Mathematical Models for Immunology: Current State of the Art and Future Research Directions.

PubMed

Eftimie, Raluca; Gillard, Joseph J; Cantrell, Doreen A

2016-10-01

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years.

Global Regulatory T-Cell Research from 2000 to 2015: A Bibliometric Analysis

PubMed Central

Zongyi, Yin; Dongying, Chen

2016-01-01

We aimed to analyze the global scientific output of regulatory T-cell (Treg) research and built a model to qualitatively and quantitatively evaluate publications from 2000 to 2015. Data were obtained from the Web of Science Core Collection (WoSCC) of Thomson Reuters on January 1, 2016. The bibliometric method and Citespace III were used to analyze authors, journals, publication outputs, institutions, countries, research areas, research hotspots, and trends. In total, we identified 35,741 publications on Treg research from 2000 to 2015, and observed that the annual publication rate increased with time. The Journal of Immunology published the highest number of articles, the leading country was the USA, and the leading institute was Harvard University. Sakaguchi, Hori, Fontenot, and Wang were the top authors in Treg research. Immunology accounted for the highest number of publications, followed by oncology, experimental medicine, cell biology, and hematology. Keyword analysis indicated that autoimmunity, inflammation, cytokine, gene expression, foxp3, and immunotherapy were the research hotspots, whereas autoimmune inflammation, gene therapy, granzyme B, RORγt, and th17 were the frontiers of Treg research. This bibliometric analysis revealed that Treg-related studies are still research hotspots, and that Treg-related clinical therapies are the research frontiers; however, further study and collaborations are needed worldwide. Overall, our findings provide valuable information for the editors of immunology journals to identify new perspectives and shape future research directions. PMID:27611317

Deciphering the proteome of the in vivo diagnostic reagent “purified protein derivative” from Mycobacterium tuberculosis

PubMed Central

Cho, Yun Sang; Dobos, Karen M.; Prenni, Jessica; Yang, Hongliang; Hess, Ann; Rosenkrands, Ida; Andersen, Peter; Ryoo, Sung Weon; Bai, Gill-Han; Brennan, Michael J.; Izzo, Angelo; Bielefeldt-Ohmann, Helle; Belisle, John T.

2013-01-01

Purified protein derivative (PPD) has served as a safe and effective diagnostic reagent for 60 years and is the only broadly available material to diagnose latent tuberculosis infections. This reagent is also used as a standard control for a number of in vitro immunological assays. Nevertheless, the molecular composition and specific products that contribute to the extraordinary immunological reactivity of PPD are poorly defined. Here, a proteomic approach was applied to elucidate the gene products in the U.S. FDA standard PPD-S2. Many known M. tuberculosis T cell antigens were detected. Of significance, four heat shock proteins (GroES, GroEL2, HspX, and DnaK) dominated the composition of PPD. The chaperone activities and capacity of these proteins to influence immunological responses may explain the exquisite solubility and immunological potency of PPD. Spectral counting analysis of three separate PPD reagents revealed significant quantitative variances. Gross delayed type hypersensitivity (DTH) responses in M. tuberculosis infected guinea pigs were comparable among these PPD preparations; however, detailed histopathology of the DTH lesions exposed unique differences, which may be explained by the variability observed in the presence and abundance of early secretory system (esx) proteins. Variability in PPD reagents may explain differences in DTH responses reported among populations. PMID:22522804

Protective pathways against colitis mediated by appendicitis and appendectomy.

PubMed

Cheluvappa, R; Luo, A S; Palmer, C; Grimm, M C

2011-09-01

Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). Using a novel murine appendicitis model, we showed that AA protected against subsequent experimental colitis. To delineate genes/pathways involved in this protection, AA was performed and samples harvested from the most distal colon. RNA was extracted from four individual colonic samples per group (AA group and double-laparotomy control group) and each sample microarray analysed followed by gene-set enrichment analysis (GSEA). The gene-expression study was validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) of 14 selected genes across the immunological spectrum. Distal colonic expression of 266 gene-sets was up-regulated significantly in AA group samples (false discovery rates < 1%; P-value < 0·001). Time-course RT-PCR experiments involving the 14 genes displayed down-regulation over 28 days. The IBD-associated genes tnfsf10, SLC22A5, C3, ccr5, irgm, ptger4 and ccl20 were modulated in AA mice 3 days after surgery. Many key immunological and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. The down-regulation of 14 selected genes over 28 days after surgery indicates activation, repression or de-repression of these genes leading to downstream AA-conferred anti-colitis protection. Further analysis of these genes, profiles and biological pathways may assist in developing better therapeutic strategies in the management of intractable IBD. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Common Variable Immunodeficiency Caused by FANC Mutations.

PubMed

Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

2017-07-01

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

Re-evaluation of Sepharose-insulin as a tool for the study of insulin action.

PubMed Central

Kolb, H J; Renner, R; Hepp, K D; Weiss, L; Wieland, O H

1975-01-01

The biological activity of Sepharose-insulin in different assays in vitro, e.g., stimulation of glucose oxidation, lipogenesis, and antilipolysis and activation of pyruvate dehydrogenase (EC 1.2.4.1) activity, has been investigated. According to amino acid analysis, between 270 and 330 mug (6.9-8.2 U) of insulin were coupled per ml of packed beads. Related to the total insulin content, 0.2-0.7% of the insulin was biologically active. Comparable biological activity was observed with isolated fat cells and fat pad pieces. After incubation with tissue or cells, Sepharose-insulin particles were separated by centrifugation from the medium. The clear supernatant was assayed for biologically and immunologically reactive insulin and contained soluble insulin activity. A quantitative evaluation of the soluble biological and immunological insulin activity in the supernatant accounted for the total insulin activity of Sepharose-insulin. PMID:1054501

Fast multiclonal clusterization of V(D)J recombinations from high-throughput sequencing.

PubMed

Giraud, Mathieu; Salson, Mikaël; Duez, Marc; Villenet, Céline; Quief, Sabine; Caillault, Aurélie; Grardel, Nathalie; Roumier, Christophe; Preudhomme, Claude; Figeac, Martin

2014-05-28

V(D)J recombinations in lymphocytes are essential for immunological diversity. They are also useful markers of pathologies. In leukemia, they are used to quantify the minimal residual disease during patient follow-up. However, the full breadth of lymphocyte diversity is not fully understood. We propose new algorithms that process high-throughput sequencing (HTS) data to extract unnamed V(D)J junctions and gather them into clones for quantification. This analysis is based on a seed heuristic and is fast and scalable because in the first phase, no alignment is performed with germline database sequences. The algorithms were applied to TR γ HTS data from a patient with acute lymphoblastic leukemia, and also on data simulating hypermutations. Our methods identified the main clone, as well as additional clones that were not identified with standard protocols. The proposed algorithms provide new insight into the analysis of high-throughput sequencing data for leukemia, and also to the quantitative assessment of any immunological profile. The methods described here are implemented in a C++ open-source program called Vidjil.

Cloning of fox (Vulpes vulpes) Il2, Il6, Il10 and IFNgamma and analysis of their expression by quantitative RT-PCR in fox PBMC after in vitro stimulation by Concanavalin A.

PubMed

Rolland-Turner, Magali; Farré, Guillaume; Boué, Franck

2006-04-15

The immune response in the fox (Vulpes vulpes), despite the success of the oral rabies vaccine is not well characterised, and specific immunological tools are needed. A quantitative RT-PCR using SyBR Green to investigate fox cytokine expression after antigen PBMC in vitro re-stimulation is presented here. First, we cloned by homology with dog cytokine sequences the fox IL2, IL6, IL10, IFNgamma and a partial 18S sequence. Fox specific primers were then defined and used to set up a species-specific quantitative RT-PCR assay using SyBR Green and 18S housekeeping gene as internal standard. The technique was validated using total RNA from fox PBMC stimulated with a polyclonal activator, Concanavaline A.

Development of analytical methods for multiplex bio-assay with inductively coupled plasma mass spectrometry.

PubMed

Ornatsky, Olga I; Kinach, Robert; Bandura, Dmitry R; Lou, Xudong; Tanner, Scott D; Baranov, Vladimir I; Nitz, Mark; Winnik, Mitchell A

2008-01-01

Advances in the development of highly multiplexed bio-analytical assays with inductively coupled plasma mass spectrometry (ICP-MS) detection are discussed. Use of novel reagents specifically designed for immunological methods utilizing elemental analysis is presented. The major steps of method development, including selection of elements for tags, validation of tagged reagents, and examples of multiplexed assays, are considered in detail. The paper further describes experimental protocols for elemental tagging of antibodies, immunostaining of live and fixed human leukemia cells, and preparation of samples for ICP-MS analysis. Quantitative analysis of surface antigens on model cell lines using a cocktail of seven lanthanide labeled antibodies demonstrated high specificity and concordance with conventional immunophenotyping.

Defining immunological dysfunction in sepsis: A requisite tool for precision medicine.

PubMed

Bermejo-Martin, Jesús F; Andaluz-Ojeda, David; Almansa, Raquel; Gandía, Francisco; Gómez-Herreras, Jose Ignacio; Gomez-Sanchez, Esther; Heredia-Rodríguez, María; Eiros, Jose Maria; Kelvin, David J; Tamayo, Eduardo

2016-05-01

Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

[Quantitative variations of lymphocyte subsets in various kinds of cancer patients in the terminal stage].

PubMed

Nakajima, Y; Akimoto, M; Iwasaki, H; Matano, S; Hirakawa, H; Kimura, M

1986-12-01

Immunological studies of the peripheral blood were made in terminal breast cancer and terminal abdominal cancer patients. Two immunological parameters were studied: (1) lymphocyte subsets and (2) proliferative response to PHA. A decrease in the number of OKT-3(+) cells and an increase in that of OKT-8(+) cells were observed in abdominal cancer. It was suggested that the immunological status in abdominal cancer is more suppressive than in breast cancer. Increases in the number of OK-M1(+) cells and Leu-7(+) cells were observed in breast cancer. It is suggested that cytotoxic lymphocytes increase in number in breast cancer more than in abdominal cancer.

Precision medicine in myasthenia graves: begin from the data precision

PubMed Central

Hong, Yu; Xie, Yanchen; Hao, Hong-Jun; Sun, Ren-Cheng

2016-01-01

Myasthenia gravis (MG) is a prototypic autoimmune disease with overt clinical and immunological heterogeneity. The data of MG is far from individually precise now, partially due to the rarity and heterogeneity of this disease. In this review, we provide the basic insights of MG data precision, including onset age, presenting symptoms, generalization, thymus status, pathogenic autoantibodies, muscle involvement, severity and response to treatment based on references and our previous studies. Subgroups and quantitative traits of MG are discussed in the sense of data precision. The role of disease registries and scientific bases of precise analysis are also discussed to ensure better collection and analysis of MG data. PMID:27127759

Quantitative evaluation of learning and memory trace in studies of mnemotropic effects of immunotropic drugs.

PubMed

Kiseleva, N M; Novoseletskaya, A V; Voevodina, Ye B; Kozlov, I G; Inozemtsev, A N

2012-12-01

Apart from restoration of disordered immunological parameters, tactivin and derinat exhibit a pronounced effect on the higher integrative functions of the brain. Experiments on Wistar rats have shown that these drugs accelerated conditioning of food and defense responses. New methods for quantitative evaluation of memory trace consolidation are proposed.

Development of analytical methods for multiplex bio-assay with inductively coupled plasma mass spectrometry

PubMed Central

Ornatsky, Olga I.; Kinach, Robert; Bandura, Dmitry R.; Lou, Xudong; Tanner, Scott D.; Baranov, Vladimir I.; Nitz, Mark; Winnik, Mitchell A.

2008-01-01

Advances in the development of highly multiplexed bio-analytical assays with inductively coupled plasma mass spectrometry (ICP-MS) detection are discussed. Use of novel reagents specifically designed for immunological methods utilizing elemental analysis is presented. The major steps of method development, including selection of elements for tags, validation of tagged reagents, and examples of multiplexed assays, are considered in detail. The paper further describes experimental protocols for elemental tagging of antibodies, immunostaining of live and fixed human leukemia cells, and preparation of samples for ICP-MS analysis. Quantitative analysis of surface antigens on model cell lines using a cocktail of seven lanthanide labeled antibodies demonstrated high specificity and concordance with conventional immunophenotyping. PMID:19122859

Systems Biology in Immunology – A Computational Modeling Perspective

PubMed Central

Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra; Fraser, Iain D. C.

2011-01-01

Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and conduct simulations of immune function, We provide descriptions of the key data gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease. PMID:21219182

Immunological responses induced by the combination of phototherapy and immunotherapy in the treatment of metastatic tumors

NASA Astrophysics Data System (ADS)

Chen, Wei R.; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Liu, Hong

2008-02-01

Combination therapy using laser photothermal interaction and immunological stimulation has demonstrated its ability to induce immunological responses. Glycated chitosan (GC), an immunological stimulant, and imiquimod, a new type of immune response modifier (IRM), when used in conjunction with laser phototherapy, have shown to have a great immunological stimulation function. Specifically, imiquimod can help release cytokines from immunocompetent cells, stimulate TH1 lymphocyte responses (CD8+ T-cells), and recruit additional dendritic cells. To study the effects of immunoadjuvnats in combination of laser photo-irradiation, we treated animal tumors with laser-ICG-GC combination and late-stage melanoma patients with laser-ICG-imiquimod combination. At designated times, tumors, blood, and spleens in both treated and untreated animals were colleted for analysis. The major immunological indicators, such as IL-6, IL-12, IFN-gamma, CD4, and CD8 were analyzed. The same immunological analysis was also performed for melanoma patients treated by the laser-imiquimod combination.

Gene expression profile and immunological evaluation of unique hypothetical unknown proteins of Mycobacterium leprae by using quantitative real-time PCR.

PubMed

Kim, Hee Jin; Prithiviraj, Kalyani; Groathouse, Nathan; Brennan, Patrick J; Spencer, John S

2013-02-01

The cell-mediated immunity (CMI)-based in vitro gamma interferon release assay (IGRA) of Mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of M. leprae infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential M. leprae-specific proteins called "hypothetical unknowns." Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the M. leprae-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in M. leprae. Fifteen of 26 selected antigen candidates were expressed and purified in Escherichia coli. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited M. leprae-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy.

Gene Expression Profile and Immunological Evaluation of Unique Hypothetical Unknown Proteins of Mycobacterium leprae by Using Quantitative Real-Time PCR

PubMed Central

Prithiviraj, Kalyani; Groathouse, Nathan; Brennan, Patrick J.; Spencer, John S.

2013-01-01

The cell-mediated immunity (CMI)-based in vitro gamma interferon release assay (IGRA) of Mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of M. leprae infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential M. leprae-specific proteins called “hypothetical unknowns.” Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the M. leprae-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in M. leprae. Fifteen of 26 selected antigen candidates were expressed and purified in Escherichia coli. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited M. leprae-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy. PMID:23239802

The Known Immunologically Active Components of Astragalus Account for Only a Small Proportion of the Immunological Adjuvant Activity When Combined with Conjugate Vaccines

PubMed Central

Hong, Feng; Xiao, Weilie; Ragupathi, Govind; Lau, Clara B. S.; Leung, Ping Chung; Yeung, K. Simon; George, Constantine; Cassileth, Barrie; Kennelly, Edward; Livingston, Philip O.

2013-01-01

The 95% ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids. The antibody responses against cancer antigens and KLH were quantitated in ELISA assays, and toxicity was calculated by weight loss. Astragalosides II and IV were the most active components, but the toxicity of these two differed dramatically. Astragaloside II was the most toxic Astragalus component with 5–10% weight loss at a dose of 500 µg while astragaloside IV showed no weight loss at all at this dose, suggesting that astragaloside IV might be utilized as an immunological adjuvant in future studies. Several flavonoids also had significant adjuvant activity. However, when the activities of these known immunologically active components of Astragalus (and of endotoxin) are calculated based on the extent of their presence in the 95% ethanol extract, they provide only a small proportion of the immunological activity. This raises the possibility that additional uniquely active components of Astragalus may contribute to adjuvant activity, or that the adjuvant activity of Astragalus is greater than the activity of the sum of its parts. PMID:21128203

Consortium biology in immunology: the perspective from the Immunological Genome Project.

PubMed

Benoist, Christophe; Lanier, Lewis; Merad, Miriam; Mathis, Diane

2012-10-01

Although the field has a long collaborative tradition, immunology has made less use than genetics of 'consortium biology', wherein groups of investigators together tackle large integrated questions or problems. However, immunology is naturally suited to large-scale integrative and systems-level approaches, owing to the multicellular and adaptive nature of the cells it encompasses. Here, we discuss the value and drawbacks of this organization of research, in the context of the long-running 'big science' debate, and consider the opportunities that may exist for the immunology community. We position this analysis in light of our own experience, both positive and negative, as participants of the Immunological Genome Project.

Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

PubMed

Genser, Bernd; Fischer, Joachim E; Figueiredo, Camila A; Alcântara-Neves, Neuza; Barreto, Mauricio L; Cooper, Philip J; Amorim, Leila D; Saemann, Marcus D; Weichhart, Thomas; Rodrigues, Laura C

2016-05-20

Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes.

Isolation, activity and immunological characterisation of a secreted aspartic protease, CtsD, from Aspergillus fumigatus.

PubMed

Vickers, Imelda; Reeves, Emer P; Kavanagh, Kevin A; Doyle, Sean

2007-05-01

Aspergillus fumigatus is an opportunistic fungal pathogen that infects immunocompromised patients. A putative aspartic protease gene (ctsD; 1425 bp; intron-free) was identified and cloned. CtsD is evolutionarily distinct from all previously identified A. fumigatus aspartic proteases. Recombinant CtsD was expressed in inclusion bodies in Escherichia coli (0.2mg/g cells) and subjected to extensive proteolysis in the baculovirus expression system. Activation studies performed on purified, refolded, recombinant CtsD resulted in protease activation with a pH(opt)4.0 and specific activity=10 U/mg. Pepstatin A also inhibited recombinant CtsD activity by up to 72% thereby confirming classification as an aspartic protease. Native CtsD was also immunologically identified in culture supernatants and purified from fungal cultures using pepstatin-agarose affinity chromatography (7.8 microg CtsD/g mycelia). In A. fumigatus, semi-quantitative RT-PCR analysis revealed expression of ctsD in minimal and proteinaceous media only. Expression of ctsD was absent under nutrient-rich conditions. Expression of ctsD was also detected, in vivo, in the Galleria mellonella virulence model following A. fumigatus infection.

Interleukin-17 immunity in pediatric Crohn disease and ulcerative colitis.

PubMed

Hölttä, Veera; Klemetti, Paula; Salo, Harri M; Koivusalo, Antti; Pakarinen, Mikko; Westerholm-Ormio, Mia; Kolho, Kaija-Leena; Vaarala, Outi

2013-09-01

The present understanding of inflammatory bowel disease pathogenesis mainly relies on studies of adult patients. Therefore, we studied the balance between T-effector and regulatory cells in pediatric inflammatory bowel disease. Quantitative polymerase chain reaction and immunohistochemistry served to quantify the expression of immunological markers in mucosal biopsies and flow cytometry analysis was used in peripheral blood mononuclear cells. Colonic interleukin (IL)-17+, IL-22, and IL-6 mRNA upregulation and increase in the number of colonic IL-17 cells were demonstrated in both Crohn disease (CD) and ulcerative colitis (UC). Likewise, colonic forkhead box P3 (FOXP3+) mRNA expression and the number of colonic FOXP3 cells were increased both in CD and in UC and were accompanied in CD also with increased numbers of FOXP3+CD25 High CD4 cells in peripheral blood. Ileal relation of IL-17/CD4 cells was increased only in CD. We showed activation of colonic IL-17/IL-22 axis and upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared immunological characteristics. Upregulation of IL-17 was restricted to colon in UC, but existed in the ileum and in the colon in active CD.

Engineering approaches to immunotherapy.

PubMed

Swartz, Melody A; Hirosue, Sachiko; Hubbell, Jeffrey A

2012-08-22

As the science of immunology grows increasingly mechanistic, motivation for developing quantitative, design-based engineering approaches has also evolved, both for therapeutic interventions and for elucidating immunological pathways in human disease. This has seeded the nascent field of "immunoengineering," which seeks to apply engineering analyses and design approaches to problems in translational immunology. For example, cell engineers are creating ways to tailor and use immune cells as living therapeutics; protein engineers are devising new methods of rapid antibody discovery; biomaterials scientists are guiding vaccine delivery and immune-cell activation with novel constructs; and systems immunologists are deciphering the evolution and maintenance of T and B cell receptor repertoires, which could help guide vaccine design. The field is multidisciplinary and collaborative, with engineers and immunologists working together to better understand and treat disease. We discuss the scientific progress in this young, yet rapidly evolving research area, which has yielded numerous start-up companies that are betting on impact in clinical and commercial translation in the near future.

Microscopic quantification of bacterial invasion by a novel antibody-independent staining method.

PubMed

Agerer, Franziska; Waeckerle, Stephanie; Hauck, Christof R

2004-10-01

Microscopic discrimination between extracellular and invasive, intracellular bacteria is a valuable technique in microbiology and immunology. We describe a novel fluorescence staining protocol, called FITC-biotin-avidin (FBA) staining, which allows the differentiation between extracellular and intracellular bacteria and is independent of specific antibodies directed against the microorganisms. FBA staining of eukaryotic cells infected with Gram-negative bacteria of the genus Neisseria or the Gram-positive pathogen Staphylococcus aureus are employed to validate the novel technique. The quantitative evaluation of intracellular pathogens by the FBA staining protocol yields identical results compared to parallel samples stained with conventional, antibody-dependent methods. FBA staining eliminates the need for cell permeabilization resulting in robust and rapid detection of invasive microbes. Taken together, FBA staining provides a reliable and convenient alternative for the differential detection of intracellular and extracellular bacteria and should be a valuable technical tool for the quantitative analysis of the invasive properties of pathogenic bacteria and other microorganisms.

A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

PubMed

Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

2018-01-01

There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

21 CFR 866.6030 - AFP-L3% immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... system is an in vitro device that consists of reagents and an automated instrument used to quantitatively measure, by immunochemical techniques, AFP and AFP-L3 subfraction in human serum. The device is intended for in vitro diagnostic use as an aid in the risk assessment of patients with chronic liver disease...

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

PubMed

Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

2017-06-01

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiplex quantification of protein toxins in human biofluids and food matrices using immunoextraction and high-resolution targeted mass spectrometry.

PubMed

Dupré, Mathieu; Gilquin, Benoit; Fenaille, François; Feraudet-Tarisse, Cécile; Dano, Julie; Ferro, Myriam; Simon, Stéphanie; Junot, Christophe; Brun, Virginie; Becher, François

2015-08-18

The development of rapid methods for unambiguous identification and precise quantification of protein toxins in various matrices is essential for public health surveillance. Nowadays, analytical strategies classically rely on sensitive immunological assays, but mass spectrometry constitutes an attractive complementary approach thanks to direct measurement and protein characterization ability. We developed here an innovative multiplex immuno-LC-MS/MS method for the simultaneous and specific quantification of the three potential biological warfare agents, ricin, staphylococcal enterotoxin B, and epsilon toxin, in complex human biofluids and food matrices. At least 7 peptides were targeted for each toxin (43 peptides in total) with a quadrupole-Orbitrap high-resolution instrument for exquisite detection specificity. Quantification was performed using stable isotope-labeled toxin standards spiked early in the sample. Lower limits of quantification were determined at or close to 1 ng·mL(-1). The whole process was successfully applied to the quantitative analysis of toxins in complex samples such as milk, human urine, and plasma. Finally, we report new data on toxin stability with no evidence of toxin degradation in milk in a 48 h time frame, allowing relevant quantitative toxin analysis for samples collected in this time range.

Image analysis of the blood cells for cytomorphodiagnostics and control of the effectiveness treatment

NASA Astrophysics Data System (ADS)

Zhukotsky, Alexander V.; Kogan, Emmanuil M.; Kopylov, Victor F.; Marchenko, Oleg V.; Lomakin, O. A.

1994-07-01

A new method for morphodensitometric analysis of blood cells was applied for medically screening some ecological influence and infection pathologies. A complex algorithm of computational image processing was created for supra molecular restructurings of interphase chromatin of lymphocytes research. It includes specific methods of staining and unifies different quantitative analysis methods. Our experience with the use of a television image analyzer in cytological and immunological studies made it possible to carry out some research in morphometric analysis of chromatin structure in interphase lymphocyte nuclei in genetic and virus pathologies. In our study to characterize lymphocytes as an image-forming system by a rigorous mathematical description we used an approach involving contaminant evaluation of the topography of chromatin network intact and victims' lymphocytes. It is also possible to digitize data, which revealed significant distinctions between control and experiment. The method allows us to observe the minute structural changes in chromatin, especially eu- and hetero-chromatin that were previously studied by genetics only in chromosomes.

Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving.

PubMed

Han, Qing; Bradshaw, Elizabeth M; Nilsson, Björn; Hafler, David A; Love, J Christopher

2010-06-07

The large diversity of cells that comprise the human immune system requires methods that can resolve the individual contributions of specific subsets to an immunological response. Microengraving is process that uses a dense, elastomeric array of microwells to generate microarrays of proteins secreted from large numbers of individual live cells (approximately 10(4)-10(5) cells/assay). In this paper, we describe an approach based on this technology to quantify the rates of secretion from single immune cells. Numerical simulations of the microengraving process indicated an operating regime between 30 min-4 h that permits quantitative analysis of the rates of secretion. Through experimental validation, we demonstrate that microengraving can provide quantitative measurements of both the frequencies and the distribution in rates of secretion for up to four cytokines simultaneously released from individual viable primary immune cells. The experimental limits of detection ranged from 0.5 to 4 molecules/s for IL-6, IL-17, IFNgamma, IL-2, and TNFalpha. These multidimensional measures resolve the number and intensities of responses by cells exposed to stimuli with greater sensitivity than single-parameter assays for cytokine release. We show that cells from different donors exhibit distinct responses based on both the frequency and magnitude of cytokine secretion when stimulated under different activating conditions. Primary T cells with specific profiles of secretion can also be recovered after microengraving for subsequent expansion in vitro. These examples demonstrate the utility of quantitative, multidimensional profiles of single cells for analyzing the diversity and dynamics of immune responses in vitro and for identifying rare cells from clinical samples.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frost, J.K.; Ball, W.C. Jr.; Levin, M.L.

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytologicalmore » specimens collected over years of screening workers considered at risk may be important to eventually understanding development and prevention of major occupational diseases.« less

Aspergillus fumigatus viability drives allergic responses to inhaled conidia.

PubMed

Nayak, Ajay P; Croston, Tara L; Lemons, Angela R; Goldsmith, W T; Marshall, Nikki B; Kashon, Michael L; Germolec, Dori R; Beezhold, Donald H; Green, Brett J

2018-04-13

Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue. Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-γ (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult. Our studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease. Copyright © 2018. Published by Elsevier Inc.

Global foot-and-mouth disease research update and gap analysis: 6 - immunology

USDA-ARS?s Scientific Manuscript database

In 2014, the Global Foot-and-mouth disease Research Alliance (GFRA) conducted a gap analysis of FMD research. This has been updated with findings reported in a series of papers. Here we present findings for FMD immunology research. The paper consists of the following four sections: 1. Research prior...

The Symptomatic Persian Gulf Veterans Protocol: An Analysis of Risk Factors with an Immunologic and Neuropsychiatric Assessment

DTIC Science & Technology

2001-01-01

for these complaints and include exposure and infection with mycoplasma or related organisms and alterations in immunological responsiveness. To...of mycoplasma or ureaplasma organisms by culture and PCR revealed no discernable significant differences. Similarly, no significant differences have...suggest increased exposure to mycoplasma . 6. Body: This study will determine whether specific in-vitro immunological abnormalities or evidence of

Quantitative analysis of periodontal pathogens by ELISA and real-time polymerase chain reaction.

PubMed

Hamlet, Stephen M

2010-01-01

The development of analytical methods enabling the accurate identification and enumeration of bacterial species colonizing the oral cavity has led to the identification of a small number of bacterial pathogens that are major factors in the etiology of periodontal disease. Further, these methods also underpin more recent epidemiological analyses of the impact of periodontal disease on general health. Given the complex milieu of over 700 species of microorganisms known to exist within the complex biofilms found in the oral cavity, the identification and enumeration of oral periodontopathogens has not been an easy task. In recent years however, some of the intrinsic limitations of the more traditional microbiological analyses previously used have been overcome with the advent of immunological and molecular analytical methods. Of the plethora of methodologies reported in the literature, the enzyme-linked immunosorbent assay (ELISA), which combines the specificity of antibody with the sensitivity of simple enzyme assays and the polymerase chain reaction (PCR), has been widely utilized in both laboratory and clinical applications. Although conventional PCR does not allow quantitation of the target organism, real-time PCR (rtPCR) has the ability to detect amplicons as they accumulate in "real time" allowing subsequent quantitation. These methods enable the accurate quantitation of as few as 10(2) (using rtPCR) to 10(4) (using ELISA) periodontopathogens in dental plaque samples.

Protective pathways against colitis mediated by appendicitis and appendectomy

PubMed Central

Cheluvappa, R; Luo, A S; Palmer, C; Grimm, M C

2011-01-01

Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). Using a novel murine appendicitis model, we showed that AA protected against subsequent experimental colitis. To delineate genes/pathways involved in this protection, AA was performed and samples harvested from the most distal colon. RNA was extracted from four individual colonic samples per group (AA group and double-laparotomy control group) and each sample microarray analysed followed by gene-set enrichment analysis (GSEA). The gene-expression study was validated by quantitative reverse transcription–polymerase chain reaction (RT–PCR) of 14 selected genes across the immunological spectrum. Distal colonic expression of 266 gene-sets was up-regulated significantly in AA group samples (false discovery rates < 1%; P-value < 0·001). Time–course RT–PCR experiments involving the 14 genes displayed down-regulation over 28 days. The IBD-associated genes tnfsf10, SLC22A5, C3, ccr5, irgm, ptger4 and ccl20 were modulated in AA mice 3 days after surgery. Many key immunological and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. The down-regulation of 14 selected genes over 28 days after surgery indicates activation, repression or de-repression of these genes leading to downstream AA-conferred anti-colitis protection. Further analysis of these genes, profiles and biological pathways may assist in developing better therapeutic strategies in the management of intractable IBD. PMID:21707591

Regulatory immune cells and functions in autoimmunity and transplantation immunology.

PubMed

Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

2017-05-01

In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of the quantitative dermatoglyphics of the digito-palmar complex in patients with multiple sclerosis.

PubMed

Supe, S; Milicić, J; Pavićević, R

1997-06-01

Recent studies on the etiopathogenesis of multiple sclerosis (MS) all point out that there is a polygenetical predisposition for this illness. The so called "MS Trait" determines the reactivity of the immunological system upon ecological factors. The development of the glyphological science and the study of the characteristics of the digito-palmar dermatoglyphic complex (for which it was established that they are polygenetically determined characteristics) all enable a better insight into the genetic development during early embriogenesis. The aim of this study was to estimate certain differences in the dermatoglyphics of digito-palmar complexes between the group with multiple sclerosis and the comparable, phenotypically healthy groups of both sexes. This study is based on the analysis of 18 quantitative characteristics of the digito-palmar complex in 125 patients with multiple sclerosis (41 males and 84 females) in comparison to a group of 400 phenotypically healthy patients (200 males and 200 females). The conducted analysis pointed towards a statistically significant decrease of the number of digital and palmar ridges, as well as with lower values of atd angles in a group of MS patients of both sexes. The main discriminators were the characteristic palmar dermatoglyphics with the possibility that the discriminate analysis classifies over 80% of the examinees which exceeds the statistical significance. The results of this study suggest a possible discrimination of patients with MS and the phenotypically health population through the analysis of the dermatoglyphic status, and therefore the possibility that multiple sclerosis is genetically predisposed disease.

Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

PubMed

Scarpellini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

2016-01-01

We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

Quantitative PCR and disaccharide profiling to characterize the animal origin of low-molecular-weight heparins.

PubMed

Houiste, Céline; Auguste, Cécile; Macrez, Céline; Dereux, Stéphanie; Derouet, Angélique; Anger, Pascal

2009-02-01

Low-molecular-weight heparins (LMWHs) are widely used in the management of thrombosis and acute coronary syndromes. They are obtained by the enzymatic or chemical depolymerization of porcine intestinal heparin. Enoxaparin sodium, a widely used LMWH, has a unique and reproducible oligosaccharide profile which is determined by the origin of the starting material and a tightly controlled manufacturing process. Although other enoxaparin-like LMWHs do exist, specific release criteria including the origin of the crude heparin utilized for their production, have not been established. A quantitative polymerase chain reaction method has been developed to ensure the purity of the porcine origin of crude heparin, with a DNA detection limit as low as 1 ppm for bovine, or 10 ppm for ovine contaminants. This method is routinely used as the release acceptance criterion during enoxaparin sodium manufacturing. Furthermore, when the process removes DNA, other analytical techniques can be used to assess any contamination. Disaccharide profiling after exhaustive depolymerization can determine the presence of at least 10% bovine or 20% ovine material; multivariate analysis is useful to perform the data analysis. Consistent with the availability of newer technology, these methods should be required as acceptance criteria for crude heparins used in the manufacture of LMWHs to ensure their safety, quality, and immunologic profile.

Contextual analysis of immunological response through whole-organ fluorescent imaging.

PubMed

Woodruff, Matthew C; Herndon, Caroline N; Heesters, B A; Carroll, Michael C

2013-09-01

As fluorescent microscopy has developed, significant insights have been gained into the establishment of immune response within secondary lymphoid organs, particularly in draining lymph nodes. While established techniques such as confocal imaging and intravital multi-photon microscopy have proven invaluable, they provide limited insight into the architectural and structural context in which these responses occur. To interrogate the role of the lymph node environment in immune response effectively, a new set of imaging tools taking into account broader architectural context must be implemented into emerging immunological questions. Using two different methods of whole-organ imaging, optical clearing and three-dimensional reconstruction of serially sectioned lymph nodes, fluorescent representations of whole lymph nodes can be acquired at cellular resolution. Using freely available post-processing tools, images of unlimited size and depth can be assembled into cohesive, contextual snapshots of immunological response. Through the implementation of robust iterative analysis techniques, these highly complex three-dimensional images can be objectified into sortable object data sets. These data can then be used to interrogate complex questions at the cellular level within the broader context of lymph node biology. By combining existing imaging technology with complex methods of sample preparation and capture, we have developed efficient systems for contextualizing immunological phenomena within lymphatic architecture. In combination with robust approaches to image analysis, these advances provide a path to integrating scientific understanding of basic lymphatic biology into the complex nature of immunological response.

Rival approaches to mathematical modelling in immunology

NASA Astrophysics Data System (ADS)

Andrew, Sarah M.; Baker, Christopher T. H.; Bocharov, Gennady A.

2007-08-01

In order to formulate quantitatively correct mathematical models of the immune system, one requires an understanding of immune processes and familiarity with a range of mathematical techniques. Selection of an appropriate model requires a number of decisions to be made, including a choice of the modelling objectives, strategies and techniques and the types of model considered as candidate models. The authors adopt a multidisciplinary perspective.

COMPARATIVE HISTOLOGIC AND IMMUNOLOGIC STUDIES IN RABBITS OF INDUCED HYPERSENSITIVITY OF THE SERUM SICKNESS TYPE

PubMed Central

Germuth, Frederick G.; Pace, Mary Geraldine; Tippett, Jack C.

1955-01-01

Sensitization of rabbits with bovine albumin and the cross-reactive antigen, egg albumin, increased the rate of bovine albumin elimination following its intravenous administration. Elimination of this antigen was complete in 7 and 10 days respectively instead of approximately 2 weeks as in unsensitized normal animals. The peak incidence of allergic tissue alteration was proportionately accelerated. Certain qualitative and quantitative differences between the histologic responses of the sensitized and unsensitized rabbits were noted. These differences were probably due to the shorter period of antigen-antibody interaction in the sensitized animals in which the antigen was quickly eliminated. The temporal relationship between the histologic and immunologic responses in sensitized animals adds further support to the hypothesis that the lesions which occur after the injection of foreign protein are the result of antigen-antibody combination. PMID:13233442

Bayesian Immunological Model Development from the Literature: Example Investigation of Recent Thymic Emigrants†

PubMed Central

Holmes, Tyson H.; Lewis, David B.

2014-01-01

Bayesian estimation techniques offer a systematic and quantitative approach for synthesizing data drawn from the literature to model immunological systems. As detailed here, the practitioner begins with a theoretical model and then sequentially draws information from source data sets and/or published findings to inform estimation of model parameters. Options are available to weigh these various sources of information differentially per objective measures of their corresponding scientific strengths. This approach is illustrated in depth through a carefully worked example for a model of decline in T-cell receptor excision circle content of peripheral T cells during development and aging. Estimates from this model indicate that 21 years of age is plausible for the developmental timing of mean age of onset of decline in T-cell receptor excision circle content of peripheral T cells. PMID:25179832

Analytical requirements, perspectives and limits of immunological methods for drugs in hair.

PubMed

Cassani, M; Spiehler, V

1993-12-01

The analytical requirements for analysis of drugs in hair are sensitivity in the range of picograms per milligram of hair, specificity for lipophilic drugs and absence of matrix effects with hair digests. These requirements are met by immunoassays which are also inexpensive, rapid and easy to use. However, in applying immunoassays to hair testing, certain limitations of the assay and of interpretation of assay results should be kept in perspective. These limitations are illustrated in this review with examples of the analysis of opiates in hair from patients and opiate addicts. The first requirement for immunological analysis of hair digests is that the digest must not denature the antibody proteins of the immunoassay reagents. For this reason enzymatic digests are better for immunological assay than chemical digests. Strongly acidic or alkaline digests must be brought to a neutral pH before immunoassay. Immunoassays used for analysis of hair should be calibrated with spiked hair digest standards to correct for possible matrix effects. The second requirement is that the immunoassay have the sensitivity and specificity to detect the drug in hair. Drugs of abuse are found in hair in the range of 10 pg-10 ng/mg hair. Radioimmunoassays are capable of detection and quantitation in this concentration range. Although the mechanism of drug incorporation into hair is not known, it is now apparent that primarily the parent drug and lipophilic metabolites are found in hair. For example, the ratio of cocaine/benzoylecgonine averages 10 (range 2-50) in published reports of analysis of hair from cocaine users. Therefore, immunoassays which are highly sensitive for the parent drug are required and results of immunoassays should be expressed as equivalents. When spiking standards for calibration of hair digest immunoassays, parent drug known to be present in hair should be used, e.g. cocaine not benzoylecgonine. With immunoassays which are specific for the lipophilic metabolite found in hair such as 6-MAM, differential radioimmunoassay can be used to discriminate between medical and illicit sources for the opiate drugs found in hair. Because of the low concentrations of drugs encountered in hair, immunoassays for hair have been used at cutoff concentrations at their limits of detection. The limit of detection (LOD) has been determined by calculating the mean and standard deviation (S.D.) for the assay response for a number of negative hair samples. The cutoff was then set at a distance of 2, 3, or 5 S.D.s from the mean response.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment

PubMed Central

Scarpelini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M.; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

2016-01-01

Background We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Results Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine‐1‐phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Conclusions Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease. PMID:27941971

Domestic trends in malaria research and development in China and its global influence.

PubMed

Huang, Yang-Mu; Shi, Lu-Wen; She, Rui; Bai, Jing; Jiao, Shi-Yong; Guo, Yan

2017-01-10

Though many countries, including China, are moving towards malaria elimination, malaria remains a major global health threat. Due to the spread of antimalarial drug resistance and the need for innovative medical products during the elimination phase, further research and development (R&D) of innovative tools in both epidemic and elimination areas is needed. This study aims to identify the trends and gaps in malaria R&D in China, and aims to offer suggestions on how China can be more effectively involved in global malaria R&D. Quantitative analysis was carried out by collecting data on Chinese malaria-related research programmes between 1985 and 2014, invention patents in China from 1985 to 2014, and articles published by Chinese researchers in PubMed and Chinese databases from 2005 to 2014. All data were screened and extracted for numerical analysis and were categorized into basic sciences, drug/drug resistance, immunology/vaccines, or diagnostics/detection for chronological and subgroup comparisons. The number of malaria R&D activities have shown a trend of increase during the past 30 years, however these activities have fluctuated within the past few years. During the past 10 years, R&D on drug/drug resistance accounted for the highest percentages of research programmes (32.4%), articles (55.0% in PubMed and 50.6% in Chinese databases) and patents (45.5%). However, these R&D activities were mainly related to artemisinin. R&D on immunology/vaccines has been a continuous interest for China's public entities, but the focus remains on basic science. R&D in the area of high-efficiency diagnostics has been rarely seen or reported in China. China has long been devoted to malaria R&D in multiple areas, including drugs, drug resistance, immunology and vaccines. R&D on diagnostics has received significantly less attention, however, it should also be an area where China can make a contribution. More focus on malaria R&D is needed, especially in the area of diagnostics, if China would like to contribute in a more significant way to global malaria control and elimination.

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis.

PubMed

Ammann, Sandra; Lehmberg, Kai; Zur Stadt, Udo; Klemann, Christian; Bode, Sebastian F N; Speckmann, Carsten; Janka, Gritta; Wustrau, Katharina; Rakhmanov, Mirzokhid; Fuchs, Ilka; Hennies, Hans C; Ehl, Stephan

2017-11-01

We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results. In 10 patients, degranulation could not be tested. Among the 166 patients with normal screening, genetic analysis was not performed in 107 (all with uneventful follow-up), while 154 single gene tests by Sanger sequencing in the remaining 59 patients only identified a single atypical CHS patient. Flow cytometry correctly predicted all 29 patients with FHL-2, XLP1 or 2. Among 85 patients with defective NK degranulation (including 13 asymptomatic siblings), 70 were Sanger sequenced resulting in a genetic diagnosis in 55 (79%). Eight patients underwent WES, revealing mutations in two known and one unknown cytotoxicity genes and one metabolic disease. FHL3 was the most frequent genetic diagnosis. Immunological screening provided an excellent decision tool for the need and depth of genetic analysis of HLH patients and provided functionally relevant information for rapid patient classification, contributing to a significant reduction in the time from diagnosis to transplantation in recent years.

Gingival changes during pregnancy: III. Impact of clinical, microbiological, immunological and socio-demographic factors on gingival inflammation.

PubMed

Carrillo-de-Albornoz, Ana; Figuero, Elena; Herrera, David; Cuesta, Pedro; Bascones-Martínez, Antonio

2012-03-01

To identify predictor variables involved in exacerbated gingival inflammation associated with pregnancy. In this cohort study, 48 pregnant and 28 non-pregnant women without periodontitis were included. The pregnant women were evaluated in the first, second and third trimester and at 3 months postpartum, whilst the non-pregnant women were evaluated twice, with a 6-month interval. At each visit, clinical [plaque index (PlI) and gingival index (GI)], hormonal (salivary progesterone and estradiol), immunological [gingival crevicular fluid interleukin-1β, interleukin-6, tumour necrosis factor-α (TNF-α) and prostaglandin-E(2) ] and microbiological (periodontal pathogens culture) evaluations were performed. Statistical analysis was undertaken using exhaustive chi-square automatic interaction detection (exhaustive CHAID) to analyse the predictive value of the independent outcomes to develop pregnancy GI. PlI was the strongest predictor implicated in the GI throughout pregnancy and after delivery. During the second and third trimesters the presence of Porphyromonas gingivalis significantly contributed to the worsening of gingival inflammation. When compared with the non-pregnant group, significant differences were found in TNF-α amounts and concentrations and in the third trimester site-specific GI. Bacterial challenge to the gingival tissues, both quantitatively (PlI) and qualitatively (harbouring P. gingivalis) appears to affect the level of gingival inflammation observed during pregnancy. © 2011 John Wiley & Sons A/S.

Exploring local immunological adaptation of two stickleback ecotypes by experimental infection and transcriptome-wide digital gene expression analysis.

PubMed

Lenz, Tobias L; Eizaguirre, Christophe; Rotter, Björn; Kalbe, Martin; Milinski, Manfred

2013-02-01

Understanding the extent of local adaptation in natural populations and the mechanisms that allow individuals to adapt to their native environment is a major avenue in molecular ecology research. Evidence for the frequent occurrence of diverging ecotypes in species that inhabit multiple ecological habitats is accumulating, but experimental approaches to understanding the biological pathways as well as the underlying genetic mechanisms are still rare. Parasites are invoked as one of the major selective forces driving evolution and are themselves dependent on the ecological conditions in a given habitat. Immunological adaptation to local parasite communities is therefore expected to be a key component of local adaptation in natural populations. Here, we use next-generation sequencing technology to compare the transcriptome-wide response of experimentally infected three-spined sticklebacks from a lake and a river population, which are known to evolve under selection by distinct parasite communities. By comparing overall gene expression levels as well as the activation of functional pathways in response to parasite exposure, we identified potential differences between the two stickleback populations at several levels. Our results suggest locally adapted patterns of gene regulation in response to parasite exposure, which may reflect different local optima in the trade-off between the benefits and the disadvantages of mounting an immune response because of quantitative differences of the local parasite communities. © 2012 Blackwell Publishing Ltd.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples.

PubMed

Simon, Stéphanie; Fiebig, Uwe; Liu, Yvonne; Tierney, Rob; Dano, Julie; Worbs, Sylvia; Endermann, Tanja; Nevers, Marie-Claire; Volland, Hervé; Sesardic, Dorothea; Dorner, Martin B

2015-11-26

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A-G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as "category A" bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

PubMed Central

Simon, Stéphanie; Fiebig, Uwe; Liu, Yvonne; Tierney, Rob; Dano, Julie; Worbs, Sylvia; Endermann, Tanja; Nevers, Marie-Claire; Volland, Hervé; Sesardic, Dorothea; Dorner, Martin B.

2015-01-01

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future. PMID:26703727

Hepatitis C Virus Antigenic Convergence

PubMed Central

Campo, David S.; Dimitrova, Zoya; Yokosawa, Jonny; Hoang, Duc; Perez, Nestor O.; Ramachandran, Sumathi; Khudyakov, Yury

2012-01-01

Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development. PMID:22355779

Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes

PubMed Central

Liepe, Juliane; Holzhütter, Hermann-Georg; Bellavista, Elena; Kloetzel, Peter M; Stumpf, Michael PH; Mishto, Michele

2015-01-01

Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predicted by the model, and experimentally supported. The analysis suggests that the rate-limiting step of hydrolysis is the transport of the substrates into the proteasome. The transport efficiency varies between human standard- and immuno-proteasomes thereby impinging upon total degradation rate and substrate cleavage-site usage. DOI: http://dx.doi.org/10.7554/eLife.07545.001 PMID:26393687

Integration of lyoplate based flow cytometry and computational analysis for standardized immunological biomarker discovery.

PubMed

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R; Nestle, Frank O

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases.

Integration of Lyoplate Based Flow Cytometry and Computational Analysis for Standardized Immunological Biomarker Discovery

PubMed Central

Villanova, Federica; Di Meglio, Paola; Inokuma, Margaret; Aghaeepour, Nima; Perucha, Esperanza; Mollon, Jennifer; Nomura, Laurel; Hernandez-Fuentes, Maria; Cope, Andrew; Prevost, A. Toby; Heck, Susanne; Maino, Vernon; Lord, Graham; Brinkman, Ryan R.; Nestle, Frank O.

2013-01-01

Discovery of novel immune biomarkers for monitoring of disease prognosis and response to therapy in immune-mediated inflammatory diseases is an important unmet clinical need. Here, we establish a novel framework for immunological biomarker discovery, comparing a conventional (liquid) flow cytometry platform (CFP) and a unique lyoplate-based flow cytometry platform (LFP) in combination with advanced computational data analysis. We demonstrate that LFP had higher sensitivity compared to CFP, with increased detection of cytokines (IFN-γ and IL-10) and activation markers (Foxp3 and CD25). Fluorescent intensity of cells stained with lyophilized antibodies was increased compared to cells stained with liquid antibodies. LFP, using a plate loader, allowed medium-throughput processing of samples with comparable intra- and inter-assay variability between platforms. Automated computational analysis identified novel immunophenotypes that were not detected with manual analysis. Our results establish a new flow cytometry platform for standardized and rapid immunological biomarker discovery with wide application to immune-mediated diseases. PMID:23843942

Multivariate Analysis As a Support for Diagnostic Flowcharts in Allergic Bronchopulmonary Aspergillosis: A Proof-of-Concept Study.

PubMed

Vitte, Joana; Ranque, Stéphane; Carsin, Ania; Gomez, Carine; Romain, Thomas; Cassagne, Carole; Gouitaa, Marion; Baravalle-Einaudi, Mélisande; Bel, Nathalie Stremler-Le; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Gaudart, Jean

2017-01-01

Molecular-based allergy diagnosis yields multiple biomarker datasets. The classical diagnostic score for allergic bronchopulmonary aspergillosis (ABPA), a severe disease usually occurring in asthmatic patients and people with cystic fibrosis, comprises succinct immunological criteria formulated in 1977: total IgE, anti- Aspergillus fumigatus ( Af ) IgE, anti- Af "precipitins," and anti- Af IgG. Progress achieved over the last four decades led to multiple IgE and IgG(4) Af biomarkers available with quantitative, standardized, molecular-level reports. These newly available biomarkers have not been included in the current diagnostic criteria, either individually or in algorithms, despite persistent underdiagnosis of ABPA. Large numbers of individual biomarkers may hinder their use in clinical practice. Conversely, multivariate analysis using new tools may bring about a better chance of less diagnostic mistakes. We report here a proof-of-concept work consisting of a three-step multivariate analysis of Af IgE, IgG, and IgG4 biomarkers through a combination of principal component analysis, hierarchical ascendant classification, and classification and regression tree multivariate analysis. The resulting diagnostic algorithms might show the way for novel criteria and improved diagnostic efficiency in Af -sensitized patients at risk for ABPA.

Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model.

PubMed

Park, Soomin; Baek, Seung-Hun; Cho, Sang-Nae; Jang, Young-Saeng; Kim, Ahreum; Choi, In-Hong

2017-01-01

There is a substantial need for biomarkers to distinguish latent stage from active Mycobacterium tuberculosis infections, for predicting disease progression. To induce the reactivation of tuberculosis, we present a new experimental animal model modified based on the previous model established by our group. In the new model, the reactivation of tuberculosis is induced without administration of immunosuppressive agents, which might disturb immune responses. To identify the immunological status of the persistent and chronic stages, we analyzed immunological genes in lung tissues from mice infected with M. tuberculosis . Gene expression was screened using cDNA microarray analysis and confirmed by quantitative RT-PCR. Based on the cDNA microarray results, 11 candidate cytokines genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: (1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs; CXCL9, CXCL10, CXCL11, CCL5, CCL19); (2) MCP genes (CCL2, CCL7, CCL8, CCL12); and (3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19, and CXCL9) and three MCPs (CCL7, CCL2, and CCL12) were noticeably increased in the chronic stage compared with the persistent stage by cDNA microarray ( p < 0.01, except CCL12) or RT-PCR ( p < 0.01). Therefore, these six significantly increased cytokines in lung tissue from the mouse tuberculosis model might be candidates for biomarkers to distinguish the two disease stages. This information can be combined with already reported potential biomarkers to construct a network of more efficient tuberculosis markers.

Novel method for quantitative ANA measurement using near-infrared imaging.

PubMed

Peterson, Lisa K; Wells, Daniel; Shaw, Laura; Velez, Maria-Gabriela; Harbeck, Ronald; Dragone, Leonard L

2009-09-30

Antinuclear antibodies (ANA) have been detected in patients with systemic rheumatic diseases and are used in the screening and/or diagnosis of autoimmunity in patients as well as mouse models of systemic autoimmunity. Indirect immunofluorescence (IIF) on HEp-2 cells is the gold standard for ANA screening. However, its usefulness is limited in diagnosis, prognosis and monitoring of disease activity due to the lack of standardization in performing the technique, subjectivity in interpreting the results and the fact that it is only semi-quantitative. Various immunological techniques have been developed in an attempt to improve upon the method to quantify ANA, including enzyme-linked immunosorbent assays (ELISAs), line immunoassays (LIAs), multiplexed bead immunoassays and IIF on substrates other than HEp-2 cells. Yet IIF on HEp-2 cells remains the most common screening method for ANA. In this study, we describe a simple quantitative method to detect ANA which combines IIF on HEp-2 coated slides with analysis using a near-infrared imaging (NII) system. Using NII to determine ANA titer, 86.5% (32 of 37) of the titers for human patient samples were within 2 dilutions of those determined by IIF, which is the acceptable range for proficiency testing. Combining an initial screening for nuclear staining using microscopy with titration by NII resulted in 97.3% (36 of 37) of the titers detected to be within two dilutions of those determined by IIF. The NII method for quantitative ANA measurements using serum from both patients and mice with autoimmunity provides a fast, relatively simple, objective, sensitive and reproducible assay, which could easily be standardized for comparison between laboratories.

The effect of incident tuberculosis on immunological response of HIV patients on highly active anti-retroviral therapy at the university of Gondar hospital, northwest Ethiopia: a retrospective follow-up study.

PubMed

Assefa, Abate; Gelaw, Baye; Getnet, Gebeyaw; Yitayew, Gashaw

2014-08-27

Human immunodeficiency virus (HIV) infection is usually complicated by high rates of tuberculosis (TB) co-infection. Impaired immune response has been reported during HIV/TB co-infection and may have significant effect on anti-retroviral therapy (ART). TB/HIV co - infection is a major public health problem in Ethiopia. Therefore, the aim of the study was to assess the effect of TB incidence on immunological response of HIV patients during ART. A retrospective follow-up study was conducted among adult HIV patients who started ART at the University of Gondar Hospital. Changes in CD4+ T - lymphocyte count and incident TB episodes occurring during 42 months of follow up on ART were assessed. Life table was used to estimate the cumulative immunologic failure. Kaplan-Meier curve was used to compare survival curves between the different categories. Cox-proportional hazard model was employed to examine predictors of immunological failure. Among 400 HIV patients, 89(22.2%) were found to have immunological failure with a rate of 8.5 per 100 person-years (PY) of follow-up. Incident TB developed in 26(6.5%) of patients, with an incidence rate of 2.2 cases per 100 PY. The immunological failure rate was high (20.1/100PY) at the first year of treatment. At multivariate analysis, Cox regression analysis showed that baseline CD4+ T - cell count <100 cells/mm3 (adjusted hazard ratio (AHR) 1.8; 95%CI: 1.10 - 2.92, p = 0.023) and being male sex (AHR 1.6; 95%CI: 1.01 - 2.68, p = 0.046) were found to be significant predictors of immunological failure. There was borderline significant association with incident TB (AHR 2.2; 95%CI: 0.94 - 5.09, p = 0.06). The risk of immunological failure was significantly higher (38.5%) among those with incident TB compared with TB - free (21.1%) (Log rank p = 0.036). High incidence of immunological failure occurred within the first year of initiating ART. The proportions of patients with impaired immune restoration were higher among patients with incident TB. Lower baseline CD4+ T - cells count of <100 cells/mm3 and being male sex were significant predictors of immunological failure. The result highlighted the beneficial effects of earlier initiation of ART on CD4+ T - cell count recovery.

Seventeen-Year Journey Working With a Master.

PubMed

Zhu, Jinfang

2018-01-01

It had been a great honor for me to work with the late Dr. William E. Paul for 17 years in the Laboratory of Immunology (LI) from 1998 until his passing in 2015. He was such a master in the immunology field. Under his outstanding guidance, my research has been focusing on transcriptional regulation of T helper (Th) cell differentiation, especially, on the role of a master transcription factor GATA3 during Th2 cell differentiation. Just as enormous scientific contributions of Dr. Paul (we all call him Bill) to the immunology community are far beyond his serving as the Chief of the LI, GATA3 also plays important roles in different lymphocytes at various developmental stages besides its critical functions in Th2 cells. In this special review dedicated to the memory of Bill, I will summarize the research that I have carried out in Bill's lab working on GATA3 in the context of related studies by other groups in the field of T cell differentiation and innate lymphoid cell (ILC) development. These include the essential role of GATA3 in regulating Th2/ILC2 differentiation/development and their functions, the critical role of GATA3 during the development of T cells and innate lymphoid cells, and dynamic and quantitative expression of GATA3 in controlling lymphocyte homeostasis and functions.

Improving cancer treatment with cyclotron produced radionuclides. Progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Improving cancer treatment with cyclotron produced radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Evolution of immune functions of the mammary gland and protection of the infant.

PubMed

Goldman, Armond S

2012-06-01

Abstract The evolution of immunological agents in milk is intertwined with the general aspects of the evolution of the mammary gland. In that respect, mammalian precursors emerged from basal amniotes some 300 million years ago. In contrast to the predominant dinosaurs, proto-mammals possessed a glandular skin. A secondary palate in the roof of the mouth that directed airflow from the nostrils to the oropharynx and thus allowed mammals to ingest and breathe simultaneously first appeared in cynodonts 230 million years ago. This set the stage for mammalian newborns to nurse from the future mammary gland. Interplays between environmental and genetic changes shaped mammalian evolution including the mammary gland from dermal glands some 160 millions of years ago. It is likely that secretions from early mammary glands provided nutrients and immunological agents for the infant. Natural selection culminated in milks uniquely suited to nourish and protect infants of each species. In human milk, antimicrobial, anti-inflammatory, and immunoregulatory agents and living leukocytes are qualitatively or quantitatively different from those in other mammalian milks. Those in human milk compensate for developmental delays in the immunological system of the recipient infant. Consequently, the immune system in human milk provided by evolution is much of the basis for encouraging breastfeeding for human infants.

Anopheles salivary gland proteomes from major malaria vectors

PubMed Central

2012-01-01

Background Antibody responses against Anopheles salivary proteins can indicate individual exposure to bites of malaria vectors. The extent to which these salivary proteins are species-specific is not entirely resolved. Thus, a better knowledge of the diversity among salivary protein repertoires from various malaria vector species is necessary to select relevant genus-, subgenus- and/or species-specific salivary antigens. Such antigens could be used for quantitative (mosquito density) and qualitative (mosquito species) immunological evaluation of malaria vectors/host contact. In this study, salivary gland protein repertoires (sialomes) from several Anopheles species were compared using in silico analysis and proteomics. The antigenic diversity of salivary gland proteins among different Anopheles species was also examined. Results In silico analysis of secreted salivary gland protein sequences retrieved from an NCBInr database of six Anopheles species belonging to the Cellia subgenus (An. gambiae, An. arabiensis, An. stephensi and An. funestus) and Nyssorhynchus subgenus (An. albimanus and An. darlingi) displayed a higher degree of similarity compared to salivary proteins from closely related Anopheles species. Additionally, computational hierarchical clustering allowed identification of genus-, subgenus- and species-specific salivary proteins. Proteomic and immunoblot analyses performed on salivary gland extracts from four Anopheles species (An. gambiae, An. arabiensis, An. stephensi and An. albimanus) indicated that heterogeneity of the salivary proteome and antigenic proteins was lower among closely related anopheline species and increased with phylogenetic distance. Conclusion This is the first report on the diversity of the salivary protein repertoire among species from the Anopheles genus at the protein level. This work demonstrates that a molecular diversity is exhibited among salivary proteins from closely related species despite their common pharmacological activities. The involvement of these proteins as antigenic candidates for genus-, subgenus- or species-specific immunological evaluation of individual exposure to Anopheles bites is discussed. PMID:23148599

ImmPort, toward repurposing of open access immunological assay data for translational and clinical research.

PubMed

Bhattacharya, Sanchita; Dunn, Patrick; Thomas, Cristel G; Smith, Barry; Schaefer, Henry; Chen, Jieming; Hu, Zicheng; Zalocusky, Kelly A; Shankar, Ravi D; Shen-Orr, Shai S; Thomson, Elizabeth; Wiser, Jeffrey; Butte, Atul J

2018-02-27

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components-Private Data, Shared Data, Data Analysis, and Resources-for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the Shared Data portal (www.immport.org/immport-open), which allows research data to be repurposed to accelerate the translation of new insights into discoveries.

Immunological Tools: Engaging Students in the Use and Analysis of Flow Cytometry and Enzyme-linked Immunosorbent Assay (ELISA)

ERIC Educational Resources Information Center

Ott, Laura E.; Carson, Susan

2014-01-01

Flow cytometry and enzyme-linked immunosorbent assay (ELISA) are commonly used techniques associated with clinical and research applications within the immunology and medical fields. The use of these techniques is becoming increasingly valuable in many life science and engineering disciplines as well. Herein, we report the development and…

Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells.

PubMed

Gardiner, Erin J; Cairns, Murray J; Liu, Bing; Beveridge, Natalie J; Carr, Vaughan; Kelly, Brian; Scott, Rodney J; Tooney, Paul A

2013-04-01

Peripheral blood mononuclear cells (PBMCs) represent an accessible tissue source for gene expression profiling in schizophrenia that could provide insight into the molecular basis of the disorder. This study used the Illumina HT_12 microarray platform and quantitative real time PCR (QPCR) to perform mRNA expression profiling on 114 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric controls from the Australian Schizophrenia Research Bank (ASRB). Differential expression analysis revealed altered expression of 164 genes (59 up-regulated and 105 down-regulated) in the PBMCs from patients with schizophrenia compared to controls. Bioinformatic analysis indicated significant enrichment of differentially expressed genes known to be involved or associated with immune function and regulating the immune response. The differential expression of 6 genes, EIF2C2 (Ago 2), MEF2D, EVL, PI3, S100A12 and DEFA4 was confirmed by QPCR. Genome-wide expression analysis of PBMCs from individuals with schizophrenia was characterized by the alteration of genes with immune system function, supporting the hypothesis that the disorder has a significant immunological component in its etiology. Copyright © 2012 Elsevier Ltd. All rights reserved.

RImmPort: an R/Bioconductor package that enables ready-for-analysis immunology research data.

PubMed

Shankar, Ravi D; Bhattacharya, Sanchita; Jujjavarapu, Chethan; Andorf, Sandra; Wiser, Jeffery A; Butte, Atul J

2017-04-01

: Open access to raw clinical and molecular data related to immunological studies has created a tremendous opportunity for data-driven science. We have developed RImmPort that prepares NIAID-funded research study datasets in ImmPort (immport.org) for analysis in R. RImmPort comprises of three main components: (i) a specification of R classes that encapsulate study data, (ii) foundational methods to load data of a specific study and (iii) generic methods to slice and dice data across different dimensions in one or more studies. Furthermore, RImmPort supports open formalisms, such as CDISC standards on the open source bioinformatics platform Bioconductor, to ensure that ImmPort curated study datasets are seamlessly accessible and ready for analysis, thus enabling innovative bioinformatics research in immunology. RImmPort is available as part of Bioconductor (bioconductor.org/packages/RImmPort). rshankar@stanford.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

PubMed

Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

2016-01-19

Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantile regression for the statistical analysis of immunological data with many non-detects.

PubMed

Eilers, Paul H C; Röder, Esther; Savelkoul, Huub F J; van Wijk, Roy Gerth

2012-07-07

Immunological parameters are hard to measure. A well-known problem is the occurrence of values below the detection limit, the non-detects. Non-detects are a nuisance, because classical statistical analyses, like ANOVA and regression, cannot be applied. The more advanced statistical techniques currently available for the analysis of datasets with non-detects can only be used if a small percentage of the data are non-detects. Quantile regression, a generalization of percentiles to regression models, models the median or higher percentiles and tolerates very high numbers of non-detects. We present a non-technical introduction and illustrate it with an implementation to real data from a clinical trial. We show that by using quantile regression, groups can be compared and that meaningful linear trends can be computed, even if more than half of the data consists of non-detects. Quantile regression is a valuable addition to the statistical methods that can be used for the analysis of immunological datasets with non-detects.

Arabinogalactan Proteins From Baobab and Acacia Seeds Influence Innate Immunity of Human Keratinocytes In Vitro.

PubMed

Zahid, Abderrakib; Despres, Julie; Benard, Magalie; Nguema-Ona, Eric; Leprince, Jerome; Vaudry, David; Rihouey, Christophe; Vicré-Gibouin, Maité; Driouich, Azeddine; Follet-Gueye, Marie-Laure

2017-09-01

Plant derived arabinogalactan proteins (AGP) were repeatedly confirmed as immunologically as well as dermatologically active compounds. However, little is currently known regarding their potential activity toward skin innate immunity. Here, we extracted and purified AGP from acacia (Acacia senegal) and baobab (Adansonia digitata) seeds to investigate their biological effects on the HaCaT keratinocyte cell line in an in vitro system. While AGP from both sources did not exhibit any cytotoxic effect, AGP from acacia seeds enhanced cell viability. Moreover, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that AGP extracted from both species induced a substantial overexpression of hBD-2, TLR-5, and IL1-α genes. These data suggest that plant AGP, already known to control plant defensive processes, could also modulate skin innate immune responses. J. Cell. Physiol. 232: 2558-2568, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Single-cell technologies to study the immune system.

PubMed

Proserpio, Valentina; Mahata, Bidesh

2016-02-01

The immune system is composed of a variety of cells that act in a coordinated fashion to protect the organism against a multitude of different pathogens. The great variability of existing pathogens corresponds to a similar high heterogeneity of the immune cells. The study of individual immune cells, the fundamental unit of immunity, has recently transformed from a qualitative microscopic imaging to a nearly complete quantitative transcriptomic analysis. This shift has been driven by the rapid development of multiple single-cell technologies. These new advances are expected to boost the detection of less frequent cell types and transient or intermediate cell states. They will highlight the individuality of each single cell and greatly expand the resolution of current available classifications and differentiation trajectories. In this review we discuss the recent advancement and application of single-cell technologies, their limitations and future applications to study the immune system. © 2015 The Authors. Immunology Published by John Wiley & Sons Ltd.

qPCR for second year undergraduates: A short, structured inquiry to illustrate differential gene expression.

PubMed

McCauslin, Christine Seitz; Gunn, Kathryn Elaine; Pirone, Dana; Staiger, Jennifer

2015-01-01

We describe a structured inquiry laboratory exercise that examines transcriptional regulation of the NOS2 gene under conditions that simulate the inflammatory response in macrophages. Using quantitative PCR and the comparative CT method, students are able determine whether transcriptional activation of NOS2 occurs and to what degree. The exercise is aimed at second year undergraduates who possess basic knowledge of gene expression events. It requires only 4-5 hr of dedicated laboratory time and focuses on use of the primary literature, data analysis, and interpretation. Importantly, this exercise provides a mechanism to introduce the concept of differential gene expression and provides a starting point for development of more complex guided or open inquiry projects for students moving into upper level molecular biology, immunology, and biochemistry course work. © 2015 The International Union of Biochemistry and Molecular Biology.

Numerical modelling in biosciences using delay differential equations

NASA Astrophysics Data System (ADS)

Bocharov, Gennadii A.; Rihan, Fathalla A.

2000-12-01

Our principal purposes here are (i) to consider, from the perspective of applied mathematics, models of phenomena in the biosciences that are based on delay differential equations and for which numerical approaches are a major tool in understanding their dynamics, (ii) to review the application of numerical techniques to investigate these models. We show that there are prima facie reasons for using such models: (i) they have a richer mathematical framework (compared with ordinary differential equations) for the analysis of biosystem dynamics, (ii) they display better consistency with the nature of certain biological processes and predictive results. We analyze both the qualitative and quantitative role that delays play in basic time-lag models proposed in population dynamics, epidemiology, physiology, immunology, neural networks and cell kinetics. We then indicate suitable computational techniques for the numerical treatment of mathematical problems emerging in the biosciences, comparing them with those implemented by the bio-modellers.

Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway analysis in inflammatory bowel disease.

PubMed

Fransen, Karin; van Sommeren, Suzanne; Westra, Harm-Jan; Veenstra, Monique; Lamberts, Letitia E; Modderman, Rutger; Dijkstra, Gerard; Fu, Jingyuan; Wijmenga, Cisca; Franke, Lude; Weersma, Rinse K; van Diemen, Cleo C

2014-05-01

The Th17/IL23 pathway has both genetically and biologically been implicated in the pathogenesis of the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. So far, it is unknown whether and how associated risk variants affect expression of the genes encoding for Th17/IL23 pathway proteins. Ten IBD-associated SNPs residing near Th17/IL23 genes were used to construct a genetic risk model in 753 Dutch IBD cases and 1045 controls. In an independent cohort of 40 Crohn's disease, 40 ulcerative colitis, and 40 controls, the genetic risk load and presence of IBD were correlated to quantitative PCR-generated messenger RNA (mRNA) expression of 9 representative Th17/IL23 genes in both unstimulated and PMA/CaLo stimulated peripheral blood mononuclear cells. In 1240 individuals with various immunological diseases with whole genome genotype and mRNA-expression data, we also assessed correlation between genetic risk load and differential mRNA expression and sought for SNPs affecting expression of all currently known Th17/IL23 pathway genes (cis-expression quantitative trait locus). The presence of IBD, but not the genetic risk load, was correlated to differential mRNA expression for IL6 in unstimulated peripheral blood mononuclear cells and to IL23A and RORC in response to stimulation. The cis-expression quantitative trait locus analysis showed little evidence for correlation between genetic risk load and mRNA expression of Th17/IL23 genes, because we identified for only 2 of 22 Th17/IL23 genes a cis-expression quantitative trait locus single nucleotide polymorphism that is also associated to IBD (STAT3 and CCR6). Our results suggest that only the presence of IBD and not the genetic risk load alters mRNA expression levels of IBD-associated Th17/IL23 genes.

HLA-typing analysis following allogeneic bone grafting for sinus lifting.

PubMed

Piaia, Marcelo; Bub, Carolina Bonet; Succi, Guilherme de Menezes; Torres, Margareth; Costa, Thiago Henrique; Pinheiro, Fabricio Costa; Napimoga, Marcelo Henrique

2017-03-01

According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical technique itself has a respectable number of reports regarding its clinical efficacy, as measured by long-term survival of dental implants in grafted areas. Uncertainty remains, however, as to whether fresh frozen grafts from human bone donors remain immunologically innocuous in the body of the host. Six male with no previous medical history of note, including systemic diseases, surgery or blood transfusion were selected. These patients underwent reconstructive procedures (sinus lifting) using fresh frozen human bone from a tissue bank. All patients had venous blood samples collected prior to surgery and 6 months after the procedure. Anti-HLA analysis for the detection of HLA (human leukocyte antigen) antibodies was performed using methods such as the LABScreen PRA Class I and Class II, LABScreen Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the screening tests (LABScreen PRA) were further investigated to determine the specificity of the antibodies detected (LABScreen Single Antigen) with a cutoff value of median fluorescence intensity ≥500. As a result, it was observed that two patients (33%) were positive in screening tests, one presenting with anti-HLA Class I and II sensitization and the other with anti-HLA class II. The specificity analysis showed that the patients sensitized to HLA class II presented 4 specificities, 3 of which immunologically relevant. In the second individual, 23 specificities were identified, 6 of which immunologically important for HLA class I and 4 specificities for HLA class II, 3 of these were immunologically important. All specificities detected had average fluorescence. These findings are suggestive that sinus-lifting procedures with allogeneic bone can induce immunological sensitization.

In-depth characterization of the fluorescent signal of HyPer, a probe for hydrogen peroxide, in bacteria exposed to external oxidative stress.

PubMed

Lim, Joseph B; Barker, Kimberly A; Huang, Beijing K; Sikes, Hadley D

2014-11-01

Genetically encoded, fluorescent biosensors have been developed to probe the activities of various signaling molecules inside cells ranging from changes in intracellular ion concentrations to dynamics of lipid second messengers. HyPer is a member of this class of biosensors and is the first to dynamically respond to hydrogen peroxide (H2O2), a reactive oxygen species that functions as a signaling molecule. However, detailed characterization of HyPer's signal is not currently available within the context of bacteria exposed to external oxidative stress, which occurs in the immunological response of higher organisms against invasive pathogenic bacteria. Here, we performed this characterization, specifically in Escherichia coli exposed to external H2O2. We found that the temporal behavior of the signal does not correspond exactly to peroxide concentration in the system as a function of time and expression of the sensor decreases the peroxide scavenging activity of the cell. We also determined the effects of cell number, both before and after normalization of externally added H2O2 to the number of cells. Finally, we report quantitative characteristics of HyPer's signal in this context, including the dynamic range of the signal, the signal-to-noise ratio, and the half saturation constant. These parameters show statistically meaningful differences in signal between two commonly used strains of E. coli, demonstrating how signal can vary with strain. Taken together, our results establish a systematic, quantitative framework for researchers seeking to better understand the role of H2O2 in the immunological response against bacteria, and for understanding potential differences in the details of HyPer's quantitative performance across studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Immunological characteristics of patients infected with common intestinal helminths: results of a study based on reverse-transcriptase PCR.

PubMed

Lertanekawattana, S; Wichatrong, T; Chaisari, K; Uchikawa, R; Arizono, N

2005-01-01

To determine whether common helminth infections could modify the intestinal immunopathological status of the host, the expression in the human duodenal mucosa of cytokines, eosinophil- and mast-cell-specific molecules and monosaccharide transporters of the glucose-transporter (GLUT) family was explored. The 31 subjects were all patients at the gastro-intestinal disease unit of Nongkhai Hospital, Thailand. Four of the 10 patients who presented with eosinophilia (> or = 6.0% of their leucocytes were eosinophils), and five of the other 21 patients, had intestinal infections with helminths when they presented or within the previous 3 months. Studies based on semi-quantitative, reverse-transcriptase PCR revealed that the interleukin-5/interferon-gamma ratio was significantly higher in the noneosinophilic, helminth-infected patients than in the non-eosinophilic, uninfected patients, whereas the IgE receptor type I (Fc epsilon RI)/mast-cell tryptase ratio was significantly higher in the eosinophilic, helminth-infected patients than in the eosinophilic, uninfected patients. Expression of Charcot-Leyden-crystal protein, GLUT-1 and GLUT-5, however, showed no significant inter-group differences. Principal-components analysis of the data on eosinophils, interleukin-5, interferon-gamma, Fc epsilon RI and mast-cell tryptase revealed that one principal component could discriminate the patients who had helminth infection from the non-eosinophilic, uninfected patients, but not from the eosinophilic, uninfected patients. These results indicate that, whatever the intestinal pathology, patients infected with common intestinal helminths tend to develop a mucosal immunological response of the Th2 type.

Characterization and functional analysis of cellular immunity in mice with biotinidase deficiency.

PubMed

Pindolia, Kirit; Li, Hong; Cardwell, Cisley; Wolf, Barry

2014-05-01

Biotinidase deficiency is an autosomal recessively inherited metabolic disorder that can be easily and effectively treated with pharmacological doses of the vitamin, biotin. Untreated children with profound biotinidase deficiency may exhibit neurological, cutaneous and cellular immunological abnormalities, specifically candida infections. To better understand the immunological dysfunction in some symptomatic individuals with biotinidase deficiency, we studied various aspects of immunological function in a genetically engineered knock-out mouse with biotinidase deficiency. The mouse has no detectable biotinidase activity and develops neurological and cutaneous symptoms similar to those seen in symptomatic children with the disorder. Mice with profound biotinidase deficiency on a biotin-restricted diet had smaller thymuses and spleens than identical mice fed a biotin-replete diet or wildtype mice on either diet; however, the organ to body weight ratios were not significantly different. Thymus histology was normal. Splenocyte subpopulation study showed a significant increase in CD4 positive cells. In addition, in vitro lymphocyte proliferation assays consistently showed diminished proliferation in response to various immunological stimuli. Not all symptomatic individuals with profound biotinidase deficiency develop immunological dysfunction; however, our results do show significant alterations in cellular immunological function that may contribute and/or provide a mechanism(s) for the cellular immunity abnormalities in individuals with biotinidase deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Citizens unite for computational immunology!

PubMed

Belden, Orrin S; Baker, Sarah Catherine; Baker, Brian M

2015-07-01

Recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for such 'crowdsourcing' efforts in immunology. Tools for developing applications, new funding opportunities, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real - it is time to jump in! Copyright © 2015 Elsevier Ltd. All rights reserved.

Publication trends of Allergy, Pediatric Allergy and Immunology, and Clinical and Translational Allergy journals: a MeSH term-based bibliometric analysis.

PubMed

Martinho-Dias, Daniel; Sousa-Pinto, Bernardo; Botelho-Souza, Júlio; Soares, António; Delgado, Luís; Fonseca, João Almeida

2018-01-01

We performed a MeSH term-based bibliometric analysis aiming to assess the publication trends of EAACI journals, namely Allergy, Pediatric Allergy and Immunology (PAI) (from 1990 to 2015) and Clinical and Translational Allergy (CTA) (from its inception in 2011 to 2015). We also aimed to discuss the impact of the creation of CTA in the publication topics of Allergy and PAI. We analysed a total of 1973 articles and 23,660 MeSH terms. Most MeSH terms in the three journals fell in the category of "basic immunology and molecular biology" (BIMB). During the studied period, we observed an increase in the proportion of MeSH terms on BIMB, and a decreasing proportion of terms on allergic rhinitis and aeroallergens. The observed changes in Allergy and PAI publication topics hint at a possible impact from CTA creation.

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda.

PubMed

Ruiseñor-Escudero, Horacio; Familiar-Lopez, Itziar; Sikorskii, Alla; Jambulingam, Nikita; Nakasujja, Noelline; Opoka, Robert; Bass, Judith; Boivin, Michael

2016-04-15

To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children aged 1-6 years, participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z scores (WAZs), antiretroviral therapy status, and immunological biomarkers. In the final analysis, 111 children were included. Lower levels of CD4 CD38 T cells (P = 0.04) were associated to higher immediate and total recall scores (P = 0.04). Higher levels of CD8 HLA-DR T cells were associated with higher total recall score (P = 0.04) of the COAT. Higher CD4 CD38 HLA-DR T cells levels were associated with higher gross motor scores of the MSEL (P = 0.02). WAZ was positively correlated to visual reception, fine motor, expressive language, and composite score of the MSEL. Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4 CD38 T cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship.

[Critical analysis of the immunological self/non-self model and of its implicit metaphysical foundations].

PubMed

Pradeu, Thomas; Carosella, Edgardo D

2004-05-01

An examination of the concepts used in immunology prompts us to wonder about the origins and the legitimacy of the notions of self and non-self, which constitute the core of the dominant theoretical model in this science. All theoretical reflection concerning immunology must aim at determining a criterion of immunogenicity, that is, an operational definition of the conditions in which an immune reaction occurs or does not occur. By criticizing both conceptually and experimentally the self/non-self vocabulary, we can demonstrate the inaccuracy and even the inadequacy of the dichotomy of self/non-self. Accordingly, the self/non-self model must be reexamined, or even rejected. On the basis of this critique, we can suggest an alternative theoretical hypothesis for immunology, based on the notion of continuity. The 'continuity hypothesis' developed here attempts to give a criterion of immunogenicity that avoids the reproaches leveled at the self model.

Evaluation of reference genes for quantitative real-time RT-PCR analysis of gene expression in Nile tilapia (Oreochromis niloticus).

PubMed

Yang, Chang Geng; Wang, Xian Li; Tian, Juan; Liu, Wei; Wu, Fan; Jiang, Ming; Wen, Hua

2013-09-15

Quantitative real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) has been used frequently to study gene expression related to fish immunology. In such studies, a stable reference gene should be selected to correct the expression of the target gene. In this study, seven candidate reference genes (glyceraldehyde-3-phosphate dehydrogenase (GADPH), ubiquitin-conjugating enzyme (UBCE), 18S ribosomal RNA (18S rRNA), beta-2-microglobulin (B2M), elongation factor 1 alpha (EF1A), tubulin alpha chain-like (TUBA) and beta actin (ACTB)), were selected to analyze their stability and normalization in seven tissues (liver, spleen, kidney, brain, heart, muscle and intestine) of Nile tilapia (Oreochromis niloticus) challenged with Streptococcus agalactiae or Streptococcus iniae, respectively. The results showed that all the candidate reference genes exhibited tissue-dependent transcriptional variations. With PBS injection as a control, UBCE was the most stable and suitable single reference gene in the intestine, liver, brain, kidney, and spleen after S. iniae infection, and in the liver, kidney, and spleen after S. agalactiae infection. EF1A was the most suitable in heart and muscle after S. iniae or S. agalactiae infection. GADPH was the most suitable gene in intestine and brain after S. agalactiae infection. In normal conditions, UBCE and 18S rRNA were the most stably expressed genes across the various tissues. These results showed that for RT-qPCR analysis of tilapia, selecting two or more reference genes may be more suitable for cross-tissue analysis of gene expression. Copyright © 2013 Elsevier B.V. All rights reserved.

A CD4+ cell count <200 cells per cubic millimeter at 2 years after initiation of combination antiretroviral therapy is associated with increased mortality in HIV-infected individuals with viral suppression.

PubMed

Loutfy, Mona R; Genebat, Miguel; Moore, David; Raboud, Janet; Chan, Keith; Antoniou, Tony; Milan, David; Shen, Anya; Klein, Marina B; Cooper, Curtis; Machouf, Nima; Rourke, Sean B; Rachlis, Anita; Tsoukas, Chris; Montaner, Julio S G; Walmsley, Sharon L; Smieja, Marek; Bayoumi, Ahmed; Mills, Edward; Hogg, Robert S

2010-12-01

To determine the long-term impact of immunologic discordance (viral load <50 copies/mL and CD4+ count <=200 cells/mm3) in antiretroviral-naive patients initiating combination antiretroviral therapy (cART). Our analysis included antiretroviral-naive individuals from a population-based Canadian Observational Cohort that initiated cART after January 1, 2000, and achieved virologic suppression. Multivariable Cox proportional hazards regression was used to examine the association between 1-year and 2-year immunologic discordance and time to death from all-causes. Correlates of immunologic discordance were assessed with logistic regression. Immunologic discordance was observed in 19.9% (404 of 2028) and 10.2% (176 of 1721) of individuals at 1 and 2 years after cART initiation, respectively. Two-year immunologic discordance was associated with an increased risk of death [adjusted hazard ratio = 2.69; 95% confidence interval (CI): 1.26 to 5.78]. One-year immunologic discordance was not associated with death (adjusted hazard ratio = 1.12; 95% CI: 0.54 to 2.30). Two-year immunologic discordance was associated with older age (aOR per decade = 1.23; 95% CI: 1.03 to 1.48), male gender (aOR = 1.86; 95% CI: 1.09 to 3.16), injection drug use (aOR = 2.75; 95% CI: 1.81 to 4.17), and lower baseline CD4+ count (aOR per 100 cells = 0.24; 95% CI: 0.19 to 0.31) and viral load (aOR per log10 copies/mL = 0.46; 95% CI: 0.33 to 0.65). Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.

Antibody Profile of Colostrum and the Effect of Processing in Human Milk Banks: Implications in Immunoregulatory Properties.

PubMed

Rodríguez-Camejo, Claudio; Puyol, Arturo; Fazio, Laura; Rodríguez, Analía; Villamil, Emilia; Andina, Eliana; Cordobez, Vanira; Díaz, Hernán; Lemos, Mary; Siré, Gabriela; Carroscia, Lilián; Castro, Mara; Panizzolo, Luis; Hernández, Ana

2018-02-01

When feeding preterm infants, donor milk is preferred if the mother's own milk is unavailable. Pasteurization may have detrimental effects on bioactivity, but more information is needed about its effects on the immunological compounds. Research aim: This work has two main aims: evaluate the antibody profile of colostrum and study the quantitative variations in the antibodies' level and specific reactivity after undergoing Holder pasteurization. The authors focused on immunoregulatory components of colostrum (antidietary antibodies and TGF-β2) in the neonatal gut. This is a descriptive cross-sectional study of a convenience sample of 67 donated colostrum samples at different days after delivery, both raw and pasteurized. Antibody profiles were analyzed at different times during breastfeeding, and total and specific antibodies (IgM, IgA, and IgG subclasses) were compared with tetanus toxoid and ovalbumin using enzyme-linked immunosorbent assay. The processing effect on total and specific antibodies, as well as TGF-β2, was evaluated by paired analyses. No variations in immunological compounds were observed throughout the colostrum stage. The TGF-β2, antibodies' concentrations, and antibodies' specific reactivity after pasteurization did not vary significantly as days of lactation varied. Changes in antibody levels were dependent on isotype and IgG subclass, and IgG4 showed remarkable resistance to heating. Moreover, the effect of the pasteurization on specific reactivity was antigen dependent. The supply of relevant immunological components is stable throughout the colostrum stage. The effects of pasteurization on antibodies depend on isotype, subclass, and specificity. This information is relevant to improving the immunological quality of colostrum, especially for preterm newborns.

Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents.

PubMed

Baral, Subhasish; Roy, Rahul; Dixit, Narendra M

2018-05-09

A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT + /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT + /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment. Whether the hypothesis is consistent with data of viral load changes in patients who experienced EOT + /SVR is unknown. Here, we constructed a mathematical model of viral kinetics incorporating the immunologic hypothesis and compared its predictions with patient data. We found the predictions to be in quantitative agreement with patient data. Using the model, we unraveled an underlying bistability that gives rise to EOT + /SVR and presents a new avenue to optimize treatment durations. Infected cells trigger both activation and exhaustion of CTLs. CTLs in turn kill infected cells. Due to these competing interactions, two stable steady states, chronic infection and viral clearance, emerge, separated by an unstable steady state with intermediate viremia. When treatment during chronic infection drives viremia sufficiently below the unstable state, spontaneous viral clearance results post-treatment, marking EOT + /SVR. The duration to achieve this desired reduction in viremia defines the minimum treatment duration required for ensuring SVR, which our model can quantify. Estimating parameters defining the CTL response of individuals to HCV infection would enable the application of our model to personalize treatment durations. © 2018 The Authors Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.

Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients.

PubMed

Sung, Cynthia; Wei, Yuan; Watanabe, Satoru; Lee, How Sung; Khoo, Yok Moi; Fan, Lu; Rathore, Abhay P S; Chan, Kitti Wing-Ki; Choy, Milly M; Kamaraj, Uma S; Sessions, October M; Aw, Pauline; de Sessions, Paola F; Lee, Bernett; Connolly, John E; Hibberd, Martin L; Vijaykrishna, Dhanasekaran; Wijaya, Limin; Ooi, Eng Eong; Low, Jenny Guek-Hong; Vasudevan, Subhash G

2016-08-01

CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients' isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue infection. Optimization of the dosing regimen and patient stratification may enhance the ability of a clinical trial to demonstrate celgosivir activity in treating dengue fever based on hematological endpoints. A new clinical trial with a revised dosing regimen is slated to start in 2016 (NCT02569827). Furthermore celgosivir's potential value for treatment of other flaviruses such as Zika virus should be investigated urgently. ClinicalTrials.gov NCT01619969.

[Analysis of the etiological structure of sexually transmitted infections and immunological responsiveness in women with papillomavirus infection of the cervix uteri].

PubMed

Shevchenko, E A; Uspenskaia, O A

2009-01-01

Two sexually transmitted infections or more were more frequently encountered in persistent papillomavirus infection (PVI) than those in transient PVI. The found immunological parameters in PVI arrested further infection progression, suppressed the persistence of human papillomavirus infection types 16 and 18, and prevented related cancer. This might eliminate the virus from the body.

Donkey's milk detailed lipid composition.

PubMed

Gastaldi, Daniela; Bertino, Enrico; Monti, Giovanna; Baro, Cristina; Fabris, Claudio; Lezo, Antonela; Medana, Claudio; Baiocchi, Claudio; Mussap, Michele; Galvano, Fabio; Conti, Amedeo

2010-01-01

Donkey's milk (DM) has recently aroused scientific interest, above all among paediatric allergologists. A deeper knowledge of both proteins and fats in donkey's milk is necessary to evaluate the immunological, physiological and nutritional properties. By using the most refined techniques for fatty acids analysis, the paper offers a detailed comparative analysis of the lipid fractions of DM as well as of human and cow milk, also indicating the distribution of fatty-acid moieties among sn-1/3 and sn-2 positions of the glycerol backbone. In DM the position of fatty acids on glycerol backbone, above all of long chain saturated fatty acids, is very similar to that of human milk: this fact, in conjunction with the relatively high contents of medium-chain triglycerides, makes the lipids in DM, through quantitatively reduced, highly bioavailable. The high PUFA n-3 content of donkey's milk, and especially its low n-6/n-3 ratio, acquires particular interest in subjects affected by cow's milk protein allergy. Whole DM might also constitute the basis for formulas suitable for subjects in the first year of life.

A Rapid and Sensitive Method for the Quantitation of Legionella Pneumophila Antigen from Human Urine.

DTIC Science & Technology

1980-11-12

320-325. 4. Hedlund, K. W., V. G. McGann, D. S . Copeland, S . F. Little, and R. G. Allen. 1979. Immunologic protection against the Legionnaires ’ disease ...reverse% passive hemagglutination test was developed to assay concentrations of solubl4 antigen of Legionnaires ’ Disease (Legionella pneumophila) in...URINE U. S . Arm" Medical Research Institute of Infectious Diseases Fort Detrick, Frederick, Maryland 21701 The views of the authors do not purport to

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

PubMed Central

Baxter, Samantha; Menon, Arjun; Alaarg, Amr; Sanchez-Gaytan, Brenda L.; Fay, Francois; Zhao, Yiming; Ouimet, Mireille; Braza, Mounia S.; Longo, Valerie A.; Abdel-Atti, Dalya; Duivenvoorden, Raphael; Calcagno, Claudia; Storm, Gert; Tsimikas, Sotirios; Moore, Kathryn J.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Pérez-Medina, Carlos; Fayad, Zahi A.; Reiner, Thomas; Mulder, Willem J. M.

2016-01-01

Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library’s nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe−/−) mouse model of atherosclerosis, we quantitatively evaluated the library’s immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases. PMID:27791119

Gaucher disease: Physical, kinetic and immunologic investigations of human and canine acid. beta. -glucosidase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fabbro, D.E.

1988-01-01

Kinetic and immunologic techniques were developed to investigate the nature of the acid {beta}-glucosidase ({beta}-Glc) defects which results in human and canine Gaucher disease (GD). Two new affinity columns, using the potent inhibitors of {beta}-Glc (N-alkyl-deoxynojirimycins) as affinity ligands, were synthesized and methods were developed to obtain homogeneous {beta}-Glc from normal human placenta. Polyclonal and monoclonal (representing 14 different epitopes from 18 clones) antibodies were produced to the pure normal {beta}-Glc. Monospecific polyclonal IgG and tritiated-bromo-conduritol B epoxide (({sup 3}H)Br-CBE), a specific covalent active site directed inhibitor of {beta}-Glc, were used to quantitate the functional catalytic sites in normal andmore » Type 1 Ashkenazi Jewish GD (AJGD) enzyme preparations: The k{sub cat} values for several new substrates with the mutant enzymes from spleen were about 1.5-fold less than the respective normal enzyme, indicating a nearly normal catalytic capacity of the mutant enzymes. Immunoblotting studies with polyclonal or several monoclonal antibodies indicated three molecular forms of {beta}-Glc (M{sub r} = 67,000, 62,000 to 65,000 and 58,000) in fibroblast extracts from normals and Type 1 AJGD patients. In comparison, only one form of cross-reacting immunologic material (CRIM) was detected in fibroblast extracts from Types 2 and 3 or several non-Jewish Type 1 GD patients.« less

Conformationally selective biophysical assay for influenza vaccine potency determination.

PubMed

Wen, Yingxia; Han, Liqun; Palladino, Giuseppe; Ferrari, Annette; Xie, Yuhong; Carfi, Andrea; Dormitzer, Philip R; Settembre, Ethan C

2015-10-05

Influenza vaccines are the primary intervention for reducing the substantial health burden from pandemic and seasonal influenza. Hemagglutinin (HA) is the most important influenza vaccine antigen. Subunit and split influenza vaccines are formulated, released for clinical use, and tested for stability based on an in vitro potency assay, single-radial immunodiffusion (SRID), which selectively detects HA that is immunologically active (capable of eliciting neutralizing or hemagglutination inhibiting antibodies in an immunized subject). The time consuming generation of strain-specific sheep antisera and calibrated antigen standards for SRID can delay vaccine release. The limitation in generating SRID reagents was evident during the early days of the 2009 pandemic, prompting efforts to develop more practical, alternative, quantitative assays for immunologically active HA. Here we demonstrate that, under native conditions, trypsin selectively digests HA produced from egg or mammalian cell in monovalent vaccines that is altered by stress conditions such as reduced pH, elevated temperature, or deamidation, leaving native, pre-fusion HA, intact. Subsequent reverse-phase high pressure liquid chromatography (RP-HPLC) can separate trypsin-resistant HA from the digested HA. Integration of the resulting RP-HPLC peak yields HA quantities that match well the values obtained by SRID. Therefore, trypsin digestion, to pre-select immunologically active HA, followed by quantification by RP-HPLC is a promising alternative in vitro potency assay for influenza vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5210 Ceruloplasmin immunolog-ical test system. (a) Identification. A ceruloplasmin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210...

Enhancing the Breadth of Efficacy of Therapeutic Vaccines for Breast Cancer

DTIC Science & Technology

2014-10-01

4b. Generate specific tumor antigen lysates from recombinant baculovirus- infected insect cells. *Currently expressing antigens in C1R cells since... Immunology Conference, Breckenridge CO (invited by Jim Hagman). Sept 20, 2014, Analysis of the T cell repertoire in breast cancer using emulsion...by Jonathan Bramson).   13 Nov 11, 2014 (anticipated), Elimination of the bottlenecks in T cell receptor antigen discovery, Immunology Forum

Immunohistochemical analysis of immune response in breast cancer and melanoma patients after laser immunotherapy

NASA Astrophysics Data System (ADS)

Nordquist, Robert E.; Bishop, Shelly L.; Ferguson, Halie; Vaughan, Melville B.; Jose, Jessnie; Kastl, Katherine; Nguyen, Long; Li, Xiaosong; Liu, Hong; Chen, Wei R.

2011-03-01

Laser immunotherapy (LIT) has shown great promise in pre-clinical studies and preliminary clinical trials. It could not only eradicate treated local tumors but also cause regression and elimination of untreated metastases at distant sites. Combining a selective photothermal therapy with an active immunological stimulation, LIT can induce systemic anti-tumor immune responses. Imiquimod (IMQ), a toll-like receptor agonist, was used for the treatment of late-stage melanoma patients and glycated chitosan (GC), a biological immunological modulator, was used for the treatment of late-stage breast cancer patients, in combination of irradiation of a near-infrared laser light. To observe the immunological changes before and after LIT treatment, the pathological tissues of melanoma and breast cancer patients were processed for immunohistochemical analysis. Our results show that LIT changed the expressions of several crucial T cell types. Specifically, we observed significant decreases of CD3+ T-cells and a significant increase of CD4+,CD8+, and CD68+ T-cells in the tumor samples after LIT treatment. While not conclusive, our study could shed light on one the possible mechanisms of anti-tumor immune responses induced by LIT. Further studies will be conducted to identify immunological biomarkers associated with LIT-induced clinical response.

Nutritional and immunological correlates of memory and neurocognitive development among HIV infected children living in Kayunga, Uganda

PubMed Central

Horacio, Ruiseñor-Escudero; Itziar, Familiar-Lopez; Alla, Sikorskii; Nikita, Jambulingam; Noelline, Nakasujja; Robert, Opoka; Judith, Bass; Michael, Boivin

2015-01-01

Objective To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. Design This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children ages 1–6 years participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Methods Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z-scores (WAZ), antiretroviral therapy (ART) status and immunological biomarkers. Results 111 children were included in the final analysis. Lower levels of CD4+ CD38+ T-cells (p=0.04) were associated to higher Immediate and Total Recall scores (p=0.04). Higher levels of CD8+ HLA-DR+ T-cells were associated with higher Total Recall score (p=0.04) of the COAT. Higher CD4+ CD38+ HLA-DR+ T-cells levels were associated with higher Gross Motor scores of the MSEL (p=0.02). WAZ was positively correlated to Visual Reception, Fine Motor, Expressive Language and composite score of the MSEL. Conclusions Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4+ CD38+ T-cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship. PMID:26605506

21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160...

Big data analytics in immunology: a knowledge-based approach.

PubMed

Zhang, Guang Lan; Sun, Jing; Chitkushev, Lou; Brusic, Vladimir

2014-01-01

With the vast amount of immunological data available, immunology research is entering the big data era. These data vary in granularity, quality, and complexity and are stored in various formats, including publications, technical reports, and databases. The challenge is to make the transition from data to actionable knowledge and wisdom and bridge the knowledge gap and application gap. We report a knowledge-based approach based on a framework called KB-builder that facilitates data mining by enabling fast development and deployment of web-accessible immunological data knowledge warehouses. Immunological knowledge discovery relies heavily on both the availability of accurate, up-to-date, and well-organized data and the proper analytics tools. We propose the use of knowledge-based approaches by developing knowledgebases combining well-annotated data with specialized analytical tools and integrating them into analytical workflow. A set of well-defined workflow types with rich summarization and visualization capacity facilitates the transformation from data to critical information and knowledge. By using KB-builder, we enabled streamlining of normally time-consuming processes of database development. The knowledgebases built using KB-builder will speed up rational vaccine design by providing accurate and well-annotated data coupled with tailored computational analysis tools and workflow.

Arsenic, Cadmium and Lead Exposure and Immunologic Function in Workers in Taiwan.

PubMed

Wu, Chin-Ching; Sung, Fung-Chang; Chen, Yi-Chun

2018-04-05

There has been growing concern over the impact of environmental exposure to heavy metals and other trace elements on immunologic functions. This study investigated men's arsenic (As), cadmium (Cd) and lead (Pb) contents in hair samples and their associations with immunological indicators, including white blood cell (WBC), lymphocyte and monocyte counts, and the immunoglobulin (Ig) levels including IgA, IgG and IgE. We recruited 133 men from one antimony trioxide manufacturing plant, two glass manufacturing plants and two plastics manufacturing plants. The mean concentration of Cd [0.16 (SD = 0.03) ug/g] was lower than means of As [0.86 (SD = 0.16) ug/g] and Pb [0.91 (SD = 0.22) ug/g] in hair samples, exerting no relationship with immunologic functions for Cd. The Spearman's correlation analysis showed a positive relationship between monocyte counts and hair Pb levels, but negative relations between As and IgG and between As and IgE. In conclusion, findings from these industry workers suggest that As levels in hair may have a stronger relation with immunologic function than Cd and PB have. Further research is needed to confirm the negative relationship.

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

PubMed Central

El-Khatib, Ziad; Katzenstein, David; Marrone, Gaetano; Laher, Fatima; Mohapi, Lerato; Petzold, Max; Morris, Lynn; Ekström, Anna Mia

2011-01-01

Background Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO). Results After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure. PMID:21408071

Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting.

PubMed

Khan, Tarik A; Friedensohn, Simon; Gorter de Vries, Arthur R; Straszewski, Jakub; Ruscheweyh, Hans-Joachim; Reddy, Sai T

2016-03-01

High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion-the intraclonal diversity index-which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology.

Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting

PubMed Central

Khan, Tarik A.; Friedensohn, Simon; de Vries, Arthur R. Gorter; Straszewski, Jakub; Ruscheweyh, Hans-Joachim; Reddy, Sai T.

2016-01-01

High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion—the intraclonal diversity index—which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology. PMID:26998518

How and why does the immunological synapse form? Physical chemistry meets cell biology.

PubMed

Chakraborty, Arup K

2002-03-05

During T lymphocyte (T cell) recognition of an antigen, a highly organized and specific pattern of membrane proteins forms in the junction between the T cell and the antigen-presenting cell (APC). This specialized cell-cell junction is called the immunological synapse. It is several micrometers large and forms over many minutes. A plethora of experiments are being performed to study the mechanisms that underlie synapse formation and the way in which information transfer occurs across the synapse. The wealth of experimental data that is beginning to emerge must be understood within a mechanistic framework if it is to prove useful in developing modalities to control the immune response. Quantitative models can complement experiments in the quest for such a mechanistic understanding by suggesting experimentally testable hypotheses. Here, a quantitative synapse assembly model is described. The model uses concepts developed in physical chemistry and cell biology and is able to predict the spatiotemporal evolution of cell shape and receptor protein patterns observed during synapse formation. Attention is directed to how the juxtaposition of model predictions and experimental data has led to intriguing hypotheses regarding the role of null and self peptides during synapse assembly, as well as correlations between T cell effector functions and the robustness of synapse assembly. We remark on some ways in which synergistic experiments and modeling studies can improve current models, and we take steps toward a better understanding of information transfer across the T cell-APC junction.

Proteomic analysis of protective effects of polysaccharides from Salvia miltiorrhiza against immunological liver injury in mice.

PubMed

Sun, Xue-Gang; Fu, Xiu-Qiong; Cai, Hong-Bing; Liu, Qiang; Li, Chun-Hua; Liu, Ya-Wei; Li, Ying-Jia; Liu, Zhi-Feng; Song, Yu-Hong; Lv, Zhi-Ping

2011-07-01

This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guérin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation. Copyright © 2011 John Wiley & Sons, Ltd.

Electrochemical analysis of gold-coated magnetic nanoparticles for detecting immunological interaction

NASA Astrophysics Data System (ADS)

Pham, Thao Thi-Hien; Sim, Sang Jun

2010-01-01

An electrochemical impedance immunosensor was developed for detecting the immunological interaction between human immunoglobulin (IgG) and protein A from Staphylococcus aureus based on the immobilization of human IgG on the surface of modified gold-coated magnetic nanoparticles. The nanoparticles with an Au shell and Fe oxide cores were functionalized by a self-assembled monolayer of 11-mercaptoundecanoic acid. The electrochemical analysis was conducted on the modified magnetic carbon paste electrodes with the nanoparticles. The magnetic nanoparticles were attached to the surface of the magnetic carbon paste electrodes via magnetic force. The cyclic voltammetry technique and electrochemical impedance spectroscopy measurements of the magnetic carbon paste electrodes coated with magnetic nanoparticles-human IgG complex showed changes in its alternating current (AC) response both after the modification of the surface of the electrode and the addition of protein A. The immunological interaction between human IgG on the surface of the modified magnetic carbon paste electrodes and protein A in the solution could be successfully monitored.

Prior pregnancy and antenatal rubella sero-negativity-evidence of persistent maternal immunologic alteration?

PubMed

Lao, Terence T; Hui, Annie S Y; Sahota, Daljit S

2017-09-01

It is unclear if the immunologic alterations induced by pregnancy could persist. Antenatal rubella sero-negativity was correlated with gravidity, abortions and parity in 112 083 gravidae managed during 1997-2015, with further analysis stratified for factors known to influence rubella serology. The 10.2% sero-negative gravidae had different characteristics, and the incidence showed significant difference and positive trend (P<.001 for both) with gravidity, abortions and parity. The pattern remained consistent when analysis was stratified for advanced age, high body mass index and medical history, but was negated by hepatitis B virus infection except for abortions, and by high body mass index for parity. For gravidity 2-4, no difference in rubella sero-negativity was found between gravidae with all previous pregnancies ended in abortion vs delivery. Prior pregnancies diminished rubella immunity in a dose-dependent manner, which may be a reflection of the cumulative effect of pregnancy-associated maternal immunologic alteration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spaceflight and Immune Responses of Rhesus Monkeys

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1997-01-01

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

HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology

PubMed Central

Zhang, Guang Lan; Riemer, Angelika B.; Keskin, Derin B.; Chitkushev, Lou; Reinherz, Ellis L.; Brusic, Vladimir

2014-01-01

High-risk human papillomaviruses (HPVs) are the causes of many cancers, including cervical, anal, vulvar, vaginal, penile and oropharyngeal. To facilitate diagnosis, prognosis and characterization of these cancers, it is necessary to make full use of the immunological data on HPV available through publications, technical reports and databases. These data vary in granularity, quality and complexity. The extraction of knowledge from the vast amount of immunological data using data mining techniques remains a challenging task. To support integration of data and knowledge in virology and vaccinology, we developed a framework called KB-builder to streamline the development and deployment of web-accessible immunological knowledge systems. The framework consists of seven major functional modules, each facilitating a specific aspect of the knowledgebase construction process. Using KB-builder, we constructed the Human Papillomavirus T cell Antigen Database (HPVdb). It contains 2781 curated antigen entries of antigenic proteins derived from 18 genotypes of high-risk HPV and 18 genotypes of low-risk HPV. The HPVdb also catalogs 191 verified T cell epitopes and 45 verified human leukocyte antigen (HLA) ligands. Primary amino acid sequences of HPV antigens were collected and annotated from the UniProtKB. T cell epitopes and HLA ligands were collected from data mining of scientific literature and databases. The data were subject to extensive quality control (redundancy elimination, error detection and vocabulary consolidation). A set of computational tools for an in-depth analysis, such as sequence comparison using BLAST search, multiple alignments of antigens, classification of HPV types based on cancer risk, T cell epitope/HLA ligand visualization, T cell epitope/HLA ligand conservation analysis and sequence variability analysis, has been integrated within the HPVdb. Predicted Class I and Class II HLA binding peptides for 15 common HLA alleles are included in this database as putative targets. HPVdb is a knowledge-based system that integrates curated data and information with tailored analysis tools to facilitate data mining for HPV vaccinology and immunology. To our best knowledge, HPVdb is a unique data source providing a comprehensive list of HPV antigens and peptides. Database URL: http://cvc.dfci.harvard.edu/hpv/ PMID:24705205

HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology.

PubMed

Zhang, Guang Lan; Riemer, Angelika B; Keskin, Derin B; Chitkushev, Lou; Reinherz, Ellis L; Brusic, Vladimir

2014-01-01

High-risk human papillomaviruses (HPVs) are the causes of many cancers, including cervical, anal, vulvar, vaginal, penile and oropharyngeal. To facilitate diagnosis, prognosis and characterization of these cancers, it is necessary to make full use of the immunological data on HPV available through publications, technical reports and databases. These data vary in granularity, quality and complexity. The extraction of knowledge from the vast amount of immunological data using data mining techniques remains a challenging task. To support integration of data and knowledge in virology and vaccinology, we developed a framework called KB-builder to streamline the development and deployment of web-accessible immunological knowledge systems. The framework consists of seven major functional modules, each facilitating a specific aspect of the knowledgebase construction process. Using KB-builder, we constructed the Human Papillomavirus T cell Antigen Database (HPVdb). It contains 2781 curated antigen entries of antigenic proteins derived from 18 genotypes of high-risk HPV and 18 genotypes of low-risk HPV. The HPVdb also catalogs 191 verified T cell epitopes and 45 verified human leukocyte antigen (HLA) ligands. Primary amino acid sequences of HPV antigens were collected and annotated from the UniProtKB. T cell epitopes and HLA ligands were collected from data mining of scientific literature and databases. The data were subject to extensive quality control (redundancy elimination, error detection and vocabulary consolidation). A set of computational tools for an in-depth analysis, such as sequence comparison using BLAST search, multiple alignments of antigens, classification of HPV types based on cancer risk, T cell epitope/HLA ligand visualization, T cell epitope/HLA ligand conservation analysis and sequence variability analysis, has been integrated within the HPVdb. Predicted Class I and Class II HLA binding peptides for 15 common HLA alleles are included in this database as putative targets. HPVdb is a knowledge-based system that integrates curated data and information with tailored analysis tools to facilitate data mining for HPV vaccinology and immunology. To our best knowledge, HPVdb is a unique data source providing a comprehensive list of HPV antigens and peptides. Database URL: http://cvc.dfci.harvard.edu/hpv/.

Solving Immunology?

PubMed Central

Vodovotz, Yoram; Xia, Ashley; Read, Elizabeth L.; Bassaganya-Riera, Josep; Hafler, David A.; Sontag, Eduardo; Wang, Jin; Tsang, John S.; Day, Judy D.; Kleinstein, Steven; Butte, Atul J.; Altman, Matthew C; Hammond, Ross; Sealfon, Stuart C.

2016-01-01

Emergent responses of the immune system result from integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology. Here, we present the perspectives that emerged from the NIAID workshop “Complex Systems Science, Modeling and Immunity” and subsequent discussions regarding the potential synergy of high-throughput data acquisition, data-driven modeling and mechanistic modeling to define new mechanisms of immunological disease and to accelerate the translation of these insights into therapies. PMID:27986392

Maternal immunomodulation of the offspring's immunological system.

PubMed

Campos, Sylvia M N; de Oliveira, Vivian L; Lessa, Leonardo; Vita, Melissa; Conceição, Marcia; Andrade, Luiz Antonio Botelho; Teixeira, Gerlinde Agate Platais Brasil

2014-11-01

The mother's and the offspring's immunological system are closely related thus one can influence the other. This hypothesis drove our aim to study the impact of the mother's immunological status over the immunological response of their offspring. For this, female mice tolerant or allergic to peanuts were exposed or not to a challenge diet containing peanuts during the gestation-lactation period (TEP/AEP; TNEP/ANEP, respectively). After weaning the offspring was submitted to the peanut allergy or peanut tolerization protocol and then challenged with a peanut diet. Our results showed that when the offspring is submitted to the allergy induction protocol, they behave differently depending on their mother's immunological status. Offspring born to TEP mothers produced the lowest antibody titters while those born to AEP mothers produced the highest antibody titters compared to mice born to TNEP and ANEP. On the other hand when the offspring was submitted to the tolerization protocol all groups presented low antibody titers with no significant difference between groups, independent of the mothers immunological status and/or contact with peanuts during the gestation-lactation period. The analysis of the histological profile of the offspring correlates well to the serological response. In other words, offspring born to TEP mothers and submitted to the allergy induction protocol presented a normal histological profile, while the offspring born to AEP mothers produced the worst gut inflammation. These results indicate that mothers, exposed to the antigen (by the oral route) during gestation, actively influence the immune response of their offspring. This work sheds some light on the importance of the immunomodulation induced by dietary antigens during gestation and their influence on the immunological response of their offspring. However, more work is needed to elucidate the molecular and cellular components of this regulatory phenomenon. Copyright © 2014 Elsevier GmbH. All rights reserved.

Immunological responses to Clostridium perfringens alpha-toxin in two genetically divergent lines of chickens as influenced by major histocompatibility complex genotype.

PubMed

Sumners, L H; Cox, C M; Kim, S; Salevsky, J E; Siegel, P B; Dalloul, R A

2012-03-01

Chickens genetically selected for low (LA) or high (HA) antibody response to SRBC displayed a correlated change in MHC, so that LA chickens were 96% B13 and HA chickens were 96% B21. The LA line appears to be less susceptible to invasion by extracellular pathogens, whereas HA chickens are more resistant to infection by intracellular organisms. Resistance to Clostridium perfringens is one instance in which the lines do not follow their established trend of pathogen susceptibility, where during a clinical outbreak of necrotic enteritis, B21B21 genotypes experienced significantly less mortality than B13B13 genotypes. A study was carried out to assess immunological differences between LA and HA lines during exposure to C. perfringens α-toxin. Peripheral blood mononuclear cells were isolated from each genetic line, cultured with or without lipopolysaccharide (4 h), and exposed to varying concentrations of α-toxin (1; 10; 100; and 1,000 U/L) for 2 and 4 h. Evaluation of cellular proliferation, percentage of cytotoxicity, and immunological gene expression was carried out in a series of experiments. Cells isolated from HA chickens had significantly increased proliferation than those from LA chickens at low toxin levels (1 and 10 U/L) and significantly decreased proliferation at high toxin levels (100 and 1,000 U/L). Following exposure to lipopolysaccharide, the percentage of cytotoxicity was higher for LA than HA cells. In both assays, HA cells displayed superior performance following lipopolysaccharide-stimulation. Gene expression analysis of immune transcripts by quantitative real-time PCR revealed significantly upregulated expression of interferon (IFN)-γ, interleukin (IL)-8, IL-13 (2 h), IL-15, and CXCLi1 (4 h) in HA than LA chickens. Cells isolated from the LA line displayed significantly elevated expression of IL-2, IL-10, IL-13 (4 h), IL-16, IL-18, inducible nitric oxide synthase (iNOS), CXCLi1 (2 h), and lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) compared with the HA line. Clearly, these 2 genetic lines display highly divergent immune responses in regards to C. perfringens toxin exposure.

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells.

PubMed

Ribeiro, Kleber Silva; Vasconcellos, Camilla Ioshida; Soares, Rodrigo Pedro; Mendes, Maria Tays; Ellis, Cameron C; Aguilera-Flores, Marcela; de Almeida, Igor Correia; Schenkman, Sergio; Iwai, Leo Kei; Torrecilhas, Ana Claudia

2018-01-01

Trypanosoma cruzi , the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi , which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans -sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host-parasite interaction.

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells

PubMed Central

Ribeiro, Kleber Silva; Vasconcellos, Camilla Ioshida; Soares, Rodrigo Pedro; Ellis, Cameron C.; Aguilera-Flores, Marcela; de Almeida, Igor Correia

2018-01-01

ABSTRACT Trypanosoma cruzi, the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi, which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans-sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host–parasite interaction. PMID:29696081

Environmental conditions, immunologic phenotypes, atopy, and asthma: new evidence of how the hygiene hypothesis operates in Latin America.

PubMed

Figueiredo, Camila Alexandrina; Amorim, Leila D; Alcantara-Neves, Neuza M; Matos, Sheila M A; Cooper, Philip J; Rodrigues, Laura C; Barreto, Mauricio L

2013-04-01

It has been proposed that improved hygiene and reduced experience of infections in childhood influences the development of allergic diseases. The mechanisms by which the hygiene operates are not well established but are underpinned by two apparently incompatible immunologic paradigms, the balance of TH1 versus TH2 cytokines and IL-10-mediated regulation of TH2 cytokines. This study defined immunologic phenotypes with the use of latent class analysis and investigated their associations with environmental factors, markers of allergy and asthma, in a Latin American population. We studied 1127 children living in urban Brazil. Data on wheeze and environmental exposures were collected with standardized questionnaires. Atopy was measured by specific IgE in serum and skin prick test reactivity to aeroallergens. Cytokines were measured in culture after the stimulation of peripheral blood leukocytes with mitogen. Infections with pathogens were assessed by serology and stool examinations. Children were classified as having high or low burden of infection. Latent class analysis was used to identify immune phenotypes on the basis of cytokine production. Logistic regression was used to evaluate the adjusted effects of environment and burden of infection on the immunologic phenotypes and the effect of the phenotypes on atopy and asthma. Three phenotypes were identified, labeled underresponsive, intermediate, and responsive. Children of more educated mothers, living in improved environmental conditions, and with a low burden of infection were significantly more likely to have the responsive phenotype. The responsive phenotype was significantly associated with an increased prevalence of atopy but not asthma. Our findings contribute to a better understanding of the immune mechanisms by which the hygiene hypothesis operates in urban Latin America. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Radiobacteriolysis: a New Technique Using Chromium-51 for Assaying Anti- Vibrio cholerae Antibodies

PubMed Central

Blachman, Uzy; Clark, W. R.; Pickett, M. J.

1973-01-01

A new method for detecting and quantitating antibodies against Vibrio cholerae is described. The reaction involves the release of radiochromium from prelabeled vibrios in the presence of specific antibody and complement. The entire assay can be completed within 5 hr. The method is highly reproducible, immunologically specific, temperature- and complement-dependent, and significantly more sensitive than other methods currently used for titration of anti-Vibrio cholerae antibodies. The technique is also potentially applicable to titration of antibodies against other gram-negative bacteria. PMID:4570279

Regulation of immunological and inflammatory functions by biotin.

PubMed

Kuroishi, Toshinobu

2015-12-01

Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear protein involved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.

Tumor immunology.

PubMed

Mocellin, Simone; Lise, Mario; Nitti, Donato

2007-01-01

Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

Comparison of systemic and local immunity in dogs with canine parvovirus gastroenteritis.

PubMed

Rice, J B; Winters, K A; Krakowka, S; Olsen, R G

1982-12-01

To determine whether resistance to canine parvovirus (CPV) gastroenteritis is mediated by local or systemic immunity or both, an enzyme-linked immunospecific antibody assay (ELISA) was developed that quantitated different classes of antibody to CPV. Antibody levels in serum and feces of dogs with CPV-associated gastroenteritis were compared with their clinical signs and viral hemagglutination (HA) titers. Dogs with high levels of CPV coproantibody had a favorable clinical prognosis, high serum antibody levels (hemagglutination inhibition [HI] and ELISA), and low viral HA titers in feces. Conversely, dogs with little or no detectable CPV coproantibody had severe clinical signs and associated mortality rates and high viral HA titers in feces. Many of these dogs had high HI antibody titers. Statistical analysis revealed that only coproantibody level correlated (inversely) with HA titer; serum antibody, whether measured by HI or ELISA, did not. These data suggest that local intestinal immunity is more important than humoral immunity in developing immunological resistance to CPV gastroenteritis.

Earth Mover's Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations.

PubMed

Orlova, Darya Y; Zimmerman, Noah; Meehan, Stephen; Meehan, Connor; Waters, Jeffrey; Ghosn, Eliver E B; Filatenkov, Alexander; Kolyagin, Gleb A; Gernez, Yael; Tsuda, Shanel; Moore, Wayne; Moss, Richard B; Herzenberg, Leonore A; Walther, Guenther

2016-01-01

Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational "gating" tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover's Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains.

Principles and applications of flow cytometry and cell sorting in companion animal medicine.

PubMed

Wilkerson, Melinda J

2012-01-01

Flow cytometry measures multiple characteristic of single cells using light scatter properties and fluorescence properties of fluorescent probes with specificity to cellular constituents. The use of flow cytometry in the veterinary clinical laboratory has become more routine in veterinary diagnostic laboratories and institutions (http://www.vet.k-state.edu/depts/dmp/service/immunology/index.htm), and reference laboratories. The most common applications in small animal medicine includes quantitation of erythrocytes and leukocytes in automated hematology instruments, detection of antibodies to erythrocytes and platelets in cases of immune-mediated diseases, immunophenotyping of leukocytes and lymphocytes in immunodeficiency syndromes, or leukemias and lymphomas. DNA content analysis to identify aneuploidy or replicating cells in tumor preparations has not gained routine acceptance because of the variability of prognostic results. Other applications including cell sorting and multiplexing using microspheres are potential assays of the future once they become validated and the instrumentation footprint becomes more and more compact, less expensive, and easier to use.

Flow cytometric analysis of cell-surface and intracellular antigens in leukemia diagnosis.

PubMed

Knapp, W; Strobl, H; Majdic, O

1994-12-15

New technology allows highly sensitive flow cytometric detection and quantitative analysis of intracellular antigens in normal and malignant hemopoietic cells. With this technology, the earliest stages of myeloid and lymphoid differentiation can easily and reliably be identified using antibodies directed against (pro-)myeloperoxidase/MPO, CD22 and CD3 antigens, respectively. Particularly for the analysis of undifferentiated acute myeloblastic leukemia (AML) cells, the immunological demonstration of intracellular MPO or its enzymatically inactive proforms is highly relevant, since other myeloid marker molecules such as CD33, CD13, or CDw65 are either not restricted to the granulomonocytic lineage or appear later in differentiation. By combining MPO staining with staining for lactoferrin (LF), undifferentiated cells can be distinguished from the granulomonocytic maturation compartment in bone marrow, since LF is selectively expressed from the myelocyte stage of differentiation onward. The list of informative intracellular antigens to be used in leukemia cell analysis will certainly expand in the near future. One candidate, intracellular CD68, has already been tested by us, and results are presented. Also dealt within this article are surface marker molecules not (as yet) widely used in leukemia cell analysis but with the potential to provide important additional information. Among them are the surface structures CD15, CD15s, CDw65, CD79a (MB-1), CD79b (B29), CD87 (uPA-R), and CD117 (c-kit).

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

Dynamic Patterns of Clonal Evolution in Tumor Vasculature Underlie Alterations in Lymphocyte-Endothelial Recognition to Foster Tumor Immune Escape.

PubMed

Corey, Daniel M; Rinkevich, Yuval; Weissman, Irving L

2016-03-15

Although tumor blood vessels have been a major therapeutic target for cancer chemotherapy, little is known regarding the stepwise development of the tumor microenvironment. Here, we use a multicolor Cre-dependent marker system to trace clonality within the tumor microenvironment to show that tumor blood vessels follow a pattern of dynamic clonal evolution. In an advanced melanoma tumor microenvironment, the vast majority of tumor vasculature clones are derived from a common precursor. Quantitative lineage analysis reveals founder clones diminish in frequency and are replaced by subclones as tumors evolve. These tumor-specific blood vessels are characterized by a developmental switch to a more invasive and immunologically silent phenotype. Gene expression profiling and pathway analysis reveals selection for traits promoting upregulation of alternative angiogenic programs such as unregulated HGF-MET signaling and enhanced autocrine signaling through VEGF and PDGF. Furthermore, we show a developmental switch in the expression of functionally significant primary lymphocyte adhesion molecules on tumor endothelium, such as the loss in expression of the mucosal addressin MAdCAM-1, whose counter receptor a4β7 on lymphocytes controls lymphocyte homing. Changes in adhesive properties on tumor endothelial subclones are accompanied by decreases in expression of lymphocyte chemokines CXCL16, CXCL13, CXCL12, CXCL9, CXCL10, and CCL19. These evolutionary patterns in the expressed genetic program within tumor endothelium will have both a quantitative and functional impact on lymphocyte distribution that may well influence tumor immune function and underlie escape mechanisms from current antiangiogenic pharmacotherapies. ©2015 American Association for Cancer Research.

Recommendations for Competency in Allergy Training for Undergraduates Qualifying as Medical Practitioners: A Position Paper of the World Allergy Organization

PubMed Central

2009-01-01

The Council acknowledges specific comments from: The American Academy of Allergy, Asthma and Immunology (AAAAI) (Amal H Assa'ad); The American College of Allergy, Asthma and Immunology (ACAAI) (Mark Dykewicz, D. Betty Lew, Bryan L. Martin); The Argentine Association of Allergy and Immunology (Ledit RF Ardusso); The Argentine Society of Allergy and Immunopathology (Estrella Asayag); The Australasian Society of Clinical Immunology and Allergy (ASCIA) (Jill Smith); The British Society for Allergy and Clinical Immunology (Stephen Durham); The Brazilian Society of Allergy and Immunopathology (Nelson Rosario); The Bulgarian Society of Allergology (Vasil Dimitrov); The Canadian Society of Allergy and Clinical Immunology (CSACI) (Richard Warrington); The Chilean Society of Allergy and Immunology (Jessica Salinas); The Chinese Society of Allergology (Zhang Hongyu, Yin Jia); The Czech Society of Allergology and Clinical Immunology (Jiri Litzman); The Danish Society of Allergology (Lone Winther, Peter Plaschke); The Egyptian Society of Allergy and Clinical Immunology (Kamal Maurice Hanna); The Egyptian Society of Pediatric Allergy and Immunology (Yehia El-Gamal); The German Society for Allergy and Clinical Immunology (Thilo Jakob, Claus Bachert, Bernhard Przybilla); The Hungarian Society of Allergology and Clinical Immunology (Kristof Nekam); The Icelandic Society of Allergy and Clinical Immunology (Björn R. Lúðvíksson); The Italian Association of Territorial and Hospital Allergists (Riccardo Asero); The Italian Society of Allergy and Clinical Immunology (Luigi Fontana); The Japanese Society of Allergology (Sankei Nishima); The Korean Academy of Asthma Allergy and Clinical Immunology (Joon Sung Lee, Hae-Sim Park); The Latvian Association of Allergists (Ieva Cirule); The Lebanese Society of Allergy & Immunology (Fares Zaitoun); The Mongolian Society of Allergology (S. Munkhbayarlakh); The Allergy and Clinical Immunology Society (Singapore) (Chng Hiok Hee); The Allergy Society of South Africa (Sharon Kling); The Spanish Society of Allergy and Clinical Immunology (Tomás Chivato); The Swiss Society for Allergology and Immunology (SSAI-SGAI) (Beat A. Imhof, Andreas Bircher); The Allergy and Immunology Society of Thailand (Pakit Vichyanond); The Turkish National Society of Allergy and Clinical Immunology (Omer Kalayci); and The Venezuelan Society of Allergy, Asthma and Immunology (Luis F Sarmiento). PMID:23283109

Chemotherapeutic Studies on Schistosomiasis and Clinical, Epidemiological and Immunological Studies on Malaria in Amazonas, Brazil, along the Ituxi River. Report Number VII.

DTIC Science & Technology

1980-10-01

Chemotherapeutic Studies on Schistosomiasis and Clinical, Epidemio- logical and Immunological Studies on Malaria in Amazonas ,- Brazil,.Along the Ituxi River...30 Sep 80. logical Studies on Malaria in Amazonas , Brazil, Along the Ituxi River. S. PERFORMING ORGANIZATION 14AME AND0 ADDRESS I0. PROGRAM ELEMENT...DDT-sprayed and unsprayed houses and analysis of the results relative to the incidence of malaria in the Amazonas study area.Efforts with the in vitro

Lymphoidal involution and delayed homograft rejection in hypoxia-exposed mice.

NASA Technical Reports Server (NTRS)

Kmetz, J. M.; Anthony, A.

1972-01-01

Investigation of the relationship between histologic and cytochemical response patterns of the thymus, spleen, and lymph nodes of mice exposed to moderate hypoxia (380 mm Hg), and study, by histologic analysis, of the effect of hypoxia exposure on the skin homograft reaction used as an index of immunologic potential. The results obtained include the finding that functional changes in lymphatic organs occur during early weeks of hypoxia acclimation and that these changes probably reduce the ability of an animal to react to an immunological challenge.

Dependence of the results of ecological-epidemic investigation of influenza A(H1N1) on immunity

NASA Astrophysics Data System (ADS)

Fathudinova, Mohinav; Alimova, Barno; Rahimova, Halima

2016-07-01

This report presents the results of ecology-epidemical and immunological researches influ-enza virus A (H1 N1) and acute respiratory infection in Dushanbe from 2011 till 2015. The received results epidemiological and immunological analysis showed us, that last years has been changed not only characteristics of influenza epidemic, but it can not be notice the low-er of intensively of the collective immunity to actual versions influenza viruses A and B

An in vitro investigation of immunomodulatory properties of Lactobacillus plantarum and L. delbrueckii cells and their extracellular polysaccharides

PubMed Central

KISHIMOTO, Mana; NOMOTO, Ryohei; MIZUNO, Masashi; OSAWA, Ro

2017-01-01

Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have beneficial immunological properties. However, it is unclear how they elicit the host immune response. We thus investigated the immunological properties of UV-killed Lactobacillus delbrueckii TU-1 and L. plantarum KM-9 cells as well as their extracellular polysaccharides (EPSs). High-performance liquid chromatography and ion exchange chromatography analyses showed that their EPSs differ in sugar composition and sugar fractionation. The immunological properties were evaluated in a semi-intestinal model using a Transwell co-culture system that employed human intestinal epithelial (Caco-2) cells on the apical side and murine macrophage (RAW264.7) cells on the basolateral side. The UV-killed cells and EPSs were added to the apical side to allow direct contact with Caco-2 cells and incubated for 6 hr. After incubation, the amounts of tumor necrosis factor-α and several cytokines released by RAW264.7 or Caco-2 cells were quantified by cytotoxic activity on L929 cells (murine fibrosarcoma cell line) and quantitative reverse-transcriptase PCR. We found that the UV-killed cells and their EPSs had immunological effects on RAW264.7 cells via Caco-2 cells. The RAW264.7 cells showed different cytokine production profiles when treated with UV-killed cells and EPSs. The UV-killed cells and EPSs promoted a Th1-type cellular response. Furthermore, we found that the UV-killed cells sent positive signals through Toll-like receptor (TLR) 2. Meanwhile, neither EPS sent a positive signal through TLR4 and TLR2. This evidence suggests that both UV-killed cells of the lactobacillus strains and their EPSs trigger a Th1-type immune response in a human host, with the former triggering the response via the TLRs expressed on its epithelium and the latter employing a mechanism yet to be determined, possibly involving a novel receptor that is designed to recognize specific patterns of repeating sugar in the EPSs. PMID:28748131

An in vitro investigation of immunomodulatory properties of Lactobacillus plantarum and L. delbrueckii cells and their extracellular polysaccharides.

PubMed

Kishimoto, Mana; Nomoto, Ryohei; Mizuno, Masashi; Osawa, Ro

2017-01-01

Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have beneficial immunological properties. However, it is unclear how they elicit the host immune response. We thus investigated the immunological properties of UV-killed Lactobacillus delbrueckii TU-1 and L. plantarum KM-9 cells as well as their extracellular polysaccharides (EPSs). High-performance liquid chromatography and ion exchange chromatography analyses showed that their EPSs differ in sugar composition and sugar fractionation. The immunological properties were evaluated in a semi-intestinal model using a Transwell co-culture system that employed human intestinal epithelial (Caco-2) cells on the apical side and murine macrophage (RAW264.7) cells on the basolateral side. The UV-killed cells and EPSs were added to the apical side to allow direct contact with Caco-2 cells and incubated for 6 hr. After incubation, the amounts of tumor necrosis factor-α and several cytokines released by RAW264.7 or Caco-2 cells were quantified by cytotoxic activity on L929 cells (murine fibrosarcoma cell line) and quantitative reverse-transcriptase PCR. We found that the UV-killed cells and their EPSs had immunological effects on RAW264.7 cells via Caco-2 cells. The RAW264.7 cells showed different cytokine production profiles when treated with UV-killed cells and EPSs. The UV-killed cells and EPSs promoted a Th1-type cellular response. Furthermore, we found that the UV-killed cells sent positive signals through Toll-like receptor (TLR) 2. Meanwhile, neither EPS sent a positive signal through TLR4 and TLR2. This evidence suggests that both UV-killed cells of the lactobacillus strains and their EPSs trigger a Th1-type immune response in a human host, with the former triggering the response via the TLRs expressed on its epithelium and the latter employing a mechanism yet to be determined, possibly involving a novel receptor that is designed to recognize specific patterns of repeating sugar in the EPSs.

Bead-based competitive fluorescence immunoassay for sensitive and rapid diagnosis of cyanotoxin risk in drinking water.

PubMed

Yu, Hye-Weon; Jang, Am; Kim, Lan Hee; Kim, Sung-Jo; Kim, In S

2011-09-15

Due to the increased occurrence of cyanobacterial blooms and their toxins in drinking water sources, effective management based on a sensitive and rapid analytical method is in high demand for security of safe water sources and environmental human health. Here, a competitive fluorescence immunoassay of microcystin-LR (MCYST-LR) is developed in an attempt to improve the sensitivity, analysis time, and ease-of-manipulation of analysis. To serve this aim, a bead-based suspension assay was introduced based on two major sensing elements: an antibody-conjugated quantum dot (QD) detection probe and an antigen-immobilized magnetic bead (MB) competitor. The assay was composed of three steps: the competitive immunological reaction of QD detection probes against analytes and MB competitors, magnetic separation and washing, and the optical signal generation of QDs. The fluorescence intensity was found to be inversely proportional to the MCYST-LR concentration. Under optimized conditions, the proposed assay performed well for the identification and quantitative analysis of MCYST-LR (within 30 min in the range of 0.42-25 μg/L, with a limit of detection of 0.03 μg/L). It is thus expected that this enhanced assay can contribute both to the sensitive and rapid diagnosis of cyanotoxin risk in drinking water and effective management procedures.

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

PubMed Central

Vandooren, Jennifer; Berghmans, Nele; Dillen, Chris; Van Aelst, Ilse; Ronsse, Isabelle; Israel, Liron Limor; Rosenberger, Ina; Kreuter, Jörg; Lellouche, Jean-Paul; Michaeli, Shulamit; Locatelli, Erica; Franchini, Mauro Comes; Aiertza, Miren K; Sánchez-Abella, Laura; Loinaz, Iraida; Edwards, Dylan R; Shenkman, Louis; Opdenakker, Ghislain

2013-01-01

The need for test systems for nanoparticle biocompatibility, toxicity, and inflammatory or adaptive immunological responses is paramount. Nanoparticles should be free of microbiological and chemical contaminants, and devoid of toxicity. Nevertheless, in the absence of contamination, these particles may still induce undesired immunological effects in vivo, such as enhanced autoimmunity, hypersensitivity reactions, and fibrosis. Here we show that artificial particles of specific sizes affect immune cell recruitment as tested in a dermal air pouch model in mice. In addition, we demonstrate that the composition of nanoparticles may influence immune cell recruitment in vivo. Aside from biophysical characterizations in terms of hydrodynamic diameter, zeta potential, concentration, and atomic concentration of metals, we show that – after first-line in vitro assays – characterization of cellular and molecular effects by dermal air pouch analysis is straightforward and should be included in the quality control of nanoparticles. We demonstrate this for innate immunological effects such as neutrophil recruitment and the production of immune-modulating matrix metalloproteases such as MMP-9; we propose the use of air pouch leukocytosis analysis as a future standard assay. PMID:24379662

Infectious disease research investments: systematic analysis of immunology and vaccine research funding in the UK.

PubMed

Fitchett, Joseph R; Head, Michael G; Atun, Rifat

2013-12-05

Financing for global health is a critical element of research and development. Innovations in new vaccines are critically dependent on research funding given the large sums required, however estimates of global research investments are lacking. We evaluate infectious disease research investments, focusing on immunology and vaccine research by UK research funding organisations. In 1997-2010, £2.6 billion were spent by public and philanthropic organisations, with £590 million allocated to immunology and vaccine research. Preclinical studies received the largest funding amount £505 million accounting for 85.6% of total investment. In terms of specific infection, "the big three" infections dominated funding: HIV received £127 million (21.5% of total), malaria received £59 million (10.0% of total) and tuberculosis received £36 million (6.0% of total). We excluded industry funding from our analysis, as open-access data were unavailable. A global investment surveillance system is needed to map and monitor funding and guide allocation of scarce resources. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessment of reference genes for reliable analysis of gene transcription by RT-qPCR in ovine leukocytes.

PubMed

Mahakapuge, T A N; Scheerlinck, J-P Y; Rojas, C A Alvarez; Every, A L; Hagen, J

2016-03-01

With the availability of genetic sequencing data, quantitative reverse transcription PCR (RT-qPCR) is increasingly being used for the quantification of gene transcription across species. Too often there is little regard to the selection of reference genes and the impact that a poor choice has on data interpretation. Indeed, RT-qPCR provides a snapshot of relative gene transcription at a given time-point, and hence is highly dependent on the stability of the transcription of the reference gene(s). Using ovine efferent lymph cells and peripheral blood mono-nuclear cells (PBMCs), the two most frequently used leukocytes in immunological studies, we have compared the stability of transcription of the most commonly used ovine reference genes: YWHAZ, RPL-13A, PGK1, B2M, GAPDH, HPRT, SDHA and ACTB. Using established algorithms for reference gene normalization "geNorm" and "Norm Finder", PGK1, GAPDH and YWHAZ were deemed the most stably transcribed genes for efferent leukocytes and PGK1, YWHAZ and SDHA were optimal in PBMCs. These genes should therefore be considered for accurate and reproducible RT-qPCR data analysis of gene transcription in sheep. Copyright © 2016. Published by Elsevier B.V.

Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients

PubMed Central

Sung, Cynthia; Wei, Yuan; Watanabe, Satoru; Lee, How Sung; Khoo, Yok Moi; Fan, Lu; Rathore, Abhay P. S.; Chan, Kitti Wing-Ki; Choy, Milly M.; Kamaraj, Uma S.; Sessions, October M.; Aw, Pauline; de Sessions, Paola F.; Lee, Bernett; Connolly, John E.; Hibberd, Martin L.; Vijaykrishna, Dhanasekaran; Wijaya, Limin; Ooi, Eng Eong; Low, Jenny Guek-Hong

2016-01-01

CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients’ isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue infection. Optimization of the dosing regimen and patient stratification may enhance the ability of a clinical trial to demonstrate celgosivir activity in treating dengue fever based on hematological endpoints. A new clinical trial with a revised dosing regimen is slated to start in 2016 (NCT02569827). Furthermore celgosivir’s potential value for treatment of other flaviruses such as Zika virus should be investigated urgently. Trial Registration: ClinicalTrials.gov NCT01619969 PMID:27509020

Proteomics: from hypothesis to quantitative assay on a single platform. Guidelines for developing MRM assays using ion trap mass spectrometers.

PubMed

Han, Bomie; Higgs, Richard E

2008-09-01

High-throughput HPLC-mass spectrometry (HPLC-MS) is routinely used to profile biological samples for potential protein markers of disease, drug efficacy and toxicity. The discovery technology has advanced to the point where translating hypotheses from proteomic profiling studies into clinical use is the bottleneck to realizing the full potential of these approaches. The first step in this translation is the development and analytical validation of a higher throughput assay with improved sensitivity and selectivity relative to typical profiling assays. Multiple reaction monitoring (MRM) assays are an attractive approach for this stage of biomarker development given their improved sensitivity and specificity, the speed at which the assays can be developed and the quantitative nature of the assay. While the profiling assays are performed with ion trap mass spectrometers, MRM assays are traditionally developed in quadrupole-based mass spectrometers. Development of MRM assays from the same instrument used in the profiling analysis enables a seamless and rapid transition from hypothesis generation to validation. This report provides guidelines for rapidly developing an MRM assay using the same mass spectrometry platform used for profiling experiments (typically ion traps) and reviews methodological and analytical validation considerations. The analytical validation guidelines presented are drawn from existing practices on immunological assays and are applicable to any mass spectrometry platform technology.

21 CFR 866.5230 - Colostrum immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system. (a) Identification. A colostrum immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Colostrum immunological test system. 866.5230...

21 CFR 866.5570 - Lactoferrin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5570 Lactoferrin immunological test system. (a) Identification. A lactoferrin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactoferrin immunological test system. 866.5570...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5340 Ferritin immunological test system. (a) Identification. A ferritin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340...

21 CFR 866.5735 - Prothrombin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5735 Prothrombin immunological test system. (a) Identification. A prothrombin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin immunological test system. 866.5735...

21 CFR 866.5680 - Myoglobin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5680 Myoglobin immunological test system. (a) Identification. A myoglobin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Myoglobin immunological test system. 866.5680...

21 CFR 866.5715 - Plasminogen immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5715 Plasminogen immunological test system. (a) Identification. A plasminogen immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plasminogen immunological test system. 866.5715...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5470 Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin immunological test system. 866.5470...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5880 Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Transferrin immunological test system. 866.5880...

21 CFR 866.5060 - Prealbumin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5060 Prealbumin immunological test system. (a) Identification. A prealbumin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prealbumin immunological test system. 866.5060...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5460 Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Haptoglobin immunological test system. 866.5460...

Macrophage biospecific extraction and HPLC-ESI-MSn analysis for screening immunological active components in Smilacis Glabrae Rhizoma.

PubMed

Zheng, Zhao-Guang; Duan, Ting-Ting; He, Bao; Tang, Dan; Jia, Xiao-Bin; Wang, Ru-Shang; Zhu, Jia-Xiao; Xu, You-Hua; Zhu, Quan; Feng, Liang

2013-04-15

A cell-permeable membrane, as typified by Transwell insert Permeable Supports, permit accurate repeatable invasion assays, has been developed as a tool for screening immunological active components in Smilacis Glabrae Rhizoma (SGR). In this research, components in the water extract of SGR (ESGR) might conjugate with the receptors or other targets on macrophages which invaded Transwell inserts, and then the eluate which contained components biospecific binding to macrophages was identified by HPLC-ESI-MS(n) analysis. Six compounds, which could interact with macrophages, were detected and identified. Among these compounds, taxifolin (2) and astilbin (4) were identified by comparing with the chromatography of standards, while the four others including 5-O-caffeoylshikimic acid (1), neoastilbin (3), neoisoastilbin (5) and isoastilbin (6), were elucidated by their structure clearage characterizations of tandem mass spectrometry. Then compound 1 was isolated and purified from SGR, along with 2 and 4, was applied to the macrophage migration and adhesion assay in HUVEC (Human Umbilical Vein Endothelial Cells) -macrophages co-incultured Transwell system for immunological activity assessment. The results showed that compounds 1, 2 and 4 with concentration of 5μM (H), 500nM (M) and 50nM (L) could remarkably inhibit the macrophage migration and adhesion (Vs AGEs (Advanced Glycation End Produces) group, 1-L, 2-H and 4-L groups: p<0.05; other groups: p<0.01). Moreover, 1 and 4 showed satisfactory dose-effect relationship. In conclusion, the application of macrophage biospecific extraction coupled with HPLC-ESI-MS(n) analysis is a rapid, simple and reliable method for screening immunological active components from Traditional Chinese Medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. (a) Identification. An alpha-globulin immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866...

21 CFR 866.5350 - Fibrinopeptide A immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5350 Fibrinopeptide A immuno-logical test system. (a) Identification. A fibrinopeptide A immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinopeptide A immuno-logical test system. 866...

Non-specific immunological effects of selected routine childhood immunisations: systematic review.

PubMed

Kandasamy, Rama; Voysey, Merryn; McQuaid, Fiona; de Nie, Karlijn; Ryan, Rebecca; Orr, Olivia; Uhlig, Ulrike; Sande, Charles; O'Connor, Daniel; Pollard, Andrew J

2016-10-13

 To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus.  Systematic review of randomised controlled trials, cohort studies, and case-control studies.  Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included.  All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines, no vaccine at all, or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify, assemble, and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps, measles, and rubella (MMR); diphtheria; tetanus; and pertussis vaccines.  The initial search yielded 11 168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies, with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported, which, in conjunction with differences in measurement units and summary statistics, created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-γ production in vitro in the vaccinated groups. Increases were also observed for IFN-γ measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans, tetanus toxoid, Staphylococcus aureas, lipopolysaccharide, and hepatitis B. Cohort studies of measles vaccination showed an increase in lymphoproliferation to microbial antigens from tetanus toxoid and C albicans Increases in immunogenicity to heterologous antigens were noted after diphtheria-tetanus (herpes simplex virus and polio antibody titres) and diphtheria-tetanus-pertussis (pneumococcus serotype 14 and polio neutralising responses) vaccination.  The papers reporting non-specific immunological effects had heterogeneous study designs and could not be conventionally meta-analysed, providing a low level of evidence quality. Some studies, such as BCG vaccine studies examining in vitro IFN-γ responses and measles vaccine studies examining lymphoproliferation to microbial antigen stimulation, showed a consistent direction of effect suggestive of non-specific immunological effects. The quality of the evidence, however, does not provide confidence in the nature, magnitude, or timing of non-specific immunological effects after vaccination with BCG, diphtheria, pertussis, tetanus, or measles containing vaccines nor the clinical importance of the findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5170 Breast milk immunological test system. (a) Identification. A breast milk immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breast milk immunological test system. 866.5170...

21 CFR 866.5360 - Cohn fraction IV immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5360 Cohn fraction IV immuno-logical test system. (a) Identification. A Cohn fraction IV immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cohn fraction IV immuno-logical test system. 866...

21 CFR 866.5040 - Albumin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. An albumin immunological test system is a device that consists of... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040...

Impact of Early Enteral Nutrition on Nutritional and Immunological Outcomes of Gastric Cancer Patients Undergoing Gastrostomy: A Systematic Review and Meta-Analysis.

PubMed

Nikniaz, Zeinab; Somi, Mohammad Hossein; Nagashi, Shahnaz; Nikniaz, Leila

2017-07-01

The present systematic review and meta-analysis study evaluated the impact of early enteral nutrition (EN) on postoperative nutritional and immunological outcomes of gastric cancer (GC) patients. The databases of PubMed, Embase, Springer, and Cochrane library were searched till September 2016 to identify studies which evaluated the effects of EN compared with parenteral nutrition (PN) on postoperative immunological and nutritional status and hospitalization time in GC patients. Mean difference (MD) or standard mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. The present systematic review and meta-analysis have consisted of seven trials, containing 835 GC patients. According to the result of meta-analysis, compared with PN, EN significantly resulted in more increase in the level of albumin [MD = 2.07 (0.49, 3.64)], prealbumin [MD = 9.41 (049, 33.55)], weight [MD = 1.52 (0.32, 2.72)], CD3+ [SMD = 1.96 (1.50, 2.43)], CD4+ [SMD = 2.45 (1.97, 2.93)], natural killers [MD = 5.80 (3.75, 7.85)], and also a decrease in the hospitalization time [MD=-2.39 (-2.74, -2.03)]. The results demonstrated that early administration of EN is more effective in improving postsurgical nutrition status and immune index in GC patients. So, based on these results, postoperative early administration of EN is recommended for GC patients where possible.

Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine.

PubMed

Snape, Matthew D; Maclennan, Jenny M; Lockhart, Stephen; English, Mike; Yu, Ly-Mee; Moxon, Richard E; Pollard, Andrew J

2009-02-01

Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.

Solving Immunology?

PubMed

Vodovotz, Yoram; Xia, Ashley; Read, Elizabeth L; Bassaganya-Riera, Josep; Hafler, David A; Sontag, Eduardo; Wang, Jin; Tsang, John S; Day, Judy D; Kleinstein, Steven H; Butte, Atul J; Altman, Matthew C; Hammond, Ross; Sealfon, Stuart C

2017-02-01

Emergent responses of the immune system result from the integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for the systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology. Here, we present the perspectives that emerged from the National Institute of Allergy and Infectious Disease (NIAID) workshop 'Complex Systems Science, Modeling and Immunity' and subsequent discussions regarding the potential synergy of high-throughput data acquisition, data-driven modeling, and mechanistic modeling to define new mechanisms of immunological disease and to accelerate the translation of these insights into therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation

PubMed Central

Do, Catherine; Lang, Charles F.; Lin, John; Darbary, Huferesh; Krupska, Izabela; Gaba, Aulona; Petukhova, Lynn; Vonsattel, Jean-Paul; Gallagher, Mary P.; Goland, Robin S.; Clynes, Raphael A.; Dwork, Andrew; Kral, John G.; Monk, Catherine; Christiano, Angela M.; Tycko, Benjamin

2016-01-01

Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A∗-ILF2, associated with immune phenotypes, MYT1L, PTPRN2, CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites were over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to macaques, indicated that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; and variation in CTCF and TF binding sites is an underlying mechanism, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supra- and sub-threshold GWAS peaks in immunological and neurological disorders. PMID:27153397

Cervicovaginal cytokines, sialidase activity and bacterial load in reproductive-aged women with intermediate vaginal flora.

PubMed

Santos-Greatti, Mariana Morena de Vieira; da Silva, Márcia Guimarães; Ferreira, Carolina Sanitá Tafner; Marconi, Camila

2016-11-01

Studies have shown that not only bacterial vaginosis, but also intermediate vaginal flora has deleterious effects for women's reproductive health. However, literature still lacks information about microbiological and immunological aspects of intermediate flora. To characterize intermediate flora regarding levels of Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, interleukin 1 receptor antagonist (IL-1ra), IL-10, sialidase; loads of Gardnerella vaginalis, total bacteria and to verify whether it is closer related to normal flora or bacterial vaginosis. This cross-sectional study enrolled 526 non-pregnant reproductive-aged women distributed in 3 groups according to pattern of vaginal flora using Nugent's system in normal, intermediate and bacterial vaginosis. Cervicovaginal levels of cytokines, sialidases, loads of G. vaginalis and total bacteria were assessed by ELISA, conversion of MUAN and quantitative real-time PCR, respectively. A principal component analysis(PCA) using all measured parameters was performed to compare the three different types of flora. Results showed that intermediate flora is associated with increased cervicovaginal IL-1beta in relation to normal flora(P<0.0001). When compared to bacterial vaginosis, intermediate flora has higher IL-8 and IL-10 levels(P<0.01). Sialidases were in significantly lower levels in normal and intermediate flora than bacterial vaginosis(P<0.0001). Loads of G. vaginalis and total bacterial differed among all groups(P<0.0001), being highest in bacterial vaginosis. PCA showed that normal and intermediate flora were closely scattered, while bacterial vaginosis were grouped separately. Although intermediate flora shows some differences in cytokines, sialidases and bacterial loads in relation to normal flora and bacterial vaginosis, when taken together, general microbiological and immunological pattern pattern of intermediate flora resembles the normal flora. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparative genomics of Toll-like receptor signalling in five species

PubMed Central

Jann, Oliver C; King, Annemarie; Corrales, Nestor Lopez; Anderson, Susan I; Jensen, Kirsty; Ait-ali, Tahar; Tang, Haizhou; Wu, Chunhua; Cockett, Noelle E; Archibald, Alan L; Glass, Elizabeth J

2009-01-01

Background Over the last decade, several studies have identified quantitative trait loci (QTL) affecting variation of immune related traits in mammals. Recent studies in humans and mice suggest that part of this variation may be caused by polymorphisms in genes involved in Toll-like receptor (TLR) signalling. In this project, we used a comparative approach to investigate the importance of TLR-related genes in comparison with other immunologically relevant genes for resistance traits in five species by associating their genomic location with previously published immune-related QTL regions. Results We report the genomic localisation of TLR1-10 and ten associated signalling molecules in sheep and pig using in-silico and/or radiation hybrid (RH) mapping techniques and compare their positions with their annotated homologues in the human, cattle and mouse whole genome sequences. We also report medium-density RH maps for porcine chromosomes 8 and 13. A comparative analysis of the positions of previously published relevant QTLs allowed the identification of homologous regions that are associated with similar health traits in several species and which contain TLR related and other immunologically relevant genes. Additional evidence was gathered by examining relevant gene expression and association studies. Conclusion This comparative genomic approach identified eight genes as potentially causative genes for variations of health related traits. These include susceptibility to clinical mastitis in dairy cattle, general disease resistance in sheep, cattle, humans and mice, and tolerance to protozoan infection in cattle and mice. Four TLR-related genes (TLR1, 6, MyD88, IRF3) appear to be the most likely candidate genes underlying QTL regions which control the resistance to the same or similar pathogens in several species. Further studies are required to investigate the potential role of polymorphisms within these genes. PMID:19432955

Immunology for rheumatology residents: working toward a Canadian national curriculum consensus.

PubMed

Chow, Shirley L; Herman-Kideckel, Sari; Mahendira, Dharini; McDonald-Blumer, Heather

2015-01-01

Immunologic mechanisms play an integral role in understanding the pathogenesis and management of rheumatic conditions. Currently, there is limited access to formal instruction in immunology for rheumatology trainees across Canada. The aims of this study were (1) to describe current immunology curricula among adult rheumatology training programs across Canada and (2) to compare the perceived learning needs of rheumatology trainees from the perspective of program directors and trainees to help develop a focused nationwide immunology curriculum. Rheumatology trainees and program directors from adult rheumatology programs across Canada completed an online questionnaire and were asked to rank a comprehensive list of immunology topics. A modified Delphi approach was implemented to obtain consensus on immunology topics. Only 42% of program directors and 31% of trainees felt the current method of teaching immunology was effective. Results illustrate concordance between program directors and trainees for the highest-ranked immunology topics including innate immunity, adaptive immunity, and cells and tissues of the immune system. However, there was discordance among other topics, such as diagnostic laboratory immunology and therapeutics. There is a need to improve immunology teaching in rheumatology training programs. Results show high concordance between the basic immunology topics. This study provides the groundwork for development of future immunology curricula.

Removal of detergents from protein extracts using activated charcoal prior to immunological analysis.

PubMed

Malhas, Ashraf N; Abuknesha, Ramadan A; Price, Robert G

2002-06-01

The use of dextran-coated activated charcoal (DCC) powder to absorb solubilising detergents from cell lysates is described. Normal embryonic epithelial cells were lysed in the presence of sodium dodecyl sulphate (SDS). The detergent was then absorbed with DCC to facilitate analysis of polycystin-1 with antibody-based methods. Polycystin-1 is a membrane protein that is involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The adverse effect of SDS on antibody-polycystin-1 binding was studied and the improvement resulting from its removal demonstrated using enzyme-linked immunosorbent assays (ELISAs). The results indicate that DCC can be used in a simple manner to remove highly reactive membrane-solubilising reagents from protein mixtures prior to immunological analysis. This procedure may be relevant to a variety of other techniques that are normally affected by detergents.

CD4 responses in the setting or suboptimal virological responses to antiretroviral therapy: features, outcomes, and associated factors.

PubMed

Collazos, Julio; Asensi, Víctor; Cartón, José Antonio

2009-07-01

The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

The Interaction Affinity between Vascular Cell Adhesion Molecule-1 (VCAM-1) and Very Late Antigen-4 (VLA-4) Analyzed by Quantitative FRET

PubMed Central

Wu, Shu-Han; Karmenyan, Artashes; Chiou, Arthur

2015-01-01

Very late antigen-4 (VLA-4), a member of integrin superfamily, interacts with its major counter ligand vascular cell adhesion molecule-1 (VCAM-1) and plays an important role in leukocyte adhesion to vascular endothelium and immunological synapse formation. However, irregular expressions of these proteins may also lead to several autoimmune diseases and metastasis cancer. Thus, quantifying the interaction affinity of the VCAM-1/VLA-4 interaction is of fundamental importance in further understanding the nature of this interaction and drug discovery. In this study, we report an ‘in solution’ steady state organic fluorophore based quantitative fluorescence resonance energy transfer (FRET) assay to quantify this interaction in terms of the dissociation constant (Kd). We have used, in our FRET assay, the Alexa Fluor 488-VLA-4 conjugate as the donor, and Alexa Fluor 546-VCAM-1 as the acceptor. From the FRET signal analysis, Kd of this interaction was determined to be 41.82 ± 2.36 nM. To further confirm our estimation, we have employed surface plasmon resonance (SPR) technique to obtain Kd = 39.60 ± 1.78 nM, which is in good agreement with the result obtained by FRET. This is the first reported work which applies organic fluorophore based ‘in solution’ simple quantitative FRET assay to obtain the dissociation constant of the VCAM-1/VLA-4 interaction, and is also the first quantification of this interaction. Moreover, the value of Kd can serve as an indicator of abnormal protein-protein interactions; hence, this assay can potentially be further developed into a drug screening platform of VLA-4/VCAM-1 as well as other protein-ligand interactions. PMID:25793408

Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia.

PubMed

Yirdaw, Kesetebirhan Delele; Hattingh, Susan

2015-01-01

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources.

Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia

PubMed Central

2015-01-01

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources. PMID:25961732

21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimitochondrial antibody immunological test...

21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5750 Radioallergosorbent (RAST) immunological test system. (a) Identification. A... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radioallergosorbent (RAST) immunological test...

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test...

21 CFR 866.5180 - Fecal calprotectin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5180 Fecal calprotectin immunological test system. (a) Identification. A fecal calprotectin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fecal calprotectin immunological test system. 866...

21 CFR 866.5560 - Lactic dehydrogenase immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5560 Lactic dehydrogenase immunological test system. (a) Identification. A lactic dehydrogenase... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactic dehydrogenase immunological test system...

21 CFR 866.5660 - Multiple autoantibodies immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5660 Multiple autoantibodies immunological test system. (a) Identification. A multiple autoantibodies... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid autoantibody immunological test system...

21 CFR 866.5110 - Antiparietal antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5110 Antiparietal antibody immunological test system. (a) Identification. An antiparietal antibody... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antiparietal antibody immunological test system...

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system...

21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5240 Complement components immunological test system. (a) Identification. A complement components... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement components immunological test system...

Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos.

PubMed

Matsuzaki, Hidenori; Kumagai-Takei, Naoko; Lee, Suni; Maeda, Megumi; Sada, Nagisa; Hatayama, Tamayo; Yamamoto, Shoko; Ikeda, Miho; Yoshitome, Kei; Min, Yu; Nishimura, Yasumitsu; Otsuki, Takemi

2017-06-09

The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.

An Investigation of Immunological Tolerance Based on Chimaera Analysis

PubMed Central

Michie, Donald; Woodruff, M. F. A.; Zeiss, Irmgard M.

1961-01-01

Newborn mice of strain A were injected intravenously at birth with 9–15 million spleen cells from adult CBA donors. The recipients exhibited splenomegaly and other signs of graft-versus-host reaction during the first 3 weeks of life. Adult survivors were uniformly tolerant of CBA skin. They showed no sign of a continuing graft-versus-host reaction. The spleens of the treated mice were tested for the presence of immunologically competent donor and host cells by Simonsen's discriminant spleen assay. From the age of 7 days onwards the spleens were found to contain a small percentage of donor cells which were immunologically active against antigens of a third strain. In spleens from adult survivors activity, attributable to the host component, against third-party antigens was undiminished as compared with that of untreated A-strain mice. But activity against the CBA donor strain was absent. PMID:14473459

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antichymotrypsin immunological test system...

21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5120 Antismooth muscle antibody immunological test system. (a) Identification. An antismooth... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antismooth muscle antibody immunological test...

Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society.

PubMed

Mallone, R; Mannering, S I; Brooks-Worrell, B M; Durinovic-Belló, I; Cilio, C M; Wong, F S; Schloot, N C

2011-01-01

Autoimmune T cell responses directed against insulin-producing β cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5630 Beta-2-microglobulin immunological test system. (a) Identification. A beta-2-microglobulin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-microglobulin immunological test system...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) immunological test system. 866.5530 Section 866.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-macroglobulin immunological test system...

21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a...

21 CFR 866.5130 - Alpha-1-antitrypsin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5130 Alpha-1-antitrypsin immunological test system. (a) Identification. An alpha-1-antitrypsin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antitrypsin immunological test system. 866...

21 CFR 866.5800 - Seminal fluid (sperm) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5800 Seminal fluid (sperm) immunological test system. (a) Identification. A seminal fluid (sperm... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Seminal fluid (sperm) immunological test system...

21 CFR 866.5600 - Low-density lipoprotein immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system...

21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5890 Inter-alpha trypsin inhibitor immunological test system. (a) Identification. An inter... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inter-alpha trypsin inhibitor immunological test...

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human allotypic marker immunological test system...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Retinol-binding protein immunological test system...

21 CFR 866.5380 - Free secretory component immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5380 Free secretory component immuno-logical test system. (a) Identification. A free... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Free secretory component immuno-logical test...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tumor-associated antigen immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen immunological Test Systems § 866.6010 Tumor-associated antigen immunological test system. (a) Identification. A...

Immunological Response of Hiv-Infected Children to Highly Active Antiretoviral Therapy at Gondar University Hospital, North-Western Ethiopia.

PubMed

Kokeb, Mehretie; Degu, Getu

2016-01-01

The effectiveness of highly active antiretroviral therapy (HAART) in children has not been well studied specially in developing countries where the burden of HIV is high. This study was aimed to assess the immunologic response of HIV-infected children to HAART at Pediatric ART Clinic Gondar University Hospital. Institution based cross-sectional study was conducted at the Pediatric ART Clinic Gondar University Hospital from March 01-April 30, 2014. The study included 283 HIV-infected children who were on HAART for 6 months and above. Medical records of HIV-infected children were reviewed using pre-tested questionnaire. CD4 count/percent was collected every 6 months retrospectively. For all statistical significance tests, the cut-off value was p<0.05. Poison Regression was used for further analysis. The mean age of children was 6.9 years with a standard deviation of 3.4 years. The median CD4 count/percent was 232/13%, 450/21%, 540/25% and 608/27% at the time of initiation, 6, 12 and 18 months of ART, respectively. HAART initiated at higher CD4 count, good adherence and HIV status disclosure were found to have positive effects for immunological response. The study revealed that there was good Immunological response to ART, and that the maximum response was in the 1(st) 6 months of ART. Low CD4 count at initiation, undisclosed HIV status and lack of good adherence were found to cause low immunological response to HAART.

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5270 C-reactive protein immuno-logical test system. (a) Identification. A C-reactive protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-reactive protein immuno-logical test system. 866...

21 CFR 866.5440 - Beta-2-glycoprotein III immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5440 Beta-2-glycoprotein III immunological test system. (a) Identification. A beta-2-glycoprotein III... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-glycoprotein III immunological test system...

21 CFR 866.5200 - Carbonic anhydrase B and C immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5200 Carbonic anhydrase B and C immunological test system. (a) Identification. A carbonic... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Carbonic anhydrase B and C immunological test...

21 CFR 866.5430 - Beta-2-glycoprotein I immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5430 Beta-2-glycoprotein I immunological test system. (a) Identification. A beta-2-glycoprotein I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-glycoprotein I immunological test system...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5260 Complement C3b inactivator immunological test system. (a) Identification. A complement... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement C3b inactivator immunological test...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-lipoprotein immuno-logical test system...

Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

PubMed

Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

2013-06-01

Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at p<0.05, and the analysis was performed using SPSS (v16). A total of 354 HIV-infected patients were included. Seventy-five percent (268/354) of patients completed the SD HBVV, an 84% (226/268) returned for the hepatitis B surface antibody evaluation. Only 47.3% (107/226) responded to standard-dose hepatitis B vaccination. Responders had higher absolute numbers (p=0.017) and percentages of CD4 cells (p<0.001) and were more likely to be receiving HAART (p=0.001). There was a 70% (48/69) response rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

PubMed

Simpson, Elizabeth

2015-04-19

'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

Analysis of the Heterogeneity of the 40,000 Molecular Weight Tuber Glycoprotein of Potatoes by Immunological Methods and by NH2-Terminal Sequence Analysis 1

PubMed Central

Park, William D.; Blackwood, Cheri; Mignery, Greg A.; Hermodson, Mark A.; Lister, Richard M.

1983-01-01

Among the major soluble tuber proteins of potato (Solanum tuberosum L.) is a group of glycoproteins having apparent molecular weights of approximately 40,000. This group of proteins as purified by ion-exchange and affinity chromatography has been given the trivial name `patatin.' Patatin exists in a number of charge forms which differ between potato cultivars and in some cases can also be resolved into a number of bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, by immunodiffusion and immunoelectrophoresis, it was found that the isoforms of patatin are immunologically identical both within a cultivar as well as between cultivars. A high degree of homology between the isoforms of patatin is also indicated by NH2-terminal amino acid sequence analysis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:16662777

Can vitamin E and selenium alleviate the immunologic impact of aluminium on pregnant rats' spleens?

PubMed

Ayuob, Nasra Naeim

2013-01-01

This study aimed to assess if simultaneous administration of vitamin E, selenium and aluminium could alleviate the latter's immunologic impact on the spleen. Twenty eight virgin albino Sprague Dawley rats were randomly divided into two main groups: control (n=12) and experimental (n=18). These groups were divided into two subgroups each. The first control group received distiled water and the second one vitamin E and selenium for 3months through intragastric tubes. Of the two experimental subgroups, the first received oral aluminium chloride (AlCl3) at a dose 150mg/kg of body weight/day, and the second received AlCl3 plus vitamin E and selenium for 3months. Sixteen (out of eighteen) subject rats became pregnant. At day 20 of gestation, dams were sacrificed, and spleens were dissected and processed for histologic examination with routine and immunohistologic staining and semi-quantitative assessment. Aluminium administration induced a significant decrease in the number and density of T-lymphocytes and macrophages in the spleen as well as splenic fibrosis during pregnancy. Vitamin E and selenium reduced but did not completely prevent these changes. Copyright © 2013 Elsevier Inc. All rights reserved.

Heterogeneity of colon cancer: from bench to bedside

PubMed Central

Merlano, Marco C; Granetto, Cristina; Fea, Elena; Ricci, Vincenzo; Garrone, Ornella

2017-01-01

The large bowel shows biomolecular, anatomical and bacterial changes that proceed from the proximal to the distal tract. These changes account for the different behaviour of colon cancers arising from the diverse sides of the colon–rectum as well as for the sensitivity to the therapy, including immunotherapy. The gut microbiota plays an important role in the modulation of the immune response and differs between the right colon cancer and the left colorectal cancer. The qualitative and quantitative difference of the commensal bacteria between the right side and the left side induces epigenetic changes in the intestinal epithelial cells as well as in the resident immune population. The second player in the pathological homeostasis of colorectal cancer is the differences of the genetic features of cancer cells and the different effects that microsatellite instability, chromosomal instability and the CpG island methylator phenotype induce on the immunological organisation of the tumour microenvironment. The third player is the immunological composition of the tumour microenvironment, which changes under the influence of both genetic structures and gut microbiota. All these three players influence each other. This review describes these three aspects, highlights their interactions and discusses data from reported clinical trials. Click here to listen to the Podcast PMID:29209524

Lung Microbiome for Clinicians. New Discoveries about Bugs in Healthy and Diseased Lungs

PubMed Central

Rom, William N.; Weiden, Michael D.

2014-01-01

Microbes are readily cultured from epithelial surfaces of the skin, mouth, and colon. In the last 10 years, culture-independent DNA-based techniques demonstrated that much more complex microbial communities reside on most epithelial surfaces; this includes the lower airways, where bacterial culture had failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial environment is important for adequate immunological development. The most common microbes found in the lower airways are also found in the upper airways. Increasing abundance of oral characteristic taxa is associated with increased inflammatory cells and exhaled nitric oxide, suggesting that the airway microbiome induces an immunological response in the lung. Furthermore, rhinovirus infection leads to outgrowth of Haemophilus in patients with chronic obstructive pulmonary disease, and human immunodeficiency virus–infected subjects have more Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction in which the host immune defenses also influence the microbial niche. Quantitative and/or qualitative changes in the lung microbiome may be relevant for disease progression and exacerbations in a number of pulmonary diseases. Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. PMID:24460444

21 CFR 866.5330 - Factor XIII, A, S, immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5330 Factor XIII, A, S, immuno-logical test system. (a) Identification. A factor XIII, A, S... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Factor XIII, A, S, immuno-logical test system. 866...

Correlation analysis for the incubation period of prion disease.

PubMed

Bae, Se-Eun; Jung, Sunghoon; Kim, Ha-Yeon; Son, Hyeon S

2012-07-01

Previous studies have shown that genetic quantitative trait loci (QTL), strain barriers, inoculation dose and inoculation method modulate the incubation period of prion diseases. We examined the relationship between a diverse set of physical, genetic and immunological characteristics and the incubation period of prion disease using correlation analyses. We found that incubation period was highly correlated with brain weight. In addition, mean corpuscular volume and cell size were strongly correlated with incubation period, indicating that the physical magnitude of prion-infected organs or individual cells may be important in determining the incubation period. Given the same prion inoculation dose, animals with a lower brain weight, mean corpuscular volume or cell size may experience more virulent disease, as the effective concentration of abnormal prion, which might regulate the attachment rate of prions to aggregates, is increased with smaller capacity of brains and cells. This is partly consistent with previous theoretical modeling. The strong correlations between incubation period and physical properties of the brain and cells in this study suggest that the mechanism underlying prion disease pathology may be physical, indicating that the incubation process is governed by simple chemical stoichiometry.

Modeling of cytometry data in logarithmic space: When is a bimodal distribution not bimodal?

PubMed

Erez, Amir; Vogel, Robert; Mugler, Andrew; Belmonte, Andrew; Altan-Bonnet, Grégoire

2018-02-16

Recent efforts in systems immunology lead researchers to build quantitative models of cell activation and differentiation. One goal is to account for the distributions of proteins from single-cell measurements by flow cytometry or mass cytometry as readout of biological regulation. In that context, large cell-to-cell variability is often observed in biological quantities. We show here that these readouts, viewed in logarithmic scale may result in two easily-distinguishable modes, while the underlying distribution (in linear scale) is unimodal. We introduce a simple mathematical test to highlight this mismatch. We then dissect the flow of influence of cell-to-cell variability proposing a graphical model which motivates higher-dimensional analysis of the data. Finally we show how acquiring additional biological information can be used to reduce uncertainty introduced by cell-to-cell variability, helping to clarify whether the data is uni- or bimodal. This communication has cautionary implications for manual and automatic gating strategies, as well as clustering and modeling of single-cell measurements. © 2018 International Society for Advancement of Cytometry. © 2018 International Society for Advancement of Cytometry.

Synthesis of a select group of proteins by Neisseria gonorrhoeae in response to thermal stress.

PubMed

Woods, M L; Bonfiglioli, R; McGee, Z A; Georgopoulos, C

1990-03-01

We report the thermal conditions that induce the heat shock response in Neisseria gonorrhoeae. Under conditions of thermal stress, Neisseria gonorrhoeae synthesizes heat shock proteins (hsps), which differ quantitatively from conventionally studied gonococcal proteins. Gonococci accelerate the rate of synthesis of the hsps as early as 5 min after the appropriate stimulus is applied, with synthesis continuing for 30 min, as demonstrated by in vivo labeling experiments with L-[35S]methionine. Two of the gonococcal hsps are immunologically cross-reactive with the hsps of Escherichia coli, DnaK and GroEL, as demonstrated by Western blot (immunoblot) analysis. Ten hsps can be identified on two-dimensional autoradiograms of whole gonococci (total protein). Four hsps can be identified on two-dimensional autoradiograms of 1% N-lauroylsarcosine (sodium salt) (Sarkosyl)-insoluble membrane fractions. Two of the hsps from the 1% Sarkosyl-insoluble fraction are found exclusively in this fraction, suggesting that they are membrane proteins. The identification of this group of proteins will facilitate further study of the function of these proteins and provide insight into the possible role of hsps in disease pathogenesis.

Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol.

PubMed

Hettick, Justin M; Law, Brandon F; Lin, Chen-Chung; Wisnewski, Adam V; Siegel, Paul D

2018-06-01

1. Diisocyanates are highly reactive electrophiles utilized in the manufacture of a wide range of polyurethane products and have been identified as causative agents of occupational allergic respiratory disease. However, in spite of the significant occupational health burden associated with diisocyanate-induced asthma, the mechanism of disease pathogenesis remains largely unknown. 2. To better understand the fate of inhaled diisocyanates, a nose-only aerosol exposure system was constructed and utilized to expose a BALB/c mouse model to an aerosol generated from 4,4'-methylene diphenyl diisocyanate (MDI). Tissue and bronchoalveolar lavage samples were evaluated 4 and 24 h post-exposure for evidence of diisocyanate-protein haptenation, and a label-free quantitative proteomics strategy was employed to evaluate relative changes to the protein content of the cellular fraction of the lavage fluid. 3. Following MDI aerosol exposure, expression of the number of proteins with immunological or xenobiotic metabolism relevance is increased, including endoplasmin, cytochrome P450 and argininosuccinate synthase. Western blot analysis indicated MDI-conjugated protein in the lavage fluid, which was identified as serum albumin. 4. Tandem mass spectrometry analysis of MDI-albumin revealed MDI conjugation occurs at a dilysine motif at Lys525, as well as at a glutamine-lysine motif at Lys414, in good agreement with previously published in vitro data on diisocyanate-conjugated serum albumin.

21 CFR 866.6030 - AFP-L3% immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AFP-L3% immunological test system. 866.6030 Section 866.6030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen immunological Test Systems § 866.6030 AFP-L3% immunological test...

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia.

PubMed

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Wasihun, Araya Gebreyesus; Dejene, Tsehaye Asmelash

2018-01-01

Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. The current result shows that immunological and virological failure is a problem in a setting where highly active antiretroviral therapy has been largely scale up. The problem is more in patients with poor adherence. This will in turn affect the global targets of 90% viral suppression by 2020. This may indicate the need for more investment and commitment to improving patient adherence in the study area.

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia

PubMed Central

Hailu, Genet Gebrehiwet; Hagos, Dawit Gebregziabher; Hagos, Amlsha Kahsay; Dejene, Tsehaye Asmelash

2018-01-01

Background Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available. Methods A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05. Result A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL. Conclusions The current result shows that immunological and virological failure is a problem in a setting where highly active antiretroviral therapy has been largely scale up. The problem is more in patients with poor adherence. This will in turn affect the global targets of 90% viral suppression by 2020. This may indicate the need for more investment and commitment to improving patient adherence in the study area. PMID:29715323

[Immune status in infantile autism. Correlation between the immune status, autistic symptoms and levels of serotonin].

PubMed

Ferrari, P; Marescot, M R; Moulias, R; Bursztejn, C; Deville Chabrolle, A; Thiollet, M; Lesourd, B; Braconnier, A; Dreux, C; Zarifian, E

1988-01-01

In sixteen autistic children high values of IgG and a high level of lymphocyte stimulation with PHA were observed. Principal component analysis showed: 1) a significant correlation between basic lymphocyte mitogenic activity and the clinical symptoms opposition and hyperactivity, 2) a significant correlation between high Ig levels, high PHA stimulation responses and the main autistic symptoms (withdrawal, inaffectivity, hypoactivity, mannerism, stereotypy and negatively echolalia), 3) a significant correlation with serotonin uptake by platelets and high immunological responses. Such correlations are strongly in favor of an immunologic component in autistic disease.

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

PubMed Central

Beltrame, Anna; Guerriero, Massimo; Angheben, Andrea; Gobbi, Federico; Requena-Mendez, Ana; Zammarchi, Lorenzo; Formenti, Fabio; Perandin, Francesca; Bisoffi, Zeno

2017-01-01

Background Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. Methodology/Principal findings A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. Conclusions The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants. PMID:28582412

Identification of organ tissue types and skin from forensic samples by microRNA expression analysis.

PubMed

Sauer, Eva; Extra, Antje; Cachée, Philipp; Courts, Cornelius

2017-05-01

The identification of organ tissues in traces recovered from scenes and objects with regard to violent crimes involving serious injuries can be of considerable relevance in forensic investigations. Molecular genetic approaches are provably superior to histological and immunological assays in characterizing organ tissues, and micro-RNAs (miRNAs), due to their cell type specific expression patterns and stability against degradation, emerged as a promising molecular species for forensic analyses, with a range of tried and tested indicative markers. Thus, herein we present the first miRNA based approach for the forensic identification of organ tissues. Using quantitative PCR employing an empirically derived strategy for data normalization and unbiased statistical decision making, we assessed the differential expression of 15 preselected miRNAs in tissues of brain, kidney, lung, liver, heart muscle, skeletal muscle and skin. We show that not only can miRNA expression profiling be used to reliably differentiate between organ tissues but also that this method, which is compatible with and complementary to forensic DNA analysis, is applicable to realistic forensic samples e.g. mixtures, aged and degraded material as well as traces generated by mock stabbings and experimental shootings at ballistic models. Copyright © 2017 Elsevier B.V. All rights reserved.

Semi-Quantitative Method for Streptococci Magnetic Detection in Raw Milk.

PubMed

Duarte, Carla; Costa, Tiago; Carneiro, Carla; Soares, Rita; Jitariu, Andrei; Cardoso, Susana; Piedade, Moisés; Bexiga, Ricardo; Freitas, Paulo

2016-04-27

Bovine mastitis is the most costly disease for dairy farmers and the most frequent reason for the use of antibiotics in dairy cattle; thus, control measures to detect and prevent mastitis are crucial for dairy farm sustainability. The aim of this study was to develop and validate a sensitive method to magnetically detect Streptococcus agalactiae (a Group B streptococci) and Streptococcus uberis in raw milk samples. Mastitic milk samples were collected aseptically from 44 cows with subclinical mastitis, from 11 Portuguese dairy farms. Forty-six quarter milk samples were selected based on bacterial identification by conventional microbiology. All samples were submitted to PCR analysis. In parallel, these milk samples were mixed with a solution combining specific antibodies and magnetic nanoparticles, to be analyzed using a lab-on-a-chip magnetoresistive cytometer, with microfluidic sample handling. This paper describes a point of care methodology used for detection of bacteria, including analysis of false positive/negative results. This immunological recognition was able to detect bacterial presence in samples spiked above 100 cfu/mL, independently of antibody and targeted bacteria used in this work. Using PCR as a reference, this method correctly identified 73% of positive samples for streptococci species with an anti-S. agalactiae antibody, and 41% of positive samples for an anti-GB streptococci antibody.

Semi-Quantitative Method for Streptococci Magnetic Detection in Raw Milk

PubMed Central

Duarte, Carla; Costa, Tiago; Carneiro, Carla; Soares, Rita; Jitariu, Andrei; Cardoso, Susana; Piedade, Moisés; Bexiga, Ricardo; Freitas, Paulo

2016-01-01

Bovine mastitis is the most costly disease for dairy farmers and the most frequent reason for the use of antibiotics in dairy cattle; thus, control measures to detect and prevent mastitis are crucial for dairy farm sustainability. The aim of this study was to develop and validate a sensitive method to magnetically detect Streptococcus agalactiae (a Group B streptococci) and Streptococcus uberis in raw milk samples. Mastitic milk samples were collected aseptically from 44 cows with subclinical mastitis, from 11 Portuguese dairy farms. Forty-six quarter milk samples were selected based on bacterial identification by conventional microbiology. All samples were submitted to PCR analysis. In parallel, these milk samples were mixed with a solution combining specific antibodies and magnetic nanoparticles, to be analyzed using a lab-on-a-chip magnetoresistive cytometer, with microfluidic sample handling. This paper describes a point of care methodology used for detection of bacteria, including analysis of false positive/negative results. This immunological recognition was able to detect bacterial presence in samples spiked above 100 cfu/mL, independently of antibody and targeted bacteria used in this work. Using PCR as a reference, this method correctly identified 73% of positive samples for streptococci species with an anti-S. agalactiae antibody, and 41% of positive samples for an anti-GB streptococci antibody. PMID:27128950

Buffalo's Center for Immunology: A New Answer to an Old Dilemma

ERIC Educational Resources Information Center

Rose, Noel R.; Bogazzi, Pierluigi E.

1972-01-01

The Center for Immunology at the University of Buffalo provides a viable resource for educating medical students in immunology until a department of immunology can be developed within the medical school. (HS)

Methods and materials relating to IMPDH and GMP production

DOEpatents

Collart, Frank R.; Huberman, Eliezer

1997-01-01

Disclosed are purified and isolated DNA sequences encoding eukaryotic proteins possessing biological properties of inosine 5'-monophosphate dehydrogenase ("IMPDH"). Illustratively, mammalian (e.g., human) IMPDH-encoding DNA sequences are useful in transformation or transfection of host cells for the large scale recombinant production of the enzymatically active expression products and/or products (e.g., GMP) resulting from IMPDH catalyzed synthesis in cells. Vectors including IMPDH-encoding DNA sequences are useful in gene amplification procedures. Recombinant proteins and synthetic peptides provided by the invention are useful as immunological reagents and in the preparation of antibodies (including polyclonal and monoclonal antibodies) for quantitative detection of IMPDH.

Towards a liquid self: how time, geography, and life experiences reshape the biological identity.

PubMed

Grignolio, Andrea; Mishto, Michele; Faria, Ana Maria Caetano; Garagnani, Paolo; Franceschi, Claudio; Tieri, Paolo

2014-01-01

The conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of "liquid self," which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body's ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call "immunological biography." Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between "self" and "non-self" states in a dynamical, "liquid" fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host.

Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India.

PubMed

Kaushal, H; Bras-Gonçalves, R; Avishek, K; Kumar Deep, D; Petitdidier, E; Lemesre, J-L; Papierok, G; Kumar, S; Ramesh, V; Salotra, P

2016-07-01

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic dermal complication that occurs usually after recovery from visceral leishmaniasis (VL). The disease manifests into macular, papular and/or nodular clinical types with mono- or polymorphic presentations. Here, we investigated differences in immunological response between these two distinct clinical forms in Indian PKDL patients. Peripheral blood mononuclear cells of PKDL and naive individuals were exposed in vitro to total soluble Leishmania antigen (TSLA). The proliferation index was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based lymphoproliferative assay. Cytokines and granzyme B levels were determined by cytometric bead array. Parasite load in tissue biopsy samples of PKDL was quantified by quantitative polymerase chain reaction (qPCR). The proportion of different lymphoid subsets in peripheral blood and the activated T cell population were estimated using flow cytometry. The study demonstrated heightened cellular immune responses in the polymorphic PKDL group compared to the naive group. The polymorphic group showed significantly higher lymphoproliferation, increased cytokines and granzyme B levels upon TSLA stimulation, and a raised proportion of circulating natural killer (NK) T cells against naive controls. Furthermore, the polymorphic group showed a significantly elevated proportion of activated CD4(+) and CD8(+) T cells upon in-vitro TSLA stimulation. Thus, the polymorphic variants showed pronounced cellular immunity while the monomorphic form demonstrated a comparatively lower cellular response. Additionally, the elevated level of both activated CD4(+) and CD8(+) T cells, coupled with high granzyme B secretion upon in-vitro TSLA stimulation, indicated the role of cytotoxic cells in resistance to L. donovani infection in polymorphic PKDL. © 2016 British Society for Immunology.

Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity

PubMed Central

Grignolio, Andrea; Mishto, Michele; Faria, Ana Maria Caetano; Garagnani, Paolo; Franceschi, Claudio; Tieri, Paolo

2014-01-01

The conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of “liquid self,” which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body’s ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call “immunological biography.” Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between “self” and “non-self” states in a dynamical, “liquid” fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host. PMID:24782860

Mastitomics, the integrated omics of bovine milk in an experimental model of Streptococcus uberis mastitis: 3. Untargeted metabolomics.

PubMed

Thomas, Funmilola Clara; Mudaliar, Manikhandan; Tassi, Riccardo; McNeilly, Tom N; Burchmore, Richard; Burgess, Karl; Herzyk, Pawel; Zadoks, Ruth N; Eckersall, P David

2016-08-16

Intramammary infection leading to bovine mastitis is the leading disease problem affecting dairy cows and has marked effects on the milk produced by infected udder quarters. An experimental model of Streptococcus uberis mastitis has previously been investigated for clinical, immunological and pathophysiological alteration in milk, and has been the subject of peptidomic and quantitative proteomic investigation. The same sample set has now been investigated with a metabolomics approach using liquid chromatography and mass spectrometry. The analysis revealed over 3000 chromatographic peaks, of which 690 were putatively annotated with a metabolite. Hierarchical clustering analysis and principal component analysis demonstrated that metabolite changes due to S. uberis infection were maximal at 81 hours post challenge with metabolites in the milk from the resolution phase at 312 hours post challenge being closest to the pre-challenge samples. Metabolic pathway analysis revealed that the majority of the metabolites mapped to carbohydrate and nucleotide metabolism show a decreasing trend in concentration up to 81 hours post-challenge whereas an increasing trend was found in lipid metabolites and di-, tri- and tetra-peptides up to the same time point. The increase in these peptides coincides with an increase in larger peptides found in the previous peptidomic analysis and is likely to be due to protease degradation of milk proteins. Components of bile acid metabolism, linked to the FXR pathway regulating inflammation, were also increased. Metabolomic analysis of the response in milk during mastitis provides an essential component to the full understanding of the mammary gland's response to infection.

A global "imaging'' view on systems approaches in immunology.

PubMed

Ludewig, Burkhard; Stein, Jens V; Sharpe, James; Cervantes-Barragan, Luisa; Thiel, Volker; Bocharov, Gennady

2012-12-01

The immune system exhibits an enormous complexity. High throughput methods such as the "-omic'' technologies generate vast amounts of data that facilitate dissection of immunological processes at ever finer resolution. Using high-resolution data-driven systems analysis, causal relationships between complex molecular processes and particular immunological phenotypes can be constructed. However, processes in tissues, organs, and the organism itself (so-called higher level processes) also control and regulate the molecular (lower level) processes. Reverse systems engineering approaches, which focus on the examination of the structure, dynamics and control of the immune system, can help to understand the construction principles of the immune system. Such integrative mechanistic models can properly describe, explain, and predict the behavior of the immune system in health and disease by combining both higher and lower level processes. Moving from molecular and cellular levels to a multiscale systems understanding requires the development of methodologies that integrate data from different biological levels into multiscale mechanistic models. In particular, 3D imaging techniques and 4D modeling of the spatiotemporal dynamics of immune processes within lymphoid tissues are central for such integrative approaches. Both dynamic and global organ imaging technologies will be instrumental in facilitating comprehensive multiscale systems immunology analyses as discussed in this review. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A cross-sectional study on the relationship of job stress with natural killer cell activity and natural killer cell subsets among healthy nurses.

PubMed

Morikawa, Yuko; Kitaoka-Higashiguchi, Kazuyo; Tanimoto, Chie; Hayashi, Midori; Oketani, Reiko; Miura, Katsuyuki; Nishijo, Muneko; Nakagawa, Hideaki

2005-09-01

The present study investigated the effects of job stress on cellular immune function, such as NK cell activity and NK cell subsets. The participants were 61 female nurses aged 23-59, who worked in a public psychiatric hospital in Ishikawa, Japan. Each subject completed the Nursing Job Stressor Scale (NJSS) and their NK cell activity and lymphocyte surface antigens (CD16+56+) were evaluated as immune system parameters. The NJSS has seven subscales: conflict with other nursing staff, nursing role conflict, conflict with physicians or autonomy, conflict with death or dying, quantitative work load, qualitative work load and conflict with patients. Factors influencing NK cell activity, and the proportion and cell counts of CD16+56+ lymphocytes were evaluated. Increase in quantitative work load significantly decreased NK cell activity. Conversely, no linear relationship was observed between qualitative work load and immunological variables, with the highest percentage of CD16+56+ lymphocytes observed among participants in the medium work load group. The other five NJSS subscales did not relate to immune parameters. In conclusion, the results suggest that perceived job strains, particularly quantitative work load, decreased NK cell function.

A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.

PubMed

Kimmel, M; Keller, D; Farmer, S; Warrino, D E

2010-03-01

GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Food avoidance and restriction in adults: a cross-sectional pilot study comparing patients from an immunology clinic to a general practice.

PubMed

Fitzgerald, Michael; Frankum, Brad

2017-01-01

With the introduction of avoidant/restrictive food intake disorder (ARFID) in the Diagnostic and Statistical Manual - fifth edition, there is an increased need to understand the prevalence and pattern of food avoidance and restriction in adults. High rates of food allergy and intolerance in immunology clinic populations, and subsequent high rates of elimination diets, place these individuals at a greater risk of developing pathological eating behaviours. This descriptive cross sectional pilot study aims to provide preliminary data on the prevalence and nature of food avoidance and restriction in an adult population, and to explore the reasons for this behaviour. A self-administered questionnaire was designed and distributed to adults presenting to an immunology clinic and a general practice over the course of 6 months to describe the prevalence and nature of avoidant and restrictive eating behaviours in this population. Pearson's chi square test was used to examine the strength of a potential link to a formal diagnosis of avoidant restrictive food intake disorder in these patients. A total of 102 completed questionnaires were used for data analysis. Food avoidance or restriction was detected in 81 respondents (79%), with rates not significantly higher in the immunology clinic group compared to the general practice group ( p  = .242). Food allergy and intolerance were the most common reasons for disturbed eating patterns. Life impact secondary to food avoidance and restriction was reported by 26% of respondents, with significantly higher rates observed in the immunology clinic cohort compared to the general practice ( p  = .011). Eating disturbances similar to those characteristic of ARFID are very common in adults. Food avoidance and restriction due to perceived food allergy and intolerance are significant reasons for such disordered eating patterns, particularly in an immunology clinic population. Further investigation is needed to determine if such eating behaviours are pathological and whether they qualify for a diagnosis of ARFID.

Dysregulation in microRNA Expression Is Associated with Alterations in Immune Functions in Combat Veterans with Post-Traumatic Stress Disorder

PubMed Central

Zhou, Juhua; Nagarkatti, Prakash; Zhong, Yin; Ginsberg, Jay P.; Singh, Narendra P.; Zhang, Jiajia; Nagarkatti, Mitzi

2014-01-01

While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD) has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR) in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC) and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs) decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD. PMID:24759737

Dysregulation in microRNA expression is associated with alterations in immune functions in combat veterans with post-traumatic stress disorder.

PubMed

Zhou, Juhua; Nagarkatti, Prakash; Zhong, Yin; Ginsberg, Jay P; Singh, Narendra P; Zhang, Jiajia; Nagarkatti, Mitzi

2014-01-01

While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD) has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR) in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC) and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs) decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD.

Environmental conditions, immunologic phenotypes, atopy, and asthma: New evidence of how the hygiene hypothesis operates in Latin America

PubMed Central

Alcantara-Neves, Neuza M.; Matos, Sheila M. A.; Cooper, Philip J.; Rodrigues, Laura C.; Barreto, Mauricio L.

2016-01-01

Background It has been proposed that improved hygiene and reduced experience of infections in childhood influences the development of allergic diseases. The mechanisms by which the hygiene operates are not well established but are underpinned by two apparently incompatible immunologic paradigms, the balance of TH1 versus TH2 cytokines and IL-10–mediated regulation of TH2 cytokines. Objective This study defined immunologic phenotypes with the use of latent class analysis and investigated their associations with environmental factors, markers of allergy and asthma, in a Latin American population. Methods We studied 1127 children living in urban Brazil. Data on wheeze and environmental exposures were collected with standardized questionnaires. Atopy was measured by specific IgE in serum and skin prick test reactivity to aeroallergens. Cytokines were measured in culture after the stimulation of peripheral blood leukocytes with mitogen. Infections with pathogens were assessed by serology and stool examinations. Children were classified as having high or low burden of infection. Latent class analysis was used to identify immune phenotypes on the basis of cytokine production. Logistic regression was used to evaluate the adjusted effects of environment and burden of infection on the immunologic phenotypes and the effect of the phenotypes on atopy and asthma. Results Three phenotypes were identified, labeled underresponsive, intermediate, and responsive. Children of more educated mothers, living in improved environmental conditions, and with a low burden of infection were significantly more likely to have the responsive phenotype. The responsive phenotype was significantly associated with an increased prevalence of atopy but not asthma. Conclusion Our findings contribute to a better understanding of the immune mechanisms by which the hygiene hypothesis operates in urban Latin America. PMID:23414599

Immunological and molecular polymorphisms of OspC, an immunodominant major outer surface protein of Borrelia burgdorferi.

PubMed Central

Wilske, B; Preac-Mursic, V; Jauris, S; Hofmann, A; Pradel, I; Soutschek, E; Schwab, E; Will, G; Wanner, G

1993-01-01

The gene of the immunodominant major protein pC of Borrelia burgdorferi was previously cloned and sequenced (R. Fuchs, S. Jauris, F. Lottspeich, V. Preac-Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503-509, 1992). pC is abundantly expressed on the outer surface of B. burgdorferi, as demonstrated by immunoelectron microscopy with monoclonal antibody L22 1F8. Accordingly, pC is renamed OspC, by analogy to the outer surface proteins OspA and OspB. Western immunoblot analysis of 45 B. burgdorferi isolates with monoclonal antibodies revealed that OspC is immunologically heterogeneous. Partial sequence analysis of the ospC gene confirmed the protein heterogeneity at the genetic level. We found that the degree of identity between the ospC partial sequences of five strains representing different OspA serotypes was only 63.3 to 85.4%. Immunological heterogeneity was also observed among representatives of the three newly designated genospecies of B. burgdorferi sensu lato, B. burgdorferi sensu stricto, B. garinii, and group VS461. Heterogeneity was confirmed for B. garinii at the genetic level. The ospC gene was also cloned from strains that did not express OspC, and antibody-reactive OspC was expressed in Escherichia coli. In addition, OspC-expressing variants were obtained from a nonexpressing strain by plating single colonies on solid medium. These findings confirm that the ospC gene is also present in nonexpressing strains. Because OspC is an immunodominant protein for the early immune response in Lyme borreliosis and was effective as a vaccine in an animal model, the immunological and molecular polymorphisms of ospC and OspC have important implications for the development of diagnostic reagents and vaccines. Images PMID:8478108

Collection, handling and analysis of specimens for studies of mucosal immunity in animals of veterinary importance - Appendix III

USDA-ARS?s Scientific Manuscript database

The validity of data in science depends on the reliability of the collection procedure and the methods used for data analysis. This becomes a major challenge in studies of mucosal immunology since samples for analysis come from various anatomical sources which differ remarkably in their content and ...

Molecular analysis, biochemical characterization, antimicrobial activity and immunological analysis of proteus mirabilis isolated from broilers

USDA-ARS?s Scientific Manuscript database

Proteus mirabilis, a peritrichously flagellated Gram-negative bacterium, is ubiquitous in the environment and is the normal microflora in the human gastrointestinal tract. However, this bacterium is an opportunistic pathogen for human, often causing urinary tract infection. Moreover, Proteus has b...

A novel pathogenesis of inflammatory bowel disease from the perspective of glyco-immunology.

PubMed

Shinzaki, Shinichiro; Iijima, Hideki; Fujii, Hironobu; Kamada, Yoshihiro; Naka, Tetsuji; Takehara, Tetsuo; Miyoshi, Eiji

2017-05-01

Oligosaccharide modifications play an essential role in various inflammatory diseases and cancers, but their pathophysiologic roles, especially in inflammation, are not clear. Inflammatory bowel disease (IBD) is an intractable chronic inflammatory disorder with an unknown aetiology, and the number of patients with IBD is increasing throughout the world. Certain types of immunosuppressant drugs, such as corticosteroids, are effective for IBD, suggesting that immune function is closely associated with the pathophysiology of IBD. Recent progress in the analysis of oligosaccharides revealed a role for oligosaccharides in intestinal inflammation based on both experimental models and human samples from IBD patients. Moreover, changes in the oligosaccharide structures on glycoproteins in the sera and tissue samples may serve as biomarkers of IBD. Here, we present current studies of IBD with regard to the immunologic aspects of glycobiology, suggesting a novel concept for IBD pathogenesis and the function of oligosaccharides on immune cells, termed "glyco-immunology". © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations

NASA Technical Reports Server (NTRS)

Meehan, R.; Whitson, P.; Sams, C.

1993-01-01

This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.

Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.

PubMed

Zhang, Allen W; McPherson, Andrew; Milne, Katy; Kroeger, David R; Hamilton, Phineas T; Miranda, Alex; Funnell, Tyler; Little, Nicole; de Souza, Camila P E; Laan, Sonya; LeDoux, Stacey; Cochrane, Dawn R; Lim, Jamie L P; Yang, Winnie; Roth, Andrew; Smith, Maia A; Ho, Julie; Tse, Kane; Zeng, Thomas; Shlafman, Inna; Mayo, Michael R; Moore, Richard; Failmezger, Henrik; Heindl, Andreas; Wang, Yi Kan; Bashashati, Ali; Grewal, Diljot S; Brown, Scott D; Lai, Daniel; Wan, Adrian N C; Nielsen, Cydney B; Huebner, Curtis; Tessier-Cloutier, Basile; Anglesio, Michael S; Bouchard-Côté, Alexandre; Yuan, Yinyin; Wasserman, Wyeth W; Gilks, C Blake; Karnezis, Anthony N; Aparicio, Samuel; McAlpine, Jessica N; Huntsman, David G; Holt, Robert A; Nelson, Brad H; Shah, Sohrab P

2018-05-07

High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispersion. Copyright © 2018 Elsevier Inc. All rights reserved.

Biomolecular aspects of depression: A retrospective analysis.

PubMed

Peacock, Brandon N; Scheiderer, David J; Kellermann, Gottfried H

2017-02-01

The effects of psychological stress, oxidative stress, and chronic low grade inflammation on the neuro-immune connection have been implicated in the pathogenesis of depression. Thus, in the recent past, there has been a growing effort in determining the mechanism of this pathogenesis. While attempting to map out, this mechanism researchers and clinicians have searched for clinically relevant biomarkers for use in the diagnosis and for the assessment of those suffering from depression. In this study, we have performed a retrospective analysis of biomarkers with clinically relevant potentials, including peripheral catecholamines, chemokines, cytokines, and neurotransmitters. The retrospective analysis was performed on data collected over a six-year period of time (July 2009 to July 2015), gathered from patients (N=1399; Mage=42, SD=13; 71% female, 29% male) who submitted samples with complaints of feeling hopeless, worthless, isolated, alone, general sadness, overwhelmed, and/or a lack of interest in things they once enjoyed. The data collected consisted of quantitative values of urinary catecholamines and neurotransmitters (peripheral dopamine, epinephrine, histamine, kynurenic acid, norepinephrine, β-PEA, and serotonin), salivary hormones (peripheral cortisol and melatonin), and peripheral blood mononuclear cell secreted cytokines and chemokines (Interleukins 1β, 6, 8, 10, MCP-1, GCSF, and TNFα). Statistical and clinical significance was assessed by comparison with a control group (N=2395; Mage=42, SD=13; 70% female, 30% male), calculating the percent mean difference, p value, and effect size (Cohen's ɗ) for each parameter between groups. The findings of this study suggested that, in a model of general depression, there is a dysregulation in the enzymatic production and degradation of catecholamines, neurotransmitters, hormones, and immunological proteins. A cycle of interaction was found between all of these biomolecules, where an increase or decrease in one marker could result in a stimulatory or inhibitory effect on others. The mechanism of this was proposed to occur through the interaction of psychological stress, inflammation, and oxidative stress pathways. All of these biomolecules were found to be significantly altered in the general depression group and are key components of the interaction between the neurological and immunological systems. This study serves to further elucidate the role of biomolecules in the regulation of affective disorders, such as depression. Resulting in providing a network of clinically relevant biomarkers to objectively assess and monitor general depression. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

Virtual immunology: software for teaching basic immunology.

PubMed

Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

2013-01-01

As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available free of charge in Portuguese and English, which can be used by teachers and students in physiology, immunology, and cellular biology classes. We discuss the development of the initial two modules: "Organs and Lymphoid Tissues" and "Inflammation" and the use of interactive activities to provide microscopic and macroscopic understanding in immunology. Students, both graduate and undergraduate, were questioned along with university level professors about the quality of the software and intuitiveness of use, facility of navigation, and aesthetic organization using a Likert scale. An overwhelmingly satisfactory result was obtained with both students and immunology teachers. Programs such as "Virtual Immunology" are offering more interactive, multimedia approaches to complex scientific principles that increase student motivation, interest, and comprehension. © 2013 by The International Union of Biochemistry and Molecular Biology.

Single blinded, randomized, placebo-controlled study on the effects of ciclosporin on cutaneous barrier function and immunological response in atopic beagles.

PubMed

White, Amelia G; Santoro, Domenico; Ahrens, Kim; Marsella, Rosanna

2018-03-01

Ciclosporin (CsA) is a common treatment for canine atopic dermatitis (cAD). cAD is a very common skin disease with a multifactorial pathogenesis due to complex interactions between the host and the environment. The purpose of this study was to describe the physical and immunological effects of CsA in cAD using a canine model of AD. Fourteen beagles were enrolled; seven received CsA orally every 24 h for 28 days, and seven received placebo. All dogs were exposed to relevant allergens, house dust mite solution, one day prior to treatment and once weekly thereafter for 28 consecutive days. Canine atopic dermatitis extent and severity index-03 (CADESI-03) and skin biopsies were performed on day 0, 14, and 28. Quantitative RT-PCR was used to determine levels of cutaneous cytokines and barrier function markers. Indirect immunofluorescence was used to determine protein expression and distribution of nuclear messengers, barrier function and inflammatory [thymic stromal lymphopoietin (TSLP)] markers. The data were tested for normality and then the upaired two samples Student's t-test and the repeated measurements ANOVA, followed by the Dunnett's Multiple Comparison Test as post-hoc analysis, were performed. A P value of <0.05 was considered statistically significant. A significant decrease in CADESI-03 occurred for the treatment group compared to placebo (p = 0.023) on day 28. On day 14, a significant increase in TSLP protein expression [p = 0.019 (placebo); p = 0.02 (CsA)] and a significant decrease in Transforming Growth Factor (TGF)-β mRNA [p = 0.01 (placebo); p = 0.015 (CsA)] were noted in both groups compared to baseline. On day 28, a significant increase in canine beta defensin (cBD)103 [p = 0.012 (placebo)] and cBD3-like mRNAs [p = 0.044 (placebo)], and filaggrin [p = 0.035 (CsA)] and TSLP protein expressions [p = 0.0092 (CsA)] were seen compared to baseline. In contrast, a significant decrease in mRNA of Tumor Necrosis factor (TNF)-α [p = 0.013 (CsA)], Interleukin (IL)-10 [p = 0.038 (CsA)], TGF-β [p = 0.017 (CsA)], and caspase 14 [p = 0.014 (CsA)] was seen on day 28 compared to baseline. Comparison of the groups revealed no significant effect on skin immunologic milieu or barrier markers despite evident improvement of physical signs in the treatment group. Although this study confirmed the usefulness of CsA for the treatment of cAD, a clear involvement of CsA on some of the currently known immunological alterations present in cAD was not determined. However, it is important to note that there was no measurable exacerbation of skin barrier dysfunction secondary to CsA administration in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

Virtual Immunology: Software for Teaching Basic Immunology

ERIC Educational Resources Information Center

Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

2013-01-01

As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

Need for immunologic stimulators during immunosuppression produced by major cancer surgery.

PubMed Central

Cole, W H; Humphrey, L

1985-01-01

Although surgery, radiology, and anticancer chemicals have been effective in the treatment of cancer, the immunologic phase of therapy deserves more effort and thought, because the possibilities are considerable. However, the immunologic phase is so complicated that, without the advances made during the past few years, little could be expected from immunology. The focus of this paper is on the immunosuppression produced by major cancer operations, at which time the patient needs immunologic help. PMID:3893336

Immunologic Regulation in Pregnancy: From Mechanism to Therapeutic Strategy for Immunomodulation

PubMed Central

Chen, Shyi-Jou; Liu, Yung-Liang; Sytwu, Huey-Kang

2012-01-01

The immunologic interaction between the fetus and the mother is a paradoxical communication that is regulated by fetal antigen presentation and/or by recognition of and reaction to these antigens by the maternal immune system. There have been significant advances in understanding of abnormalities in the maternal-fetal immunologic relationship in the placental bed that can lead to pregnancy disorders. Moreover, immunologic recognition of pregnancy is vital for the maintenance of gestation, and inadequate recognition of fetal antigens may cause abortion. In this paper, we illustrate the complex immunologic aspects of human reproduction in terms of the role of human leukocyte antigen (HLA), immune cells, cytokines and chemokines, and the balance of immunity in pregnancy. In addition, we review the immunologic processes of human reproduction and the current immunologic therapeutic strategies for pathological disorders of pregnancy. PMID:22110530

Comprehensive Analysis of Immunological Synapse Phenotypes Using Supported Lipid Bilayers.

PubMed

Valvo, Salvatore; Mayya, Viveka; Seraia, Elena; Afrose, Jehan; Novak-Kotzer, Hila; Ebner, Daniel; Dustin, Michael L

2017-01-01

Supported lipid bilayers (SLB) formed on glass substrates have been a useful tool for study of immune cell signaling since the early 1980s. The mobility of lipid-anchored proteins in the system, first described for antibodies binding to synthetic phospholipid head groups, allows for the measurement of two-dimensional binding reactions and signaling processes in a single imaging plane over time or for fixed samples. The fragility of SLB and the challenges of building and validating individual substrates limit most experimenters to ~10 samples per day, perhaps increasing this few-fold when examining fixed samples. Successful experiments might then require further days to fully analyze. We present methods for automation of many steps in SLB formation, imaging in 96-well glass bottom plates, and analysis that enables >100-fold increase in throughput for fixed samples and wide-field fluorescence. This increased throughput will allow better coverage of relevant parameters and more comprehensive analysis of aspects of the immunological synapse that are well reconstituted by SLB.

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

Graduate Students' Interest in Immunology as a Discipline

ERIC Educational Resources Information Center

Kwarteng, Alexander; Frimpong, Michael; Sylverken, Augustina Angelina; Arthur, Yarhands D.; Ahuno, Samuel T.; Owusu-Dabo, Ellis

2017-01-01

Interest and motivation significantly influence achievement; however, interest in immunology remains to be determined. Using a structured questionnaire, the current study assessed for the first time interest in immunology among biomedical graduate students in Ghana after a one-week introduction to immunology course. Our results revealed that…

21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... test system. 866.5510 Section 866.5510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5230 - Colostrum immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Colostrum immunological test system. 866.5230... Colostrum immunological test system. (a) Identification. A colostrum immunological test system is a device... colostrum. Colostrum is a substance excreted by the mammary glands during pregnancy and until production of...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

SPECIAL ISSUE VETERINARY IMMUNOLOGY IMMUNOPATHOLOGY: PROCEEDINGS 8TH INTERNATIONAL VETERINARY IMMUNOLOGY SYMPOSIUM

USDA-ARS?s Scientific Manuscript database

This is the Special Issue of Vet. Immunol. Immunopathol. that summarizes the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto, Brazil. The 8 th IVIS highlighted the importance of veterinary immunology for animal health, vaccinology, reproducti...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

AZT Impairs Immunological Recovery on First-line ART: Collaborative analysis of cohort studies in Southern Africa

PubMed Central

WANDELER, Gilles; GSPONER, Thomas; MULENGA, Lloyd; GARONE, Daniela; WOOD, Robin; MASKEW, Mhairi; PROZESKY, Hans; HOFFMANN, Christopher; EHMER, Jochen; DICKINSON, Diana; DAVIES, Mary-Ann; EGGER, Matthias; KEISER, Olivia

2013-01-01

Objectives Zidovudine (AZT) is recommended for first-line antiretroviral therapy (ART) in resource limited settings. AZT may, however, lead to anemia and impaired immunological response. We compared CD4 counts over 5 years between patients starting ART with and without AZT in Southern Africa. Design Cohort study Methods Patients aged ≥16 years who started first-line ART in South Africa, Botswana, Zambia or Lesotho were included. We used linear mixed-effect models to compare CD4 cell count trajectories between patients on AZT-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4 count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4 count and haemoglobin level, age, gender, type of regimen, viral load monitoring and calendar year. Results 72,597 patients starting ART, including 19,758 (27.2%) on AZT, were analysed. Patients on AZT had higher CD4 cell counts (150 vs.128 cells/μl) and haemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be female than those on other regimens. Adjusted differences in CD4 counts between regimens containing and not containing AZT were −16 cells/μl (95% CI −18 to −14) at 1 year and −56 cells/μl (95% CI −59 to −52) at 5 years. Impaired immunological recovery was more likely with AZT compared to other regimens (odds ratio 1.40, 95% CI 1.22–1.61). Conclusions In Southern Africa AZT is associated with inferior immunological recovery compared to other backbones. Replacing AZT with another NRTI could avoid unnecessary switches to second-line ART. PMID:23660577

A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

PubMed

Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

2014-01-01

We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Overall, at therapy start, 27% of patients had FPR ≤ 10 (6%, FPR ≤ 2; 7%, FPR 2-5; 14%, FPR 5-10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%. Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

21 CFR 866.5820 - Systemic lupus erythema-tosus immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Systemic lupus erythema-tosus immunological test... Systems § 866.5820 Systemic lupus erythema-tosus immunological test system. (a) Identification. A systemic lupus erythematosus (SLE) immunological test system is a device that consists of the reagents used to...

Hepatitis C virus and the immunological response to hepatitis B virus vaccine in dialysis patients: meta-analysis of clinical studies.

PubMed

Fabrizi, F; Dixit, V; Martin, P; Messa, P

2011-12-01

It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection. © 2011 Blackwell Publishing Ltd.

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

PubMed Central

Korutla, Laxminarayana; Habertheuer, Andreas; Yu, Ming; Rostami, Susan; Yuan, Chao-Xing; Reddy, Sanjana; Korutla, Varun; Koeberlein, Brigitte; Trofe-Clark, Jennifer; Rickels, Michael R.; Naji, Ali

2017-01-01

In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation. In the xenogeneic model, we quantified islet transplant exosomes in recipient blood over long-term follow-up using anti-HLA antibody, which was detectable only in xenoislet recipients of human islets. Transplant islet exosomes were purified using anti-HLA antibody–conjugated beads, and their cargoes contained the islet endocrine hormone markers insulin, glucagon, and somatostatin. Rejection led to a marked decrease in transplant islet exosome signal along with distinct changes in exosomal microRNA and proteomic profiles prior to appearance of hyperglycemia. In the clinical settings of islet and renal transplantation, donor exosomes with respective tissue specificity for islet β cells and renal epithelial cells were reliably characterized in recipient plasma over follow-up periods of up to 5 years. Collectively, these findings demonstrate the biomarker potential of transplant exosome characterization for providing a noninvasive window into the conditional state of transplant tissue. PMID:28319051

Evaluation of immunologic effect of Enniatin A and quantitative determination in feces, urine and serum on treated Wistar rats.

PubMed

Juan, Cristina; Manyes, Lara; Font, Guillermina; Juan-García, Ana

2014-09-01

Study of dietary supplementation with ENN A mycotoxin during 28 days of exposure time on Wistar rats to determinate its levels in serum, urine and feces and, to evaluate the immunologic effect in peripheral blood lymphocytes (PBL) is presented. The first method for ENN A extraction, determination and detection by LC-MS/MS in serum, urine and feces samples is reported. ENN A food dose administrated was detected in serum samples and influenced lymphocyte phenotyping. Levels in serum were founded from the second week of the experiment; reaching values of 4.76 μg/ml on the fourth week, which corresponds to 3.24 μg/ml in blood. PBL as T helper (CD4(+)) were presented in greater percentages compared to control (p ≤ 0.001), while T cytotoxic (CD8(+)) decreased significantly compared to control (p ≤ 0.001). ENN A treatment significantly increased CD4(+)/CD3(+) and CD4(+)/CD8(+) ratios but significantly decreased CD8(+)/CD3(+) ratio. CD4(+)/CD8(+) ratio was 2.94:1, indicating that PBL surface antigen expression and immune status in Wistar rats treated were impaired by the ENN A mycotoxin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Magnetic Labeling of Activated Microglia in Experimental Gliomas1

PubMed Central

Fleige, Gerrit; Nolte, Christiane; Synowitz, Michael; Seeberger, Florian; Kettenmann, Helmut; Zimmer, Claus

2001-01-01

Abstract Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS. PMID:11774031

Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis

PubMed Central

Sears-Kraxberger, Ilse; Keirstead, Hans S.

2013-01-01

The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells. PMID:24319469

Introduction for Diffusion Chamber Culture Symposium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carsten, A. L.

The diffusion-chamber system has been applied to studies of cell kinetics, progenitor cell quantitation, humoral effects, immunological effects, cytogenetics, organogenesis, and the cellular effects of drugs and physical factors such as radiation, hypoxia, etc. Chamber contents have been analyzed by clot dissolution with measuring of cell content, limiting dilution evaluation, radionuclide utilization (tritiated thymidine labeling), growth of colony number, size and type, CFU-S or CFU-C content, or proliferation by secondary culture in mice or in vitro systems, and chromosome changes. Cell types ranging from embryonal tissues to adult normal and neoplastic tissues have been grown in hosts across species barriers.more » Advantages and disadvantages of this system are discussed.« less

Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

PubMed

Dhami, Sangeeta; Nurmatov, Ulugbek; Varga, Eva-Maria; Sturm, Gunter; Muraro, Antonella; Akdis, Cezmi A; Antolín-Amérigo, Darío; Bilò, M Beatrice; Bokanovic, Danijela; Calderon, Moises A; Cichocka-Jarosz, Ewa; Elberink, Joanna N G Oude; Gawlik, Radoslaw; Jakob, Thilo; Kosnik, Mitja; Lange, Joanna; Mingomataj, Ervin; Mitsias, Dimitris I; Mosbech, Holger; Pfaar, Oliver; Pitsios, Constantinos; Pravettoni, Valerio; Roberts, Graham; Ruëff, Franziska; Sin, Betül Ayşe; Sheikh, Aziz

2015-01-01

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT.

A roadmap towards personalized immunology.

PubMed

Delhalle, Sylvie; Bode, Sebastian F N; Balling, Rudi; Ollert, Markus; He, Feng Q

2018-01-01

Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions. There is still a long way ahead on translating our capability to identify potentially targetable personalized biomarkers into effective personalized therapy in immune-centralized diseases. Here, we discuss the recent advances and successful applications in "Omics" data utilization and network analysis on patients' samples of clinical trials and studies, as well as the major challenges and strategies towards personalized stratification and treatment for infectious or non-communicable inflammatory diseases such as autoimmune diseases or allergies. We provide a roadmap and highlight experimental, clinical, computational analysis, data management, ethical and regulatory issues to accelerate the implementation of personalized immunology.

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

Medical immunology: two-way bridge connecting bench and bedside.

PubMed

Rijkers, Ger T; Damoiseaux, Jan G M C; Hooijkaas, Herbert

2014-12-01

Medical immunology in The Netherlands is a laboratory specialism dealing with immunological analyses as well as pre- and post-analytical consultation to clinicians (clinical immunologists and other specialists) involved in patients with immune mediated diseases. The scope of medical immunology includes immunodeficiencies, autoimmune diseases, allergy, transfusion and transplantation immunology, and lymphoproliferative disorders plus the monitoring of these patients. The training, professional criteria, quality control of procedures and laboratories is well organized. As examples of the bridge function of medical immunology between laboratory (bench) and patient (bedside) the contribution of medical immunologists to diagnosis and treatment of primary immunodeficiency diseases (in particular: humoral immunodeficiencies) as well as autoantibodies (anti-citrullinated proteins in rheumatoid arthritis) are given. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural shifts of fecal microbial communities in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Luo, Zhuanbo; Li, Zhengfeng; Deng, Min; Liu, Hao; Zhu, Biao; Ruan, Bing; Li, Lanjuan

2012-08-01

Bacterial translocation and the development of sepsis after orthotopic liver transplantation (OLT) may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microbiota. This study monitored structural shifts of gut microbiota in rats with OLT using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR (RT-qPCR). RT-qPCR targets six major microorganisms (Domain Bacteria, Bacteroides, Bifidobacteria, Enterobacteriaceae, Lactobacillus and Clostridium leptum subgroup). Isograft, Allograft and Sham model were studied. Bacterial translocation to host organs and plasma endotoxin were determined. Alteration in gut microbiota was associated with the elevation of plasma endotoxin and a higher rate of bacterial translocation (BT) to liver in rats with acute rejection. Dynamic analysis of DGGE fingerprints showed that the gut microbiota structure of animals in the three groups was similar before the operation. But significant alterations in the composition of fecal microbiota in Allograft group were observed at 1 and 2 weeks after the OLT. The acute rejection was accompanied by the shifts of gut microbiota towards members of Bacteroides and Ruminococcus. Results from RT-qPCR indicated that Bacteroides significantly increased at 2 weeks after the OLT, whereas numbers of Bifidobacterium spp. decreased at 1 week and recovered at 2 weeks after the OLT. In summary, our data showed that rats with acute rejection after OLT exhibited significant structure shifts in the gut microbiota which dominant by overgrowth of Bacteroides and Ruminococcus, and these were associated with elevation of plasma endotoxin and higher rate of BT.

Functional interaction analysis of GM1-related carbohydrates and Vibrio cholerae toxins using carbohydrate microarray.

PubMed

Kim, Chang Sup; Seo, Jeong Hyun; Cha, Hyung Joon

2012-08-07

The development of analytical tools is important for understanding the infection mechanisms of pathogenic bacteria or viruses. In the present work, a functional carbohydrate microarray combined with a fluorescence immunoassay was developed to analyze the interactions of Vibrio cholerae toxin (ctx) proteins and GM1-related carbohydrates. Ctx proteins were loaded onto the surface-immobilized GM1 pentasaccharide and six related carbohydrates, and their binding affinities were detected immunologically. The analysis of the ctx-carbohydrate interactions revealed that the intrinsic selectivity of ctx was GM1 pentasaccharide ≫ GM2 tetrasaccharide > asialo GM1 tetrasaccharide ≥ GM3trisaccharide, indicating that a two-finger grip formation and the terminal monosaccharides play important roles in the ctx-GM1 interaction. In addition, whole cholera toxin (ctxAB(5)) had a stricter substrate specificity and a stronger binding affinity than only the cholera toxin B subunit (ctxB). On the basis of the quantitative analysis, the carbohydrate microarray showed the sensitivity of detection of the ctxAB(5)-GM1 interaction with a limit-of-detection (LOD) of 2 ng mL(-1) (23 pM), which is comparable to other reported high sensitivity assay tools. In addition, the carbohydrate microarray successfully detected the actual toxin directly secreted from V. cholerae, without showing cross-reactivity to other bacteria. Collectively, these results demonstrate that the functional carbohydrate microarray is suitable for analyzing toxin protein-carbohydrate interactions and can be applied as a biosensor for toxin detection.

Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes.

PubMed

Kerr, J R; Burke, B; Petty, R; Gough, J; Fear, D; Mattey, D L; Axford, J S; Dalgleish, A G; Nutt, D J

2008-06-01

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity. In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype. Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression). It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.

Preliminary Hormonal Correlations in Female Patients as a Function of Somatic and Neurological Symptom Clusters: An Exploratory Development of a Multi-Hormonal Map for Bio-Identical Replacement Therapy (MHRT).

PubMed

Braverman, Eric R; Oscar-Berman, Marlene; Kreuk, Florian; Kerner, Mallory; Dushaj, Kristina; Li, Mona; Stratton, Danielle; Trudesdell, Courtney; Blum, Kenneth

2013-12-06

Females develop multiple hormonal alterations and certain genes may be involved in the intensity of subsequent symptoms including both mood and drug seeking. Seventy Four (74) females were included (mean age=60.23, SD=9.21, [43-87]). A medical evaluation was completed with hormone screening using a number of statistical analyses such as Pearson product moment; one way ANOVA and Regression analysis along with a Bonferroni significance correction p<.004. Of 120 correlations performed, significant hormone/domain correlations were as follows: DHEA/Genitourinary (r=.30, p<.05); FSH/Pulmonary (r=-.29, p<.05); Pregnenolone/Genitourinary (r=.40, p<.006) /Immunological (r=.38, p<.008); Testosterone/total endorsed symptoms (r=-0.34, p<.016); TSH/Pulmonary (r=-.33, p<.03) /Gynecological (r=.30, p<.05). Estrone/Musculoskeletal (r=-0.43, p<.012). After a Bonferroni correction (experiment-wise p<.00045) for statistical significance, no hormones remained significance. In the follow-up phase FSH/Neuropsychiatric (r=.56, p<.05) and Musculoskeletal (r=.67, p<.013); DHEA/Immunological (r=.64, p<.04); LH/ Musculoskeletal (r=.59, p<.34); Free Testosterone/Neuropsychiatric (r=.64, p<.019), Musculoskeletal (r=.68, p<.01), and Dermatologic (r=.57, p<.04); Total Testosterone/Immunological (r=.63, p<.028); TSH/Endocrinological (r=-.62, p<.031). Factor analysis of the MQ yielded two factors with eigenvalues > 1.0 (high loadings: first: Pulmonary, GI, Cardiovascular, and Immunological; second: Musculoskeletal, Gynecological, and the three Neurological domains). Both factors had significant correlations: first/pregnenolone (r=.37, p<.019); second/TSH (r=.33, p<.034). An additional factor analysis of hormone level clusters showed significant correlations with various domains. This study highlights the need to test the core biological endocrine hormones associated with females. Future research will focus on the relationship of for example Leptin and the electrophysiology of the brain. We are cautiously proposing a new paradigm shift whereby we replace the old nomenclature of HRT to MHRT.

Desensitization: Overcoming the Immunologic Barriers to Transplantation

PubMed Central

Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

Immunological biomarkers in salt miners exposed to salt dust, diesel exhaust and nitrogen oxides.

PubMed

Backé, Eva; Lotz, Gabriele; Tittelbach, Ulrike; Plitzko, Sabine; Gierke, Erhardt; Schneider, Wolfram Dietmar

2004-06-01

Air pollutants can affect lung function and also the immune system. In a study about lung function of salt miners in relation to the complex exposure in a salt mine, we also analysed selected immunological parameters and inflammation markers in the blood of miners. Effect of salt dust, diesel exhaust, nitrogen oxides (NOx) and smoking on the biomarkers was analysed. Blood was drawn from 286 salt miners, and the soluble intercellular adhesion molecule-1 (s-ICAM), monocyte chemotactic protein (MCP-1) and clara cell protein (CC16) were analysed by an immunoassay, blood profile was done and lymphocyte subpopulations (CD3, CD3/CD4, CD3/CD8, CD19, NK-cells, CD3/HLA-DR) were determined by flow cytometry. Salt dust was measured by two-step gravimetry (personal sampling). Diesel exhaust was measured as elemental carbon concentration by coulometry. NOx were determined by an electrochemical cell method. Differences between non-smokers, former smokers and active smokers were analysed by analysis of variance. Linear regression analysis to describe exposure-response relationships was done with regard to confounding factors [smoking, inflammatory diseases, time of blood drawing, respiratory infection and body-mass index (BMI)]. Significant differences between non-smokers and active smokers were found for most of the leukocyte types (e.g. granulocytes P = 0.000, lymphocytes P = 0.002, T-cells P = 0.033) and for some soluble parameters (ICAM P = 0.000, IgM P = 0.007, IgE P = 0.035). Increasing numbers of total lymphocytes, T-cells and HLA-DR positive T-cells in relation to exposure were found by linear regression analysis (e.g. for inhalable dust:total lymphocytes P = 0.011, T-cells P = 0.061, HLA-DR positive T-cells P = 0.007). CONCLUSION. Comparison of immunological markers in non-smokers and active smokers confirms leukocytosis and inflammation following tobacco consumption. The combined exposure of salt dust, diesel exhaust and NOx seems to influence the immune system. Together, the results suggest that the analysis of leukocytes and their subsets can complete other investigations (lung function, questionnaire) to monitor exposure-response relationships in occupational studies investigating the effect of inhaled substances. Longitudinal studies will be necessary to determine the predictive value of the immunological changes. Copyright 2004 Springer-Verlag

Imaging of blood antigen distribution on blood cells by thermal lens microscopy

NASA Astrophysics Data System (ADS)

Kimura, Hiroko; Sekiguchi, Kazuya; Nagao, Fumiko; Mukaida, Masahiro; Kitamori, Takehiko; Sawada, Tsuguo

2000-05-01

Blood group antigens on a cell were measured by a new microscopic method, i.e. thermal lens microscopy which involves spectrometry using a laser-induced thermal-lens effect. The blood group antigen was immunologically stained using antibody labeled with colloidal gold. Human leukocyte antigens (HLA) on lymphocytes and mononuclear leukocytes were observed by the thermal lens microscope, and Lewis blood group antigens on erythrocytes and polymorphonuclear leukocytes were also observed. The antigen distribution on each cell-surface was imaged using this technique. In spite of convex surface of living cells, colloidal gold was correctly quantified by adjusting the deviation of the focal point of the probe laser by the phase of the signal. In the measurement of leukocyte antigens, antigens of HLA-A, -B, -C loci on the lymphocytes were identified and quantitated by using a single cell. The image of HLA-A, -B, -C antigen distribution on a mononuclear leukocyte was obtained. In the measurement of erythrocyte antigens, a small quantity of Lewis antigens was detected on the cord erythrocytes. Localized small quantities of membrane antigens are better quantitated without extraction or cytolysis. Our thermal lens microscope is a powerful and highly sensitive analytical tool for detecting and quantitating localized antigens in single cells and/or cell-surface-associated molecules.

The Protein Disease Database of human body fluids: II. Computer methods and data issues.

PubMed

Lemkin, P F; Orr, G A; Goldstein, M P; Creed, G J; Myrick, J E; Merril, C R

1995-01-01

The Protein Disease Database (PDD) is a relational database of proteins and diseases. With this database it is possible to screen for quantitative protein abnormalities associated with disease states. These quantitative relationships use data drawn from the peer-reviewed biomedical literature. Assays may also include those observed in high-resolution electrophoretic gels that offer the potential to quantitate many proteins in a single test as well as data gathered by enzymatic or immunologic assays. We are using the Internet World Wide Web (WWW) and the Web browser paradigm as an access method for wide distribution and querying of the Protein Disease Database. The WWW hypertext transfer protocol and its Common Gateway Interface make it possible to build powerful graphical user interfaces that can support easy-to-use data retrieval using query specification forms or images. The details of these interactions are totally transparent to the users of these forms. Using a client-server SQL relational database, user query access, initial data entry and database maintenance are all performed over the Internet with a Web browser. We discuss the underlying design issues, mapping mechanisms and assumptions that we used in constructing the system, data entry, access to the database server, security, and synthesis of derived two-dimensional gel image maps and hypertext documents resulting from SQL database searches.

Consensus Communication on Early Peanut Introduction and Prevention of Peanut Allergy in High-Risk Infants.

PubMed

Fleischer, David M; Sicherer, Scott; Greenhawt, Matthew; Campbell, Dianne; Chan, Edmond; Muraro, Antonella; Halken, Susanne; Katz, Yitzhak; Ebisawa, Motohiro; Eichenfield, Lawrence; Sampson, Hugh; Lack, Gideon; Du Toit, George; Roberts, Graham; Bahnson, Henry; Feeney, Mary; Hourihane, Jonathan; Spergel, Jonathan; Young, Michael; As'aad, Amal; Allen, Katrina; Prescott, Susan; Kapur, Sandeep; Saito, Hirohisa; Agache, Ioana; Akdis, Cezmi A; Arshad, Hasan; Beyer, Kirsten; Dubois, Anthony; Eigenmann, Philippe; Fernandez-Rivas, Monserrat; Grimshaw, Kate; Hoffman-Sommergruber, Karin; Host, Arne; Lau, Susanne; O'Mahony, Liam; Mills, Clare; Papadopoulos, Nikolaus; Venter, Carina; Agmon-Levin, Nancy; Kessel, Aaron; Antaya, Richard; Drolet, Beth; Rosenwasser, Lanny

2016-01-01

The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology. © 2015 the Authors. Published by Wiley Periodicals, Inc.

The 14th European Immunology Meeting--EFIS 2000. 23-27 September 2000, Poznañ, Poland.

PubMed

Wysocki, P J; Nawrocki, S; Mackiewicz, A

2001-01-01

The 14th European Immunology Meeting--EFIS 2000, held in Poznan, Poland on 23-27 September 2000, was the last major meeting of European immunologists in the second millennium. This conference was intended to summarise past achievements and to present future prospects in immunology. The philosophy of the scientific program was to fuse fundamental and clinical immunology and give a chance for basic scientists and clinicians to discuss mutual topics in a general view. There were eight state-of-art lectures, 12 'meet an expert' sessions, 20 plenary sessions and 46 workshops. More than 900 works were presented. Significant interest was focused on several aspects of cancer immunology and immunotherapy. EFIS 2000 was accompanied by six pre-congress satellite symposia held in various Polish cities. The topics were, 'Heat shock proteins: immune, stress response and apoptosis' (Gdansk), 'Infectious immunity and vaccines' (Kazimierz Dolny), 'Mononuclear phagocytes in basic and clinical immunology' (Cracow), 'Immunology of reproduction' (Poznan), 'Primary immunodeficiencies' (Warsaw) and 'Glycoimmunology' (Wroclaw).

Fibromyalgia and chronic fatigue syndrome in children.

PubMed

Itoh, Yasuhiko; Shigemori, Tomoko; Igarashi, Tohru; Fukunaga, Yoshitaka

2012-04-01

Fibromyalgia (FM) is characterized by widespread persistent pain and the presence of multiple discrete tender points. Chronic fatigue syndrome (CFS) is a syndrome characterized by debilitating fatigue associated with a variable number of non-specific complaints. Because neither condition had necessarily been recognized in children until recently, those patients have been treated as having school refusal without being diagnosed as having either syndrome. There is a considerable overlap of clinical symptoms between these two syndromes. It is therefore controversial as to whether these syndromes have the same pathogenesis or not. The aim of the present study was to clarify the relationship between these syndromes in children. Fifteen patients with FM and 21 patients with CFS were investigated both clinically and immunologically. Immunological assessments included thorough analysis of autoantibodies using several techniques. Anti-nuclear antibody titers were higher and the prevalence of anti-Sa antibody was far more frequent in CFS patients than in FM patients. CFS and FM are different from each other at least in childhood, from an immunological aspect, although some patients could have both conditions. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

21 CFR 866.5380 - Free secretory component immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis or... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

21 CFR 866.5380 - Free secretory component immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis or... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

21 CFR 866.5380 - Free secretory component immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis or... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

21 CFR 866.5380 - Free secretory component immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... body fluids. Measurement of free secretory component (protein molecules) aids in the diagnosis or... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

Face-offs in reproductive immunology: the Montreal forum meeting report.

PubMed

Croy, B Anne; Baines, Malcolm G

2004-10-01

The combined 12th International Congress of Immunology (ICI) and the 4th Annual Conference of the Federation of Clinical Immunological Societies (FOCIS) was held in Montreal, Canada July 18-23, 2004 and attracted over 6000 immunologists and almost 4000 abstracts. The host society, the Canadian Society for Immunology (CSI) spent many years in preparation for this large meeting and encouraged its members to propose topics for symposia and mini-symposia and to sponsor satellite meetings. With sponsorship of CSI; the Canadian Institutes of Health Research; the University of Guelph, Guelph, ON; Queen's University, Kingston, ON; McGill University, Montreal, QU, Canada; and the American Society for Reproductive Immunology, a focused, highly successful, one day satellite meeting on human uterine immunology was held. The highlights of the presentations and discussions are reported.

Correlation analysis for the incubation period of prion disease

PubMed Central

Bae, Se-Eun; Jung, Sunghoon; Kim, Ha-Yeon; Son, Hyeon S.

2012-01-01

Previous studies have shown that genetic quantitative trait loci (QTL), strain barriers, inoculation dose and inoculation method modulate the incubation period of prion diseases. We examined the relationship between a diverse set of physical, genetic and immunological characteristics and the incubation period of prion disease using correlation analyses. We found that incubation period was highly correlated with brain weight. In addition, mean corpuscular volume and cell size were strongly correlated with incubation period, indicating that the physical magnitude of prion-infected organs or individual cells may be important in determining the incubation period. Given the same prion inoculation dose, animals with a lower brain weight, mean corpuscular volume or cell size may experience more virulent disease, as the effective concentration of abnormal prion, which might regulate the attachment rate of prions to aggregates, is increased with smaller capacity of brains and cells. This is partly consistent with previous theoretical modeling. The strong correlations between incubation period and physical properties of the brain and cells in this study suggest that the mechanism underlying prion disease pathology may be physical, indicating that the incubation process is governed by simple chemical stoichiometry. PMID:22561168

Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury.

PubMed

Krieger, J R; Tellier, L E; Ollukaren, M T; Temenoff, J S; Botchwey, E A

2017-06-01

Rotator cuff tears cause muscle degeneration that is characterized by myofiber atrophy, fatty infiltration, and fibrosis and is minimally responsive to current treatment options. The underlying pathogenesis of rotator cuff muscle degeneration remains to be elucidated, and increasing evidence implicates immune cell infiltration as a significant factor. Because immune cells are comprised of highly heterogeneous subpopulations that exert divergent effects on injured tissue, understanding trafficking and accumulation of immune subpopulations may hold the key to more effective therapies. The present study quantifies subpopulations of immune cells infiltrating the murine supraspinatus muscle after severe rotator cuff injury that includes tenotomy and denervation. Rotator cuff injury stimulates dramatic infiltration of mononuclear phagocytes, enriches mononuclear phagocytes in non-classical subpopulations, and enriches T lymphocytes in T H and T reg subpopulations. The combination of tenotomy plus denervation significantly increases mononuclear phagocyte infiltration, enriches macrophages in the non-classical subpopulation, and decreases T lymphocyte enrichment in T H cells compared to tenotomy alone. Depletion of circulating monocytes via liposomal clodronate accelerates supraspinatus atrophy after tenotomy and denervation. The study may aid rational design of immunologically smart therapies that harness immune cells to enhance outcomes after rotator cuff tears.

Status and opportunities for genomics research with rainbow trout

USGS Publications Warehouse

Thorgaard, G.H.; Bailey, G.S.; Williams, D.; Buhler, D.R.; Kaattari, S.L.; Ristow, S.S.; Hansen, J.D.; Winton, J.R.; Bartholomew, J.L.; Nagler, J.J.; Walsh, P.J.; Vijayan, M.M.; Devlin, R.H.; Hardy, R.W.; Overturf, K.E.; Young, W.P.; Robison, B.D.; Rexroad, C.; Palti, Y.

2002-01-01

The rainbow trout (Oncorhynchus mykiss) is one of the most widely studied of model fish species. Extensive basic biological information has been collected for this species, which because of their large size relative to other model fish species are particularly suitable for studies requiring ample quantities of specific cells and tissue types. Rainbow trout have been widely utilized for research in carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. They are distinctive in having evolved from a relatively recent tetraploid event, resulting in a high incidence of duplicated genes. Natural populations are available and have been well characterized for chromosomal, protein, molecular and quantitative genetic variation. Their ease of culture, and experimental and aquacultural significance has led to the development of clonal lines and the widespread application of transgenic technology to this species. Numerous microsatellites have been isolated and two relatively detailed genetic maps have been developed. Extensive sequencing of expressed sequence tags has begun and four BAC libraries have been developed. The development and analysis of additional genomic sequence data will provide distinctive opportunities to address problems in areas such as evolution of the immune system and duplicate genes. ?? 2002 Elsevier Science Inc. All rights reserved.

Profiling antibody responses by multiparametric analysis of primary B cells

PubMed Central

Story, Craig M.; Papa, Eliseo; Hu, Chih-Chi Andrew; Ronan, Jehnna L.; Herlihy, Kara; Ploegh, Hidde L.; Love, J. Christopher

2008-01-01

Determining the efficacy of a vaccine generally relies on measuring neutralizing antibodies in sera. This measure cannot elucidate the mechanisms responsible for the development of immunological memory at the cellular level, however. Quantitative profiles that detail the cellular origin, extent, and diversity of the humoral (antibody-based) immune response would improve both the assessment and development of vaccines. Here, we describe a novel approach to collect multiparametric datasets that describe the specificity, isotype, and apparent affinity of the antibodies secreted from large numbers of individual primary B cells (≈103-104). The antibody/antigen binding curves obtained by this approach can be used to classify closely related populations of cells using algorithms for data clustering, and the relationships among populations can be visualized graphically using affinity heatmaps. The technique described was used to evaluate the diversity of antigen-specific antibody-secreting cells generated during an in vivo humoral response to a series of immunizations designed to mimic a multipart vaccination. Profiles correlating primary antibody-producing cells with the molecular characteristics of their secreted antibodies should facilitate both the evaluation of candidate vaccines and, broadly, studies on the repertoires of antibodies generated in response to infectious or autoimmune diseases. PMID:19004776

Synthesis of a select group of proteins by Neisseria gonorrhoeae in response to thermal stress.

PubMed Central

Woods, M L; Bonfiglioli, R; McGee, Z A; Georgopoulos, C

1990-01-01

We report the thermal conditions that induce the heat shock response in Neisseria gonorrhoeae. Under conditions of thermal stress, Neisseria gonorrhoeae synthesizes heat shock proteins (hsps), which differ quantitatively from conventionally studied gonococcal proteins. Gonococci accelerate the rate of synthesis of the hsps as early as 5 min after the appropriate stimulus is applied, with synthesis continuing for 30 min, as demonstrated by in vivo labeling experiments with L-[35S]methionine. Two of the gonococcal hsps are immunologically cross-reactive with the hsps of Escherichia coli, DnaK and GroEL, as demonstrated by Western blot (immunoblot) analysis. Ten hsps can be identified on two-dimensional autoradiograms of whole gonococci (total protein). Four hsps can be identified on two-dimensional autoradiograms of 1% N-lauroylsarcosine (sodium salt) (Sarkosyl)-insoluble membrane fractions. Two of the hsps from the 1% Sarkosyl-insoluble fraction are found exclusively in this fraction, suggesting that they are membrane proteins. The identification of this group of proteins will facilitate further study of the function of these proteins and provide insight into the possible role of hsps in disease pathogenesis. Images PMID:2106493

Transmission of Hepatitis C Virus From Organ Donors Despite Nucleic Acid Test Screening.

PubMed

Suryaprasad, A; Basavaraju, S V; Hocevar, S N; Theodoropoulos, N; Zuckerman, R A; Hayden, T; Forbi, J C; Pegues, D; Levine, M; Martin, S I; Kuehnert, M J; Blumberg, E A

2015-07-01

Nucleic acid testing (NAT) for hepatitis C virus (HCV) is recommended for screening of organ donors, yet not all donor infections may be detected. We describe three US clusters of HCV transmission from donors at increased risk for HCV infection. Donor's and recipients' medical records were reviewed. Newly infected recipients were interviewed. Donor-derived HCV infection was considered when infection was newly detected after transplantation in recipients of organs from increased risk donors. Stored donor sera and tissue samples were tested for HCV RNA with high-sensitivity quantitative PCR. Posttransplant and pretransplant recipient sera were tested for HCV RNA. Quasispecies analysis of hypervariable region-1 was used to establish genetic relatedness of recipient HCV variants. Each donor had evidence of injection drug use preceding death. Of 12 recipients, 8 were HCV-infected-6 were newly diagnosed posttransplant. HCV RNA was retrospectively detected in stored samples from donor immunologic tissue collected at organ procurement. Phylogenetic analysis showed two clusters of closely related HCV variants from recipients. These investigations identified the first known HCV transmissions from increased risk organ donors with negative NAT screening, indicating very recent donor infection. Recipient informed consent and posttransplant screening for blood-borne pathogens are essential when considering increased risk donors. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Molecular cloning, expression, and in silico structural analysis of guinea pig IL-17.

PubMed

Dirisala, Vijaya R; Jeevan, Amminikutty; Ramasamy, Suresh K; McMurray, David N

2013-11-01

Interleukin-17A (IL-17A) is a potent proinflammatory cytokine and the signature cytokine of Th17 cells, a subset which is involved in cytokine and chemokine production, neutrophil recruitment, promotion of T cell priming, and antibody production. IL-17 may play an important role in tuberculosis and other infectious diseases. In preparation for investigating its role in the highly relevant guinea pig model of pulmonary tuberculosis, we cloned guinea pig IL-17A for the first time. The complete coding sequence of the guinea pig IL-17A gene (477 nucleotides; 159 amino acids) was subcloned into a prokaryotic expression vector (pET-30a) resulting in the expression of a 17 kDa recombinant guinea pig IL-17A protein which was confirmed by mass spectrometry analysis. Homology modeling of guinea pig IL-17A revealed that the three-dimensional structure resembles that of human IL-17A. The secondary structure predicted for this protein showed the presence of one extra helix in the N-terminal region. The expression profile of IL-17A was analyzed quantitatively in spleen, lymph node, and lung cells from BCG-vaccinated guinea pigs by real-time PCR. The guinea pig IL-17A cDNA and its recombinant protein will serve as valuable tools for molecular and immunological studies in the guinea pig model of pulmonary TB and other human diseases.

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

Development and validation of a harmonized TaqMan-based triplex real-time RT-PCR protocol for the quantitative detection of normalized gene expression profiles of seven porcine cytokines.

PubMed

Petrov, Anja; Beer, Martin; Blome, Sandra

2014-01-01

Dysregulation of cytokine responses plays a major role in the pathogenesis of severe and life-threatening infectious diseases like septicemia or viral hemorrhagic fevers. In pigs, diseases like African and classical swine fever are known to show exaggerated cytokine releases. To study these responses and their impact on disease severity and outcome in detail, reliable, highly specific and sensitive methods are needed. For cytokine research on the molecular level, real-time RT-PCRs have been proven to be suitable. Yet, the currently available and most commonly used SYBR Green I assays or heterogeneous gel-based RT-PCRs for swine show a significant lack of specificity and sensitivity. The latter is however absolutely essential for an accurate quantification of rare cytokine transcripts as well as for detection of small changes in gene expressions. For this reason, a harmonized TaqMan-based triplex real-time RT-PCR protocol for the quantitative detection of normalized gene expression profiles of seven porcine cytokines was designed and validated within the presented study. Cytokines were chosen to represent different immunological pathways and targets known to be involved in the pathogenesis of the above mentioned porcine diseases, namely interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor (TNF)-α and interferon (IFN)-α. Beta-Actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) served as reference genes for normalization. For absolute quantification a synthetic standard plasmid was constructed comprising all target cytokines and reference genes within a single molecule allowing the generation of positive control RNA. The standard as well as positive RNAs from samples, and additionally more than 400 clinical samples, which were collected from animal trials, were included in the validation process to assess analytical sensitivity and applicability under routine conditions. The resulting assay allows the reliable assessment of gene expression profiles and provides a broad applicability to any kind of immunological research in swine.

Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa.

PubMed

Sempa, Joseph B; Ujeneza, Eva L; Nieuwoudt, Martin

2017-01-01

In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. 'Preferred Reporting Items for Systematic Review and Meta-Analyses' guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: 'slope', 'survival', and 'asymptote' models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to define 'prior' knowledge in the Bayesian sense. Such information has value for prospective modelling efforts.

Immunological network signatures of cancer progression and survival

PubMed Central

2011-01-01

Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides. PMID:21453479

Intensive educational course in allergy and immunology.

PubMed

Elizalde, A; Perez, E E; Sriaroon, P; Nguyen, D; Lockey, R F; Dorsey, M J

2012-09-01

A one-day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows-in-training. © 2012 John Wiley & Sons A/S.

Pediatric allergy and immunology in Turkey.

PubMed

Celik, Gülfem; Bakirtas, Arzu; Sackesen, Cansin; Reisli, Ismail; Tuncer, Ayfer

2011-06-01

Allergic diseases constitute a significant health problem in Turkey. According to a recent multicenter study, which used the ISAAC questionnaire, the mean prevalence of wheezing, rhinoconjunctivitis, and eczema in 10-yr-old school children during the past year was 15.8%, 23.5%, and 8.1%, respectively. A healthcare level system, regulated by Ministry of Health, is available in Turkey. Pediatric allergists and pediatric immunologists provide patient care at the tertiary level. Currently, 48 centers deliver care for allergic and immunologic diseases in children. There are 136 pediatric and 61 adult allergists/immunologists. Although the number of allergy/clinical immunology specialists is limited, these centers are capable of delivering many of the procedures required for the proper management and diagnosis of allergy/immunology. Pediatric allergy and/or immunology is a subspecialty lasting 3 yr and follows a 4-yr pediatric specialist training. Fellow training involves gaining knowledge in basic and clinical allergy and immunology as well as the performance and interpretation of laboratory procedures in the field of allergy and clinical immunology. The Turkish National Society of Allergy and Clinical Immunology (TNSACI) was officially established in 1989 and currently has 356 members. The society organizes a national congress annually and winter schools for fellowship training as well as training courses for patients and their relatives. TNSACI also has a strong representation in European Academy of Allergy and Clinical Immunology (EAACI) and European Society for Immunodeficiencies (ESID) through its participation in the executive committee, consensus reports, and initiatives in the diagnosis of allergic and immunologic diseases of children. The 30th Congress of the EAACI is also due to be held in Istanbul, Turkey, between June 11 and 15, 2011. © 2011 John Wiley & Sons A/S.

A Constructive Induction Approach to Computer Immunology

DTIC Science & Technology

1999-03-01

LVM98] Lamont, Gary B., David A. Van Veldhuizen , and Robert E Marmelstein, A Distributed Architecture for a Self-Adaptive Computer Virus...Artificial Intelligence, Herndon, VA, 1995. [MVL98] Marmelstein, Robert E., David A. Van Veldhuizen , and Gary B. Lamont. Modeling & Analysis

An Analysis of Operating Room Performance Metrics at Reynolds Army Community Hospital

DTIC Science & Technology

2009-06-28

and Disorders of the Male Reproductive System Diseases and Disorders of the Blood, Blood Forming Organs, Immunological Myeloproliferative Diseases and...Disorders, Poorly Differentiated Neoplasm Infectious and Parasitic Diseases, Systemic or Unspecified Sites Injuries, Poisonings and Toxic Effects

The Immunological Genome Project: networks of gene expression in immune cells.

PubMed

Heng, Tracy S P; Painter, Michio W

2008-10-01

The Immunological Genome Project combines immunology and computational biology laboratories in an effort to establish a complete 'road map' of gene-expression and regulatory networks in all immune cells.

Immunology of malignant diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byers, V.S.; Baldwin, R.W.

1987-01-01

This book contains 11 chapters. Some of the chapter titles are: Immunoscintigraphy: tumor detection with radiolabelled antitumor monoclonal antibodies; Bone marrow transplantation; Immunomodulating agents; Immunology in bowel cancer; Melanoma; and Immunological features of human bladder cancer.

WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts.

PubMed

Malinova, Dessislava; Fritzsche, Marco; Nowosad, Carla R; Armer, Hannah; Munro, Peter M G; Blundell, Michael P; Charras, Guillaume; Tolar, Pavel; Bouma, Gerben; Thrasher, Adrian J

2016-05-01

The immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability. © The Author(s).

Setting the proportion of CD4+ and CD8+ T-cells co-cultured with canine macrophages infected with Leishmania chagasi.

PubMed

Viana, Kelvinson Fernandes; Aguiar-Soares, Rodrigo Dian Oliveira; Ker, Henrique Gama; Resende, Lucilene Aparecida; Souza-Fagundes, Elaine Maria; Dutra, Walderez Ornelas; Fujiwara, Ricardo Toshio; da Silveira-Lemos, Denise; Sant'Ana, Rita de Cássia Oliveira; Wardini, Amanda Brito; Araújo, Márcio Sobreira Silva; Martins-Filho, Olindo Assis; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro

2015-07-30

New methods for evaluating the canine immune system are necessary, not only to monitor immunological disorders, but also to provide insights for vaccine evaluations and therapeutic interventions, reducing the costs of assays using dog models, and provide a more rational way for analyzing the canine immune response. The present study intended to establish an in vitro toll to assess the parasitological/immunological status of dogs, applicable in pre-clinical trials of vaccinology, prognosis follow-up and therapeutics analysis of canine visceral leishmaniasis. We have evaluated the performance of co-culture systems of canine Leishmania chagasi-infected macrophages with different cell ratios of total lymphocytes or purified CD4(+) and CD8(+) T-cells. Peripheral blood mononuclear cells from uninfected dogs were used for the system set up. Employing the co-culture systems of L. chagasi-infected macrophages and purified CD4(+) or CD8(+) T-cell subsets we observed a microenvironment compatible with the expected status of the analyzed dogs. In this context, it was clearly demonstrated that, at this selected T-cell:target ratio, the adaptive immune response of uninfected dogs, composed by L. chagasi-unprimed T-cells was not able to perform the in vitro killing of L. chagasi-infected macrophages. Our data demonstrated that the co-culture system with T-cells from uninfected dogs at 1:5 and 1:2 ratio did not control the infection, yielding to patent in vitro parasitism (≥ 80%), low NO production (≤ 5 μM) and IL-10 modulated (IFN-γ/IL-10 ≤ 2) immunological profile in vitro. CD4(+) or CD8(+) T-cells at 1:5 or 1:2 ratio to L. chagasi-infected macrophages seems to be ideal for in vitro assays. This co-culture system may have great potential as a canine immunological analysis method, as well as in vaccine evaluations, prognosis follow-up and therapeutic interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of Immunology Knowledge on Healthcare and Healthy Lifestyle.

PubMed

Abu Kassim, Noor Lide; Saleh Huddin, Afiqah Binti; Daoud, Jamal Ibrahim; Rahman, Mohammad Tariqur

2016-01-01

Completing a course in Immunology is expected to improve health care knowledge (HCK), which in turn is anticipated to influence a healthy lifestyle (HLS), controlled use of health care services (HCS) and an awareness of emerging health care concerns (HCC). This cross-sectional study was designed to determine whether these interrelationships are empirically supported. Participants involved in this study were government servants from two ministries in Malaysia (n = 356) and university students from a local university (n = 147). Participants were selected using the non-random purposive sampling method. Data were collected using a self-developed questionnaire, which had been validated in a pilot study involving similar subjects. The questionnaire items were analyzed using Rasch analysis, SPSS version 21 and AMOS version 22. Results have shown that participants who followed a course in Immunology (CoI) had a higher primary HCK (Mean = 0.69 logit, SD = 1.29 logits) compared with those who had not (Mean = -0.27logit, SD = 1.26 logits). Overall, there were significant correlations among the HLS, the awareness of emerging HCC, and the controlled use of HCS (p <0.001). However, no significant correlations were observed between primary HCK and the other variables. However, significant positive correlation was observed between primary HCK and controlled use of HCS for the group without CoI. Path analysis showed that the awareness of emerging HCC exerted a positive influence on controlled use of HCS (β = 0.156, p < .001) and on HLS (β = 0.224, p < .001). These findings suggest that having CoI helps increase primary HCK which influences controlled use of HCS but does not necessarily influence HLS. Hence, introducing Immunology at various levels of education and increasing the public awareness of emerging HCC might help to improve population health en masse. In addition, further investigations on the factors affecting HLS is required to provide a better understanding on the relationship between primary HCK and HLS.

Analysis of correlated domain motions in IgG light chain reveals possible mechanisms of immunological signal transduction.

PubMed

Król, Marcin; Roterman, Irena; Piekarska, Barbara; Konieczny, Leszek; Rybarska, Janina; Stopa, Barbara; Spólnik, Paweł

2005-05-15

It was shown experimentally that binding of a micelle composed of Congo red molecules to immunological complexes leads to the enhanced stability of the latter, and simultaneously prevents binding of a complement molecule (C1q). The dye binds in a cavity created by the removal of N-terminal polypeptide chain, as observed experimentally in a model system-immunoglobulin G (IgG) light chain dimer. Molecular Dynamics (MD) simulations of three forms of IgG light chain dimer, with and without the dye, were performed to investigate the role of N-terminal fragment and self-assembled ligand in coupling between V and C domains. Root-mean-square distance (RMSD) time profiles show that removal of N-terminal fragment leads to destabilization of V domain. A micelle composed of four self-assembled dye molecules stabilizes and fixes the domain. Analysis of root-mean-square fluctuation (RMSF) values and dynamic cross-correlation matrices (DCCM) reveals that removal of N-terminal fragment results in complete decoupling between V and C domains. Binding of self-assembled Congo red molecules improves the coupling, albeit slightly. The disruption of a small beta-sheet composed of N- and C-terminal fragments of the domain (NC sheet) is the most likely reason for the decoupling. Self-assembled ligand, bound in the place originally occupied by N-terminal fragment, is not able to take over the function of the beta-sheet. Lack of correlation of motions between residues in V and C domains denotes that light chain-Congo red complexes have hampered ability to transmit conformational changes between domains. This is a likely explanation of the lack of complement binding by immunological complexes, which bind Congo red, and supports the idea that the NC sheet is the key structural fragment taking part in immunological signal transduction. Copyright 2005 Wiley-Liss, Inc.

Current trends of reproductive immunology practices in in vitro fertilization (IVF) - a first world survey using IVF-Worldwide.com.

PubMed

Kwak-Kim, Joanne; Han, Ae Ra; Gilman-Sachs, Alice; Fishel, Simon; Leong, Milton; Shoham, Zeev

2013-01-01

Reproductive immunology has evolved from basic research studies to clinical applications. In this study, we aim to investigate the actual application of reproductive immunology concepts and findings in clinical reproductive medicine such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), and failed in vitro fertilization (IVF) cycles. A web-based survey was performed on IVF-Worldwide.com. Collected data were analyzed by the computerized software. A significant proportion of physicians recommend thrombophilia workups (86%), parental genetic study (79%), and immunologic evaluations (69%) to IVF candidates who have a history of RPL or chemical pregnancy losses. IVF physicians consider an immunologic workup when patients have two (30%) or three (21%) failed IVF cycles. Assays for anticardiolipin antibody, lupus anticoagulant, thyroid peroxidase antibody, and antinuclear antibody are the four most commonly ordered immunologic tests for RPL (88, 84, 50, 47% each) and RIF (68, 63, 38, 38% each). Cellular immune evaluations, such as NK assay, human leukocyte antigen study, Th1/Th2 study or immunophenotype assay, are less commonly ordered. Reproductive immunology principles have been applied to the clinical management of RPL, RIF, and failed IVF cycles, and a significant proportion of IVF physicians acknowledge the importance of immunologic alterations with reproductive outcomes. © 2012 John Wiley & Sons A/S.

Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

PubMed

Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei

2017-09-01

Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.

Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure.

PubMed

Hefazi, Mehrdad; Maleki, Masoud; Mahmoudi, Mahmoud; Tabatabaee, Abbas; Balali-Mood, Mahdi

2006-09-01

Extensive cutaneous burns caused by alkylating chemical warfare agent sulfur mustard (SM) have been associated with the severe suppression of the immune system in humans. We aimed to study the association between late cutaneous and immunological complications of SM poisoning. Skin examination was performed on all SM-poisoned Iranian veterans in the province of Khorasan, Iran, who had significant clinical complications, and their SM intoxication was confirmed by toxicological analysis. Light microscopy was performed on eight skin biopsies. Blood cell counts, serum immunoglobulin and complement factor, as well as flow cytometric, analyses were performed on all the patients. The severity of cutaneous complications were classified into four grades and compared with hematological and immunological parameters, using Spearman's rank correlation test. Forty male subjects, confirmed with SM poisoning 16-20 years earlier, were studied. The main objective findings were hyperpigmentation (55%), dry skin (40%), multiple cherry angiomas (37.5%), atrophy (27.5%), and hypopigmentation (25%). Histopathologic findings were nonspecific and compatible with hyperpigmented old atrophic scars. Except for the hematocrit and C4 levels, hematological and immunological parameters revealed no significant correlation with the severity grades of cutaneous complications. Sulfur mustard is an alkylating agent with prolonged adverse effects on both the skin and the immune system. Although skin is a major transporting system for SM's systemic absorption, there is probably no correlation between the severity of late cutaneous and immunological complications of SM poisoning.

Development of Quantitative Proteomics Using iTRAQ Based on the Immunological Response of Galleria mellonella Larvae Challenged with Fusarium oxysporum Microconidia

PubMed Central

Muñoz-Gómez, Amalia; Corredor, Mauricio; Benítez-Páez, Alfonso; Peláez, Carlos

2014-01-01

Galleria mellonella has emerged as a potential invertebrate model for scrutinizing innate immunity. Larvae are easy to handle in host-pathogen assays. We undertook proteomics research in order to understand immune response in a heterologous host when challenged with microconidia of Fusarium oxysporum. The aim of this study was to investigate hemolymph proteins that were differentially expressed between control and immunized larvae sets, tested with F. oxysporum at two temperatures. The iTRAQ approach allowed us to observe the effects of immune challenges in a lucid and robust manner, identifying more than 50 proteins, 17 of them probably involved in the immune response. Changes in protein expression were statistically significant, especially when temperature was increased because this was notoriously affected by F. oxysporum 104 or 106 microconidia/mL. Some proteins were up-regulated upon immune fungal microconidia challenge when temperature changed from 25 to 37°C. After analysis of identified proteins by bioinformatics and meta-analysis, results revealed that they were involved in transport, immune response, storage, oxide-reduction and catabolism: 20 from G. mellonella, 20 from the Lepidoptera species and 19 spread across bacteria, protista, fungi and animal species. Among these, 13 proteins and 2 peptides were examined for their immune expression, and the hypothetical 3D structures of 2 well-known proteins, unannotated for G. mellonella, i.e., actin and CREBP, were resolved using peptides matched with Bombyx mori and Danaus plexippus, respectively. The main conclusion in this study was that iTRAQ tool constitutes a consistent method to detect proteins associated with the innate immune system of G. mellonella in response to infection caused by F. oxysporum. In addition, iTRAQ was a reliable quantitative proteomic approach to detect and quantify the expression levels of immune system proteins and peptides, in particular, it was found that 104 microconidia/mL at 37°C over expressed many more proteins than other treatments. PMID:25379782

The 3rd international conference on reproductive immunology in Shanghai: September 27-29, 2013. Shanghai, China.

PubMed

Du, MeiRong; Piao, HaiLan; Li, DaJin

2014-03-01

After the first and second international conferences on reproductive immunology held by Dr. DaJin Li in Shanghai, the related investigators all over the world hope to get together to share their latest findings with each other. Drs. DaJin Li and MeiRong Du sponsored and organized the third international conference on reproductive immunology at the Obstetrics and Gynecology Hospital affiliated with Fudan University, Shanghai, China, in the autumn of 2013. This congress brought together more than 100 International and National investigators representing a wide range of scientific disciplines. All the investigators actively work on reproductive immunology using human or large and small animal models. A range of reproductive immunological topics including the maternal-fetal immune regulation, reproductive tract mucosal immunology, immunocontraception, and pregnancy complications were highlighted and discussed in this conference. This conference supplied a good platform for the international reproductive immunologists to exchange their latest study progression and discuss the development direction of reproductive immunology in the near future. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets

PubMed Central

Celada, Lindsay J.; Polosukhin, Vasiliy V.; Atkinson, James B.; Drake, Wonder P.

2016-01-01

Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit β), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher’s test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher’s test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative. PMID:26807608

A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

PubMed Central

Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne-Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Santoro, Maria Mercedes

2014-01-01

Background We previously found that a very low geno2pheno false positive rate (FPR ≤2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. Methods The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Results Overall, at therapy start, 27% of patients had FPR ≤10 (6%, FPR ≤2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p = 0.003) and to achieve virological success (0.50 [0.26–0.94], p = 0.031) than those with pre-HAART FPR >60%. Conclusions Beyond the genotypically-inferred tropism determination, FPR ≤2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability. PMID:25153969

Immunological Targeting of Tumor Initiating Prostate Cancer Cells

DTIC Science & Technology

2014-10-01

clinically using well-accepted immuno-competent animal models. 2) Keywords: Prostate Cancer, Lymphocyte, Vaccine, Antibody 3) Overall Project Summary...castrate animals . Task 1: Identify and verify antigenic targets from CAstrate Resistant Luminal Epithelial Cells (CRLEC) (months 1-16... animals per group will be processed to derive sufficient RNA for microarray analysis; the experiment will be repeated x 3. Microarray analysis will

Extraction of Cell-Wall Polysaccharide Antigen from Streptococci

PubMed Central

Slade, Hutton D.

1965-01-01

Slade, Hutton D. (Northwestern University Medical School, Chicago, Ill., and Max-Planck Institut für Immunbiologie, Freiburg, Germany). Extraction of cell-wall polysaccharide antigen from streptococci. J. Bacteriol. 90:667–672. 1965.—The carbohydrate grouping antigens in the cell walls of streptococci belonging to groups A, E, G, L, and T were extracted with 5% trichloroacetic acid at 90 C. The antigens were removed also from dry whole cells by extraction with trichloroacetic acid followed by treatment with phenol-water. Details of the methods are presented. The antigens obtained by use of either of these procedures were suitable for studies on immunological specificity and chemical structure. Quantitative enzymatic and chemical analyses of two group E antigens and one group T preparation showed the presence of l-rhamnose (22 to 44%), d-glucose (7 to 22%), d-galactose (T antigen only, 26%), glucosamine (2 to 16%), and galactosamine (T antigen only, 3%). In addition, analyses of A and G antigen preparations are presented. The protein and phosphate content of the A and E antigens were about 1% each. Quantitative precipitin curves of these antigens are presented. PMID:16562065

Screening and characterization of extracelluar L-asparaginase producing Bacillus subtilis strain hswx88, isolated from Taptapani hotspring of Odisha, India

PubMed Central

Pradhan, Biswaprakash; Dash, Sashi K; Sahoo, Sabuj

2013-01-01

Objective To screen and isolate an eco-friendly, a thermophilic and potent L-asparaginase producing bacterium, with novel immunological properties that may obviates hypersensitivity reactions. Methods In the present study bacterial strain isolated for extracellular L-asparaginase production from hotspring, identified by morphological, biochemical and physiological tests followed by 16S rDNA technology and the L-asparaginase production ability was tested by both semi quantitative and quantitative enzymatic assay. Result The bacterial strain was identified as Bacillus subtilis strain hswx88 (GenBank Accession Number: JQ237656.1). The extracellular enzyme yielding capacity isolate Bacillus subtilis strain hswx88 (23.8 IU/mL) was found to be 1.7 and 14.5 times higher than the reference organism Pectobacterium carotovorum MTCC 1428 (14.2 IU/mL) and Bacillus sp. BCCS 034 (1.64 IU/mL). Conclusion The isolate is eco-friendly and useful to produce bulk quantity of extracellular, thermophilic L-asparaginase for the treatment of various tumor cases and for preparation of acrylamide free fry food preparation. PMID:24093783

Quantitation of immunoadsorbed flavoprotein oxidases by luminol-mediated chemiluminescence.

PubMed

Hinkkanen, A; Maly, F E; Decker, K

1983-04-01

The detection of the flavoenzymes 6-hydroxy-L-nicotine oxidase and 6-hydroxy-D-nicotine oxidase at the sub-femtomol level was achieved by coupling the reaction of the immunoadsorbed proteins to the peroxidase-catalysed oxidation of luminol. The H2O2-producing oxidases retained their full activity when bound to the respective immobilized antibodies. This fact allowed the concentration of the enzymes from very dilute solutions and the quantitative assay of their activities in the microU range. Due to strict stereoselectivity and the absence of immunological cross-reactivity, the two flavoproteins could be determined in the same solution. This method was used to measure the 6-hydroxy-D-nicotine oxidase and 6-hydroxy-L-nicotine oxidase activities in Escherichia coli RR1 and different Arthrobacter strains cultured under non-inducing conditions. The same activity ratio of 6-hydroxy-L-nicotine oxidase/6-hydroxy-D-nicotine oxidase as in D L-nicotine-induced cells of A. oxidans was observed in non-induced wild type and in riboflavin-requiring (rf-) mutant cells of this aerob.

Investigation of the Molecular Response of Belugas to Stressors

DTIC Science & Technology

2014-09-30

beluga whale ( Delphinapterus leucas ) interleukin-1beta and tumor necrosis factor-alpha. Canadian Journal of Veterinary Research 9 (4):233–240. 6 Sitt...cloning, phylogenetic analysis and expression of beluga whale ( Delphinapterus leucas ) interleukin 6. Veterinary Immunology Immunopathology 73: 31-44

HIV and intestinal parasite co-infections among a Chinese population: an immunological profile

PubMed Central

2013-01-01

Background Parasite infections often result in a switch of the human body’s predominant immune reaction from T-helper 1 (Th1)-type to Th2-type. Hence, parasite infections are widely expected to accelerate the progression of human immunodeficiency virus (HIV) infections to acquired immunodeficiency syndrome (AIDS). In the People’s Republic of China, both parasitic diseases and AIDS are epidemic in certain rural areas, and co-infections are relatively common. However, no population-based studies have yet investigated the frequency of HIV and parasite co-infections, and its effects on immune responses. We studied (1) the immune status of an HIV-infected population, and (2) the effect of co-infection of HIV and intestinal parasites on selected parameters of the human immune system. Methods A total of 309 HIV-infected individuals were recruited and compared to an age-matched and sex-matched control group of 315 local HIV-negative individuals. Questionnaires were administered to all participants to obtain information on sociodemographic characteristics, sanitation habits, family income, and recent clinical manifestations. Two consecutive stool samples and 10 ml samples of venous blood were also collected from each individual for the diagnosis of parasite infections and quantitative measurements of selected cytokines and CD4+ T-lymphocytes, respectively. Results During the study period, 79 HIV-infected individuals were not under highly active antiretroviral therapy (HAART) and were thus included in our analysis; the prevalence of intestinal helminth infections was 6.3% and that of protozoa was 22.8%. The most common protozoan infections were Blastocystis hominis (B. hominis) (13.9%) and Cryptosporidium spp. (10.1%). The prevalence of Cryptosporidium spp. in HIV-infected individuals was significantly higher than that in HIV negative individuals (P < 0.05). Compared to the non-co-infected population, no significant difference was found for any of the measured immunological indicators (P > 0.05). However, the following trends were observed: IFN-γ levels were lower, but the IL-4 level was higher, in the population co-infected with HIV and helminths. In the population co-infected with HIV and B. hominis, the IL-2 level was higher. The population co-infected with HIV and Cryptosporidium spp. had markedly lower CD4+ T-lymphocyte counts. Conclusion According to the immunologic profile, co-infection with helminths is disadvantageous to HIV-infected individuals. It was associated with a shift in the Th1/Th2 balance in the same direction as that caused by the virus itself, which might indicate an acceleration of the progress from an HIV infection to AIDS. Co-infection with Cryptosporidium spp. was not associated with a significant change in immune factors but co-infection with Cryptosporidium spp. was associated with a reduced level of CD4 + T-lymphocytes, confirming the opportunistic nature of such infections. Co-infection with B. hominis, on the other hand, was associated with an antagonistic shift in the immunological profile compared to an HIV infection. PMID:23971713

Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

NASA Astrophysics Data System (ADS)

Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

2008-11-01

The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic material of a new prosthesis generation, more extended tests and experiments are necessary.

Blood lymphocyte ultrastructure and deoxyribonucleic acid content in children with systemic lupus erythematosis.

PubMed

Ptasekas, R; Matulis, A; Urmonas, V; Graziene, V; Zukiene, G

1980-01-01

Two varieties of peripheral blood lymphocytes have been disclosed in systemic lupus erythematosus (SLE) cases: one showing signs of degradation and nuclear chromatine elimination and the other one manifesting a state of biological activation, possibly of an immunologic nature. This karyostructural lymphocyte heterogeneity in SLE may cause a great scattering of these cells on histograms in respect to their nuclear deoxyribonucleic acid content determined by cytophotometry. On the other hand, the expressiveness of the scattering and the degree of predominance of negative tendency towards proliferation (with a shift to the left from 2 n) may thereby serve as a very objective quantitative indication of nuclear structure degradation and of loss by lymphocytes of chromatine with deoxyribonucleic acid during SLE.

Acrylamine-induced autoimmune phenomena.

PubMed

Rothschild, Bruce

2010-09-01

The objective of this study is to document a series of cases of occupationally derived autoimmune disease. Individuals with occupational exposure to acrylamides were evaluated clinically and biochemically/immunologically for evidence of autoimmune disease. Symptoms and signs and immuno-reactivity were monitored during exposure-free and re-exposure as part of the individuals' clinical evaluation. Six individuals with occupational acrylamide exposure had clinical and laboratory alterations characteristic of drug-induced autoimmune disease, specifically lupus, anti-phospholipid syndrome, Sjogren's syndrome, scleroderma, and polymyositis. The similarity of the full spectrum of disease in the reported patients to that found with procainamide strongly suggests the effects of occupational exposure. This uncontrolled study suggests the need for a full epidemiologic analysis of all individuals working with such occupational exposure, including full clinical and immunological examination.

Purification, cloning, expression and immunological analysis of Scylla serrata arginine kinase, the crab allergen.

PubMed

Shen, Yuan; Cao, Min-Jie; Cai, Qiu-Feng; Su, Wen-Jin; Yu, Hui-Lin; Ruan, Wei-Wei; Liu, Guang-Ming

2011-05-01

Although crustaceans have been reported to be one of the most common causes of IgE-mediated allergic reactions, there are no reports about the characterization and identification of arginine kinase (AK) from the mud crab (Scylla serrata) as allergen. In the present study, the purification, molecular cloning, expression and immunological analyses of the IgE allergen AK from the mud crab were investigated. The results showed that cloned DNA fragments of AK from the mud crab had open reading frames of 1021 bp, predicted to encode proteins with 356 amino acid residues. Sequence alignment revealed that mud crab AK shares high homology with other crustacean species. Mud crab AK gene was further recombined with the vector of pGEX-4T-3 and expressed in Escherichia coli BL 21. 2-D electrophoresis suggested that native AK (nAK) and recombinant AK (rAK) shared the same molecular weight of 40 kDa, and the pI is 6.5 and 6.3, respectively. The nAK and rAK were further confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Immunoblotting analysis and colloidal gold immunochromatographic assay (GICA) using sera from subjects with crustacean allergy confirmed that the nAK and rAK reacted positively with these sera, indicating AK is a specific allergen of mud crab. Both of purified nAK and rAK reacted positively with sera from subjects with crustacean allergy in immunoblotting and GICA analysis, indicating AK is a common allergen of mud crab. In vitro expressed AK is proposed as a source of the protein for immunological or clinical studies. Copyright © 2011 Society of Chemical Industry.

21 CFR 866.5640 - Infectious mononucleosis immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious... immunochemical techniques heterophile antibodies frequently associated with infectious mononucleosis in serum...

21 CFR 866.5640 - Infectious mononucleosis immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious... immunochemical techniques heterophile antibodies frequently associated with infectious mononucleosis in serum...

21 CFR 866.5640 - Infectious mononucleosis immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious... immunochemical techniques heterophile antibodies frequently associated with infectious mononucleosis in serum...

21 CFR 866.5640 - Infectious mononucleosis immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious... immunochemical techniques heterophile antibodies frequently associated with infectious mononucleosis in serum...

21 CFR 866.5640 - Infectious mononucleosis immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious... immunochemical techniques heterophile antibodies frequently associated with infectious mononucleosis in serum...

Prospective evaluation of automatized PF4/heparin immunoassays HemosIL HIT-ab (PF4-H) for the diagnosis of heparin-induced thrombocytopenia.

PubMed

Jourdy, Y; Nougier, C; Rugeri, L; Bordet, J C; Sobas, F; Negrier, C

2015-04-01

Recently, rapid immunoassays have been developed to allow the detection of antibodies anti-PF4/heparin. In this prospective study, we evaluated the performances of a automatized immunoassay (HemosIL HIT-Ab) in comparison with an ELISA (Zymutest HIA IgG) used for the diagnosis of heparin-induced thrombocytopenia (HIT) in association with the 4T's score. According to the 4T's score, samples with score ≤3 had no further analysis. Two immunological assays Zymutest HIA IgG and HemosIL HIT-Ab were performed in samples with score ≥4. In patients with at least one positive immunological assay or two negative immunological assays but with high-pretest probability (4T's score ≥6), HIT was screened by one functional assay using washed platelets. The sensitivities of both assays were excellent and comparable (100%). The specificity was 92.3% for ELISA and 91.2% for HemosIL HIT-Ab. The analysis of the operating characteristics showed that both assays have almost identical ROCs (AUROC, 0.9951 and 0.9853, respectively, for ELISA and HemosIL HIT-Ab) and the calculating of the κ coefficient revealed a good agreement (0.67). Performance characteristics of the HemosIL HIT-Ab are comparable to the Zymutest HIA IgG. The HemosIL HIT-Ab can be used in association with the 4T's score to rule out HIT. © 2014 John Wiley & Sons Ltd.

Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

PubMed Central

Oliveira, Ricardo; Krauss, Margot; Essama-Bibi, Suzanne; Hofer, Cristina; Harris, D. Robert; Tiraboschi, Adriana; de Souza, Ricardo; Marques, Heloisa; Succi, Regina; Abreu, Thalita; Della Negra, Marinella; Hazra, Rohan; Mofenson, Lynne M.; Siberry, George K.

2010-01-01

Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05–3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children. PMID:21039218

Research statistics in Atopic Eczema: what disease is this?

PubMed Central

2012-01-01

Background Atopic eczema is a common and distressing disease. This study aims to review PubMed indexed research statistics on atopic eczema over a-10 year period to investigate the clinical relevance and research interest about this disease. Methods PubMed (a service of the U.S. National Library of Medicine) was searched for the terms “atopic dermatitis” and “eczema”, with limits activated (Humans, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, English, published in the last 10 years), and editorials, letters, practice guidelines, reviews, and animal studies excluded. Journal impact factor (IF) is in accordance with Journal Citation Report (JCR) 2009, a product of Thomson ISI (Institute for Scientific Information). Results A total of 890 articles were retrieved. Taking out publications that were irrelevant and those without an impact factor, 729 articles were obtained. These articles were grouped into dermatology (n = 337, mean IF: 3.01), allergy/immunology (n = 215, mean IF: 4.89), pediatrics (n = 118, mean IF: 2.53) and miscellaneous subject categories (n = 142, mean IF: 5.10). The impact factors were highest in the miscellaneous category (p = 0.0001), which includes such prestigious journals as the New England journal of Medicine (n = 1, IF: 47.05), the Lancet (n = 4, IF: 30.76) and BMJ (n = 6, IF: 13.66). There was no publication in any family medicine or general practice journal. The British Journal of Dermatology (n = 78), Pediatric Allergy and Immunology (n = 49) and Journal of Allergy and Clinical Immunology (n = 46) had the highest number of publications on the subject. Atopic eczema ranked higher in impact factors in allergy/immunology although more publications appeared in the dermatology category. Conclusions Atopic eczema is a multidisciplinary disease. Its clinical relevance and research interests are definitely beyond that of a mere cutaneous disease. Investigators may consider allergy/immunology and miscellaneous journal categories for higher impact of their research. PMID:22682479

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

PubMed

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-06-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

Birth of the science of immunology.

PubMed

Schmalstieg, Frank C; Goldman, Armond S

2010-05-01

The science of immunology emerged in the last of the 19th and the first of the 20th century. Substantial progress in physics, chemistry and microbiology was essential for its development. Indeed, microorganisms became one of the principal investigative tools of the major founders of that science - Louis Pasteur, Robert Koch, Ilya Ilich Metchnikoff, Paul Ehrlich and Jules Bordet. It is pertinent that these pioneering scientists were born when questioning and exploration were encouraged because of the legacies of the previous century of enlightenment. Mentors greatly aided their development. Their discoveries were shaped by their individual personalities. In turn they developed other contributors to the nascent field. Their discoveries included the types of leukocytes, the roles of neutrophils in inflammation and defence, cellular lysis due to complement, the principles of humoral and cellular immunology, passive and active immunization, tissue antigens, anaphylaxis, anaphylactoid reactions and autoimmunity. Their work formed the basis of modern immunology that developed many decades later. Immunology has enormously impacted our understanding of the pathogenesis, diagnosis and treatment of infections, immune-mediated disorders and inflammation. Burgeoning advances forecast further important clinical applications of immunology. Yet, their applications will be problematic because few physicians sufficiently understand the science. We propose that understanding modern immunology requires a grasp of how that science developed - who made the discoveries, how they were made, their successes and failures, their interactions and debates all reveal the foundation of modern immunology.

[Immunological monitoring in kidney transplantation: 13 years experience of a Moroccan histocompatibility laboratory].

PubMed

Brick, C; Atouf, O; Essakalli, M

2016-05-01

The quality of the immunological monitoring is crucial because it determines the success of the kidney transplantation. The scope of this work is to describe the experience of the department of immunological unity of the Ibn Sina university hospital in Rabat regarding the immunological monitoring of patients transplanted between 2001 and 2014. Patient samples were collected from nephrology services of different public and private hospitals of Morocco. The tests conducted in the context of immunological monitoring are ABO typing, HLA-A, B, DR, DQ typing, anti-HLA antibodies detection and identification and cross-match. One hundred and fourteen benefited from a pre- and post-transplant immunological monitoring in our laboratory. The percentage of recipients having between 2 and 5 stored sera is 60.5 before transplantation and 56.1 after transplantation. Immunized patients account for 22.8% before the transplant and 17.6% after transplantation. Ninety-seven patients still have a functional graft, while 4 of them had DSA of low intensity before transplantation. Five immunological rejections were reported while the cross-match were negative and no DSA was identified before transplantation. Patient survival and graft at 1 year was 98.2% and 92.7% respectively. Conducting regular immunological monitoring is sometimes difficult in our context, however, the results are satisfactory in terms of graft and patients survival. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Multivariate analysis of cytokine profiles in pregnancy complications.

PubMed

Azizieh, Fawaz; Dingle, Kamaludin; Raghupathy, Raj; Johnson, Kjell; VanderPlas, Jacob; Ansari, Ali

2018-03-01

The immunoregulation to tolerate the semiallogeneic fetus during pregnancy includes a harmonious dynamic balance between anti- and pro-inflammatory cytokines. Several earlier studies reported significantly different levels and/or ratios of several cytokines in complicated pregnancy as compared to normal pregnancy. However, as cytokines operate in networks with potentially complex interactions, it is also interesting to compare groups with multi-cytokine data sets, with multivariate analysis. Such analysis will further examine how great the differences are, and which cytokines are more different than others. Various multivariate statistical tools, such as Cramer test, classification and regression trees, partial least squares regression figures, 2-dimensional Kolmogorov-Smirmov test, principal component analysis and gap statistic, were used to compare cytokine data of normal vs anomalous groups of different pregnancy complications. Multivariate analysis assisted in examining if the groups were different, how strongly they differed, in what ways they differed and further reported evidence for subgroups in 1 group (pregnancy-induced hypertension), possibly indicating multiple causes for the complication. This work contributes to a better understanding of cytokines interaction and may have important implications on targeting cytokine balance modulation or design of future medications or interventions that best direct management or prevention from an immunological approach. © 2018 The Authors. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.

Immunological tools: engaging students in the use and analysis of flow cytometry and enzyme-linked immunosorbent assay (ELISA).

PubMed

Ott, Laura E; Carson, Susan

2014-01-01

Flow cytometry and enzyme-linked immunosorbent assay (ELISA) are commonly used techniques associated with clinical and research applications within the immunology and medical fields. The use of these techniques is becoming increasingly valuable in many life science and engineering disciplines as well. Herein, we report the development and evaluation of a novel half-semester course that focused on introducing undergraduate and graduate students to advance conceptual and technical skills associated with flow cytometry and ELISA, with emphasis on applications, experimental design, and data analysis. This course was offered in the North Carolina State University Biotechnology Program over three semesters and consisted of weekly lectures and laboratories. Students performed and/or analyzed flow cytometry and ELISA in three separate laboratory exercises: (1) identification of transgenic zebrafish hematopoietic cells, (2) analysis of transfection efficiency, and (3) analysis of cytokine production upon lipopolysaccharide stimulation. Student learning outcomes were achieved as demonstrated by multiple means of assessment, including three laboratory reports, a data analysis laboratory practicum, and a cumulative final exam. Further, anonymous student self-assessment revealed increased student confidence in the knowledge and skill sets defined in the learning outcomes. Copyright © 2014 The International Union of Biochemistry and Molecular Biology.

21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... serum. The measurements aid in the diagnosis of chronic hepatitis (inflammation of the liver) and autoimmune connective tissue diseases (diseases resulting from antibodies produced against the body's own...

21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... serum. The measurements aid in the diagnosis of chronic hepatitis (inflammation of the liver) and autoimmune connective tissue diseases (diseases resulting from antibodies produced against the body's own...

21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... serum. The measurements aid in the diagnosis of chronic hepatitis (inflammation of the liver) and autoimmune connective tissue diseases (diseases resulting from antibodies produced against the body's own...

21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test...

The ninth international veterinary immunology symposium

USDA-ARS?s Scientific Manuscript database

This Introduction to the special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August, 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune...

Survey on medicinal plants and spices used in Beni-Sueif, Upper Egypt

PubMed Central

2011-01-01

Background This study was conducted to identify medicinal plants and spices used for medicine by the community of Beni-Sueif, Upper Egypt. Methods Ethnobotanical data from local people was collected using direct interviews and a semi-structured questionnaire. Results Forty-eight plant species belonging to twenty-seven families and forty-seven genera were encountered during the study. Their botanical and vernacular names, plant parts used and medicinal uses are given. Results of the study were analyzed using two quantitative tools. The factor informant consensus indicated the agreement in the use of plants and the fidelity level indicated the ratio between the number of informants who independently suggested the use of a species for the same major purpose and the total number of informants who mentioned the plant for any use. The results of the factor informant consensus showed that the cardiovascular category has the greatest agreement, followed by the immunological, gastrointestinal and respiratory categories. The most important species according to their fidelity are: Hibiscus sabdariffa L. for the cardiovascular category; Trigonella foenum-graecum L. for the immunological category; Mentha piperita L. for the gastrointestinal category and Pimpinella anisum L. for the respiratory category. Conclusions Medicinal plants are still used for treatment in Beni-Sueif community despite the availability of prescribed medications. Documentation of this ethnomedicinal knowledge is important. Evaluation of pharmacological activity for the promising medicinal plants is suggested. PMID:21707967

Epidemiologic Profile of Patients Transplanted With Hematopoietic Stem Cells in a Reference Service in the State of Rio Grande do Norte, Brazil.

PubMed

Campos de Azevedo, I; Ferreira Júnior, M A; Pereira de Aquino, L A; de Oliveira, A A; Cruz, G K P; de Queiroz Cardoso, A I; Ivo, M L; Santos, V E P

2018-04-01

Hematopoietic stem cell transplantation (HSCT) consists of the intravenous infusion of healthy hematopoietic stem cells to restore the medullary and immunologic function of patients affected by a series of hematologic, oncologic, immunologic, malignant and nonmalignant inherited or acquired diseases, with the possibility of cure or increase of disease-free survival. To characterize the epidemiologic profile and the cases of death of patients who underwent HSCT. This is a cohort quantitative study, nested with a retrospective, descriptive, and analytical study of a hospital-based cohort that included the patients who underwent HSCT at a referral service in the state of Rio Grande do Norte, a region of northeastern Brazil. There was a slight male prevalence (52.94%), the age of the patients ranged from 2 to 73 years old, 18.38% were brown, 47.06% were married, 15.07% were students, 78.31% had a diagnosis of multiple myeloma, 93.38% developed gastrointestinal toxicities, all patients received chemotherapeutic treatment, 54.78% had allogeneic HSCT, and the cause of the most recorded deaths was septic shock (48.19%). This study showed relevant scientific evidence on the clinical and epidemiologic profile of patients who underwent HSCT. In general, sociodemographic data are similar to national and international research results. Copyright © 2018 Elsevier Inc. All rights reserved.

Cytokines, chemokines, and colony-stimulating factors in human milk: the 1997 update.

PubMed

Garofalo, R P; Goldman, A S

1998-01-01

Epidemiologic studies conducted over the past 30 years to investigate the protective functions of human milk strongly support the notion that breast-feeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult due to its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. Nevertheless, a host of bioactive substances including hormones, growth factors, and immunological factors such as cytokines have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of the immune system. Several different cytokines and chemokines have been discovered in human milk over the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.

Cytokines in human milk.

PubMed

Garofalo, Roberto

2010-02-01

Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

Mechanisms and therapeutic effectiveness of lactobacilli

PubMed Central

Di Cerbo, Alessandro; Palmieri, Beniamino; Aponte, Maria; Morales-Medina, Julio Cesar; Iannitti, Tommaso

2016-01-01

The gut microbiome is not a silent ecosystem but exerts several physiological and immunological functions. For many decades, lactobacilli have been used as an effective therapy for treatment of several pathological conditions displaying an overall positive safety profile. This review summarises the mechanisms and clinical evidence supporting therapeutic efficacy of lactobacilli. We searched Pubmed/Medline using the keyword ‘Lactobacillus’. Selected papers from 1950 to 2015 were chosen on the basis of their content. Relevant clinical and experimental articles using lactobacilli as therapeutic agents have been included. Applications of lactobacilli include kidney support for renal insufficiency, pancreas health, management of metabolic imbalance, and cancer treatment and prevention. In vitro and in vivo investigations have shown that prolonged lactobacilli administration induces qualitative and quantitative modifications in the human gastrointestinal microbial ecosystem with encouraging perspectives in counteracting pathology-associated physiological and immunological changes. Few studies have highlighted the risk of translocation with subsequent sepsis and bacteraemia following probiotic administration but there is still a lack of investigations on the dose effect of these compounds. Great care is thus required in the choice of the proper Lactobacillus species, their genetic stability and the translocation risk, mainly related to inflammatory disease-induced gut mucosa enhanced permeability. Finally, we need to determine the adequate amount of bacteria to be delivered in order to achieve the best clinical efficacy decreasing the risk of side effects. PMID:26578541

A radioimmunoassay for ependymins beta and gamma: two goldfish brain proteins involved in behavioral plasticity.

PubMed

Schmidt, R; Shashoua, V E

1981-04-01

A radioimmunoassay (RIA) using 125I-labeled antigen was developed for the quantitative determination of two goldfish brain proteins (ependymins beta and gamma). The proteins were isolated from the cerebrospinal fluid (CSF) and cells of the ependymal zone surrounding goldfish brain ventricles. The turnover rates of beta and gamma were previously shown to be specifically enhanced after the animals successfully acquired a new pattern of swimming behavior. Femtomole quantities of ependymin beta were measurable by the RIA. In applications of the assay, beta and gamma ependymins were found to have common immunological properties, since 125I-beta-antigen bound to antibody could be displaced by unlabeled ependymin gamma as well as ependymin beta but not by a variety of other proteins including several purified glycoproteins isolated from goldfish brain. The ependymins were shown to constitute 14% of the total protein content of the brain extracellular fluid and also to be present as a minor component of the serum proteins (0.3%). Ependymins beta and gamma have an immunological reactivity in these fractions that can be increased by a factor of 30 on heating. The data suggest that the antigenicity of the molecules is highly masked, and that it may require some unraveling of the quaternary structure of the proteins before maximal interaction with the antisera becomes possible.

Survey on medicinal plants and spices used in Beni-Sueif, Upper Egypt.

PubMed

AbouZid, Sameh F; Mohamed, Abdelhalim A

2011-06-27

This study was conducted to identify medicinal plants and spices used for medicine by the community of Beni-Sueif, Upper Egypt. Ethnobotanical data from local people was collected using direct interviews and a semi-structured questionnaire. Forty-eight plant species belonging to twenty-seven families and forty-seven genera were encountered during the study. Their botanical and vernacular names, plant parts used and medicinal uses are given. Results of the study were analyzed using two quantitative tools. The factor informant consensus indicated the agreement in the use of plants and the fidelity level indicated the ratio between the number of informants who independently suggested the use of a species for the same major purpose and the total number of informants who mentioned the plant for any use. The results of the factor informant consensus showed that the cardiovascular category has the greatest agreement, followed by the immunological, gastrointestinal and respiratory categories. The most important species according to their fidelity are: Hibiscus sabdariffa L. for the cardiovascular category; Trigonella foenum-graecum L. for the immunological category; Mentha piperita L. for the gastrointestinal category and Pimpinella anisum L. for the respiratory category. Medicinal plants are still used for treatment in Beni-Sueif community despite the availability of prescribed medications. Documentation of this ethnomedicinal knowledge is important. Evaluation of pharmacological activity for the promising medicinal plants is suggested.

Transcriptome analysis of stimulated PBMC from Mycobacterium bovis infected cattle

USDA-ARS?s Scientific Manuscript database

Immunological responses of cattle to Mycobacterium bovis (M. bovis) infection are of interest in terms of understanding the biology of M. bovis infection and for the development of improved diagnostic techniques. Although considerable time and resources have been invested in understanding immune re...

Humoural immune response and pathological analysis in patients with false immune diagnosis of cystic echinococcosis

PubMed Central

Chen, X; Zhang, J; Feng, X; Chen, X; Yin, S; Wen, H; Zheng, S

2014-01-01

The patients with false immune diagnosis of hydatid disease were investigated for the humoural immune response to analyse the possible reasons and mechanism leading to false immune diagnosis. Two hundred and thirty-nine patients with nature-unknown cysts and 30 healthy controls were detected by immunological assays (four hydatid antigen-based immunogold filtration assay and enzyme-linked immune absorbent assay) and ultrasound. Sensitivity of and specificity of immunological assay and ultrasound were calculated, respectively. The serological diagnosis was compared with surgical pathology to screen the patients with false immune diagnosis for the immunoglobulin measurement and pathological analysis. The history and cyst characteristics were also reviewed. The results indicate the immunoglobulin has little influence on false immunodiagnosis. The false-negative immunodiagnosis was caused by the cysts' inactive status while the false positive caused by previous rupture, antigen cross-reaction. The clinical diagnosis of cystic echinococcosis requires a combination of immunodiagnosis and ultrasonography, which is the necessary complementary confirmation. PMID:24372157

Meta-analysis of immune epitope data for all Plasmodia: overview and applications for malarial immunobiology and vaccine-related issues

PubMed Central

Vaughan, K.; Blythe, M.; Greenbaum, J.; Zhang, Q.; Peters, B.; Doolan, D. L.; Sette, A.

2012-01-01

Summary We present a comprehensive meta-analysis of more than 500 references, describing nearly 5000 unique B cell and T cell epitopes derived from the Plasmodium genus, and detailing thousands of immunological assays. This is the first inventory of epitope data related to malaria-specific immunology, plasmodial pathogenesis, and vaccine performance. The survey included host and pathogen species distribution of epitopes, the number of antibody vs. CD4+ and CD8+ T cell epitopes, the genomic distribution of recognized epitopes, variance among epitopes from different parasite strains, and the characterization of protective epitopes and of epitopes associated with parasite evasion of the host immune response. The results identify knowledge gaps and areas for further investigation. This information has relevance to issues, such as the identification of epitopes and antigens associated with protective immunity, the design and development of candidate malaria vaccines, and characterization of immune response to strain polymorphisms. PMID:19149776

50 years of pediatric immunology: progress and future, a clinical perspective.

PubMed

Singh, Surjit; Gupta, Anju; Rawat, Amit

2013-01-08

Rapidly evolving advances in the field of immunology over the last few decades have impacted the practice of clinical medicine in many ways. In fact, understanding the immunological basis of disease has been pivotal in deciphering the pathogenesis of several disease processes, infective or otherwise. As of today, there is hardly any specialty of medicine which is not influenced by immunology. Pediatric rheumatological disorders, vasculitides, Human Immunodeficiency Virus (HIV) infection, Primary Immunodeficiency Diseases (PIDs) and autoimmune disorders fall under the domain of clinical immunology. This specialty is poised to emerge as a major clinical specialty in our country. The gulf between bench and bedside is narrowing down as our understanding of the complex immunological mechanisms gets better. However, a lot still needs to be done in this field as the morbidity and mortality of some of these conditions is unacceptably high in the Indian setup. A number of medical schools and institutes in the country now have the resources and the wherewithal to develop into specialized centres of clinical immunology. We need to concentrate on training more physicians and pediatricians in this field. The future is bright and the prospects exciting.

The New Cellular Immunology

ERIC Educational Resources Information Center

Claman, Henry N.

1973-01-01

Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

Practical immunology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudson, L.; Hay, F.C.

1989-01-01

This book covers the advances in contemporary molecular and cellular immunology which have provided the experimentalist with tools of unparalleled reproducibility and precision. Techniques for the propagation and manipulation of cells, genes and gene products have a central place in the new edition, reflecting their role in modern immunology.

Immunology of the gastrointestinal tract and liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heyworth, M.F.; Jones, A.L.

1988-01-01

This book contains 11 chapters. Some of the chapter titles are: T cells and Other Non-B Lymphocytes; Mucosal Mast Cells and IgE; Genetic Aspects of Gastrointestinal Immunology; Immunological Functions of the Liver; Lymphocyte Migration and Mucosal Immunity; and Immunoglobulin Circulation and Secretion.

Veterinary Immunology Committee Toolkit Workshop 2010: Progress and plans

USDA-ARS?s Scientific Manuscript database

The Third Veterinary Immunology Committee (VIC) Toolkit Workshop took place at the Ninth International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan on August 18, 2020. The Workshop built on previous Toolkit Workshops and covered various aspects of reagent development, commercialisation an...

50 years of Dutch immunology--founders, institutions, highlights.

PubMed

Gmelig-Meyling, Frits H J; Meyaard, Linde; Mebius, Reina E

2014-12-01

At the occasion of the 50th anniversary of the Dutch Society for Immunology (DSI, de Nederlandse Vereniging voor Immunologie), this contribution deals with some highlights of 50 years of Immunology in the Netherlands. It narrates about the founders and first board members of the DSI, their institutes, progeny and patrimony, describes major centers of immunological activities, mentions key persons in the field, and touches upon some events dear to the Society and its members. Copyright © 2014 Elsevier B.V. All rights reserved.

Update on Gender Equity in Immunology, 2001 to 2016.

PubMed

Shapiro, Virginia Smith; Kovats, Susan; Parent, Michelle A; Gaffen, Sarah L; Hedrick, Catherine C; Jain, Pooja; Denzin, Lisa K; Raghavan, Malini; Stephens, Robin

2016-11-15

In 2001, The American Association of Immunologists Committee on the Status of Women conducted a survey examining the percentage of women faculty members within immunology departments or women in immunology graduate programs across 27 institutions in the United States, comparing it to the percentage of women receiving a Ph.D. Here, we examine the representation of women across these same 27 immunology departments and programs to examine changes in gender equity over the last 15 years. Copyright © 2016 by The American Association of Immunologists, Inc.

Immunological mechanisms of vaccination

PubMed Central

Pulendran, Bali; Ahmed, Rafi

2011-01-01

Vaccines represent one of the greatest triumphs of modern medicine. Despite the common origins of vaccinology and immunology more than 200 years ago, the two disciplines have evolved along such different trajectories that most of the highly successful vaccines have been made empirically, with little or no immunological insight. Recent advances in innate immunity have offered new insights about the mechanisms of vaccine-induced immunity and have facilitated a more rational approach to vaccine design. Here we will discuss these advances and emerging themes on the immunology of vaccination. PMID:21739679

American Academy of Allergy, Asthma and Immunology (AAAAI)-2010 annual meeting. 26 February-2 March 2010, New Orleans, LA, USA.

PubMed

Bielory, Leonard

2010-05-01

The 2010 American Academy of Allergy, Asthma and Immunology (AAAAI) meeting, held in New Orleans, included topics covering new therapeutic developments in the fields of allergy, asthma and immunological diseases. This conference report highlights selected presentations on potential treatments for food and other allergies, as well as therapies for asthma and other immunological diseases. Investigational drugs discussed include Oralair Mites (Stallergenes SA/Paladin Labs Inc), PF-03654746 (Pfizer Inc) and AMG-853 (Amgen Inc).

PET Imaging of Tumor-Associated Macrophages with 89Zr-Labeled High-Density Lipoprotein Nanoparticles

PubMed Central

Pérez-Medina, Carlos; Tang, Jun; Abdel-Atti, Dalya; Hogstad, Brandon; Merad, Miriam; Fisher, Edward A.; Fayad, Zahi A.; Lewis, Jason S.; Mulder, Willem J.M.; Reiner, Thomas

2015-01-01

Tumor-associated macrophages (TAMs) are increasingly investigated in cancer immunology and are considered a promising target for better and tailored treatment of malignant growth. Although TAMs also have high diagnostic and prognostic value, TAM imaging still remains largely unexplored. Here, we describe the development of reconstituted high-density lipoprotein (rHDL)–facilitated TAM PET imaging in a breast cancer model. Methods Radiolabeled rHDL nanoparticles incorporating the long-lived positron-emitting nuclide 89Zr were developed using 2 different approaches. The nanoparticles were composed of phospholipids and apolipoprotein A-I (apoA-I) in a 2.5:1 weight ratio. 89Zr was complexed with deferoxamine (also known as desferrioxamine B, desferoxamine B), conjugated either to a phospholipid or to apoA-I to generate 89Zr-PL-HDL and 89Zr-AI-HDL, respectively. In vivo evaluation was performed in an orthotopic mouse model of breast cancer and included pharmacokinetic analysis, biodistribution studies, and PET imaging. Ex vivo histologic analysis of tumor tissues to assess regional distribution of 89Zr radioactivity was also performed. Fluorescent analogs of the radiolabeled agents were used to determine cell-targeting specificity using flow cytometry. Results The phospholipid- and apoA-I–labeled rHDL were produced at 79% ± 13% (n = 6) and 94% ± 6% (n = 6) radiochemical yield, respectively, with excellent radiochemical purity (>99%). Intravenous administration of both probes resulted in high tumor radioactivity accumulation (16.5 ± 2.8 and 8.6 ± 1.3 percentage injected dose per gram for apoA-I– and phospholipid-labeled rHDL, respectively) at 24 h after injection. Histologic analysis showed good colocalization of radioactivity with TAM-rich areas in tumor sections. Flow cytometry revealed high specificity of rHDL for TAMs, which had the highest uptake per cell (6.8-fold higher than tumor cells for both DiO@Zr-PL-HDL and DiO@Zr-AI-HDL) and accounted for 40.7% and 39.5% of the total cellular DiO@Zr-PL-HDL and DiO@Zr-AI-HDL in tumors, respectively. Conclusion We have developed 89Zr-labeled TAM imaging agents based on the natural nanoparticle rHDL. In an orthotopic mouse model of breast cancer, we have demonstrated their specificity for macrophages, a result that was corroborated by flow cytometry. Quantitative macrophage PET imaging with our 89Zr-rHDL imaging agents could be valuable for noninvasive monitoring of TAM immunology and targeted treatment. PMID:26112022

Parental investment matters for maternal and offspring immune defense in the mouthbrooding cichlid Astatotilapia burtoni.

PubMed

Keller, Isabel S; Salzburger, Walter; Roth, Olivia

2017-12-20

Parental care, while increasing parental fitness through offspring survival, also bears cost to the care-giving parent. Consequentially, trade offs between parental care and other vitally important traits, such as the immune system seem evident. In co-occurring phases of parental care and immunological challenges negative consequences through a resource allocation trade off on both the parental and the offspring conditions can be predicted. While the immune system reflects parental stress conditions, parental immunological investments also boost offspring survival via the transfer of immunological substances (trans-generational immune priming). We investigated this relationship in the mouthbrooding East African cichlid Astotatilapia burtoni. Prior to mating, females were exposed to an immunological activation, while others remained immunologically naïve. Correspondingly, the immunological status of females was either examined directly after reproduction or after mouthbrooding had ceased. Offspring from both groups were exposed to immunological challenges to assess the extent of trans-generational immune priming. As proxy for immune status, cellular immunological activity and gene expression were determined. Both reproducing and mouthbrooding females allocate their resources towards reproduction. While upon reproduction the innate immune system was impeded, mouthbrooding females showed an attenuation of inflammatory components. Juveniles from immune challenged mouthbrooding females showed downregulation of immune and life history candidate genes, implying a limitation of trans-generational plasticity when parents experience stress during the costly reproductive phase. Our results provide evidence that both parental investment via mouthbrooding and the rise of the immunological activity upon an immune challenge are costly traits. If applied simultaneously, not only mothers seem to be impacted in their performance, but also offspring are impeded in their ability to react upon a potentially virulent pathogen exposure.

Associations between immunological function and memory recall in healthy adults.

PubMed

Wang, Grace Y; Taylor, Tamasin; Sumich, Alexander; Merien, Fabrice; Borotkanics, Robert; Wrapson, Wendy; Krägeloh, Chris; Siegert, Richard J

2017-12-01

Studies in clinical and aging populations support associations between immunological function, cognition and mood, although these are not always in line with animal models. Moreover, very little is known about the relationship between immunological measures and cognition in healthy young adults. The present study tested associations between the state of immune system and memory recall in a group of relatively healthy adults. Immediate and delayed memory recall was assessed in 30 participants using the computerised cognitive battery. CD4, CD8 and CD69 subpopulations of lymphocytes, Interleukin-6 (IL-6) and cortisol were assessed with blood assays. Correlation analysis showed significant negative relationships between CD4 and the short and long delay memory measures. IL-6 showed a significant positive correlation with long-delay recall. Generalized linear models found associations between differences in all recall challenges and CD4. A multivariate generalized linear model including CD4 and IL-6 exhibited a stronger association. Results highlight the interactions between CD4 and IL-6 in relation to memory function. Further study is necessary to determine the underlying mechanisms of the associations between the state of immune system and cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors influencing participation in colorectal cancer screening programs in Spain.

PubMed

Vanaclocha-Espi, Mercedes; Ibáñez, Josefa; Molina-Barceló, Ana; Pérez, Elena; Nolasco, Andreu; Font, Rebeca; Pérez-Riquelme, Francisco; de la Vega, Mariola; Arana-Arri, Eunate; Oceja, MªElena; Espinàs, Josep Alfons; Portillo, Isabel; Salas, Dolores

2017-12-01

To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50-59years and OR 1.12 in those aged 60-69years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 53206 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

...). Contact Person: Maryam Feili-Hariri, Ph.D., Scientific Review Officer, Immunology Review Branch... Feili-Hariri, Ph.D., Scientific Review Officer, Immunology Review Branch, Scientific Review Program....gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.855, Allergy, Immunology, and...

21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure by... of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own...

21 CFR 866.5200 - Carbonic anhydrase B and C immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques specific carbonic anhydrase protein molecules in serum and other body fluids. Measurements of carbonic anhydrase B and C aid in the diagnosis of abnormal hemoglobin metabolism. (b...

21 CFR 866.5200 - Carbonic anhydrase B and C immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques specific carbonic anhydrase protein molecules in serum and other body fluids. Measurements of carbonic anhydrase B and C aid in the diagnosis of abnormal hemoglobin metabolism. (b...

21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... measure by immunochemical techniques the inter-alpha trypsin inhibitor (a protein) in serum and other body fluids. Measurement of inter-alpha trypsin inhibitor may aid in the diagnosis of acute bacterial...

21 CFR 866.5200 - Carbonic anhydrase B and C immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques specific carbonic anhydrase protein molecules in serum and other body fluids. Measurements of carbonic anhydrase B and C aid in the diagnosis of abnormal hemoglobin metabolism. (b...

21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... measure by immunochemical techniques the inter-alpha trypsin inhibitor (a protein) in serum and other body fluids. Measurement of inter-alpha trypsin inhibitor may aid in the diagnosis of acute bacterial...

21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... measure by immunochemical techniques the inter-alpha trypsin inhibitor (a protein) in serum and other body fluids. Measurement of inter-alpha trypsin inhibitor may aid in the diagnosis of acute bacterial...

21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... measure by immunochemical techniques the inter-alpha trypsin inhibitor (a protein) in serum and other body fluids. Measurement of inter-alpha trypsin inhibitor may aid in the diagnosis of acute bacterial...

21 CFR 866.5200 - Carbonic anhydrase B and C immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test... immunochemical techniques specific carbonic anhydrase protein molecules in serum and other body fluids. Measurements of carbonic anhydrase B and C aid in the diagnosis of abnormal hemoglobin metabolism. (b...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... blood cells), and leukemia (cancer of the blood-forming organs). (b) Classification. Class II...

Development and characterization of chicken CD127-cpecific antibodies

USDA-ARS?s Scientific Manuscript database

Research in avian immunology has been significantly hampered by lack of effective immunological reagents in birds cross-reactive with mammalian orthologs and lack of sensitive assay for a long time. To better serve the avian immunology community, monoclonal and polyclonal antibodies specific for av...

Immunology update: topics in basic and clinically applied reproductive immunology.

PubMed

Hunt, J S

1996-05-01

A postgraduate course covering basic and clinical reproductive immunology was held in Philadelphia, PA, U.S.A., on March 19, 1996, in conjunction with the annual meeting of the Society for Gynecological Investigation. The course was organized and chaired by Joseph A. Hill.

Regulation of immunity and inflammation by hypoxia in immunological niches.

PubMed

Taylor, Cormac T; Colgan, Sean P

2017-12-01

Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

A current perspective on availability of tools, resources and networks for veterinary immunology.

PubMed

Entrican, Gary; Lunney, Joan K; Rutten, Victor P; Baldwin, Cynthia L

2009-03-15

There are many diseases of fish, livestock and companion animals that impact negatively on animal health, welfare and productivity and for which there are no effective vaccines. The development of new vaccines is reliant on the availability of well-characterised immunological tools and reagents to understand host-pathogen interactions and identify protective immune responses. Veterinary immunology has always lagged behind mouse and human immunology in terms of development and availability of tools and reagents. However, several initiatives are underway to address this. The Veterinary Immunology Committee (VIC) Toolkit was initiated 6 years ago at the sixth International Veterinary Immunology Symposium (IVIS) in Uppsala and in the intervening period there have been several notable developments that have advanced reagent development and information exchange. This review will discuss advances in veterinary reagent development, networks, databases and commercial availability with particular reference to the second VIC Toolkit workshop held at the eighth IVIS in Ouro Preto, Brazil on the 15th of August 2007.

Cellular level models as tools for cytokine design.

PubMed

Radhakrishnan, Mala L; Tidor, Bruce

2010-01-01

Cytokines and growth factors are critical regulators that connect intracellular and extracellular environments through binding to specific cell-surface receptors. They regulate a wide variety of immunological, growth, and inflammatory response processes. The overall signal initiated by a population of cytokine molecules over long time periods is controlled by the subtle interplay of binding, signaling, and trafficking kinetics. Building on the work of others, we abstract a simple kinetic model that captures relevant features from cytokine systems as well as related growth factor systems. We explore a large range of potential biochemical behaviors, through systematic examination of the model's parameter space. Different rates for the same reaction topology lead to a dramatic range of biochemical network properties and outcomes. Evolution might productively explore varied and different portions of parameter space to create beneficial behaviors, and effective human therapeutic intervention might be achieved through altering network kinetic properties. Quantitative analysis of the results reveals the basis for tensions among a number of different network characteristics. For example, strong binding of cytokine to receptor can increase short-term receptor activation and signal initiation but decrease long-term signaling due to internalization and degradation. Further analysis reveals the role of specific biochemical processes in modulating such tensions. For instance, the kinetics of cytokine binding and receptor activation modulate whether ligand-receptor dissociation can generally occur before signal initiation or receptor internalization. Beyond analysis, the same models and model behaviors provide an important basis for the design of more potent cytokine therapeutics by providing insight into how binding kinetics affect ligand potency. (c) 2010 American Institute of Chemical Engineers

The 9th International Veterinary Immunology Symposium.

PubMed

Lunney, Joan K; Kai, Chieko; Inumaru, Shigeki; Onodera, Takashi

2012-07-15

This special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune systems of numerous food animals and wildlife, probing basic immunity and the influence of stress, genetics, nutrition, endocrinology and reproduction. Major presentations addressed defense against pathogens and alternative control and prevention strategies including vaccines, adjuvants and novel biotherapeutics. A special Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme Sponsored Conference on "Vaccination and Diagnosis for Food Safety in Agriculture" highlighted the particular issue of "Immunology in Bovine Paratuberculosis". In April 2010 there was an outbreak of foot-and-mouth disease (FMD) in the southern part of Japan. This stimulated a special 9th IVIS session on FMD, sponsored by the World Organization for Animal Health (OIE) and the Ministry of Agriculture, Forestry and Fisheries (MAFF) of Japan, to discuss improvements of FMD vaccines, their use in FMD control, and risk assessment for decision management. The 9th IVIS was supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS) and included workshops for its MHC and Toolkit Committees. Finally VIC IUIS presented its 2010 Distinguished Service Award to Dr. Kazuya Yamanouchi for "outstanding contributions to the veterinary immunology community" and its 2010 Distinguished Veterinary Immunologist Award to Dr. Douglas F. Antczak for "outstanding research on equine immunology". Published by Elsevier B.V.

Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

PubMed

Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M

2015-07-17

The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunology presentation at the 1990 NASA/NSF Antarctica Biomedical Science Working Group

NASA Technical Reports Server (NTRS)

Meehan, Richard T.

1990-01-01

An overview of methodology used for determining human in vitro lymphocyte activation, proliferation and effector cell function was presented and results of previous manned space flight immunology studies from Apollo through Shuttle were reviewed. Until the Shuttle era, lymphocyte assays were not very sensitive and had such large variations among normal subjects that it was difficult to define a consistent effect of space flight. More sensitive assay, however, even with Shuttle missions as brief as 6 days indicate depressed T-cell proliferative responses are routinely observed following space flight. Using a slight modification of the Shuttle assay, five different human stress-immunology models have been studied over the last 6 years in our lab. These have included: academic examinations of medical students having blood drawn during major test periods on three separate groups of first year students and two hypoxia studies (at 25,000 feet in a 6 week chamber ascent to the equivalent of Mount Everest and twice on Pikes Peak at 14,000 feet). These studies are particularly pertinent to Antarctica, since the altitude equivalent of 11,000 feet at the South Pole may affect some of the variables that are being measured in immunology, physiology or cognitive studies. An extravehicular study was performed drawing blood from 35 individuals before and immediately following a chamber exposure study. Preliminary results from 30 Shuttle astronauts investigated immunophenotype analysis and the role of a novel monocyte population in modulating the previously observed suppressed in vitro immune function. The results of the Air Force Academy cadet stress study were also presented.

Qualitative and Quantitative Detection of Botulinum Neurotoxins from Complex Matrices: Results of the First International Proficiency Test

PubMed Central

Worbs, Sylvia; Fiebig, Uwe; Zeleny, Reinhard; Schimmel, Heinz; Rummel, Andreas; Luginbühl, Werner; Dorner, Brigitte G.

2015-01-01

In the framework of the EU project EQuATox, a first international proficiency test (PT) on the detection and quantification of botulinum neurotoxins (BoNT) was conducted. Sample materials included BoNT serotypes A, B and E spiked into buffer, milk, meat extract and serum. Different methods were applied by the participants combining different principles of detection, identification and quantification. Based on qualitative assays, 95% of all results reported were correct. Successful strategies for BoNT detection were based on a combination of complementary immunological, MS-based and functional methods or on suitable functional in vivo/in vitro approaches (mouse bioassay, hemidiaphragm assay and Endopep-MS assay). Quantification of BoNT/A, BoNT/B and BoNT/E was performed by 48% of participating laboratories. It turned out that precise quantification of BoNT was difficult, resulting in a substantial scatter of quantitative data. This was especially true for results obtained by the mouse bioassay which is currently considered as “gold standard” for BoNT detection. The results clearly demonstrate the urgent need for certified BoNT reference materials and the development of methods replacing animal testing. In this context, the BoNT PT provided the valuable information that both the Endopep-MS assay and the hemidiaphragm assay delivered quantitative results superior to the mouse bioassay. PMID:26703724

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure by...

21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class II...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell antibody-forming...

21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class II...

21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class II...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell antibody-forming...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell antibody-forming...

21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class II...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell antibody-forming...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... that binds hemoglobin, the oxygen-carrying pigment in red blood cells) in serum. Measurement of haptoglobin may aid in the diagnosis of hemolytic diseases (diseases in which the red blood cells rupture and... Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device...

Clearing the Fog of Anticancer Patents from 1993–2013: Through an In-Depth Technology Landscape & Target Analysis from Pioneer Research Institutes and Universities Worldwide

PubMed Central

Dara, Ajay; Sangamwar, Abhay T.

2014-01-01

Background In a search for an effective anticancer therapy the R&D units from leading universities and institutes reveal numerous technologies in the form of patent documents. The article addressed comparative anticancer patent landscape and technology assessment of Council of Scientific and Industrial Research (CSIR): India’s largest R&D organisation with top twenty international public funded universities and institutes from eight different countries. Methodology/Principal Findings The methodology include quantitative and qualitative assessment based on the bibliometric parameters and manual technology categorisation to understand the changing patent trends and recent novel technologies. The research finding analysed 25,254 patent documents from the year 1993 to 2013 and reported the insights of latest anticancer technologies and targets through categorisation studies at the level of drug discovery, development and treatment & diagnosis. The article has reported the technology correlation matrix of twelve secondary class technologies with 34 tertiary sub-class research area to identify the leading technologies and scope of future research through whitespaces analysis. In addition, the results have also addressed the target analysis, leading inventor, assignee, collaboration network, geographical distribution, patent trend analysis, citation maps and technology assessment with respect to international patent classification systems such as CPC, IPC and CPI codes. Conclusions/Significance The result suggested peptide technology as the dominating research area next to gene therapy, vaccine and medical preparation containing organic compounds. The Indian CSIR has ranked itself at seventh position among the top 20 universities. Globally, the anticancer research was focused in the area of genetics and immunology, whereas Indian CSIR reported more patents related to plant extract and organic preparation. The article provided a glimpse of two decade anticancer scenario with respect to top public funded universities worldwide. PMID:25083710

Clearing the fog of anticancer patents from 1993-2013: through an in-depth technology landscape & target analysis from pioneer research institutes and universities worldwide.

PubMed

Dara, Ajay; Sangamwar, Abhay T

2014-01-01

In a search for an effective anticancer therapy the R&D units from leading universities and institutes reveal numerous technologies in the form of patent documents. The article addressed comparative anticancer patent landscape and technology assessment of Council of Scientific and Industrial Research (CSIR): India's largest R&D organisation with top twenty international public funded universities and institutes from eight different countries. The methodology include quantitative and qualitative assessment based on the bibliometric parameters and manual technology categorisation to understand the changing patent trends and recent novel technologies. The research finding analysed 25,254 patent documents from the year 1993 to 2013 and reported the insights of latest anticancer technologies and targets through categorisation studies at the level of drug discovery, development and treatment & diagnosis. The article has reported the technology correlation matrix of twelve secondary class technologies with 34 tertiary sub-class research area to identify the leading technologies and scope of future research through whitespaces analysis. In addition, the results have also addressed the target analysis, leading inventor, assignee, collaboration network, geographical distribution, patent trend analysis, citation maps and technology assessment with respect to international patent classification systems such as CPC, IPC and CPI codes. The result suggested peptide technology as the dominating research area next to gene therapy, vaccine and medical preparation containing organic compounds. The Indian CSIR has ranked itself at seventh position among the top 20 universities. Globally, the anticancer research was focused in the area of genetics and immunology, whereas Indian CSIR reported more patents related to plant extract and organic preparation. The article provided a glimpse of two decade anticancer scenario with respect to top public funded universities worldwide.

Endoparasites in the feces of arctic foxes in a terrestrial ecosystem in Canada

PubMed Central

Elmore, Stacey A.; Lalonde, Laura F.; Samelius, Gustaf; Alisauskas, Ray T.; Gajadhar, Alvin A.; Jenkins, Emily J.

2013-01-01

The parasites of arctic foxes in the central Canadian Arctic have not been well described. Canada’s central Arctic is undergoing dramatic environmental change, which is predicted to cause shifts in parasite and wildlife species distributions, and trophic interactions, requiring that baselines be established to monitor future alterations. This study used conventional, immunological, and molecular fecal analysis techniques to survey the current gastrointestinal endoparasite fauna currently present in arctic foxes in central Nunavut, Canada. Ninety-five arctic fox fecal samples were collected from the terrestrial Karrak Lake ecosystem within the Queen Maud Gulf Migratory Bird Sanctuary. Samples were examined by fecal flotation to detect helminths and protozoa, immunofluorescent assay (IFA) to detect Cryptosporidium and Giardia, and quantitative PCR with melt-curve analysis (qPCR-MCA) to detect coccidia. Positive qPCR-MCA products were sequenced and analyzed phylogenetically. Arctic foxes from Karrak Lake were routinely shedding eggs from Toxascaris leonina (63%). Taeniid (15%), Capillarid (1%), and hookworm eggs (2%), Sarcocystis sp. sporocysts 3%), and Eimeria sp. (6%), and Cystoisospora sp. (5%) oocysts were present at a lower prevalence on fecal flotation. Cryptosporidium sp. (9%) and Giardia sp. (16%) were detected by IFA. PCR analysis detected Sarcocystis (15%), Cystoisospora (5%), Eimeria sp., and either Neospora sp. or Hammondia sp. (1%). Through molecular techniques and phylogenetic analysis, we identified two distinct lineages of Sarcocystis sp. present in arctic foxes, which probably derived from cervid and avian intermediate hosts. Additionally, we detected previously undescribed genotypes of Cystoisospora. Our survey of gastrointestinal endoparasites in arctic foxes from the central Canadian Arctic provides a unique record against which future comparisons can be made. PMID:24533320

Systems integration of innate and adaptive immunity.

PubMed

Zak, Daniel E; Aderem, Alan

2015-09-29

The pathogens causing AIDS, malaria, and tuberculosis have proven too complex to be overcome by classical approaches to vaccination. The complexities of human immunology and pathogen-induced modulation of the immune system mandate new approaches to vaccine discovery and design. A new field, systems vaccinology, weds holistic analysis of innate and adaptive immunity within a quantitative framework to enable rational design of new vaccines that elicit tailored protective immune responses. A key step in the approach is to discover relationships between the earliest innate inflammatory responses to vaccination and the subsequent vaccine-induced adaptive immune responses and efficacy. Analysis of these responses in clinical studies is complicated by the inaccessibility of relevant tissue compartments (such as the lymph node), necessitating reliance upon peripheral blood responses as surrogates. Blood transcriptomes, although indirect to vaccine mechanisms, have proven very informative in systems vaccinology studies. The approach is most powerful when innate and adaptive immune responses are integrated with vaccine efficacy, which is possible for malaria with the advent of a robust human challenge model. This is more difficult for AIDS and tuberculosis, given that human challenge models are lacking and efficacy observed in clinical trials has been low or highly variable. This challenge can be met by appropriate clinical trial design for partially efficacious vaccines and by analysis of natural infection cohorts. Ultimately, systems vaccinology is an iterative approach in which mechanistic hypotheses-derived from analysis of clinical studies-are evaluated in model systems, and then used to guide the development of new vaccine strategies. In this review, we will illustrate the above facets of the systems vaccinology approach with case studies. Copyright © 2015. Published by Elsevier Ltd.

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Systems § 866.5120 Antismooth muscle antibody immunological test system. (a) Identification. An antismooth muscle antibody immunological test system is a device that consists of the reagents used to measure by... serum. The measurements aid in the diagnosis of chronic hepatitis (inflammation of the liver) and...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human allotypic marker immunological test system. 866.5065 Section 866.5065 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker...

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human allotypic marker immunological test system. 866.5065 Section 866.5065 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker...

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human allotypic marker immunological test system. 866.5065 Section 866.5065 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker...

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human allotypic marker immunological test system. 866.5065 Section 866.5065 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker...

21 CFR 866.5420 - Alpha-1-glycoproteins immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-glycoproteins immunological test system....5420 Alpha-1-glycoproteins immunological test system. (a) Identification. An alpha-1-glycoproteins... alpha-1-glycoproteins (a group of plasma proteins found in the alpha-1 group when subjected to...

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-1-antichymotrypsin immunological test system....5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... immunochemical techniques alpha-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues. Alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-1-antichymotrypsin immunological test system....5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... immunochemical techniques alpha-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues. Alpha-1...

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-1-antichymotrypsin immunological test system....5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... immunochemical techniques alpha-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues. Alpha-1...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

42 CFR 493.837 - Standard; General immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80 percent...

42 CFR 493.837 - Standard; General immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80 percent...

42 CFR 493.837 - Standard; General immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80 percent...

21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that consists...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...