa▿ †

    Science.gov (United States)

    Black, Gillian F.; Thiel, Bonnie A.; Ota, Martin O.; Parida, Shreemanta K.; Adegbola, Richard; Boom, W. Henry; Dockrell, Hazel M.; Franken, Kees L. M. C.; Friggen, Annemiek H.; Hill, Philip C.; Klein, Michel R.; Lalor, Maeve K.; Mayanja, Harriet; Schoolnik, Gary; Stanley, Kim; Weldingh, Karin; Kaufmann, Stefan H. E.; Walzl, Gerhard; Ottenhoff, Tom H. M.

    2009-01-01

    Increasing knowledge about DosR regulon-encoded proteins has led us to produce novel Mycobacterium tuberculosis antigens for immunogenicity testing in human populations in three countries in Africa to which tuberculosis (TB) is endemic. A total of 131 tuberculin skin test-positive and/or ESAT-6/CFP10-positive, human immunodeficiency virus-negative adult household contacts of active pulmonary TB cases from South Africa (n = 56), The Gambia (n = 26), and Uganda (n = 49) were tested for gamma interferon responses to 7 classical and 51 DosR regulon-encoded M. tuberculosis recombinant protein antigens. ESAT-6/CFP10 fusion protein evoked responses in >75% of study participants in all three countries. Of the DosR regulon-encoded antigens tested, Rv1733c was the most commonly recognized by participants from both South Africa and Uganda and the third most commonly recognized antigen in The Gambia. The four most frequently recognized DosR regulon-encoded antigens in Uganda (Rv1733c, Rv0081, Rv1735c, and Rv1737c) included the three most immunogenic antigens in South Africa. In contrast, Rv3131 induced the highest percentage of responders in Gambian contacts (38%), compared to only 3.4% of Ugandan contacts and no South African contacts. Appreciable percentages of TB contacts with a high likelihood of latent M. tuberculosis infection responded to several novel DosR regulon-encoded M. tuberculosis proteins. In addition to significant similarities in antigen recognition profiles between the three African population groups, there were also disparities, which may stem from genetic differences between both pathogen and host populations. Our findings have implications for the selection of potential TB vaccine candidates and for determining biosignatures of latent M. tuberculosis infection, active TB disease, and protective immunity. PMID:19553548

  16. Outer membrane protein antigens of Moraxella bovis.

    Science.gov (United States)

    Ostle, A G; Rosenbusch, R F

    1986-07-01

    Outer membranes were isolated from bovine isolates and type strains of Moraxella bovis, M phenylpyruvica, M lacunata, and M ovis by sodium N lauroyl sarcosinate extraction and differential centrifugation. Analysis of outer membranes from these organisms by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis revealed that all M bovis isolates shared a common polypeptide pattern that was readily distinguishable from other Moraxella spp. Nine major outer membrane protein bands were identified by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis analysis of M bovis. Immunoblotting of protein antigens of M bovis revealed several outer membrane proteins that seemed to be common antigens of all M bovis isolates.

  17. Celiac Crisis: A Rare Or Rarely Recognized Disease.

    Science.gov (United States)

    Waheed, Nadia; Cheema, Huma Arshad; Suleman, Hassan; Fayyaz, Zafar; Mushtaq, Iqra; Muhammad; Hashmi, Almas

    2016-01-01

    Celiac crisis is a serious life threatening complication of celiac disease characterized by profuse diarrhoea, severe dehydration and metabolic disturbances leading to neuromuscular weakness, cardiac arrhythmias and sudden death. It has been described as rare condition and not well documented in the literature. To improve awareness and facilitate diagnosis of this condition, we studied risk factors, pattern of presentation and management plans of celiac crisis. It was a descriptive cross sectional study. Patients presenting in emergency room(ER) with profuse diarrhoea leading to severe dehydration, neuromuscular weakness, and metabolic acidosis and electrolyte abnormalities enrolled in the studies after positive serology and small bowel biopsy suggestive of celiac disease. Total 126 patients out of 350 fulfilled the criteria including 54 (42.8%) male and 71 (56.3%) female. The mean age at presentation was 5.25±1.18 years. Risk factors were poor social status (97.60%), consanguinity (96.77%), early weaning with gluten contained diet (93.54%), and Presenting complaints were loose motion (100%), loss of neck holding (96.77%), dehydration (96.77%), polyuria (95.96%), inability to walk (67.74%), abdominal distension (85.86%). Electrolytes imbalances were hypokalaemia (2.4±0.55), hypocalcaemia (7.29±0.66), hypomagnesaemia (1.89±0.50), hypophosphatemia (2.8±0.68), hypoalbuminemia (3.05±0.48) and metabolic acidosis (96%). One hundred & twenty patients were stabilized with GFD and correction of dehydration, acidosis and electrolyte imbalance. Six patients needed parenteral steroids ant total parenteral nutrition (TPN). Recovery time from crisis was mean 5.4±2.73 days (range 3-20 days). Celiac crisis is a common but under recognized problem in developing countries. Commonest presenting feature is neuromuscular paralysis and biochemical abnormality is hypokalaemia.

  18. Aspects of abuse: recognizing and responding to child maltreatment.

    Science.gov (United States)

    Jackson, Allison M; Kissoon, Natalie; Greene, Christian

    2015-03-01

    Child maltreatment is a public health problem and toxic stress impacting at least 1 in 8 children by the age of 18 years. Maltreatment can take the form of physical and sexual abuse, neglect, and emotional maltreatment. While some children may experience only one form of maltreatment, others may survive multiple forms, and in some cases particularly complex forms of maltreatment such as torture and medical child abuse. When considering maltreatment, providers should be adept at obtaining a thorough history not only from the parent but when appropriate also from the patient. The most common form of child maltreatment is neglect, which encompasses nutritional and medical neglect, as well as other forms such as physical and emotional neglect. Talking with caregivers about stressors and barriers to care may give insight into the etiology for neglect and is an opportunity for the provider to offer or refer for needed assistance. Familiarity with injury patterns and distribution in the context of developmental milestones and injury mechanisms is critical to the recognition of physical abuse. While most anogenital exam results of child victims of sexual abuse are normal, knowing the normal variations for the female genitalia, and thereby recognizing abnormal findings, is important not only forensically but also more importantly for patient care. Pattern recognition does not only apply to specific injuries or constellation of injuries but also applies to patterns of behavior. Harmful patterns of behavior include psychological maltreatment and medical child abuse, both of which cause significant harm to patients. As health professionals serving children and families, pediatric providers are in a unique position to identify suspected maltreatment and intervene through the health care system in order to manage the physical and psychological consequences of maltreatment and to promote the safety and well-being of children and youth by making referrals to child protective

  19. Celiac crisis: a rare or rarely recognized disease

    International Nuclear Information System (INIS)

    Waheed, N.; Cheema, H.A.; Suleman, H.; Fayyaz, Z.; Mushtaq, I.

    2017-01-01

    Celiac crisis is a serious life threatening complication of celiac disease characterized by profuse diarrhoea, severe dehydration and metabolic disturbances leading to neuromuscular weakness, cardiac arrhythmias and sudden death. It has been described as rare condition and not well documented in the literature. To improve awareness and facilitate diagnosis of this condition, we studied risk factors, pattern of presentation and management plans of celiac crisis. Methods: It was a descriptive cross sectional study. Patients presenting in emergency room(ER) with profuse diarrhoea leading to severe dehydration, neuromuscular weakness, and metabolic acidosis and electrolyte abnormalities enrolled in the studies after positive serology and small bowel biopsy suggestive of celiac disease. Results: Total 126 patients out of 350 fulfilled the criteria including 54 (42.8 percent) male and 71 (56.3 percent) female. The mean age at presentation was 5.25+-1.18 years. Risk factors were poor social status (97.60 percent), consanguinity (96.77 percent), early weaning with gluten contained diet (93.54 percent), and Presenting complaints were loose motion (100 percent), loss of neck holding (96.77 percent), dehydration (96.77 percent), polyuria (95.96 percent), inability to walk (67.74 percent), abdominal distension (85.86 percent). Electrolytes imbalances were hypokalaemia (2.4+-0.55), hypocalcaemia (7.29+-0.66), hypomagnesaemia (1.89+-0.50), hypophosphatemia (2.8+-0.68), hypoalbuminemia (3.05+-0.48) and metabolic acidosis (96 percent). One hundred and twenty patients were stabilized with GFD and correction of dehydration, acidosis and electrolyte imbalance. Six patients needed parenteral steroids ant total parenteral nutrition (TPN). Recovery time from crisis was mean 5.4+-2.73 days (range 3-20 days). Conclusion: Celiac crisis is a common but under recognized problem in developing countries. Commonest presenting feature is neuromuscular paralysis and biochemical abnormality is

  20. Using multiple linear regression and physicochemical changes of amino acid mutations to predict antigenic variants of influenza A/H3N2 viruses.

    Science.gov (United States)

    Cui, Haibo; Wei, Xiaomei; Huang, Yu; Hu, Bin; Fang, Yaping; Wang, Jia

    2014-01-01

    Among human influenza viruses, strain A/H3N2 accounts for over a quarter of a million deaths annually. Antigenic variants of these viruses often render current vaccinations ineffective and lead to repeated infections. In this study, a computational model was developed to predict antigenic variants of the A/H3N2 strain. First, 18 critical antigenic amino acids in the hemagglutinin (HA) protein were recognized using a scoring method combining phi (ϕ) coefficient and information entropy. Next, a prediction model was developed by integrating multiple linear regression method with eight types of physicochemical changes in critical amino acid positions. When compared to other three known models, our prediction model achieved the best performance not only on the training dataset but also on the commonly-used testing dataset composed of 31878 antigenic relationships of the H3N2 influenza virus.

  1. Recognition of melanoma-derived antigens by CTL: possible mechanisms involved in down-regulating anti-tumor T-cell reactivity

    DEFF Research Database (Denmark)

    Rivoltini, L; Loftus, D J; Squarcina, P

    1998-01-01

    Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine...... (detected as increased antigen-specific CTL activity in peripheral blood) was obtained by vaccinating HLA-A2.1+ melanoma patients with the immunodominant epitope (residues 27-35) of the differentiation antigen MART-1, but this immunization was not accompanied by a significant clinical response. To implement...... immunotherapeuties capable of significantly impacting disease outcome, it is necessary to identify the potential mechanisms responsible for the failure of some antigens to mediate significant anti-tumor responses in vivo. In the case of the MART-1(27-35) epitope, we hypothesize that one of these mechanisms may...

  2. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells

    Science.gov (United States)

    Vela Ramirez, J.E.; Roychoudhury, R.; Habte, H.H.; Cho, M. W.; Pohl, N. L. B.; Narasimhan, B.

    2015-01-01

    The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells, and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by dendritic cells. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and antigen presenting cells and provide foundational information for the rational design of targeted nanovaccines against HIV-1. PMID:25068589

  3. Cell-free antigens of Sporothrix brasiliensis: antigenic diversity and application in an immunoblot assay.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Bailão, Alexandre Melo; Pizzini, Cláudia Vera; Reis, Rosani Santos; Soares, Célia Maria de Almeida; Peralta, José Mauro; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely Maria

    2012-11-01

    Sporotrichosis is a subcutaneous mycosis diagnosed by isolation of the fungus in culture. Serological tests for help in diagnosis in general do not use purified or recombinant antigens, because there is a paucity of described immunoreactive proteins, especially for the new described Sporothrix species, such as Sporothrix brasiliensis. This study aims to characterise antigens from S. brasiliensis and verify their application in serodiagnosis of sporotrichosis. An immunoblot assay allied with computer-based analysis was used to identify putative antigenic molecules in a cell-free extracts of both morphological phases of this fungus, and to delineate antigenic polymorphism among seven S. brasiliensis isolates and one S. schenckii Brazilian strain. The mycelial and yeast phase of the fungus originated 14 and 23 reactive bands, respectively, which were variable in intensity. An 85 kDa antigen, verified in the yeast phase of the fungus, was observed in all strains used and the immunodominant protein was identified. This protein, however, cross-react with serum samples from patients infected with other pathogens. The results show that the S. brasiliensis cell-free antigen extract is a single and inexpensive source of antigens, and can be applied on the sporotrichosis serodiagnosis. © 2012 Blackwell Verlag GmbH.

  4. Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

    Directory of Open Access Journals (Sweden)

    Ewoud Bernardus Compeer

    2012-03-01

    Full Text Available The cross-presentation of endocytosed antigen as peptide/class I MHC complexes plays a central role in the elicitation of CD8+ T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells (APC capable of antigen cross-presentation, description of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC, there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlight DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, recycling and maturation including the sorting of membrane proteins, dynamic remodeling of endosomal structures and cell-surface directed endosomal trafficking. We will conclude with description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

  5. Antigen and Memory CD8 T Cells: Were They Both Right?

    Directory of Open Access Journals (Sweden)

    Epelman Slava

    2007-06-01

    Full Text Available Picture yourself as a researcher in immunology. To begin your project, you ask a question: Do CD8 T cells require antigen to maintain a memory response? This question is of prime importance to numerous medical fields. In chronologic order, you digest the literature, but unfortunately, you hit a major stumbling block in the 1990s. The crux of the problem is that which so often happens in science: two well-recognized, capable groups emerge with diametrically opposed conclusions, leaving you pondering which set of wellcontrolled data to believe. Fortunately, years later, a surprising group of articles sheds light on this mystery and subtly reconciles these two positions.

  6. Flavivirus-cross-reactive, HLA-DR15-restricted epitope on NS3 recognized by human CD4+ CD8- cytotoxic T lymphocyte clones.

    Science.gov (United States)

    Kurane, I; Okamoto, Y; Dai, L C; Zeng, L L; Brinton, M A; Ennis, F A

    1995-09-01

    The role of flavivirus-cross-reactive T lymphocytes in recovery from and pathogenesis of flavivirus infections is not known. In the present paper, we have defined a flavivirus-cross-reactive epitope recognized by two CD4+ CD8- cytotoxic T lymphocyte (CTL) clones, JK4 and JK43. The T cell clones were established from the peripheral blood T lymphocytes of a dengue-4-immune donor, using a limiting-dilution method with dengue-4 antigen. These two T cell clones were cross-reactive for dengue virus types 1, 2, 3 and 4, yellow fever virus and West Nile virus, and recognized NS3 protein. The smallest synthetic peptide recognized by these T cell clones was an identical 9 amino acid peptide which contains amino acids 146 to 154 (VIGLYGNGV) of dengue-4 NS3. HLA-DR15 was the restriction allele for recognition of this epitope by JK4 and JK43. JK4 and JK43 both used T cell receptor V alpha 8, but JK4 used V beta 8 and JK43 used V beta 2. This result indicates that this epitope is recognized by two flavivirus-cross-reactive CD4+ T cell clones which originated from different T cells in vivo.

  7. Identification of linear HLA class II amino acid sequences recognized by rabbit antisera against native molecules.

    Science.gov (United States)

    Chersi, A; Morganti, M C; Houghten, R; Chillemi, F; Muratti, E

    1987-12-01

    A rabbit was immunized with B lymphoblastoid cells, and subsets of the antibodies produced were isolated on affinity columns made from synthetic peptides corresponding to known amino acid sequences from the human class II antigens DQ and DP. Those peptides for which specific antibodies were isolated could be assumed to contribute to the antigenic properties of the intact antigen. The antibody subsets were tested for binding to synthetic peptides, to glycoprotein fractions isolated from cells with different DR and DQ specificities, and to the cells used for immunization of the rabbit. The isolation of those antibodies directed against well-defined amino acid stretches of the histocompatibility antigens is proof of the role of those regions in determining the antigenic properties of these molecules.

  8. Lifting as We Climb: Recognizing Intersectional Gender Violence in Law

    Directory of Open Access Journals (Sweden)

    Shreya Atrey

    2015-12-01

    Full Text Available This paper interrogates the meaning of lifting all women as we climb the ladder of gender equality and justice by recognizing that gender violence affects women differently. This is because violence against women is perpetrated not only on the basis of their gender or sex but also other identities of race, religion, caste, region, age, disability, nationality, sexual orientation etc. With reference to CEDAW jurisprudence and examples from India, I seek to explain this understanding with the help of a normative framework of ‘intersectional integrity’. The framework insists on considering claimants as a whole by tracing unique and shared patterns of gender violence when it is also based on other identities such as race, religion, caste, region, age, disability, nationality, and sexual orientation. I argue that applying the framework allows us to diagnose and address the nature of violence suffered on multiple identities, in a clear and comprehensive way. Este artículo cuestiona el sentido de levantar a todas las mujeres a medida que se asciende la escalera de la igualdad de género y la justicia, reconociendo que la violencia de género afecta a las mujeres de manera diferente. Esto se debe a que la violencia contra las mujeres se comete no sólo sobre la base de su género o sexo, sino también por su raza, religión, casta, región, edad, discapacidad, nacionalidad, orientación sexual, etc. Se pretende explicar esta afirmación con la ayuda de un marco normativo de “integridad interseccional”, a través de referencias a la jurisprudencia del CEDAW y ejemplos de la India. El marco insiste en considerar a las demandantes en su conjunto, trazando patrones únicos y compartidos de violencia de género cuando se basa también en otras identidades como raza, religión, casta, región, edad, discapacidad, nacionalidad, orientación sexual. Se sostiene que la aplicación del marco permite diagnosticar y abordar la naturaleza de la violencia

  9. Emerging antigenic variants at the antigenic site Sb in pandemic A(H1N12009 influenza virus in Japan detected by a human monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Mayo Yasugi

    Full Text Available The swine-origin pandemic A(H1N12009 virus, A(H1N1pdm09, is still circulating in parts of the human population. To monitor variants that may escape from vaccination specificity, antigenic characterization of circulating viruses is important. In this study, a hybridoma clone producing human monoclonal antibody against A(H1N1pdm09, designated 5E4, was prepared using peripheral lymphocytes from a vaccinated volunteer. The 5E4 showed viral neutralization activity and inhibited hemagglutination. 5E4 escape mutants harbored amino acid substitutions (A189T and D190E in the hemagglutinin (HA protein, suggesting that 5E4 recognized the antigenic site Sb in the HA protein. To study the diversity of Sb in A(H1N1pdm09, 58 viral isolates were obtained during the 2009/10 and 2010/11 winter seasons in Osaka, Japan. Hemagglutination-inhibition titers were significantly reduced against 5E4 in the 2010/11 compared with the 2009/10 samples. Viral neutralizing titers were also significantly decreased in the 2010/11 samples. By contrast, isolated samples reacted well to ferret anti-A(H1N1pdm09 serum from both seasons. Nonsynonymous substitution rates revealed that the variant Sb and Ca2 sequences were being positively selected between 2009/10 and 2010/11. In 7,415 HA protein sequences derived from GenBank, variants in the antigenic sites Sa and Sb increased significantly worldwide from 2009 to 2013. These results indicate that the antigenic variants in Sb are likely to be in global circulation currently.

  10. Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia

    Directory of Open Access Journals (Sweden)

    Toshiki Ochi

    2010-01-01

    Full Text Available The last decade has seen great strides in the field of cancer immunotherapy, especially the treatment of melanoma. Beginning with the identification of cancer antigens, followed by the clinical application of anti-cancer peptide vaccination, it has now been proven that adoptive T-cell therapy (ACT using cancer antigen-specific T cells is the most effective option. Despite the apparent clinical efficacy of ACT, the timely preparation of a sufficient number of cancer antigen-specific T cells for each patient has been recognized as its biggest limitation. Currently, therefore, attention is being focused on ACT with engineered T cells produced using cancer antigen-specific T-cell receptor (TCR gene transfer. With regard to human leukemia, ACT using engineered T cells bearing the leukemia antigen-specific TCR gene still remains in its infancy. However, several reports have provided preclinical data on TCR gene transfer using Wilms' tumor gene product 1 (WT1, and also preclinical and clinical data on TCR gene transfer involving minor histocompatibility antigen, both of which have been suggested to provide additional clinical benefit. In this review, we examine the current status of anti-leukemia ACT with engineered T cells carrying the leukemia antigen-specific TCR gene, and discuss the existing barriers to progress in this area.

  11. Lectin binding patterns and immunohistochemical antigen detection ...

    African Journals Online (AJOL)

    Ibrahim Eldaghayes

    2018-02-09

    Feb 9, 2018 ... examined by histological, lectin-histochemical, immunohistochemical and cultural techniques. B. abortus antigens were immunohistochemically detected in fetal lungs and placenta. An increase in the labeling with UEA-1, DBA,. PNA, RCA-1 and SBA was found in the lungs and an increase in the labeling ...

  12. Lea blood group antigen on human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Dunstan, R.A.; Simpson, M.B.; Rosse, W.F.

    1985-01-01

    One- and two-stage radioligand assays were used to determine if human platelets possess the Lea antigen. Goat IgG anti-Lea antibody was purified by multiple adsorptions with Le(a-b-) human red blood cells, followed by affinity chromatography with synthetic Lea substance and labeling with /sup 125/I. Human IgG anti-Lea antibody was used either in a two stage radioassay with /sup 125/I-labeled mouse monoclonal IgG anti-human IgG as the second antibody or, alternatively, purified by Staph protein A chromatography, labeled with /sup 125/I, and used in a one-stage radioassay. Platelets from donors of appropriate red blood cell phenotypes were incubated with the antisera, centrifuged through phthalate esters, and assayed in a gamma scintillation counter. Dose response and saturation curve analysis demonstrate the presence of Lewis a antigen on platelets from Lea+ donors. Furthermore, platelets from an Le(a-b-) donor incubated in Le (a+b-) plasma adsorb Lea antigen in a similar manner to red blood cells. The clinical significance of these antigens in platelet transfusion remains undefined.

  13. A NEW SYNTHETIC FUNCTIONALIZED ANTIGEN CARRIER

    NARCIS (Netherlands)

    DRIJFHOUT, JW; BLOEMHOFF, W

    A new synthetic functionalized antigen carrier is described. It consists of a core of seven branched lysine residues, of which each of the four N-terminal lysine residues contains two N-(S-acetylmercaptoacetyl)-glutamyl residues. After removal of the protecting S-acetyl groups affording eight thiol

  14. Non-lineage antigens: section report

    Czech Academy of Sciences Publication Activity Database

    Horváth, Ondřej; Drbal, Karel; Angelisová, Pavla; Hilgert, Ivan; Hořejší, Václav

    2005-01-01

    Roč. 236, 1-2 (2005), s. 42-47 ISSN 0008-8749 R&D Projects: GA MŠk(CZ) 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : non-lineage antigens * cytofluorometry * CD molecules Subject RIV: EC - Immunology Impact factor: 1.558, year: 2005

  15. Carcinoembryonic antigen and head and neck cancer

    NARCIS (Netherlands)

    Laarman, D. A.; van Kamp, G. J.; Balm, A. J.; Braakhuis, B. J.; Snow, G. B.

    1991-01-01

    Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated

  16. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  17. Cloning, expression, purification and antigenic evaluation of ...

    African Journals Online (AJOL)

    Streptococcus pyogenes produce an extracellular hyaluronidase which is associated with the spread of the organism during infection. Enzyme hyaluronidase is capable of degrading hyaluronic acid. The aim of the present study was to clone and express antigenic regions of the hylA of S.pyogenes in Escherichia coli.

  18. Antigenic and genetic variability of human metapneumoviruses

    NARCIS (Netherlands)

    S. Herfst (Sander); L. Sprong; P.A. Cane; E. Forleo-Neto; A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); R.L. de Swart (Rik); B.G. van den Hoogen (Bernadette)

    2004-01-01

    textabstractHuman metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For

  19. Defined carriers for synthetic antigens: Hinge Peptides

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Jan; Niederhafner, Petr; Gut, Vladimír; Hulačová, Hana; Maloň, Petr

    2005-01-01

    Roč. 29, č. 1 (2005), s. 68 ISSN 0939-4451. [International Congress on Amino Acids and Proteins /9./. 08.08.2005-12.08.2005, Gert Lubec] R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : synthetic carrier * antigen * hinge peptide Subject RIV: CC - Organic Chemistry

  20. Antigenic characterisation of lyssaviruses in South Africa

    Directory of Open Access Journals (Sweden)

    Ernest Ngoepe

    2014-09-01

    Full Text Available There are at least six Lyssavirus species that have been isolated in Africa, which include classical rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus. In this retrospective study, an analysis of the antigenic reactivity patterns of lyssaviruses in South Africa against a panel of 15 anti-nucleoprotein monoclonal antibodies was undertaken. A total of 624 brain specimens, collected between 2005 and 2009, confirmed as containing lyssavirus antigen by direct fluorescent antibody test, were subjected to antigenic differentiation. The lyssaviruses were differentiated into two species, namely rabies virus (99.5% and Mokola virus (0.5%. Furthermore, rabies virus was further delineated into two common rabies biotypes in South Africa: canid and mongoose. Initially, it was found that the canid rabies biotype had two reactivity patterns; differential staining was observed with just one monoclonal antibody. This difference was likely to have been an artefact related to sample quality, as passage in cell culture restored staining. Mongoose rabies viruses were more heterogeneous, with seven antigenic reactivity patterns detected. Although Mokola viruses were identified in this study, prevalence and reservoir host species are yet to be established. These data demonstrate the usefulness of monoclonal antibody typing panels in lyssavirus surveillance with reference to emergence of new species or spread of rabies biotypes to new geographic zones.

  1. Evaluation of an Antigen-Antibody

    African Journals Online (AJOL)

    GB

    replication would lead to the production of various antigens. Today with BMT history of over 30 years, infection ... Study design: The study involved both retrospective and prospective laboratory-based analysis of ..... core protein of a molecular mass 19 x 103 Da, one picogram (pg) of virus core corresponds to 1.3 x. 105 HCV ...

  2. Lysine acetylation of major Chlamydia trachomatis antigens

    Directory of Open Access Journals (Sweden)

    Jelena Mihailovic

    2016-03-01

    Our data show that important Ct antigens could be post-translationally modified by acetylation of lysine residues at multiple sites. Further studies are needed to investigate total acetylome of Ct and the impact PTMs might have on Ct biology and pathogenicity.

  3. Identification of immunogenic hot spots within plum pox potyvirus capsid protein for efficient antigen presentation.

    Science.gov (United States)

    Fernández-Fernández, M Rosario; Martínez-Torrecuadrada, Jorge L; Roncal, Fernando; Domínguez, Elvira; García, Juan Antonio

    2002-12-01

    PEPSCAN analysis has been used to characterize the immunogenic regions of the capsid protein (CP) in virions of plum pox potyvirus (PPV). In addition to the well-known highly immunogenic N- and C-terminal domains of CP, regions within the core domain of the protein have also shown high immunogenicity. Moreover, the N terminus of CP is not homogeneously immunogenic, alternatively showing regions frequently recognized by antibodies and others that are not recognized at all. These results have helped us to design efficient antigen presentation vectors based on PPV. As predicted by PEPSCAN analysis, a small displacement of the insertion site in a previously constructed vector, PPV-gamma, turned the derived chimeras into efficient immunogens. Vectors expressing foreign peptides at different positions within a highly immunogenic region (amino acids 43 to 52) in the N-terminal domain of CP were the most effective at inducing specific antibody responses against the foreign sequence.

  4. Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens

    DEFF Research Database (Denmark)

    Ofori, Michael F; Dodoo, Daniel; Staalsoe, Trine

    2002-01-01

    In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area......, clinical disease is caused mainly by parasites expressing VSA not recognized by preexisting VSA-specific antibodies in that child. Such malaria episodes are known to cause an increase in agglutinating antibodies specifically recognizing VSA expressed by the parasite isolate causing the illness, whereas...... antibody responses to other parasite isolates are relatively unaffected. However, the detailed kinetics of this VSA antibody acquisition are unknown and hence were the aim of this study. We show that P. falciparum malaria in Ghanaian children generally caused a rapid and sustained increase in variant...

  5. Antigenic modules in the N-terminal S1 region of the transmissible gastroenteritis virus spike protein

    Science.gov (United States)

    Reguera, Juan; Ordoño, Desiderio; Santiago, César; Enjuanes, Luis

    2011-01-01

    The N-terminal S1 region of the transmissible gastroenteritis virus (TGEV) spike (S) glycoprotein contains four antigenic sites (C, B, D and A, from the N- to the C-terminal end) and is engaged in host-cell receptor recognition. The most N-terminal portion of the S1 region, which comprises antigenic sites C and B, is needed for the enteric tropism of TGEV, whereas the major antigenic site A at the C-terminal moiety is required for both respiratory and enteric cell tropism, and is engaged in recognition of the aminopeptidase N (APN) receptor. This study determined the kinetics for binding of a soluble S1 protein to the APN protein. Moreover, the S1 region of the TGEV S protein was dissected, with the aim of identifying discrete modules displaying unique antigenic sites and receptor-binding functions. Following protease treatments and mammalian cell expression methods, four modules or domains (D1–D4) were defined at the S1 region. Papain treatment identified an N-terminal domain (D1) resistant to proteolysis, whereas receptor binding defined a soluble and functional APN receptor-binding domain (D3). This domain was recognized by neutralizing antibodies belonging to the antigenic site A and therefore could be used as an immunogen for the prevention of viral infection. The organization of the four modules in the S1 region of the TGEV S glycoprotein is discussed. PMID:21228126

  6. Characterizing Antibody Responses to Plasmodium vivax and Plasmodium falciparum Antigens in India Using Genome-Scale Protein Microarrays.

    Directory of Open Access Journals (Sweden)

    Swapna Uplekar

    2017-01-01

    Full Text Available Understanding naturally acquired immune responses to Plasmodium in India is key to improving malaria surveillance and diagnostic tools. Here we describe serological profiling of immune responses at three sites in India by probing protein microarrays consisting of 515 Plasmodium vivax and 500 Plasmodium falciparum proteins with 353 plasma samples. A total of 236 malaria-positive (symptomatic and asymptomatic plasma samples and 117 malaria-negative samples were collected at three field sites in Raurkela, Nadiad, and Chennai. Indian samples showed significant seroreactivity to 265 P. vivax and 373 P. falciparum antigens, but overall seroreactivity to P. vivax antigens was lower compared to P. falciparum antigens. We identified the most immunogenic antigens of both Plasmodium species that were recognized at all three sites in India, as well as P. falciparum antigens that were associated with asymptomatic malaria. This is the first genome-scale analysis of serological responses to the two major species of malaria parasite in India. The range of immune responses characterized in different endemic settings argues for targeted surveillance approaches tailored to the diverse epidemiology of malaria across the world.

  7. Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responses.

    Directory of Open Access Journals (Sweden)

    Warren L Denning

    2011-02-01

    Full Text Available Harnessing the ability of cytotoxic T lymphocytes (CTLs to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4-6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS.

  8. Increasing vaccine potency through exosome antigen targeting.

    Science.gov (United States)

    Hartman, Zachary C; Wei, Junping; Glass, Oliver K; Guo, Hongtao; Lei, Gangjun; Yang, Xiao-Yi; Osada, Takuya; Hobeika, Amy; Delcayre, Alain; Le Pecq, Jean-Bernard; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

    2011-11-21

    While many tumor associated antigens (TAAs) have been identified in human cancers, efforts to develop efficient TAA "cancer vaccines" using classical vaccine approaches have been largely ineffective. Recently, a process to specifically target proteins to exosomes has been established which takes advantage of the ability of the factor V like C1C2 domain of lactadherin to specifically address proteins to exosomes. Using this approach, we hypothesized that TAAs could be targeted to exosomes to potentially increase their immunogenicity, as exosomes have been demonstrated to traffic to antigen presenting cells (APC). To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin. We found that these C1C2 fusion proteins had enhanced expression in exosomes in vitro. We saw significant improvement in antigen specific immune responses to each of these antigens in naïve and tolerant transgenic animal models and could further demonstrate significantly enhanced therapeutic anti-tumor effects in a human HER2+ transgenic animal model. These findings demonstrate that the mode of secretion and trafficking can influence the immunogenicity of different human TAAs, and may explain the lack of immunogenicity of non-mutated TAAs found in cancer patients. They suggest that exosomal targeting could enhance future anti-tumor vaccination protocols. This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. 75 FR 9953 - Definition and Requirements for a Nationally Recognized Testing Laboratory (NRTL); Extension of...

    Science.gov (United States)

    2010-03-04

    ...] Definition and Requirements for a Nationally Recognized Testing Laboratory (NRTL); Extension of the Office of Management and Budget's (OMB) Approval of Information Collection (Paperwork) Requirements AGENCY... its Regulation on the Definition and Requirements for a Nationally Recognized Testing Laboratory (29...

  10. Identification of Novel Breast Cancer Antigens Using Phage Antibody Libraries

    National Research Council Canada - National Science Library

    Marks, James

    2002-01-01

    The purpose of this project is to use phage antibody libraries to identify novel breast tumor antigens The antibodies could be used for breast cancer immunotherapy and the antigens could be used as cancer vaccines...

  11. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt

    2011-01-01

    En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner.......En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner....

  12. Dengue viruses cluster antigenically but not as discrete serotypes

    NARCIS (Netherlands)

    L. Katzelnick (Leah); J.M. Fonville (Judith); G.D. Gromowski (Gregory D.); J.B. Arriaga (Jose Bustos); A. Green (Angela); S.L. James (Sarah ); L. Lau (Louis); M. Montoya (Magelda); C. Wang (Chunling); L.A. Van Blargan (Laura A.); C.A. Russell (Colin); H.M. Thu (Hlaing Myat); T.C. Pierson (Theodore C.); P. Buchy (Philippe); J.G. Aaskov (John G.); J.L. Muñoz-Jordán (Jorge L.); N. Vasilakis (Nikos); R.V. Gibbons (Robert V.); R.B. Tesh (Robert B.); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); A. Durbin (Anna); C.P. Simmons (Cameron P.); E.C. Holmes (Edward C.); E. Harris (Eva); S.S. Whitehead (Stephen S.); D.J. Smith (Derek James)

    2015-01-01

    textabstractThe four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution.We scharacterized antigenic diversity

  13. Recognize and classify pneumoconiosis; Pneumokoniosen erkennen und klassifizieren

    Energy Technology Data Exchange (ETDEWEB)

    Hering, K.G.; Hofmann-Preiss, K. [Klinikum Westfalen, Knappschaftskrankenhaus, Dortmund (Germany)

    2014-12-15

    In the year 2012, out of the 10 most frequently recognized occupational diseases 6 were forms of pneumoconiosis. With respect to healthcare and economic aspects, silicosis and asbestos-associated diseases are of foremost importance. The latter are to be found everywhere and are not restricted to large industrial areas. Radiology has a central role in the diagnosis and evaluation of occupational lung disorders. In cases of known exposure mainly to asbestos and quartz, the diagnosis of pneumoconiosis, with few exceptions will be established primarily by the radiological findings. As these disorders are asymptomatic for a long time they are quite often detected as incidental findings in examinations for other reasons. Therefore, radiologists have to be familiar with the pattern of findings of the most frequent forms of pneumoconiosis and the differential diagnoses. For reasons of equal treatment of the insured a quality-based, standardized performance, documentation and evaluation of radiological examinations is required in preventive procedures and evaluations. Above all, a standardized low-dose protocol has to be used in computed tomography (CT) examinations, although individualized concerning the dose, in order to keep radiation exposure as low as possible for the patient. The International Labour Office (ILO) classification for the coding of chest X-rays and the international classification of occupational and environmental respiratory diseases (ICOERD) classification used since 2004 for CT examinations meet the requirements of the insured and the occupational insurance associations as a means of reproducible and comparable data for decision-making. (orig.) [German] Im Jahr 2012 waren 6 der 10 am haeufigsten anerkannten Berufskrankheiten Pneumokoniosen. Gesundheitspolitisch und oekonomisch stehen dabei die Silikose und asbestassoziierte Erkrankungen im Vordergrund. Insbesondere Letztere treten ubiquitaer auf und sind nicht an grosse Industriestandorte gebunden

  14. Swine Leukocyte Antigen Class II Is a Xenoantigen.

    Science.gov (United States)

    Ladowski, Joseph M; Reyes, Luz M; Martens, Gregory R; Butler, James R; Wang, Zheng-Yu; Eckhoff, Devin E; Tector, Matthew; Tector, A Joseph

    2018-02-01

    Over 130 000 patients in the United States alone need a lifesaving organ transplant. Genetically modified porcine organs could resolve the donor organ shortage, but human xenoreactive antibodies destroy pig cells and are the major barrier to clinical application of xenotransplantation. The objective of this study was to determine whether waitlisted patients possess preformed antibodies to swine leukocyte antigen (SLA) class II, homologs of the class II HLA. Sera from people currently awaiting solid organ transplant were tested for IgG binding to class II SLA proteins when expressed on mammalian cells. Pig fibroblasts were made positive by transfection with the class II transactivator. As a second expression system, transgenes encoding the alpha and beta chains of class II SLA were transfected into human embryonic kidney cells. Human sera containing IgG specific for class II HLA molecules exhibited greater binding to class II SLA positive cells than to SLA negative cells. Sera lacking antibodies against class II HLA showed no change in binding regardless of the presence of class II SLA. These antibodies could recognize either SLA-DR or SLA-DQ complexes. Class II SLA proteins may behave as xenoantigens for people with humoral immunity toward class II HLA molecules.

  15. Formaldehyde scavengers function as novel antigen retrieval agents

    Science.gov (United States)

    Vollert, Craig T.; Moree, Wilna J.; Gregory, Steven; Bark, Steven J.; Eriksen, Jason L.

    2015-01-01

    Antigen retrieval agents improve the detection of formaldehyde-fixed proteins, but how they work is not well understood. We demonstrate that formaldehyde scavenging represents a key characteristic associated with effective antigen retrieval; under controlled temperature and pH conditions, scavenging improves the typical antigen retrieval process through reversal of formaldehyde-protein adduct formation. This approach provides a rational framework for the identification and development of more effective antigen retrieval agents. PMID:26612041

  16. 46 CFR 30.10-57 - Recognized classification society-TB/ALL.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Recognized classification society-TB/ALL. 30.10-57 Section 30.10-57 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-57 Recognized classification society—TB/ALL. The term recognized classification society...

  17. Identification of two epitopes on the dengue 4 virus capsid protein recognized by a serotype-specific and a panel of serotype-cross-reactive human CD4+ cytotoxic T-lymphocyte clones.

    Science.gov (United States)

    Gagnon, S J; Zeng, W; Kurane, I; Ennis, F A

    1996-01-01

    We analyzed the CD4+ T-lymphocyte response of a donor who had received an experimental live-attenuated dengue 4 virus (D4V) vaccine. Bulk culture proliferative responses of peripheral blood mononuclear cells (PBMC) to noninfectious dengue virus (DV) antigens showed the highest proliferation to D4V antigen, with lesser, cross-reactive proliferation to D2V antigen. We established CD4+ cytotoxic T-lymphocyte clones (CTL) by stimulation with D4 antigen. Using recombinant baculovirus antigens, we identified seven CTL clones that recognized D4V capsid protein. Six of these CTL clones were cross-reactive between D2 and D4, and one clone was specific for D4. Using synthetic peptides, we found that the D4V-specific CTL clone recognized an epitope between amino acids (aa) 47 and 55 of the capsid protein, while the cross-reactive CTL clones each recognized epitopes in a separate location, between aa 83 and 92, which is conserved between D2V and D4V. This region of the capsid protein induced a variety of CD4+ T-cell responses, as indicated by the fact that six clones which recognized a peptide spanning this region showed heterogeneity in their recognition of truncations of this same peptide. The bulk culture response of the donor's PBMC to the epitope peptide spanning aa 84 to 92 was also examined. Peptides containing this epitope induced proliferation of the donor's PBMC in bulk culture, but peptides not containing the entire epitope did not induce proliferation. Also, PBMC stimulated in bulk culture with noninfectious D4V antigen lysed autologous target cells pulsed with peptides containing aa 84 to 92. These results indicate that this donor exhibits memory CD4+ T-cell responses directed against the DV capsid protein and suggest that the response to the capsid protein is dominant not only in vitro at the clonal level but in bulk culture responses as well. Since previous studies have indicated that the CTL responses to DV infection seem to be directed mainly against the

  18. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this product...

  19. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, Ninke; Daemen, Toos; Helfrich, Wijnand; Boezen, H. Marike; Cohlen, Ben J.; Melief, Cornelis J. M.; Nijman, Hans W.

    2014-01-01

    BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess the feasibility of antigen-specific

  20. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, N.; Daemen, T.; Helfrich, W.; Boezen, H. M.; Cohlen, B. J.; Melief, Cornelis; Nijman, H. W.

    2010-01-01

    BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce a tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess feasibility of antigen-specific

  1. Role of HLA antigens in Rh (D) alloimmunized pregnant women ...

    Indian Academy of Sciences (India)

    Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen ...

  2. Use of magnetic nanobeads to study intracellular antigen processing

    Energy Technology Data Exchange (ETDEWEB)

    Perrin-Cocon, Laure A.; Chesne, Serge; Pignot-Paintrand, Isabelle; Marche, Patrice N.; Villiers, Christian L. E-mail: christian.villiers@cea.fr

    2001-07-01

    Magnetic nanobeads were covalently linked to antigens and used as a tool to simultaneously follow their intracellular transport into the cells and specifically purify the intracellular compartments implicated in antigen processing. The protein content of these vesicles was analysed by 2D-electrophoresis. Furthermore, nanobeads allowed intracellular localisation of the antigen in electron and fluorescence microscopy.

  3. Use of magnetic nanobeads to study intracellular antigen processing

    International Nuclear Information System (INIS)

    Perrin-Cocon, Laure A.; Chesne, Serge; Pignot-Paintrand, Isabelle; Marche, Patrice N.; Villiers, Christian L.

    2001-01-01

    Magnetic nanobeads were covalently linked to antigens and used as a tool to simultaneously follow their intracellular transport into the cells and specifically purify the intracellular compartments implicated in antigen processing. The protein content of these vesicles was analysed by 2D-electrophoresis. Furthermore, nanobeads allowed intracellular localisation of the antigen in electron and fluorescence microscopy

  4. Distribution of a centrosomal antigen during morphogenesis in the ciliated protozoan Euplotes.

    Science.gov (United States)

    Fleury, A; Lemullois, M; Coffe, G

    1998-07-01

    Ciliates assemble basal bodies in great number at many stages of the life-cycle. In order to understand their assembly mechanisms, we screened a library of monoclonal antibodies directed against pericentriolar material. One of these antibodies, CTR210, was used previously to follow steps of this assembly process: in Paraurostyla, new basal bodies appear along a scaffold of linear structures recognized by this antibody. The very unusual behavior of this antigen deserved confirmation in other species. In the present study, we show by immunofluorescence that, in another phylogenetically very distant species, Euplotes, basal bodies are assembled in the same pathway during division. In addition, this antibody recognizes a filamentous ring located at the division furrow and linking many basal body assemblages. By cell fractionation and cytoskeletal extraction, we obtained fractions enriched in basal bodies and associated material. Such fractions still display a high complexity in protein composition. These fractions were used to characterize the main target of the antibody as a doublet of 45 kDa. These results confirm previous results in terms of functionality of the protein recognized by the antibody, but raise new questions in terms of the assignment of the recognized protein to the HSP70 family as hypothesized previously.

  5. Use of flow cytometry to identify monoclonal antibodies that recognize conserved epitopes on orthologous leukocyte differentiation antigens in goats, llamas, and rabbits

    Czech Academy of Sciences Publication Activity Database

    Davis, W. C.; Drbal, Karel; El-Aziz, A.; Mosaad, A.E.; Elbagory, A.R.M.; TIbary, A.; Barrington, G.M.; Park, Y.H.; Hamilton, M.J.

    2007-01-01

    Roč. 119, 1-2 (2007), s. 123-130 ISSN 0165-2427 Institutional research plan: CEZ:AV0Z50520514 Keywords : flow cytometry * monoclonal antibodies * leukocyte s Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.957, year: 2007

  6. Inability to induce consistent T-cell responses recognizing conserved regions within HIIV-1 antigens: a potential mechanism for lack of vaccine efficacy in the step study

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory; Szinger, James [Los Alamos National Laboratory

    2009-01-01

    T cell based vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a high probability of matching the epitope induced by vaccination with the infecting viral strain. We compared the frequency and specificity of the CTL epitopes elicited by the replication defective AdS gag/pol/nef vaccine used in the STEP trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. On average vaccination elicited only one epitope per gene. Importantly, the highly conserved epitopes in gag, pol, and nef (> 80% of strains in the current collection of the Los Alamos database [www.hiv.lanl.gov]) were rarely elicited by vaccination. Moreover there was a statistically significant skewing of the T cell response to relative variable epitopes of each gene; only 20% of persons possessed > 3 T cell responses to epitopes likely to be found in circulating strains in the CladeB populations in which the Step trial was conducted. This inability to elicit T cell responses likely to be found in circulating viral strains is a likely factor in the lack of efficacy of the vaccine utilized in the STEP trial. Modeling of the epitope specific responses elicited by vaccination, we project that a median of 8-10 CD8+ T cell epitopes are required to provide >80% likelihood of eliciting at least 3 CD8+ T cell epitopes that would be found on a circulating population of viruses. Development of vaccine regimens which elicit either a greater breadth of responses or elicit responses to conserved regions of the HIV-1 genome are needed to fully evaluate the concept of whether induction of T cell immunity can alter HIV-1 in vivo.

  7. Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide modulate cytokine responses in melanoma-specific T cells

    DEFF Research Database (Denmark)

    Nielsen, M B; Kirkin, A F; Loftus, D

    2000-01-01

    enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-gamma and significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-1(27-35), also enhances the tyrosine...... phosphorylation response in anti-MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2-like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma...

  8. Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

    NARCIS (Netherlands)

    van Gisbergen, Klaas P. J. M.; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2005-01-01

    Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal

  9. The cycling and distribution of PER-like antigen in relation to neurons recognized by the antisera to PTTH and EH in Thermobia domestica

    Czech Academy of Sciences Publication Activity Database

    Závodská, Radka; Šauman, Ivo; Sehnal, František

    2003-01-01

    Roč. 33, - (2003), s. 1227-1238 ISSN 0965-1748 R&D Projects: GA ČR GA204/01/0404 Institutional research plan: CEZ:AV0Z5007907 Keywords : circadian clock * period * PTTH Subject RIV: ED - Physiology Impact factor: 2.358, year: 2003

  10. Sera of Chagasic patients react with antigens from the tomato parasite Phytomonas serpens

    Directory of Open Access Journals (Sweden)

    Viviane K Graça-de Souza

    2010-01-01

    Full Text Available The genus Phytomonas comprises trypanosomatids that can parasitize a broad range of plant species. These fagellates can cause diseases in some plant families with a wide geographic distribution, which can result in great economic losses. We have demonstrated previously that Phytomonas serpens 15T, a tomato trypanosomatid, shares antigens with Trypanosoma cruzi, the agent of human Chagas disease. Herein, two-dimensional gel electrophoresis (2-DE and mass spectrometry (MS were used to identify proteins of P. serpens 15T that are recognized by sera from patients with Chagas disease. After 2D-electrophoresis of whole-cell lysates, 31 peptides were selected and analyzed by tandem mass spectrometry. Twenty-eight polypeptides were identifed, resulting in 22 different putative proteins. The identifed proteins were classifed into 8 groups according to biological process, most of which were clustered into a cellular metabolic process category. These results generated a collection of proteins that can provide a starting point to obtain insights into antigenic cross reactivity among trypanosomatids and to explore P. serpens antigens as candidates for vaccine and immunologic diagnosis studies.

  11. Sera of chagasic patients react with antigens from the tomato parasite Phytomonas serpens.

    Science.gov (United States)

    Graça-de Souza, Viviane K; Monteiro-Góes, Viviane; Manque, Patrício; Souza, Tatiana A C B; Corrêa, Paulo R C; Buck, Gregory A; Ávila, Andréa R; Yamauchi, Lucy M; Pinge-Filho, Phileno; Goldenberg, Samuel; Krieger, Marco A; Yamada-Ogatta, Sueli F

    2010-01-01

    The genus Phytomonas comprises trypanosomatids that can parasitize a broad range of plant species. These flagellates can cause diseases in some plant families with a wide geographic distribution, which can result in great economic losses. We have demonstrated previously that Phytomonas serpens 15T, a tomato trypanosomatid, shares antigens with Trypanosoma cruzi, the agent of human Chagas disease. Herein, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to identify proteins of P. serpens 15T that are recognized by sera from patients with Chagas disease. After 2D-electrophoresis of whole-cell lysates, 31 peptides were selected and analyzed by tandem mass spectrometry. Twenty-eight polypeptides were identified, resulting in 22 different putative proteins. The identified proteins were classified into 8 groups according to biological process, most of which were clustered into a cellular metabolic process category. These results generated a collection of proteins that can provide a starting point to obtain insights into antigenic cross reactivity among trypanosomatids and to explore P. serpens antigens as candidates for vaccine and immunologic diagnosis studies.

  12. Heterologous protein secretion in Lactococcus lactis: a novel antigen delivery system

    Directory of Open Access Journals (Sweden)

    Langella P.

    1999-01-01

    Full Text Available Lactic acid bacteria (LAB are Gram-positive bacteria and are generally regarded as safe (GRAS organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV epitope-protein fusion (BCV-Nuc. BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.

  13. Design and development of therapies using chimeric antigen receptor-expressing T cells.

    Science.gov (United States)

    Dotti, Gianpietro; Gottschalk, Stephen; Savoldo, Barbara; Brenner, Malcolm K

    2014-01-01

    Investigators developed chimeric antigen receptors (CARs) for expression on T cells more than 25 years ago. When the CAR is derived from an antibody, the resultant cell should combine the desirable targeting features of an antibody (e.g. lack of requirement for major histocompatibility complex recognition, ability to recognize non-protein antigens) with the persistence, trafficking, and effector functions of a T cell. This article describes how the past two decades have seen a crescendo of research which has now begun to translate these potential benefits into effective treatments for patients with cancer. We describe the basic design of CARs, describe how antigenic targets are selected, and the initial clinical experience with CAR-T cells. Our review then describes our own and other investigators' work aimed at improving the function of CARs and reviews the clinical studies in hematological and solid malignancies that are beginning to exploit these approaches. Finally, we show the value of adding additional engineering features to CAR-T cells, irrespective of their target, to render them better suited to function in the tumor environment, and discuss how the safety of these heavily modified cells may be maintained. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies

    DEFF Research Database (Denmark)

    Salomonsen, J; Skjødt, K; Crone, M

    1987-01-01

    Mouse monoclonal antibodies with B-G antigen (major histocompatibility complex class IV) specificity were obtained after immunization with erythrocytes or partially purified B-G antigen. The specificities of the hybridoma antibodies were determined by precipitation of B-G antigens from 125I-label...

  15. Role of 30 kDa antigen of enteric bacterial pathogens as a possible arthritogenic factor in post-dysenteric reactive arthritis

    Directory of Open Access Journals (Sweden)

    Malkit Singh

    2013-01-01

    Full Text Available Background: Reactive arthritis (ReA/Reiter′s syndrome (RS may be caused as a sequel of infections caused by enteric bacterial pathogens, although the mechanisms through, which different pathogens cause similar disease are not clear. Aim: This study was done to look for the presence and role of any common bacterial antigen among the pathogens isolated from such patients. Materials and Methods: A total of 51 patients of ReA and 75 controls (three groups of 25 subjects each: Group 1: Patients who did not develop arthritic complications within 3 months after bacillary dysentery/diarrhea; Group 2: Patients with other arthritic diseases and Group 3: Normal healthy subjects were included. The isolated enteric pathogens were tested to detect the immunodominant antigens. Results and Conclusions: A common 30 kDa antigen was found to be specifically present among seven arthritogenic enteric bacterial strains belonging to three genera, Salmonella, Shigella and Hafnia. Post-dysenteric ReA patients′ sera show higher levels of immunoglobulin G, immunoglobulin M and immunoglobulin A antibodies against this antigen as compared to the controls. Lymphocytes of ReA patients recognize this antigen, proliferate and produce interleukin-2 in response to this antigen more than the lymphocytes of controls. 30 kDa antigen may be a common arthritogenic factor associated with post-dysenteric ReA/RS. The association of Hafnia alvei with post-dysenteric ReA is described for the first time. Four cases of mycobacterial ReA had an association with this antigen, suggesting that the arthritogenic antigen of mycobacteria and enteric bacteria may be of a similar nature.

  16. Generation of human scFvs antibodies recognizing a prion protein epitope expressed on the surface of human lymphoblastoid cells

    Directory of Open Access Journals (Sweden)

    Imperiale Valentina

    2007-07-01

    Full Text Available Abstract Background A hallmark of prion disease is the transformation of normal cellular prion protein (PrPc into an infectious disease-associated isoform, (PrPsc. Anti-prion protein monoclonal antibodies are invaluable for structure-function studies of PrP molecules. Furthermore recent in vitro and in vivo studies indicate that anti-PrP monoclonal antibodies can prevent the incorporation of PrPc into propagating prions. In the present article, we show two new human phage antibodies, isolated on recombinant hamster prion protein (rHaPrP. Results We adopted an antibody phage display strategy to isolate specific human antibodies directed towards rHaPrP which has been used as a bait for panning the synthetic ETH-2 antibody phage library. Two phage antibodies clones named MA3.B4 and MA3.G3 were isolated and characterized under genetic biochemical and immunocytochemical aspects. The clones were found to recognize the prion protein in ELISA studies. In flow-cytometry studies, these human single chain Fragment variable (scFv phage-antibodies show a well defined pattern of reactivity on human lymphoblastoid and myeloid cells. Conclusion Sequence analysis of the gene encoding for the antibody fragments and antigen recognition patterns determined by flow-cytometry analysis indicate that the isolated scFvs recognize novel epitopes in the PrPc molecule. These new anti PrPc human antibodies are unique reagents for prion protein detection and may represent a biologic platform to develop new reagents to treat PrPsc associated disease.

  17. Gag Protein Epitopes Recognized by CD4+ T-Helper Lymphocytes from Equine Infectious Anemia Virus-Infected Carrier Horses

    Science.gov (United States)

    Lonning, S. M.; Zhang, W.; McGuire, T. C.

    1999-01-01

    Antigen-specific T-helper (Th) lymphocytes are critical for the development of antiviral humoral responses and the expansion of cytotoxic T lymphocytes (CTL). Identification of relevant Th lymphocyte epitopes remains an important step in the development of an efficacious subunit peptide vaccine against equine infectious anemia virus (EIAV), a naturally occurring lentivirus of horses. This study describes Th lymphocyte reactivity in EIAV carrier horses to two proteins, p26 and p15, encoded by the relatively conserved EIAV gag gene. Using partially overlapping peptides, multideterminant and possibly promiscuous epitopes were identified within p26. One peptide was identified which reacted with peripheral blood mononuclear cells (PBMC) from all five EIAV-infected horses, and three other peptides were identified which reacted with PBMC from four of five EIAV-infected horses. Four additional peptides containing both CTL and Th lymphocyte epitopes were also identified. Multiple epitopes were recognized in a region corresponding to the major homology region of the human immunodeficiency virus, a region with significant sequence similarity to other lentiviruses including simian immunodeficiency virus, puma lentivirus, feline immunodeficiency virus, Jembrana disease virus, visna virus, and caprine arthritis encephalitis virus. PBMC reactivity to p15 peptides from EIAV carrier horses also occurred. Multiple p15 peptides were shown to be reactive, but not all infected horses had Th lymphocytes recognizing p15 epitopes. The identification of peptides reactive with PBMC from outbred horses, some of which encoded both CTL and Th lymphocyte epitopes, should contribute to the design of synthetic peptide or recombinant vector vaccines for EIAV. PMID:10196322

  18. Generation of human scFvs antibodies recognizing a prion protein epitope expressed on the surface of human lymphoblastoid cells

    Science.gov (United States)

    Flego, Michela; Ascione, Alessandro; Zamboni, Silvia; Dupuis, Maria L; Imperiale, Valentina; Cianfriglia, Maurizio

    2007-01-01

    Background A hallmark of prion disease is the transformation of normal cellular prion protein (PrPc) into an infectious disease-associated isoform, (PrPsc). Anti-prion protein monoclonal antibodies are invaluable for structure-function studies of PrP molecules. Furthermore recent in vitro and in vivo studies indicate that anti-PrP monoclonal antibodies can prevent the incorporation of PrPc into propagating prions. In the present article, we show two new human phage antibodies, isolated on recombinant hamster prion protein (rHaPrP). Results We adopted an antibody phage display strategy to isolate specific human antibodies directed towards rHaPrP which has been used as a bait for panning the synthetic ETH-2 antibody phage library. Two phage antibodies clones named MA3.B4 and MA3.G3 were isolated and characterized under genetic biochemical and immunocytochemical aspects. The clones were found to recognize the prion protein in ELISA studies. In flow-cytometry studies, these human single chain Fragment variable (scFv) phage-antibodies show a well defined pattern of reactivity on human lymphoblastoid and myeloid cells. Conclusion Sequence analysis of the gene encoding for the antibody fragments and antigen recognition patterns determined by flow-cytometry analysis indicate that the isolated scFvs recognize novel epitopes in the PrPc molecule. These new anti PrPc human antibodies are unique reagents for prion protein detection and may represent a biologic platform to develop new reagents to treat PrPsc associated disease. PMID:17605808

  19. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However......, the barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce...... this complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  20. Radionuclide-labelled antigens in serological epidemiology

    International Nuclear Information System (INIS)

    Felsenfeld, O.; Parrott, M.W.

    1977-01-01

    The feasibility of tests using radionuclide-labelled antigens in serological surveys was studied, with particular attention to the likely availability of facilities and personnel in the tropics and arctics, where measurements may be disturbed by climatic influences. The methodology required was to be simple, rapid and suitable for examining large numbers of sera, as for epidemological surveys. In the introduction, limitations of labelled antigen tests are discussed, the choice of radionuclide and measurement methods, test procedures and evaluation of results. Collection, preservation and shipment of speciments (serum, faeces, cerebrospinal fluid, sputum, etc.) are described. Experiments with bacteria and bacterial toxins (Enterobacteriaceae, vibrios, staphylococci, meningococci, etc.), with protozoa and metazoa (Entamoeba hystolytica, Schistosoma mansoni, Trypanosoma cruzi, Plasmodia and other parasites), with viruses (vaccinia, adeno-, polio-, and influenza viruses, etc.), and with fungi are discussed